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NURS 500
Research Proposal: Ethical Principles Assignment Instructions
Overview
The purpose of this assignment is to increase awareness of the ethical issues related to research. There are multiple ethical principles that must be considered when conduction a research study. In this assignment participant. protection is primary to understand. This goes beyond HIPPA as HIPPA related to patient medical issues and medical record privacy. A research proposal requires multiple other issues of privacy.
Read Chapter 9: Gray, J. R. & Grove, S. K. (2021). Burns and Grove’s the practice of nursing research: Appraisal, synthesis, and generation of evidence (9th ed.). St. Louis, MO: Elsevier Saunders.
Instructions
1. Write a 2 – 4-page paper that includes the following:
a. Explanation of the informed consent process for your research proposal. Even if your proposal qualifies for expedited review, you still must address informed consent specifically for your proposal.
b. Description of how you will protect participant privacy. HIPPA is insufficient for a research proposal. Address protection of data and confidentiality.
c. Review of the IRB process for your proposal.
d. The risk benefit ratio for the participant in your proposed study.
2. The page requirement excludes the title and reference pages.
3. Utilize current APA format.
A minimum of 2 scholarly references is required (excluding the textbook and Bible) to support/justify your topic and provide enough background information to make your idea(s) clear to the reader.
Note: Your assignment will be checked for originality via the Turnitin plagiarism tool.
Criteria Ratings Points
Research
Question or
Hypothesis
60 to >54.
0 pts
Advanced
The following
requirements are
specifically and
comprehensively
addressed: 1. Informed
consent 2. Participant
Privacy 3. IRB Process
4. Risk-benefit ratio for
the participants.
54 to >49.0 pts
Proficient
The following
requirements are
partially addressed and
lack sufficient detail:
1. Informed consent
2. Participant Privacy
3. IRB Process
4. Risk-benefit ratio for
the participants.
49 to >0.0 pts
Developing
The following requirements
are poorly addressed, and
information is missing for
one or more requirements:
1. Informed consent
2. Participant Privacy
3. IRB Process
4. Risk-benefit ratio for the
participants.
0 pts
Not
Present
60 pts
Sources 10 to >9.0 pts
Advanced
All sources (information
and graphics) are
scholarly, current, and
accurate.
9 to >7.0 pts
Proficient
Some sources
(information and
graphics) are scholarly,
current, or accurate.
7 to >0.0 pts
Developing
Sources (information and
graphics) are not scholarly,
current, or accurate.
0 pts
Not
Present
10 pts
Professional
Writing
Factors
(APA,
Grammar,
Spelling,
Sentence
Structure)
30 to >27.0 pts
Advanced
There are minimal or no
grammatical, spelling or
punctuation errors.
Sources are documented
in current APA format. A
minimum of 2 scholarly
references is included.
The paper is 2-4 pages
long.
27 to >24.0 pts
Proficient
There are a few
grammatical, spelling, or
punctuation errors.
Some sources are
documented in current
APA format. There is 1
scholarly reference
included. The paper is
1-2 pages long.
24 to >0.0 pts
Developing
There are many
grammatical, spelling, or
punctuation errors. The
sources are not documented
in current APA format and/or
there are 0-1 scholarly
references included. The
paper is 1 page or less.
0 pts
Not
Present
30 pts
Total Points: 100
Research Proposal: Ethical Principles Grading Rubric |
NURS500_B02_202220
“Many factors affected your decision to be a nurse but, for most of you, a key motivation was the desire to help others. Nursing as a profession is firmly based on the ethical principles of respect for persons, beneficence, and justice. These ethical principles that guide clinical practice must also be the standards for the conduct of nursing research (Fowler, 2017). In research, the application of ethics begins with identifying a study topic and continues through publication of the study findings. Ethical research is essential for generating evidence for nursing practice (Lach, 2019), but what does the ethical conduct of research involve? This question has been debated for many years by researchers, politicians, philosophers, lawyers, and even study participants. The debate continues because of the complexity of human rights issues; the focus of research in new, challenging arenas of technology, stem cells, and genomics; the complex ethical codes and regulations governing research; and the various interpretations of these codes and regulations. Unfortunately, specific standards of ethical research were developed in response to historical events in which the rights of participants were egregiously violated or the behavior of research scientists was blatantly dishonest (Grady, 2018). To provide an understanding of the rationale for today’s human participant protection requirements, this chapter begins by reviewing five historical events, and the mandates and regulations for ethical research that were generated as a result of them. In your clinical setting, you are probably familiar with the Health Insurance Portability and Accountability Act (HIPAA) and the necessity of protecting the privacy of a person’s health information (Department of Health and Human Services [DHHS], 2003). HIPAA, which identified the elements of private health information, has had a significant impact on researchers and institutional review boards (IRBs) in universities and healthcare agencies. The chapter also discusses the actions essential for conducting research in an ethical manner through protection of the rights of human participants. This includes making an unbiased assessment of the potential benefits and risks inherent in a study and ensuring that informed consent is obtained properly. The submission of a research proposal for institutional review is also presented. An ethical problem that has received increasing attention since the 1980s is researcher misconduct, also called scientific misconduct. Scientific misconduct is the violation of human rights during a study, including falsifying results or behaving dishonestly when disseminating the findings. Misconduct has occurred during all study phases, including reporting and publication of studies. Many disciplines, including nursing, have experienced episodes of research misconduct that have affected the quality of research evidence generated and disseminated. A discussion of current ethical issues related to research misconduct and to the use of animals in research concludes the chapter. Historical events affecting the development of ethical codes and regulations The ethical conduct of research has been a focus since the 1940s because of mistreatment of human participants in selected studies. Although these are not the only examples of unethical research, five historical experimental projects have been publicized for their unethical treatment of participants and will be described in the order in which the projects began: (1) the syphilis studies in Tuskegee, Alabama (1932–1972); (2) Nazi medical experiments (1941–1946) and resulting trials at Nuremberg; (3) the sexually transmitted infection study in Guatemala (1946–1948); (4) the Willowbrook State School study (1955–1970); and (5) the Jewish Chronic Disease Hospital study (1963–1965). More recent examples are included in the chapter, in relation to specific aspects of research. Although these five projects were biomedical and the primary investigators were physicians, nurses were aware of the research, identified potential participants, delivered treatments to participants, and served as data collectors in all of them. As indicated earlier, these and other incidences of unethical treatment of participants and research misconduct were important catalysts in the formulation of the ethical codes and regulations that direct research today. Tuskegee syphilis study In 1932, the US Public Health Service (USPHS) initiated a study of syphilis in African American men in the small, rural town of Tuskegee, Alabama (Brandt, 1978; Reverby, 2012; Rothman, 1982). The study, which continued for 40 years, was conducted to observe the natural course of syphilis in African American men. The researcher hired an African American nurse, Eunice Rivers, to recruit and retain participants. The research participants were organized into two groups: one group consisted of 400 men who had untreated syphilis, and the other was a control group of approximately 200 men without syphilis. Most of the men who consented to participate in the study were not informed about the purpose and procedures of the research. Some men were unaware that they were participants in a study. Some were subjected to spinal taps and told the procedure was treatment for their “bad blood” (Reverby, 2012), the colloquial term for syphilis and other diseases of the blood. By 1936, the group of men with syphilis experienced more health complications than did the control group. Ten years later, the death rate of the group with syphilis was twice as high as that of the control group. The participants with syphilis were examined periodically but were never administered penicillin, even after it became the standard treatment in the 1940s (Brandt, 1978). These results could have been predicted because untreated syphilis was and is the most damaging of the bacterial venereal diseases, with degeneration occurring from cardiac lesions, brain deterioration, or involvement of other organ systems. The findings of the Tuskegee syphilis study were published beginning in 1936, and additional papers were published every 4 to 6 years. In 1953, Nurse Rivers was the first author on a publication about the study procedures to retain participants (Rivers, Schuman, Simpson, & Olansky, 1953). At least 13 articles were published in medical journals reporting the results of the study. In 1969, the US Centers for Disease Control and Prevention (CDC) reviewed the study and decided that it should continue. In 1972, a story published in the Washington Star about the study sparked public outrage. Only then did the US Department of Health, Education, and Welfare (DHEW) stop the study. An investigation of the Tuskegee study found it to be ethically unjustified. In 1997, President Clinton publicly apologized for the government’s role in this event (Baker, Brawley, & Marks, 2005; Reverby, 2012). Nazi medical experiments From 1933 to 1945, the Third Reich in Europe implemented atrocious, unethical activities, some of which they called research (Steinfels & Levine, 1976). Their goal was to produce a population of racially pure Germans, also known as Aryan. Most notably, the Nazis targeted all Jews for imprisonment and systematic genocide, resulting in millions of deaths. Population growth among the Aryans was encouraged. In contrast, Nazi doctors sterilized people regarded as racial enemies, such as the Jews. In addition, Nazis killed people whom they considered racially impure or disabled, such as persons with mental illness, disabilities, and dementia. Almost 0.25 million Germans who were physically or mentally disabled (Jacobs, 2008) and 300,000 psychiatric patients (Foth, 2013) were killed. These same people were also used as research participants. The medical experiments involved exposing participants to high altitudes, freezing temperatures, malaria, poisons, spotted fever (typhus), new drugs, and unproven surgeries, usually without anesthesia (Steinfels & Levine, 1976). For example, participants were immersed in freezing water to determine how long German pilots could survive if shot down over the North Sea. Identical twins were forced to be participants of experiments in which one would be infected with a disease. Both were later killed for postmortem examination of their organs to determine differences due to the disease. These medical experiments purportedly were conducted to generate knowledge to benefit Aryans at the cost of suffering and death for prisoners in no position to give consent. In addition to the atrocities and coercion, however, the studies were poorly designed and conducted. As a result, little if any useful scientific knowledge was generated. The Nazi experiments violated ethical principles and rights of the research participants. Researchers selected participants on the basis of race, affliction, or sexual orientation, demonstrating an unfair selection process. The participants also had no opportunity to refuse participation; they were prisoners who were coerced or forced to participate. Frequently, study participants were killed during the experiments or sustained permanent physical, mental, and social damage (Levine, 1986; Steinfels & Levine, 1976). The doctors who propagated the mistreatment of human participants were brought to trial, along with other Nazi soldiers and officers, in Nuremberg, Germany, beginning in 1945. Nuremberg code At the conclusion of the trials of Nazi doctors involved in research, the defense presented 10 guidelines for appropriate research with human participants, which collectively became known as the Nuremberg Code (1949). Among the principles were the following: (1) participants’ voluntary consent to participate in research; (2) the right of participants to withdraw from studies; (3) protection of participants from physical and mental suffering, injury, disability, and death during studies; and (4) an assessment of the benefits and risks in a study. The Nuremberg Code (1949) forms the basis for protection for all human participants, regardless of a researcher’s disciplinary affiliation. Declaration of helsinki The members of the World Medical Organization (WMO) were understandably alarmed by the actions of Nazi researchers during World War II. The World Medical Assembly (WMA) of the WMO drafted a document called the Declaration of Helsinki in 1964. The Declaration of Helsinki (WMO, 1996) has subsequently been reviewed and amended, with the last amendment being approved in 2013 (WMA, 2013). The declaration forms the foundation for current research protection practices, such as research ethics committees. A research ethics committee must review proposed human participant research for possible approval; if the study is approved, the committee is responsible for monitoring its methods and outcomes as well as reviewing and approving any alterations in the research plan before such changes are implemented. The declaration also differentiates therapeutic research from nontherapeutic research. Therapeutic research gives the patient an opportunity to receive an experimental treatment that might have beneficial results. Nontherapeutic research is conducted to generate knowledge for a discipline: The results from the study might benefit future patients with similar conditions but will probably not benefit those acting as research participants. Box 9.1 contains several ethical principles from the declaration. The complete document is available from the WMA (2018). BOX 9.1 Key Ideas of the Declaration of Helsinki 1. Well-being of the individual research participant must take precedence over all other interests. 2. Investigators must protect the life, health, privacy, and dignity of research participants. 3. A strong, independent justification must be documented prior to exposing healthy volunteers to risk of harm, merely to gain new scientific information. 4. Extreme care must be taken in making use of placebo-controlled trials, which should be used only in the absence of an existing proven therapy. 5. Clinical trials must focus on improving diagnostic, therapeutic, and prophylactic procedures for patients with selected diseases without exposing participants to any additional risk of serious or irreversible harm. From Declaration of Helsinki. (1964, 2013). WMA declaration of Helsinki—Ethical principles for medical research involving human subjects. Retrieved from https:// www.wma.net/ policies-post/ wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ Worldwide, most institutions in which clinical research is conducted have adopted the Declaration of Helsinki. It has been revised, with the most recent revision increasing protection for vulnerable populations and requiring compensation for participants harmed by research (WMA, 2018). However, neither this document nor the Nuremberg Code has prevented some investigators from conducting unethical research (Beecher, 1966). Remember that the Tuskegee study continued after the Declaration of Helsinki was first released. Guatemala sexually transmitted disease study Beginning in 1946, a USPHS employee, Dr. John C. Cutler, conducted a study in Guatemala in which participants were intentionally exposed to syphilis and other sexually transmitted diseases. The participants were “sex workers, prisoners, mental patients, and soldiers” (Reverby, 2012, p. 8). Initially, participants were to be given penicillin or an arsenic compound (the treatment prior to penicillin) between exposure and infection to determine the prophylactic efficacy of each medication. The records for the study are incomplete, and it is not known how many persons developed an infection, died from the infection, or were harmed by the administered treatment (Reverby, 2012). The researchers suppressed information about their interventions and findings because they anticipated negative publicity due to the unethical nature of the study. After Dr. Cutler left in 1948, the USPHS continued to fund researchers to monitor the research participants and conduct serological testing through 1955 (Presidential Commission for the Study of Bioethical Issues, 2011). In 2010, Reverby (2012) was reviewing the records of researchers who participated in the Tuskegee study and found the papers of Dr. Cutler in which the Guatemala study was described. She shared her discovery with the CDC, and, subsequently, President Obama was informed. A public apology ensued. The Presidential Commission for the Study of Bioethical Issues (2011) investigated and wrote a report confirming the facts of the Guatemala study. Willowbrook study From the mid-1950s to the early 1970s, Dr. Saul Krugman practiced at Willowbrook State School, a large institution for cognitively impaired persons in Brooklyn, New York, and conducted research on hepatitis A infection (Rothman, 1982). The participants, all children, were deliberately infected with the hepatitis A virus. During the 20-year study, Willowbrook closed its doors to new children because of overcrowded conditions. However, the research ward continued to admit new children. To gain a child’s admission to the institution, parents were required to give permission for the child to be a study participant. Hepatitis A affects the liver, producing vomiting, nausea, and tiredness, accompanied by jaundice. The infected children suffered pain and potentially long-term effects. From the late 1950s to early 1970s, Krugman’s research team published several articles describing the study protocol and findings. Beecher (1966) cited the Willowbrook study as an example of unethical research. The investigators defended exposing the children to the virus by citing their own belief that most of the children would have acquired the infection after admission to the institution. They based their belief on the high hepatitis infection rates of children during their first year of living at Willowbrook. The investigators also stressed the benefits that the participants received on the research ward, which were a cleaner environment, better supervision, and a higher nurse-patient ratio (Rothman, 1982). Despite the controversy, this unethical study continued until the early 1970s. Jewish chronic disease hospital study Another highly publicized example of unethical research was a study conducted at the Jewish Chronic Disease Hospital in the 1960s. The USPHS, the American Cancer Society, and Sloan-Kettering Cancer Center funded the study (Nelson-Marten & Rich, 1999). Its purpose was to determine the patients’ rejection responses to live cancer cells. Twenty-two patients were injected with a suspension containing live cancer cells that had been generated from human cancer tissue (Levine, 1986). Most of the patients and their physicians were unaware of the study. An extensive investigation revealed that the patients were not informed they were research participants. They were informed that they were receiving an injection of cells, but the word cancer was omitted (Beecher, 1966). In addition, the Jewish Chronic Disease Hospital’s IRB never reviewed the study. The physician directing the research was an employee of the Sloan-Kettering Institute for Cancer Research, and there was no indication that this institution had reviewed the study (Hershey & Miller, 1976). The study was considered unethical and was terminated, with the lead researcher found to be in violation of the Nuremberg Code (1949) and the Declaration of Helsinki (WMA, 2013). This research had the potential to cause study participants serious or irreversible harm and possibly death, reinforcing the importance of conscientious institutional review and ethical researcher conduct. Early US government research regulations Following World War II, the US government increased funding for research. Federal funding by the National Institutes of Health (NIH) for research grew rapidly from less than $ 1 million in 1945 to over $ 435 million in 1965 (Beecher, 1966). This influx of funds along with newly discovered advances in medical treatment raised the potential for increased numbers of research violations. Dr. Henry Beecher (1966) published a paper with 22 examples of experimental treatments implemented without patient consent, raising concerns that the interests of science could override the interests of the patient. The government recognized the need for additional oversight. This section describes three government regulations that were developed as a result. US department of health, education, and welfare In 1973, the DHEW published its first set of regulations intended to protect human participants (Advisory Committee on Human Radiation Experiments, 1995). Clinical researchers were required to be compliant with the new stricter regulations for human research, with additional regulations to protect persons with limited capacity to consent, such as ill, cognitively impaired, or dying individuals (Levine, 1986). All research proposals involving human participants were required to undergo full institutional review, a task that became overwhelming and greatly prolonged the time required for study approval. Even studies conducted by nurses and other health professionals that involved minimal or no risks to study participants were subjected to full board review. Despite the advancement of the protection of participants’ rights, the government recognized the need for additional strategies to manage the extended time now required for study approval. National commission for the protection of human subjects of biomedical and behavioral research Because of the problems related to the DHEW regulations, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978) was formed. The commission’s charge was to identify basic ethical principles and develop guidelines based on these principles that would underlie the conduct of biomedical and behavioral research involving human participants. The commission developed what is now called the Belmont Report (DHHS, 1979). This report identified three ethical principles as relevant to research involving human participants: respect for persons, beneficence, and justice (Grady, 2018; Thakur & Lahiry, 2019). The principle of respect for persons holds that persons have the right to self-determination and the freedom to participate or not participate in research. The principle of beneficence requires the researcher to do good and avoid causing harm. The principle of justice holds that human participants should be treated fairly (Gravetter & Forzano, 2018). The commission developed ethical research guidelines based on these three principles, made recommendations to the DHHS, and was dissolved in 1978. The three ethical principles that the report identified are still followed for all federally supported research, whether implemented in the United States or internationally. Subsequent to the work of the commission, the DHHS developed federal regulations in 1981 to protect human research participants, which have been revised as needed over the past 35 years (DHHS, 1981). The first of these was the Code of Federal Regulations (CFR), Title 45, Part 46, Protection of Human Subjects, with the most recent edition being available online (DHHS, 2018). Box 9.2 lists the types of research governed by DHHS. An arm of the DHHS is the Federal Drug Administration (FDA), and its research activities are governed by CFR Title 21, Food and Drugs, Part 50, Protection of Human Subjects (FDA, 2019b), and Part 56, Institutional Review Boards (IRBs) (FDA, 2019a). Box 9.3 lists the research covered by the FDA regulations. BOX 9.2 Research Regulated by DHHS: CFR Title 45, Part 46, Protection of Human Subjects 1. Studies conducted by, supported by, or otherwise subject to regulations by any federal department or agency 2. Research conducted in educational and healthcare settings 3. Research involving the use of biophysical measures, educational tests, survey procedures, scales, interview procedures, or observation 4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens. Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5ad32ac566ecdb2466df8f068b6036a27& mc5true& node5pt45.1.46& rgn5div5 BOX 9.3 Research Regulated by the FDA: CFR Title 21, Parts 50 and 56 • Studies that test 1. Drugs for humans 2. Medical devices for human use 3. Biological products for human use 4. Human dietary supplements 5. Electronic healthcare products used with humans • Responsible for the management of new drugs and medical devices Data from U.S. Food and Drug Administration. (2019b). Protection of human subjects. Code of Federal Regulations, Title 21 Food and Drugs, Department of Health and Human Services, Parts 50 and 56. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5d494ea202a7a4e40a8f63306fd8b7142& mc5true& node5pt21.1.50& rgn5div5# se21.1.50_11 The DHHS regulations are known as the Common Rule because they are applicable across multiple DHHS agencies. The DHHS regulations are interpreted and enforced by the Office for Human Research Protection (OHRP), an agency within the DHHS (2016). In addition to providing guidance and regulatory enforcement, the OHRP develops educational programs and materials, and provides advice on ethical and regulatory issues related to biomedical and social-behavioral research. Standards for privacy for research data The concern for privacy of patient information related to the electronic storage and exchange of health information resulted in the privacy regulations known as HIPAA (Bonham, 2018). HIPAA did not require anything that was not required during routine nursing practice before its instigation; however, it addressed both electronic data security and consequences of failure to protect such data. The HIPAA Privacy Rule established the category of protected health information (PHI). The rule allows covered entities, such as health plans, healthcare clearinghouses, and healthcare providers, to use or disclose PHI to others only in certain situations. The Privacy Rule also applies to research that involves the collection of PHI (DHHS & Office for Civil Rights, 2013; HIPAA Journal, 2018). Individuals must provide a signed authorization before their PHI can be used or disclosed for research purposes. This chapter covers these regulations in the sections on protection of human rights, obtaining informed consent, and institutional review of research. Protection of human rights Human rights are justifiable claims and demands that are necessary for the self-respect, dignity, and freedom of choice for an individual (Grady, 2018). Our professional code of ethics, the American Nurses Association (ANA) Code of Ethics for Nurses (ANA, 2015), includes protection for the rights of human participants in biological and behavioral research, founded on the ethical principles of beneficence, nonmaleficence, autonomy, and justice. The human rights that require protection in research are (1) the right to self-determination, (2) the right to privacy, (3) the right to anonymity and confidentiality, (4) the right to fair treatment or justice, and (5) the right to protection from discomfort and harm (ANA, 2015; Fowler, 2017). These rights are described as follows, including situations in which they can be violated. Right to self-determination The right to self-determination is based on the ethical principle of respect for persons. Respect for persons means that humans are capable of self-determination or making their own decisions. Because of this right, humans should be treated as autonomous agents who have the freedom to conduct their lives as they choose without external controls. As a researcher, you treat prospective participants as autonomous agents when you inform them about a proposed study and allow them to choose voluntarily whether to participate (Thakur & Lahiry, 2019). In addition, participants have the right to withdraw from a study at any time without penalty (Grady, 2018). A participant’s right to self-determination can be violated through covert data collection and deception. The right of self-determination may also be threatened when potential research participants are susceptible to coercion or have diminished capacity to make independent decisions. Specific groups who have been identified as being susceptible to coercion needing additional protection include persons of racial/ ethnic minorities, prisoners, pregnant women, fetuses, neonates, and children. Each of these threats and groups requiring additional protection will be described in the following sections. Covert data collection An individual’s right to self-determination can be violated if he or she becomes a research participant without realizing it. Some researchers have exposed persons to experimental treatments without their knowledge, a prime example being the Jewish Chronic Disease Hospital study. With covert data collection, participants are unaware that research data are being collected because the investigator’s study involves collecting data about normal activity or routine health care (Reynolds, 1979). Studies in which observation is used to collect data, such as ethnographic research, are especially challenging because the researcher does not want to interfere with what would normally happen by identifying that observational data are being collected. Covert data collection can occur if participants’ behaviors are public. For example, a researcher could observe and record the number of people walking down a street who are smoking. However, covert data collection is considered unethical when research deals with sensitive aspects of an individual’s behavior, such as illegal conduct, sexual behavior, and drug use. In keeping with the HIPAA Privacy Rule (DHHS & Office for Civil Rights, 2013), PHI data collected in any manner can only be used if there is minimal risk of harm to the participants. This means the use of any type of covertly collected data would be questionable and unethical, and illegal if PHI data were being used or disclosed without prior approval. Deception The use of deception in research also can violate a participant’s right to self-determination. Deception is misinforming participants of the study’s purpose or withholding some information about the study (Gravetter & Forzano, 2018; Kazdin, 2017). A classic example of deception is the Milgram (1963) study, in which participants thought they were administering electric shocks to another person. The participants did not know the person being shocked was a professional actor who pretended to feel pain. Because of participating in this study, some participants experienced severe mental tension, almost to the point of collapse (Algahtani, Bajunaid, & Shirah, 2018; Kazdin, 2017). A researcher developing a study involving deception must be prepared to justify the deception by providing evidence that the benefits of the study are greater than the potential risks (Gravetter & Forzano, 2018; Kazdin, 2017). For example, the researcher must argue that deception is the only way the research question can be answered. The research question must be significant, and the researcher will need to specify how debriefing will occur (Gravetter & Forzano, 2018). After data collection is complete, the researcher provides debriefing of the participant by presenting the complete, accurate purpose of the study with the goal of minimizing the possible negative effects of the study. The debriefing also includes why the deception was deemed necessary (Kazdin, 2017). Covert data collection is passive deception. It may be approved by an IRB in situations in which the research is essential, the data cannot be obtained any other way, and the participants will not be harmed. For an example, on a clinical unit, the researcher may indicate that a study is about the number and type of interruptions that occurred during a nurse’s day. In reality, the researchers are observing the nurses’ compliance with hand hygiene guidelines. Covert direct observation might be approved in such a situation if the results were not going to be linked to individual nurses. In the rare situations in which covert data collection is allowable, participants must be informed of the deception once the study is completed, provided full disclosure of the study activities that were conducted (Gravetter & Forzano, 2018; Kazdin, 2017), and given the opportunity to withdraw their data from the study. Susceptible to coercion Coercion occurs when one person intentionally presents another with an overt threat of harm or the lure of excessive reward to obtain his or her compliance. The older version of the Common Rule (DHHS, 2013) identified specific vulnerable groups, including pregnant women, human fetuses, neonates, children, persons with mental incompetence, and prisoners. Conducting research with members of these groups required additional protection in the conduct of research. The revised Common Rule (DHHS, 2018) does not identify vulnerable populations but describes persons and situations in which persons may be sensitive to coercion or undue influence. The persons sensitive to coercion include some of those who were previously classified as being vulnerable, such as children, prisoners, and persons with diminished decision-making ability. However, persons who are economically or educationally disadvantaged and members of racial and ethnic minorities were included among those susceptible to coercion (DHHS, 2018). This new approach broadens the concept and puts additional responsibility on researchers to consider their inclusion and exclusion criteria and recruitment procedures. However, in many situations, the data needed to determine evidence-based care are dependent on the inclusion of persons who may be sensitive to coercion (Grady, 2018). Subjects may feel coerced to participate in research because they fear that they will suffer harm or discomfort if they do not participate. Students may feel forced to participate in research to protect their grades or prevent negative relationships with the faculty member conducting the research (Boileau, Patenaude, & St-Ong, 2018). Some patients believe that their medical or nursing care will be negatively affected if they do not agree to be research participants, a belief that may be reinforced if a healthcare provider is the one who attempts to recruit them for a study. Therapeutic misconception is the belief that research participation will result in better clinical care (Bailey & Ladores, 2018). Therapeutic misconception has also been defined as participants’ failure to distinguish between the therapeutic relationship between a patient and a healthcare provider and the protocol-driven relationship between a participant and a researcher (McConville, 2017). Despite what the clinician-researcher said about the participant’s care not being based on their consent, persons with cystic fibrosis (CF) believed their care would be better because they participated in research studies (Christofides, Stroud, Tullis, & O’Doherty, 2017). Subjects may feel coerced to participate in studies because the study offers a potential treatment and they have exhausted all other treatment options (Grady, 2018). Other participants believe that they cannot refuse the excessive rewards offered, such as large sums of money, specialized health care, special privileges, and jobs. Another example of coercion is what happened at Willowbrook State School. The school offered a specialized education for children with disabilities. The only way that parents could secure admission was to allow their child to be in the study and deliberately infected with hepatitis. Most nursing studies do not offer excessive rewards to participants. A researcher may offer reasonable payment for time and transportation costs, such as $ 10 to $ 30, or a gift certificate for this amount. When participants have a rare disorder and must travel long distances for data collection, the researcher or sponsor of the study should pay travel and lodging expenses (Gelinas, Crawford, Kelman, & Bierer, 2019). An IRB will evaluate whether a proposed payment is coercive compared to the effort and time required to participate in a study (Grady, 2018). Conducting research ethically requires that persons who are susceptible to coercion have additional protection during the conduct of research (DHHS, 2018). One protective strategy is to have waiting periods between hearing about a study and obtaining informed consent (Grady, 2018). The waiting period allows participants to consult with family and friends or think of questions that they want to ask. Thoughtful planning and open dialogue between researchers and participants can create conditions to ensure informed consent is not coercive. Diminished autonomy Autonomy is the ability to make a voluntary decision based on comprehending information about the study (Kaye, Chongwe, & Sewankambo, 2019). Some persons have diminished autonomy because of legal or mental incompetence, terminal illness, or confinement to an institution (Kazdin, 2017). Persons are said to be incompetent if a qualified healthcare provider judges them to be unable to comprehend and voluntarily decide about participation in a study. Incompetence can be temporary (e.g., substance use), permanent (e.g., intellectual disability), or transitory (e.g., delirium or psychosis). Unconscious patients and those with reduced cognitive abilities are seen as legally incompetent to give informed consent because they lack the ability to comprehend information about a study. The concern is that a person who, for whatever reason, is unable to absorb, retain, and evaluate the information about a study cannot protect themselves from possible harm or make an informed decision about whether to participate in a study. However, without finding ways to ethically obtain informed consent and including them in studies, the evidence upon which to base their safe, quality care will continue to be lacking and not grow (Ho, Downs, Bulsara, Patman, & Hill, 2018). Persons living with psychosis are the logical participants for studies of the safety and efficacy of antipsychotic medications. Nurse researchers conducted a systematic review of 646 clinical trials with participants who had been diagnosed with a psychosis. The purpose of the review was to determine the extent to which the participants were assessed for their capacity to provide informed consent (Weissinger & Ulrich, 2019). They learned that less than 10% of the studies included the capacity to provide informed consent in their inclusion/ exclusion criteria. Only 34 studies (5%) reported using a capacity assessment to determine the ability of potential participants to give consent. Patients with mild to severe dementia or Alzheimer disease may have a compromised capacity to understand the information necessary to giving informed consent. Chester, Clarkson, Davies, Hughes, and Islam (2018) published their study protocol of a pragmatic clinical trial conducted in England comparing caregivers being taught to use memory aids with a person who has early dementia to usual treatment. The researchers elicited input from an advisory group called the Public, Patient, and Carer Reference Group (PPCRG). The process and documents used to recruit potential participants were designed “following guidance from the PPCRG on language and format, to ensure that those with cognitive impairment are fully informed and engaged in the decision to take part” (Chester et al., 2018, p. 4). Using an advisory group such as the PPCRG is a robust strategy for designing appropriate recruitment procedures for any group of persons who may have diminished capacity to provide informed consent. The use of persons with decreased decision-making ability as research participants is more acceptable if several conditions exist. When the research is therapeutic, there is less concern because the participants have the potential to benefit directly from the experimental process (DHHS, 2018). Samples including persons with diminished autonomy are more acceptable when the researcher is recruiting persons with adequate autonomy as well as those with reduced autonomy as participants. Another positive factor is the availability of preclinical and clinical studies that provide evidence upon which to base the assessment of potential risks for participants. Research with persons with diminished decision-making ability is also more acceptable when risk is minimal and the consent process is strictly followed to protect the rights of the prospective participants (DHHS, 2018). Other ways to include persons with diminished capacity in studies is to assess their ability to comprehend using a standard instrument. Ho et al. (2018) recommended that researchers develop relationships with potential participants with diminished capacity and their caregivers, observing the potential participant multiple times prior to obtaining consent from the caregiver or the participant. To assess the capacity of the participant to give consent, they used an assessment tool called the “Three-Item Decisional Questionnaire (3-IDQ) adopted from Palmer et al., 2005” (Ho et al., 2018, p. 94). Another assessment, the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR), was identified as one of the strongest instruments available for assessing an individual’s capacity to give informed consent (Simpson, 2010). The companion tool, the MacArthur Competency Assessment Tool for Treatment (MacCAT-T), has been identified as the gold standard for assessing mental capacity to consent to treatment (Elzakkers, Danner, Grisso, Hoek, & van Elburg, 2018). Evidence has been published for interrater reliability, concurrent validity, and effective use of the tools across a wide range of patients (see Chapter 16) (Elzakkers et al., 2018). For a research study, the persons responsible for recruiting participants and obtaining informed consent would need to be trained in using the MacCAT-CR. Using this instrument or similar tools, researchers can make an objective decision about a participant’s ability to consent to research. If an individual is judged incompetent and incapable of consent, you must seek approval from the prospective participant and his or her legally authorized representative. A legally authorized representative means an individual or a group is authorized under law to consent on behalf of a prospective participant to his or her participation in research. The authorized representative is sometimes called a proxy. The legally authorized representative or proxy may be a spouse or close relative, if the potential participant has not designated a power of attorney. If no spouse or close relative can be accessed, a legal representative can be appointed by the state. Groups needing additional protection The groups identified as susceptible to coercion require additional protection to participate in research. Five groups requiring additional protection are described in this section: prisoners, terminally ill persons, pregnant women, fetuses and neonates, and children. Prisoners. Prisoners have diminished autonomy to consent for research because of their confinement. They may feel coerced to participate in research because they fear harm if they refuse (Midwest Nursing Research Society [MNRS], 2018) or because they desire the benefits of special treatment, monetary gain, or relief from boredom. In the past, prisoners were used for drug studies in which the medications had no health-related benefits and, instead, potential harmful side effects. Current regulations regarding research involving prisoners require that “the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers” and “procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners” (DHHS, 2018, Section 46.305). An IRB that is considering a study that include prisoners must add a prisoner or prisoner representative prior to reviewing the study. When a proposal is reviewed by multiple IRBs, only one of the IRBs must have a member that represents the prisoners. Terminally ill participants. Two factors need to be considered when designing a study with a sample that includes persons with terminal illness: (1) Who will benefit from the research? and (2) Is it ethical to conduct research on individuals who are unlikely to benefit from the study? Participating in research could have greater risks and minimal or no benefits for these participants. In addition, the dying participant’s condition could affect the results, leading to misinterpretation of the findings. Another consideration is persons with terminal illness have limited time remaining in their lives. Is it fair to ask them to spend time on a study instead of spending it with family or engaged in preferred activities? However, unless persons with terminal illness or those receiving palliative care are included in studies, the knowledge base for hospice and palliative care will not grow and be refined (Pereira & Hernández-Marrero, 2019). Some terminally ill individuals are willing participants because they believe that participating in research is a way to contribute to society before they die. Others want to take part in research because they believe that the experimental process may benefit them by slowing their disease process, potentially another example of a therapeutic misconception. Pregnant women and fetuses. Pregnant women have historically been considered vulnerable participants in regard to research (Ballantyne et al., 2017). Policies to include women, including pregnant women, in studies and policies to exclude women due to potential harm to the fetus contradict each other and result in confusion about how women should be recruited for studies (van der Graaf et al., 2018). Federal regulations define pregnancy as encompassing the period of time from implantation until delivery. “A woman is assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery” and the fetus is defined as the “product of conception from implantation until delivery” (DHHS, 2018, 45 CFR Section 46.202). Research conducted with pregnant women can occur only after studies have been done with animals and nonpregnant women to assess the potential risks. Table 9.1 lists the conditions under which a pregnant woman can be included, such as the potential for direct benefit to the woman or the fetus. If a study may benefit only the fetus, the consent of the pregnant woman and father must be obtained. TABLE 9.1 Conditions That Must Be Present for Pregnant Women to Be Included in a Study General Condition Specific Details Knowledge of potential side effects Studies with animals and nonpregnant women have been conducted and results indicated safety of the intervention. Scientifically important information Woman and fetus may benefit from the intervention. If not, risk is minimal. Knowledge cannot be gained any other way. Least possible risk Risk is minimized but study objectives can still be met. Balance of risks and benefits If no potential benefit to either mother or fetus, risk must be minimized. Consent of both parents Required if fetus is only one to benefit from the study. Father’s consent not needed if he is unavailable, incompetent, or pregnancy due to rape or incest. Fully informed Potential impact on the mother or fetus is clear in the consent form, before requesting mother to sign. No incentive or interference to terminate the pregnancy Mother does not receive any inducement to terminate pregnancy. Research staff not involved in any decision to terminate the pregnancy. Viability of the fetus Research staff not involved in any decision about neonate’s viability after delivery. Some researchers did not include pregnant women in their studies because they assumed the women would not want to participate. In New Zealand, Ballantyne et al. (2017) added a qualitative arm to a randomized intervention clinical trial for which the sample was pregnant women. This study was called the Research in Pregnancy Ethics (RIPE) study. “The RIPE study set out to ascertain views of pregnant women about research participation, by conducting semi-structured interviews and then analysing the interview transcripts using inductive thematic analysis ( Braun & Clarke, 2006). Women were recruited from a pool of participants already participating in the PiP [Probiotics in Pregnancy] study.” ( Ballantyne et al., 2017, p. 478) “The main cited benefits of the study by the participants were abstract principles of altruism, playing a valuable civic role and the importance of research. No-one cited personal benefit or gain as a motivation for participating…. The main perceived burdens related to inconvenience and time commitment…. Women wanted to clarify the time commitments and how this would fit into their schedule; they did not want to overcommit given the demands of pregnancy and having a newborn baby.” ( Ballantyne et al., 2017, pp. 479–480) “Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes.” ( Ballantyne et al., 2017, p. 483) Pregnant women should not be excluded from studies unless an increased risk to the woman or the fetus exists. Ballantyne et al. (2017) provided insight for other researchers considering recruiting pregnant women for a study. Neonates. A neonate is defined as a newborn and is further identified as either viable or nonviable on delivery. Viable neonates are able to survive after delivery through the use of technology and other therapies. An additional factor in being considered viable is the ability to maintain a heartbeat and respiration. Nonviable neonates may be living after delivery but will not be able to survive (DHHS, 2018). Neonates are extremely vulnerable and require extra protection to determine their involvement in research. However, research may involve viable neonates, neonates of uncertain viability, and nonviable neonates when the conditions identified in Box 9.4 are met. In addition, for the nonviable neonate, the vital functions of the neonate should not be artificially maintained because of the research, and the research should not terminate the heartbeat or respiration of the neonate (DHHS, 2018). BOX 9.4 Conditions to Be Met for Approval of Research With Neonates • Data available from preclinical and clinical study to assess potential risk to neonates • Potential to provide important biomedical knowledge that cannot be obtained by other means • No additional risk to the neonate • Potential to enhance the probability of the neonate’s survival • Both parents fully informed about the research and give consent • Research team has no part in determining the viability of the neonate Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.hhs.gov/ ohrp/ regulations-and-policy/ regulations/ 45-cfr-46/ index.html Children and adolescents. Children are considered vulnerable in the context of research (Singh, Siddiqi, Parameshwar, & Chandra-Mouli, 2019). However, we need more evidence upon which to base pediatric nursing practice. To develop the necessary evidence, children must be recruited for studies and assent or consent obtained (Crane & Broome, 2017). The distinction between children and adolescents is not clear. The World Health Organization (WHO, 2018) describes adolescents as being the second decade of life. The age of consenting to participate in a study is usually considered to be 18 years of age, but legal and research experts disagree among themselves (Cherry, 2017; Sade, 2017). Unfortunately, the legal definitions of the minor status of a child are statutory and vary among states and even countries. Neurophysical and psychological evidence supports the premise that adolescents lack the cognitive and affective maturity to give consent for themselves. Cherry (2017) identifies three components that comprise meaningful assent or consent for children and adolescents: intellectual development, affective development, and personal agency (Fig. 9.1). The figure is consistent with the findings of Hein, Troost, Lindeboom, Benninga, and Zwaan (2015), who found that age, followed by intelligence, explained the largest portion of the variance in a child’s or adolescent’s competence related to consent to research. Grady et al. (2014) studied the perceptions of assent/ consent among adolescents enrolled in clinical research and their parents. Approximately 40% of the sample believed that the decision for an adolescent to participate should be jointly made by parents and adolescent. Even among adolescent participants in research, however, understanding their rights and grasping the meaning of the study itself has been found to be less than desired (Cherry, 2017). Fig. 9.1Capacity to give meaningful consent. A pie chart representing capacity to give meaningful consent is divided into three sections marked clockwise as affective component, personal agency, and intellectual component. Federal regulations contain two stipulations for obtaining informed consent: The research must be of minimal risk, and both the assent of the child (when capable) and the permission of the parent or guardian must be obtained (DHHS, 2018). Assent means a child’s affirmative agreement to participate in research. Box 9.5 provides an example of an assent form. Permission to participate in a study means that the parent or guardian agrees to the participation of the child or ward in research (DHHS, 2018). If a child does not assent to participate in a study, he or she should not be included as a participant even if the parent or guardian gives permission. For therapeutic research, IRBs can approve studies with children when more than minimal risk is present, provided that potential benefit exists for the child, or when the experimental treatment is similar to usual care and the findings have potential benefit for others. Studies that do not meet these stipulations but have the potential for significant contribution to knowledge that may benefit other children with the same condition can be approved (DDHS, 2018). In all cases, procedures to obtain assent and parental permission must be implemented. BOX 9.5 Sample Assent Form for Children Ages 8 to 12 Years: Weight, Activity, and Eating Habits Before and After Mother-Child Multimedia Intervention Oral explanation We are nurses who want children like you to be strong and have energy to play and go to school. Here at your school, we are doing research on the best ways to teach you and your parents how to eat better and get more exercise using videos and computer games. If you decide to be in the study, we will measure your height and weight in a room with only your mother and the nurse. No one but them will know how much you weigh or how tall you are unless you tell them. We will ask you to answer five questions about what you eat and whether you exercise. Exercise is running, playing games outside, going for a walk, and doing things for fun where you move your body. After that, you and your mom will play a video game on the computer and watch two videos that are less than 5 minutes long. For the next five Tuesdays, we will be here after school. You and your mom will be asked the same five questions, watch two different videos, and play the video game together. We will have snacks for you and your mom to eat each time. On the sixth Tuesday, we will measure how tall you are and how much you weigh. On that day, we will ask you what you liked and didn’t like about the videos and computer games. You can change your mind about being in the study and can stop at any time. To child 1. I want to learn about what to eat to make me strong and have energy. 2. I want to answer questions about what I eat and how much exercise I get. 3. I want to watch videos and play a computer game with my mom. If the child says YES, have him/ her put an “X” here: _______________________ If the child says NO, have him/ her put an “X” here: ________________________ Date: ______________________ Child’s signature: ________________________ Another point of controversy is the age at which a child can assent to a study. A child’s competency to assent is usually governed by age, and research evidence supports the standard of a child over 10 years of age being capable of sufficient understanding to give assent (Crane & Broome, 2017). Children who are developmentally delayed, have a cognitive impairment, suffer an emotional disorder, or are physically ill must be considered on an individual basis. When designing a study in which children will be participants, it is helpful to seek consultation with a child development specialist and the primary IRB to which you will submit the study for approval. Some IRBs have developed assent guidelines or forms specific to their facilities. Assent and permission require that both the child or adolescent and parents be informed about the study. The information shared with the child about the study should be appropriate for the child’s age and culture. In the assenting process, the child must be given developmentally appropriate information on the study purpose, expectations, and benefit-risk ratio (discussed later). Media-enhanced presentations and play activities have been used as a means of providing information about the study. A group of researchers in the Netherlands conducted a participatory study to develop and test comic strips for the purpose of providing information about research participation (Grootens-Wiegers, de Vries, van Beusekom, van Dijck, & van den Broek, 2015). With the input of children at each stage of development, the comic strips evolved and, in their final version, were found to have the potential for increasing children’s knowledge about research. Yeh, Chun, Terrones, and Huang (2017) conducted a randomized controlled trial (RCT) comparing the knowledge of children and their parents about pediatric endoscopy. The intervention group (n = 37 parent-child pairs) obtained information about the procedure by watching a short, animated video and the control group (n = 40 parent-child pairs) received the information by listening to the usual verbal explanation. The 2-minute videos, one for upper endoscopy and the other for lower endoscopy, were developed based on principles of instructional design. Parents and children were interviewed separately and scored on their knowledge of key components of informed consent. The children and parents in the intervention group had significantly higher scores on knowledge of the risks of the procedure and their overall comprehension as compared to the children and parents of the control group. Continued research is needed for development and testing of innovative strategies for providing informed consent information to children and adults. A child who assents to participate in a study should sign the requisite form and be given a copy. To gain assent, the child is “meaningfully involved in the decision-making in a manner that is appropriate for the child’s capacity and age” (WHO, 2018, p. 15). Legally, a nonassenting child can be a research participant if the parents give permission, even if some potential for harm exists. Chwang (2015) argues, however, that including children in a study who have not given assent is every bit as unethical as including nonconsenting adults in a study. A child’s willingness to participate in a study should be reassessed throughout a study, reflecting respect for the child’s autonomy and dignity (Moore, McArthur, & Noble-Carr, 2018). Assent becomes more complex with children from various family dynamics and child characteristics. Oulton et al. (2016) conducted a literature review and an anonymous survey of healthcare professionals involved in pediatric research. Combining the findings of the review and the survey with their own experience of conducting pediatric research, Oulton et al. (2016) developed an algorithm that included child-related factors, family dynamics, and the complexity of the study design as components to consider in obtaining assent. A child-related factor might be a child who is bilingual. In this case, the researchers must determine the most appropriate language to use for the assent process for the child and the process to obtain parental permission. Other children who have no cognitive deficiencies, but are in unusual circumstances, may require the appointment of a legal representative by the legal system. WHO (2018) identifies the need to do this when a child has no living parents, the parents have immigrated and left the child behind, the child lives on the street with no parental supervision, the child who is unaccompanied seeks asylum in the United States, and the child is a member a of child-led household. Children under the age of 18 can give consent for their own participation in research when they have been emancipated by the legal system. In some legal jurisdictions, a girl under the age of 18 who marries is considered an emancipated minor. Other children may have previously be placed in a state’s guardianship (wards of the state). When determining the maturity of a child for the purposes of assent and consent, various professions have different standards by which maturity is assessed (WHO, 2018). Right to privacy Privacy is an individual’s right to determine the time, extent, and general circumstances under which personal information is shared with or withheld from others. This information consists of one’s attitudes, beliefs, behaviors, opinions, and records. The federal government enacted the Privacy Act (1974) to control potential infringement of privacy, related to information collected by the government, or held in federal agencies’ records. The act has four important provisions for the researcher: (1) data collection methods must be strategized so as to protect participants’ privacy, (2) data cannot be gathered from participants without their knowledge, (3) individuals have the right to access their records, and (4) individuals may prevent access by others to existent federal data (DHHS & Office of Civil Rights, 2013). The intent of this act was to prevent the invasion of privacy that occurs when private information is shared without an individual’s knowledge or against his or her will. The HIPAA Privacy Rule expanded the protection of an individual’s privacy, specifically his or her PHI that is individually identifiable, extending the protection to data held by private entities. It described the ways in which those entities covered by the rule can use or disclose this information. “Individually identifiable health information (IIHI) is information that is a subset of health information, including demographic information collected from an individual, and: (1) is created or received by healthcare provider, health plan, or healthcare clearinghouse; and (2) [is] related to past, present, or future physical or mental health or condition of an individual, the provision of health care to an individual, or the past, present, or future payment for the provision of health care to an individual, and that identifies the individual; or with respect to which there is a reasonable basis to believe that the information can be used to identify the individual” (DHHS, 2013, 45 CFR, Section 160.103). According to the HIPAA Privacy Rule, IIHI is PHI that is transmitted by electronic media, maintained in electronic media, or transmitted or maintained in any other form or medium. Thus the HIPAA privacy regulations must be followed when a nurse researcher wants to access data from a covered entity, such as reviewing a patient’s medical record in clinics or hospitals. Ahalt et al. (2019) defined de-identified data sets as having all PHI removed. De-identification consists of removing 18 items from patient records before they are released to other agencies or to researchers. These 18 items include name, contact information, identification numbers, photographs, biometrics, and other elements by which a participant could potentially be identified (Box 9.6). Because de-identification includes removing dates, researchers using de-identified data may not be able to answer some research questions such length of hospital stay and seasonal patterns to diseases (Ahalt et al., 2019). BOX 9.6 18 Elements That Could Be Used to Identify an Individual to Relatives, Employer, or Household Members 1. Names 2. All geographical subdivisions smaller than a state 3. All elements of dates (except year) for dates directly related to an individual 4. Telephone numbers 5. Facsimile numbers 6. Electronic mail (e-mail) addresses 7. Social security numbers 8. Medical record numbers 9. Health plan beneficiary numbers 10. Account numbers 11. Certificate/ license numbers 12. Vehicle identifiers and serial numbers, including license plate numbers 13. Device identifiers and serial numbers 14. Web universal resource locators (URLs) 15. Internet protocol (IP) address numbers 16. Biometric identifiers, including fingerprints and voiceprints 17. Full-face photographic images and any comparable images 18. Any other unique identifying number, characteristic, or code, unless otherwise permitted by the Privacy Rule for De-identification Office for Civil Rights, Department of Health and Human Services (DHHS). (2015). Guidance regarding methods for de-identification of protected health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) privacy rule. Retrieved from https:// www.hhs.gov/ hipaa/ for-professionals/ privacy/ special-topics/ de-identification/ index.html# standard The DHHS (2017) developed the following guidelines to help researchers, healthcare organizations, and healthcare providers determine the conditions under which they can use and disclose IIHI: • The PHI has been de-identified under the HIPAA Privacy Rule. • The data are part of a limited data set, and a data use agreement with the researcher( s) is in place. • The individual who is a potential participant for a study authorizes the researcher to use and disclose his or her PHI. • A waiver or alteration of the authorization requirement is obtained from an IRB or a privacy board. The first two items are discussed in this section of the chapter. The authorization process is discussed in the section on obtaining informed consent, and the waiver or alteration of authorization requirement is covered in the section on institutional review of research. De-identifying protected health information under the privacy rule Covered entities, such as healthcare providers and agencies, can allow researchers access to health information if the information has been de-identified, either by applying statistical methods (expert determination) or removing information (safe harbor) (Fig. 9.2). The covered entity can apply statistical methods that experts agree render the information unidentifiable. The statistical method used for de-identification of the health data must be documented. Safe harbor is certifying that the 18 elements for identification have been removed or revised to ensure the individual is not identified. The covered entity has done what it could to make the information de-identified, but has no information whether the individuals could still be identified (DHHS, 2015a). No matter the method used, you must retain this certification information for 6 years. It is important to note that the element concerning biometrics may be interpreted to include deoxyribonucleic acid (DNA) results and other particularized physiological variants, such as unusual laboratory and histological markers. Fig. 9.2Use of PHI: Two methods of de-identifying data. Source: (Information from the HIPAA Privacy Rule.) H I P P A privacy rule for de-identification methods is categorized into two methods as follows: 1. Expert determination (left): Apply statistical and scientific principles. 2. Safe horror (right): Removal of 18 types of identifiers, and no actual knowledge whether data recipient can identify person. Limited data set and data use agreement Researchers can comply with the privacy standards by accessing a limited data set (LDS) that has been de-identified (Ahalt et al., 2019). A HIPAA-limited data set includes clinical patient-specific data combined with some PHI. Patient authorization is not required to use these data sets for “research, public health, or healthcare operations research” as long as the study is approved by an IRB (Ahalt et al. 2019, p. 329). Under certain conditions, researchers and covered entities (healthcare provider, health plan, and healthcare clearinghouse) may use and disclose an LDS to a researcher for a study, without an individual participant’s authorization or an IRB waiver. These data sets are considered PHI, and the parties involved must have a data use agreement. The data use agreement limits how the data set may be used and how it will be protected, including identification of the researchers who are permitted to use the data set. The researchers receiving the data are not allowed to use or disclose the information in any way that is not permitted by the agreement, is required to protect against the unintended use or disclosure of the information, and must agree not to contact any of the individuals in the LDS (Centers for Medicare & Medicaid Services [CMS], n.d.). Secondary data analysis reuses data collected for a previous study or for other purposes, such as data in clinical or administrative databases (Wickham, 2019). Duncan, Ahmed, Dove, and Maxwell (2019) used secondary data analysis to study the cost of end-of-life (EOL) care for Medicare beneficiaries. They selected a sample (N = 114,028) from the Medicare Limited Data Set to answer their research questions. The data set was also called the Medicare 5% LDS Analytical file or Medicare 5% file. The file had been de-identified as required by HIPAA and comprised of 5% of the Medicare beneficiaries. “For the purpose of understanding cost of care at the EOL, we perform analysis of the Medicare 5% file for the years 2015 and 2016. This file is a random sample of Medicare’s claims for the 2 years, containing experience of approximately 2.9 million patients for each year.“ ( Duncan et al., 2019, p. 706) “Medicare expenditures increase sharply in the last few days of life, particularly for patients who die in hospital. Recent developments in hospice and palliative care offer the possibility of higher quality care at lower cost to Medicare if patients enter hospice earlier. Finding a lower cost site of care that does not jeopardize patients’ wishes is a realistic, worthy goal…. Identifying those who will benefit from intensive care from those in which aggressive care is likely to be futile and burdensome is a challenge for providers, patients, and families.“ ( Duncan et al., 2019, p. 709) The findings of the study conducted by Duncan et al. (2019) provided strategies by which EOL expenditures could be reduced, an important cost savings, without infringing on the desired outcome of a peaceful death. Right to anonymity and confidentiality On the basis of the right to privacy, the research participant has the right to anonymity and the right to assume that all data collected will be kept confidential. Anonymity means that even the researcher cannot link a participant’s identity to that participant’s individual responses (Adams & Lawrence, 2019). For studies that use de-identified health information or data from a limited data set, participants are anonymous to the researchers. In most studies, researchers desire to know the identity of their participants and promise that their identity will be kept confidential. Confidentiality is the researcher’s management of private information shared by a participant that must not be shared with others without the authorization of the participant (Gravetter & Forzano, 2018). Confidentiality is grounded in the premises that patients own their own information, and that only they can decide with whom to share all or part of it (Kazdin, 2017). When information is shared in confidence, the recipient (researcher) has the obligation to maintain confidentiality. Researchers, as professionals, have a duty to maintain confidentiality consistent with their profession’s code of ethics (Gravetter & Forzano, 2018). This section includes breaches in confidentiality that may occur and strategies to maintain confidentiality. Breach of confidentiality A breach of confidentiality can occur when a researcher, by accident or direct action, allows an unauthorized person to gain access to a study’s raw data. Confidentiality can be breached in the reporting or publishing phases of a study, especially in qualitative studies, in which a participant’s identity is revealed by including personal details known to other people (Creswell & Creswell, 2018; Creswell & Poth, 2018). Two other types of research are especially sensitive to breaches in confidentiality. Collecting data through online forums and social media can threaten confidentiality because of the ability to track internet protocol addresses and search the internet participant’s quotes (Hunter et al., 2018). Passive data collection also has ethical issues. Passive data collection is gathering data without the active involvement of the participant (Maher et al., 2019). The data being gathered are linked to specific participants and are generated by wearable devices such as smartphones or electronic pedometers, by global positioning systems, and by e-mails and text messages. Breaches of confidentiality can harm participants psychologically and socially as well as destroy the trust they had in the researcher. Breaches can be especially harmful to a research participant when they involve religious preferences, sexual practices, employment, personal attributes, or opinions that may be considered negative, such as racial prejudices (Gravetter & Forzano, 2018). For example, imagine that you have conducted a study of nurses’ stressful life events and work-related burnout in an acute care hospital. One of the two male participants in the study describes his anxiety disorder. Reporting that one of the male nurses in the study had an anxiety disorder would violate his confidentiality and potentially cause harm. Nurse administrators might be less likely to promote a nurse who has an anxiety disorder. There are legal limits to confidentiality that occur when a participant reveals current drug use or specific intent to harm oneself or others (Gravetter & Forzano, 2018). For example, in a phenomenological study of the experience of parenting a child with development delays, the informed consent document must describe the specific limitations on confidentiality, such as the researcher being obligated to report a mother who reveals harming her child. Maintaining confidentiality includes not allowing health professionals to access data the researcher has gathered about patients in the hospital. Sometimes, family members or close friends will ask to see data collected about a specific research participant. Sharing research data in these circumstances is a breach of confidentiality. When requesting consent for study participation, you should assure the potential participant that you will not share individual information with healthcare professionals, family members, and others in the setting. However, you may elect to share a summary of the study findings with healthcare providers, family members, and other interested parties. Maintaining confidentiality in quantitative research Researchers have a responsibility to protect the identity of participants and to maintain the confidentiality of data collected during a study. You can protect confidentiality by giving each participant a code number. For example, participant Sarah Young might be assigned the code number 001. All of the instruments and forms that Sarah completes and the data you collect about her during the study will be identified with the 001 code number, not her name. To protect participants’ identities, the master list of the participants’ names and their code numbers are kept in a locked file and room, separate from the data collected. You should not attach signed consent forms and authorization documents to instruments or other data collection tools, as this would make it easy for unauthorized persons to readily identify the participants and their responses. Consent forms are appropriately stored with the master list of participants’ names and code numbers. When entering the collected data into a database, code numbers instead of names should be used for identification. Data should be stored in at least two secure places, such as on a separate storage drive, on the researcher’s computer, on web-based or cloud storage, or on a university network. The data files need to be password-protected, and (if possible) have no personal identifiers. Another way to protect anonymity is to have participants generate their own identification codes when data will be collected over time with multiple data points (Lippe, Johnson, & Carter, 2019). The researcher does not have a master list connecting the codes to the participants’ names. You are conducting a study of the role satisfaction of new nurse employees with data collection occurring during the first month, the sixth month, and again at the twelfth month. Each nurse generates an individual code from personal information, such as the first letter of a mother’s name, the first letter of a father’s name, the number of brothers, the number of sisters, and middle initial. Thus the code would be composed of three letters and two numbers, such as BD21M. This code would be used on each form the participant completes. The premise is that the elements of the code do not change, and the participant can generate the same code each time. However, using participant-generated codes has been found to have mixed results. Although the specific components of the ID number were selected for their stability, the participant may not remember, for example, whether they included half-sisters in the number of sisters or whether they used a parent’s legal name or nickname. In quantitative research, the confidentiality of participants’ information must be ensured during the data analysis process. The data collected should undergo group analysis so that an individual cannot be identified by his or her responses. If participants are divided into groups and a group has less than five members, the results for that group should not be reported. For example, a researcher conducts a study with military veterans and collects demographic data. In reporting the results by demographic groups, if only a few women participated, the results by gender should not be reported. In writing the research report, you should describe the findings in such a way that an individual or a group of individuals cannot be identified from their responses. Maintaining confidentiality in qualitative studies Maintaining confidentiality of participants’ data in qualitative studies often requires more effort than in quantitative research. Participants are known to the data collector, so anonymity is not possible (Cypress, 2019). The smaller sample size used in a qualitative study and the depth of detail gathered on each participant requires planning to ensure confidentiality (Morse & Coulehan, 2015). Informed consent documents should contain details about who will have access to the data and how the findings will be reported. In addition, qualitative researchers should communicate to participants that direct quotes from the interview will be included in both professional publications and presentations. Sometimes qualitative participants inappropriately equate confidentiality with secrecy. Researchers should take precautions during data collection and analysis to maintain confidentiality in qualitative studies. The interviews conducted with participants frequently are recorded and later transcribed, so participants’ names should not be mentioned during the recording. Some researchers ask participants to identify pseudonyms by which they will be identified during the interview and on transcripts. Depending on the methods of the study, the researcher may return descriptions of interviews or observations to participants to allow them to correct inaccurate information or remove any information that they do not want included. Participants have the right to know whether anyone other than you will be transcribing interview information or whether other researchers will analyze the data. In addition, participants should be reminded on an ongoing basis that they have the right to withhold information. For other researchers to critically appraise the rigor and credibility of a qualitative study, an audit trail is produced. To continue to protect the participants’ confidentiality, ensure that the audit trail does not contain information linking the demographic characteristics of participants to the qualitative data. When publishing the findings, researchers must respect participants’ privacy as they decide how much detail and editing of private information are necessary to publish a study while maintaining the richness and depth of the participants’ perspectives (Morse & Coulehan, 2015). The researcher may choose to amend biographical details, removing identifiers such as cities, healthcare providers’ names, and healthcare facilities, and use pseudonyms (Cypress, 2019). Right to fair treatment The right to fair treatment is based on the ethical principle of justice. This principle holds that each person should be treated fairly and should receive what he or she is owed. In research, the selection of participants and their assignment to experimental or control group should be made impartially. In addition, their treatment during the course of a study should be fair. Fair selection of subjects As discussed earlier, historically, research was conducted on categories of individuals who were thought to be especially suitable as research participants, such as the poor, uninsured patients, prisoners, slaves, peasants, dying persons, and others who were considered undesirable (Reynolds, 1979). Researchers often treated these participants carelessly and had little regard for the harm and discomfort they experienced. The Nazi medical experiments, the Tuskegee syphilis study, and the Willowbrook study all exemplify unfair participant selection and treatment. In 1986, the NIH implemented a policy requiring the inclusion of women and minorities in federally funded studies. This policy became law in 1993 as part of the NIH Revitalization Act (Office of Research on Women’s Health, 2017). Prior to this, concerns had been raised about the exclusion of women from biomedical studies, especially women of childbearing age. From a scientific standpoint, the concern was that “monthly changes in women’s hormone levels might affect therapeutic interventions and require more complicated designs” (Clayton & Blome, 2018, p. 177). The exclusion of women to avoid harming a fetus or interfering with childbearing also excluded women from the potential benefits of new medications and treatments, for herself and her fetus. The selection of a population and the specific participants to study should be fair so that the risks and benefits of the study are distributed appropriately (Shamoo & Resnick, 2015). Subjects should be selected for reasons directly related to the problem being studied. Too often participants are selected because the researcher has easy access to them. Another concern with participant selection is that some researchers select certain people, possibly friends or patients under their care, to participate because they like them and want them to receive the specific benefits of a study. Other researchers included specific participants in study because they received gifts or money. The Common Rule requires equitable selection of participants (DHHS, 2018). Children, women, minorities, and persons who speak other languages cannot be excluded based solely on their demographic characteristics. Researchers seeking federal funding must describe in their proposals plans to recruit participants from different groups who have been traditionally underrepresented in research. The researchers must remember, if a study poses risk, no demographic group should bear an unfair burden of that risk. Conversely, when a study offers a potential benefit, no demographic group should be deprived of participation solely because of their demographic classification. Random selection of participants can eliminate some of the researcher bias that might influence participant selection. The researcher should make every effort to include fair representation across demographic characteristics, and increased cost is no longer a valid reason for not doing that. For example, the NIH has implemented stricter policies about the inclusion of women in studies and sex being a required variable in animal studies (Clayton & Blome, 2018). The only exception is when a study involves a condition, such as prostate cancer, that only affects men. Proposals for funding must include specific plans for recruiting and maintaining a diverse sample, and federally funded researchers must include demographic characteristics of participants in their annual reports. One of the most challenging tasks of a researcher is recruiting an adequate number of participants who meet the inclusion criteria and comprise a sample that includes female participants and participants from racial and ethnic minorities (Leavy, 2017). The HIPAA Privacy Rule requires that individuals give potential authorization before PHI can be shared with others, unless the researcher has IRB approval to access records for the purpose of screening. The Privacy Rule makes it more difficult for researchers to find participants for their studies; however, researchers are encouraged to work closely with their IRBs and healthcare agencies to ensure fair selection and recruitment of adequate-sized samples. Fair treatment of participants Informed consent is a specific agreement about what inclusion in the study involves and what the role of the researcher will be (Adams & Lawrence, 2019). While conducting a study, you should treat the participants fairly and respect that agreement. If the data collection requires appointments with the participants, be on time for each appointment and terminate the data collection process at the agreed-upon time. You should not change the activities or procedures that a participant is to perform unless you obtain the participant’s consent. The benefits promised the participants should be provided. For example, if you promise a participant a copy of the study findings, you should deliver on your promise when the study is completed. In addition, participants in studies should receive equal benefits, regardless of age, race, and socioeconomic status. When possible, the sample should be representative of the study population and should include participants of various ages, ethnic backgrounds, and socioeconomic levels. Treating participants fairly and respectfully facilitates the data collection process and decreases the likelihood that participants will withdrawal from a study (Clayton & Blome, 2018). Thanking participants is always appropriate; they have given you their time and their honesty. Right to protection from discomfort and harm The right to protection from discomfort and harm is based on the ethical principle of beneficence, which holds that one should do good and, above all, do no harm. Therefore researchers should protect participants from discomfort and harm while ensuring they receive the greatest possible balance of benefits in comparison with harm. Discomfort and harm can be physiological, emotional, social, or economic in nature. This section addresses the level of risk in a study, balancing benefits and risks, and the ethical responsibilities of clinicians to provide the best care possible. Level of risk In his classic text, Reynolds (1979) identified the following five categories of studies based on levels of discomfort and harm: (1) no anticipated effects, (2) temporary discomfort, (3) unusual levels of temporary discomfort, (4) risk of permanent damage, and (5) certainty of permanent damage. Each level is defined in the following discussion. Studies with no anticipated effects are studies without direct involvement of human participants. For example, studies that involve reviewing patients’ records, students’ files, pathology reports, or other documents have no anticipated effect on the participants. In these types of studies, the researcher does not interact directly with research participants. Even in these situations, however, there is a potential risk of invading a participant’s privacy. The HIPAA Privacy Rule requires that the agency providing the health information de-identify the 18 essential elements (see Box 9.6 and Fig. 9.2) that could be used to identify an individual, to promote participants’ privacy during a study. Analysis of variables from a data set that has had the 18 elements removed is usually exempt from IRB review. Participants may experience temporary discomfort in low-risk studies. In these studies, the discomfort encountered is similar to what the participant would experience in his or her daily life and ceases with the termination of the study. Many nursing studies require participants to complete questionnaires or participate in interviews, which usually involve minimal risk. Physical discomforts of such research might be fatigue, headache, or muscle tension. Emotional and social risks might entail the anxiety or embarrassment associated with responding to certain questions. Economic harms may consist of the loss of time spent participating in the study or travel costs to the study site. Most clinical nursing studies examining the impact of a treatment involve minimal risk. For example, your study might involve examining the effects of exercise on the blood glucose levels of patients with noninsulin-dependent diabetes. During the study, you ask the participants to test their blood glucose level one extra time per day. There is discomfort when the blood is obtained and a risk of physical changes that might occur with exercise. The participants might also experience anxiety and fear in association with the additional blood testing, and the testing is an added expense. Diabetic participants in this study would experience similar discomforts in their daily lives, and the discomforts would cease with the termination of the study. Other studies involve unusual levels of temporary discomfort for the participants during the study and after its termination. For example, participants might experience a deep vein thrombosis (DVT), prolonged muscle weakness, joint pain, and dizziness after participating in a study that required them to be confined to bed for 7 days to determine the effects of immobility that severe trauma patients might experience. Studies that require participants to experience failure, extreme fear, or threats to their identity or to act in unnatural ways involve unusual levels of temporary discomfort. In some qualitative studies, participants are asked questions about sensitive topics, which may reopen old emotional wounds or involve reliving traumatic events (Butler, Copnell, & Hall, 2019). For example, asking participants to describe a sexual assault experience could precipitate feelings of extreme fear, anger, and sadness. In studying sensitive topics, you should arrange prior to the study to have appropriate professionals available for referrals should the participants become upset. During the interview, you would need to be vigilant about assessing the participants’ discomfort and refer them for appropriate professional intervention as necessary. If a participant appears upset during a qualitative interview, the researcher should ask questions such as, “Do you want to pause for a moment?” or “Do you want to talk about something else for a while?” or “Do you want to stop this interview?” Some participants will want to stop the interview completely. Others will want to continue despite the discomfort because it is important for them to tell their story. Care must also be taken not to reveal a participant’s identity inadvertently when disseminating the findings, especially when studying sensitive topics (Turcotte-Tremblay & McSween-Cadieux, 2018). Studies with a potential for permanent damage are more likely to involve biomedical researchers than nurse researchers. For example, medical studies of new drugs and surgical procedures have the potential to cause participants permanent physical damage. However, nurses have investigated topics that have the potential to damage participants permanently, emotionally, spiritually, and socially. Studies examining variables such as human immunodeficiency virus (HIV) diagnosis, sexual behavior, child abuse, or drug use have the potential to cause permanent damage to a participant’s personality or reputation. There are also potential economic risks, such as reduced job performance or loss of employment. Studies in which participants will suffer certain permanent damage may be unethical, such as the Nazi medical experiments and the Tuskegee syphilis study. Conducting research that will permanently damage participants is highly questionable and must be scrutinized carefully, regardless of the benefits gained. One exception might be a study that involves participants with a life-threatening disease having the opportunity to have a medical procedure that promises a cure but causes permanent damage to hearing, to peripheral sensation, or to vision. Frequently, in studies that cause permanent damage, other people, not the participants, will receive the benefits of the study. Studies causing permanent damage to participants, without a concomitant gain, violate the Nuremberg Code (1949). Balancing benefits and risks for a study Researchers and reviewers of research must compare the benefits and risks in a study. The comparison is called the benefit-risk ratio. To begin, you must first predict the most likely outcomes of your study based on previous research findings, clinical experience, and theory. What are the benefits and risks, both actual and potential, of these outcomes? As the researcher, your goal is to maximize the benefits and minimize the risks (Fig. 9.3). Fig. 9.3Balancing benefits and risks of a study. A flow diagram for developing a study benefit-risk ratio shows the following steps: 1. Predict the outcomes of the study leading to assess benefits and risks, which collectively lead to benefit-risk ratio to maximize benefits and minimizes risks in the following two ways: a. If benefits are greater than or equal to risks, study is approved. b. If risks outweigh benefits, study is rejected. The probability and magnitude of a study’s potential benefits must be assessed. A research benefit is defined as something of value to the participant whether related to physical health, psychological status, or social gain. Participants may receive the benefit of knowing they have contributed to the acquisition of knowledge for evidence-based practice (EBP). Money and other compensations for participation in research are not benefits but remuneration for research-related inconveniences (DHHS, 2018). In study proposals and informed consent documents, the research benefits are described for the individual participants, participants’ families, and society. The type of research conducted, whether therapeutic or nontherapeutic, affects the potential benefits for the participants. In therapeutic nursing research, the individual participant has the potential to benefit from the procedures of the study, such as skin care, range of motion, touch, emotional support, and pain management strategies. The benefits might include improvement in the participant’s physical condition, which could facilitate emotional and social benefits. The participant also may benefit from the additional attention of and interaction with a healthcare professional. In addition, knowledge generated from the research may expand the participants’ and their families’ understanding of health. The conduct of nontherapeutic nursing research does not benefit the participant directly but is important to generate and refine nursing knowledge for practice. Subjects who understand the lack of therapeutic benefit for them frequently will participate because of altruism and the desire to help others with their condition (Irani & Richmond, 2015). To compare the benefits and risks, you must also assess the type, severity, and number of risks that participants might experience by participating in your study. The risks depend on the purpose of the study and the procedures used to conduct it. Studies can have actual (known) risks and potential risks for participants. As mentioned earlier, participants in a study of the effects of prolonged bed rest have the actual risk of transient muscle weakness and the potential risk of DVT. Some studies contain actual or potential risks for the participants’ families and society. You must determine the likelihood of the risks and take precautions to protect the rights of participants when implementing your study. The benefit-risk ratio is the term given to a comparison of the benefits and risks of a study and is determined on the basis of the maximized benefits and the minimized risks. The researcher attempts to maximize the benefits and minimize the risks by making changes in the study purpose or procedures, or both (Goldstein et al., 2019). If the risks entailed by your study cannot be eliminated or further minimized, you must justify their existence. If the risks outweigh the benefits, the IRB is unlikely to approve the study and you probably need to revise the study or develop a new one. If the benefits equal or outweigh the risks, you can usually justify conducting the study, and an IRB will probably approve it (see Fig. 9.3). Clinical equipoise Clinical equipoise is the responsibility of clinicians to “provide the best possible treatment for their patients” (Gravetter & Forzano, 2018, p. 90). Studies in which participants are randomly assigned to a treatment (intervention) group or control group may threaten the principle of no harm if the control group receives care that is known to be inferior. For example, in a study of patients with heart failure who have had a myocardial infarction (MI), the intervention group receives a new medication that has been shown in animal studies to be effective with fewer side effects; the control group receives an older medication that has some serious side effects. Some participants are not being protected from harm (Gravetter & Forzano, 2018), because the researchers already know that the older drug potentially can cause serious side effects. To maintain equipoise, researchers who compare clinical treatments must either believe them to be relatively equivalent, acknowledge that it is unknown which is best, or indicate professional disagreement about which is best. The informed consent process for a RCT should include benefits and potential harms of both the intervention and control condition (Kotz, Viechtbauer, Spigt, & Crutzen, 2019). Some debate exists about clinical equipoise because it implies the objective of clinical care is the same as the objective of research (Thakur & Lahiry, 2019). For valid findings to be available upon which to base clinical care, studies are needed that randomly assign participants to different groups. Chapter 11 provides information about different types of RCTs that address the issue of equipoise, specifically pragmatic clinical trials and cluster RCTs. Human subject protection in genomics research The Human Genome Project funded by the NIH recognized from the onset the ethical and legal dilemmas of genomic research and allocated 5% of the funding to study these issues (Hammer, 2019). Over $ 300 million has been invested in studying the ethical and legal issues within genomic research. The funded studies made it “evident that a delicate balance exists between major genomics scientific progress and the challenge of maintaining the ethical tenets of autonomy, beneficence, non-maleficence, and justice” (Hammer, 2019, p. 94). Several highly publicized cases have increased awareness as well as fear among the public. In 1951, Henrietta Lacks, an African American woman, only 31 years of age, was diagnosed with cervical cancer. She was admitted to the hospital for the standard treatment at the time (Jones, 1997). The specimens collected were taken to the laboratory of a scientist named Dr. Gey. Dr. Gey was trying to identify and reproduce a cell line for research purposes (Jones, 1997). When Mrs. Lacks’s cells continued to multiply, Dr. Gey developed methods to produce even more and generously provided the cell line to other researchers free of charge. These researchers, building on Dr. Gey’s research, developed a cell line from those especially hardy tumor cells, which were successfully used in research (Bledsoe & Grizzle, 2013; Skloot, 2010). Highly effective treatments, such as the polio vaccine and in vitro fertilization (IVF), were developed using the cell line and were extremely profitable for the researchers and their institutions. Literally billions of dollars were made by selling the cell line to other researchers (McEwen, Boyer, & Sun, 2013). Mrs. Lacks died never knowing her tumor cells were used for research, and her family only learned of her contribution to science in 2010. In 1990, researchers began collecting blood specimens of members of an isolated Native American Indian tribe, the Havasupai, who lived in the Grand Canyon (Caplan & Moreno, 2011). Diabetes mellitus was a devastating disease among the tribe, and researchers proposed a study to identify genetic clues of disease susceptibility. However, the researchers used the blood specimens to study other topics (McEwen et al., 2013). The publications from the subsequent studies linked schizophrenia to the tribe’s DNA and contradicted the tribe’s story of their origin. The tribe sued Arizona State University, the employer of the original researcher, and was awarded a financial settlement in 2010. In addition, tribal leaders were given the remaining blood samples to be disposed of in a culturally appropriate way. Several ethical issues in genomics research have not been resolved. The following section will include issues with de-identification of data, additional studies being conducted with specimens already collected, participants withdrawing from a study, and return of information to the research participant if beneficial to the participant. The second section will identify ethical issues about specific methods such as use of embryonic tissue. Ethical issues related to genomic specimens By its very nature, genomic data cannot be completely de-identified (Quinn & Quinn, 2018; Terry, 2015). Genomic data could be combined with data from publicly available demographic databases and be re-identified. The likelihood of linking genomic data to an individual (re-identification) has increased because genome-wide sequencing and large samples have increased the size of databases, computer processing speeds have dramatically increased, and personal data are available through public internet sources (Quinn & Quinn, 2018). Despite this issue, genomic data that have been de-identified (18 elements removed) can be used by researchers without the notification or authorization of the participants. Without links to individuals, the research is considered nonhuman research (Bledsoe, Russell-Einhorn, & Grizzle, 2018) and not subject to regulation by the Common Rule. Genomic data are being generated from the body tissues and fluids that are left over after specimens are removed during clinical care. For example, a patient has a lung biopsy. The tissue is examined to determine the presence and types of abnormal cells. Not all of the tissue is used, however, and is saved on paraffin blocks. Archival tissue and fluids have been de-identified, studied, and resulted in dramatic and rapid advances in scientific knowledge, including targeted cancer treatments, improved immunotherapy, and genome sequencing of abnormal tissues (Bledsoe et al., 2018). The issues of whether identified information will be used for future studies was directly addressed in the revised Common Rule (DHHS, 2018). The new rule includes a new type of consent, called broad consent. Broad consent asks the patient or potential study participant for permission to store, maintain, and use for future studies private information and biological specimens that are identifiable. Box 9.7 contains the required elements of broad consent. Broad consent addresses whether any profits from commercial processes developed based on participant’s biospecimen will be shared with the participant, a statement developed because of the case of Mrs. Lack. BOX 9.7 Required Elements of Broad Consent • Potential risks and discomforts • Possible benefits • Extent to which private information will be kept confidential • Participation is voluntary • Refusal to participate involves no harm or loss of benefits • May stop participation at any time • Specimens and information (identifiable and nonidentifiable) may result in commercial products and process • Whether participant will share any profits • Whether whole genome sequencing is planned From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. Voluntary participation in research and the possibility of withdrawing are hallmark characteristics of informed consent (Capron, 2018). When biospecimens have been de-identified, withdrawing from a study becomes problematic. How does a researcher delete or remove a participant’s data if the data have been de-identified? Researchers must consider this possibility when planning the study. One strategy would be to delay de-identification until data collection is complete. Another would be to de-identify the data over the course of the study but retain a code number linking the data to the participant until the study is completed. Another pressing question is what happens if the researcher’s results include information that would benefit the participants directly? For example, the researchers are studying genetic characteristics of de-identified biospecimens from 20,000 adults who have osteoarthritis and are 61 to 79 years old. They incidentally find that 3% of the 11,000 women in the study have a breast cancer gene (BRCA) mutation that is associated with an inherited predisposition to breast cancer. Should the researchers re-identify the 330 specimens with the mutation and inform the women of their results? The ethical principles of beneficence, respect of persons, and justice would support a decision to re-identify the specimens (Bledsoe et al., 2018). However, the researchers need to balance the decision with whether the original study can be completed if funding is diverted to identifying the women and whether harm would occur to women who are informed but do not have breast cancer (Bledsoe et al., 2018). Relative to harm, the researchers would need to know that Black are underrepresented in genetic testing, which means the evidence linking BRCA mutations and breast cancer among Black women is weaker than it is for White women. Therefore the researchers would be less confident about notifying Black women about a BRCA mutation (Gehlert & Mozersky, 2018). Research teams will need to discuss these issues prior to initiating a study using biospecimens. The revised Common Rule does not require re-identification but does require that a broad consent includes what the researchers would do if this situation occurred (see Box 9.7). Ethical issues with specific types of genomic research Advanced practice nurses, nurse educators, and nurse administrators are likely to confront the genomic ethical issues in their work. Warren (2016) calls for nurses to be leaders in the policy debate about stem cell and genomic research. Nurse leaders cannot be leaders in the research and policy without understanding physiological and ethical challenges, such as the moral status of embryos and organoids. Specially trained nurses are being utilized to implement the stem cell therapies in clinical trials (Perrin et al., 2018). Stem cells continue to be a controversial source of genetic material and will be discussed first. Much of the related controversy is based on the source of the cells. Ethical issues with embryos are related to the views of researchers and funders on abortion and human cloning. Organoids are produced from stem cells for research and raise some new questions about ethical use of cerebral organoids. Stem cell research We begin with a few definitions of key terms because the ethical issues are hard to understand without understanding these terms. Stem cells are human cells that can reproduce themselves or can develop into specialized cells of other types, such as blood cells or muscle cells. Stem cells have been derived from somatic cells of adults and umbilical cord blood of infants (Johnston & Zacharias, 2019). Somatic cells are any cell in the body except those cells used for reproduction, specifically any cells except sperm and eggs. Pluripotent cells are master cells and can make cells for any layer of the body. They are important because the cells they produce as they divide are used for tissue repair in the body. Scientific advances have allowed the identification or creation of stem cells from four sources: adult cells, fetal cells, embryos, and reprogrammed human cells. The ethical issues vary based on the source of the cells. For example, stem cells generated from somatic adult and child cells pose no major ethical issues for the majority of the US population. The adults involved can give informed consent to the use their cells, and parents can give consent for use of their infant’s blood. Using the cells from aborted fetuses has been more troublesome because of strong opinions about the morality of terminating a pregnancy. The revised code addresses this issue directly by removing researchers from the decision about the termination of pregnancy and not allowing them to offer any compensation for a woman having an abortion in exchange for use of the fetal tissue (DHHS, 2018). Federal funding is available for research with stem cells generated from fetal tissues or cells; however, researchers involved in fetal stem cell research need to be aware of state regulations because five states have legal bans on using fetal cells (Johnston & Zacharias, 2019). Stem cells can be extracted from preimplantation human embryos that are 4 to 7 days old because each cell has the potential to develop into all types of human cells. These stem cells are called human embryonic stem cells (hEScs). Based on initial research results, hEScs have the therapeutic potential to repair damaged human organs (Johnston & Zacharias, 2019). The opposition is great, however, because extracting the cells results in the death of the embryo, an embryo that is considered by some to be a potential human being to which ethical principles apply (Hostiuc et al., 2019). The embryos may come from IVF. Reproductive cells that were initially harvested for a future pregnancy may be donated by parents who no longer need them for that purpose. This means of generating hEScs is more acceptable on ethical grounds, because the embryos would have been destroyed anyway (Johnston & Zacharias, 2019). However, the number of donated embryos and the lack of cultural diversity of the embryos do not meet the needs of science. hEScs can be produced by cloning using a process called somatic cell nuclear transfer (SCNT). SCNT can produce embryos from which stem cells are derived, stem cells that are used for research or therapeutic purposes (Johnston & Zacharias, 2019). The embryos are destroyed after the stem cells are removed, making it ethically unacceptable to some. The hEScs derived from cloned embryo stem cells also have the potential to cause an undesired immune response or abnormal cells in a recipient (Prentice, 2019). Beginning in 1973, federal funding was not available to study embryos, hEScs, and cloned embryos. Stem cell research continued, however, funded by states, individuals, and foundations. In 1998, a change occurred in federal funding. Once the stem cells were created, federal funds were available to conduct research using the cells (Johnston & Zacharias, 2019). The specifics of funding have varied according to which US president is in office. Stem cell research has become a major political issue, with debate around which ethical principle is stronger: beneficence, nonmaleficence, or respect for persons. Beneficence supports funding and encouraging stem cell research because of its great potential in improving the health of many people suffering with diseases (Warren, 2016). Nonmaleficence supports maintaining the restrictions on any research that produces embryos that will be destroyed. When an individual views an embryo as a human life, respect for persons also supports maintaining the restrictions on destroying embryos produced for research. Induced pluripotent stem cells (iPScs) are “human somatic cells reprogrammed to develop into nearly every human cell type, and are believed to be functionally very similar or identical to embryonic stem cells” (Johnston & Zacharias, 2019, p. 1311). Ethical and legal oppositions to iPScs have been less than the opposition to hEScs. Although iPScs have some potential for negative side effects, such as immune responses and abnormal cell growth, published studies using iPScs have increased in number and are outpacing published studies with hEScs (Prentice, 2019). In 2009, the NIH released Guidelines for Human Stem Cell Research (DHHS, 2009). Other guidelines have been released by the National Academies of Science (2005) and the International Society for Stem Cell Research, with the latest revision published in 2016. Nurse researchers who are working in stem cell research will want to be familiar with these guidelines and any relevant state laws, the ethical views of other members of the research team, and the IRBs overseeing the research. Cerebral organoids Organoids are three-dimensional structures created from stem cells to mimic functions of organs (Hostiuc et al., 2019). The organs for which organoids have been generated include the retina, intestines, liver, pancreas, testes, thyroid, heart, kidneys, lungs, and brain (Hostiuc et al., 2019; Lavazza & Massimini, 2018). These miniature organs are different from human organs in that they are less complex and may not exhibit all the desired functions of the full-size organ (Lavazza & Massimini, 2018). However, the similarities to human organs have made organoids an increasingly valuable resource for biomedical research. Cerebral organoids are being used to study autism, Parkinson disease, microcephaly, and traumatic brain injury. Because human embryonic stem cells are used to make organoids, some researchers would argue against organoids on the same ethical basis as other embryonic research. However, organoids can be generated from iPScs or hEScs, with the source potentially being the deciding factor in the ethics of creating organoids (see previous section). Beyond the source of the stem cells, the functions of cerebral organoids are beginning to raise new ethical issues. Research related to developing cerebral organoids has resulted in highly complex structures with neurons specific to each of the six layers of the cortex and others that have been shown to stimulate muscle contractions (Hostiuc et al., 2019). These highly complex cerebral organoids replicate the functions of the brain in an embryo a few months old (Hostiuc et al., 2019). The complexity of these structures gives rise to questions about the extent to which cerebral organoids should be considered human: How long will it be before these tissues are conscious and sentient (Lavazza & Massimini, 2018)? At what point in their development should the ethical principles of human research apply to cerebral organoids? Sancar (2018) reported an interview with Dr. Madeline Lancaster, the scientist whose cultures began to produce the three-dimensional structures that led to the development of organoids. Dr. Lancaster argues that cerebral organoids will not progress to the point of being conscious and sentient. Research conducted with cerebral organoids will continue to be an area of knowledge to monitor. These and other organoid-related ethical questions are likely to generate lively debate in the coming years. Informed consent Obtaining informed consent from human participants is essential for the conduct of ethical research in the United States (DHHS, 2018) and in other countries. Informing is the transmission of essential ideas and content from the researcher to the prospective participant. Consent is the prospective participant’s agreement, after assimilating essential information, to participate in a study as a participant. The phenomenon of informed consent was formally defined in the first principle of the Nuremberg Code as follows: “the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the participant matter involved, as to enable him to make an understanding and enlightened decision” (Nuremberg Code, 1949, p. 181). The definition of informed consent from the Nuremberg Code provides a basis for the discussion of consent in all subsequent research codes and has wide acceptance in the research community. Informed consent can only occur when the prospective participant is mentally competent and able to comprehend that information, the researcher discloses essential information, and the prospective participant has the freedom to volunteer to participate (Fig. 9.4) (Thakur & Lahiry, 2019). Fig. 9.4 displays the informed consent process as the related components of information, comprehension, and voluntarism. Informed consent does not meet ethical standards or legal requirements unless all three components are present. Fig. 9.4Components of informed consent: information, comprehension, and voluntarism. A cyclic flow diagram shows voluntarism, information, and comprehension connected to each other. Facilitating comprehension Persons with a cognitive impairment may participate in research studies when another person can act on their behalf. To the degree that they are capable, persons with cognitive impairment should have the opportunity to choose whether to participate in research. Previously in this chapter, we discussed persons with limited capacity due to cognitive impairment, psychosis, and dementia. With careful accommodations, a study’s participants may include persons with cognitive impairment (Forster & Borasky, 2018), a diagnosis of psychosis (Weissinger & Ulrich, 2019), or dementia (Chester et al., 2018). To enhance the comprehension of all prospective participants, professional jargon in the consent document needs to be replaced by everyday language. The language of the consent document should be adapted to the expected participants. Healthcare facilities may require that the researcher make the consent form available in the most common languages spoken by their patients. Depending on the geographic area, the consent form may need to be translated into Vietnamese, French, Spanish, or another language. For example, when some of the potential participants are Spanish speakers, the researchers should provide the consent and written instruments in Spanish. However, translating the consent into Castilian Spanish is not helpful if the population is primarily from Central America. Translation of instruments is a complex process, and we recommend the book on measurement by Waltz, Strickland, and Lenz (2017) as a reference (also see Chapter 17). The reading level of the consent should be adjusted for the expected participants. The recommended reading level for informed consent documents is an eighth-grade reading level (Tamariz et al., 2019). Gehlert and Mozersky (2018) report that half of the US population has a reading level below the eighth grade. When it is likely that some participants may have limited reading ability, the researcher may read the consent aloud to all participants to avoid embarrassment. When study information is not comprehended, there is no informed consent. This section describes the information that must be included in the consent document or oral consent and the methods of documenting consent. Another way to improve comprehension is to provide the consent information in multiple modes and assess the participants’ comprehension. Lindsley (2019) conducted a quality improvement initiative that began by assessing the research participants’ knowledge of a study to which they had consented to participate. Their knowledge gaps were used as the basis for questions to use in assessing comprehension and developing a multimodal presentation with the required elements of informed consent. The text of the presentation was reduced to a sixth-grade reading level. The presentation was delivered on a touchscreen tablet. Adult volunteers were randomized to receive standard or multimodal format of consent. The comprehension of all participants was assessed. The comprehension of those participants who viewed the multimodal presentation was significantly higher than the comprehension of participants who received the standard method of consent (Lindsley, 2019). Earlier in the chapter, we identified the benefits of using visual and oral methods to enhance comprehension in children and their parents, but Lindsley’s results indicated a multimodal approach is appropriate for adults, too. Information essential for consent Informed consent requires the researcher to disclose specific information to each prospective participant. In addition to the elements that are required by federal regulations (Box 9.8), the IRB or institution where the study will be conducted may have additional elements that they require (DHHS, 2018). Typical examples of the additional elements required by some IRBs are the anticipated number of participants, whether individual clinically relevant data will be returned to participants, and the conditions under which a person’s participation in the study would be terminated by the researcher. Table 9.2 provides the required elements with examples of the corresponding information from a consent document. BOX 9.8 Required Elements of Informed Consent • Statement that the study is research • Purpose of the study • Expected time the participant will be involved • Procedures involved and which are experimental • Reasonable risks and benefits • Alternative procedures, if applicable • Extent of confidentiality • Compensation or treatment if injury occurs • Who to contact with concerns about study or rights as a study participant • Voluntary participation; no penalty for not agreeing or discontinuing the study • Whether de-identified data or specimens will be shared with other researchers • Additional information to include as applicable • Any procedures that would hurt the fetus if a woman is pregnant • Circumstances under which participation could be terminated by researchers • Any costs related to being in the study • Consequences of withdrawal and orderly termination of withdrawing • New research findings might influence participant’s decision to participate • Approximate number of participants in the study • De-identified biospecimens may be used for commercial profit • Whether and how participant’s clinically relevant results will be shared with participant • Whether biospecimens will undergo whole genome sequencing From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. TABLE 9.2 Informed Consent Language for a Descriptive Comparative Study Required Element Example Statement that the study is research You are being asked to participate in a research study about nursing students’ attitudes toward poverty. Purpose of the study The purpose of the study is to compare junior and senior nursing students’ attitudes toward poverty before and after a poverty simulation. Expected time the participant will be involved The Attitudes Toward Poverty Short-Form Scale (ATPS) takes 5 to 10 minutes to complete. Procedures involved and which are experimental The poverty simulation is a required class activity. You will be asked to complete the ATPS before and after the simulation. The researchers want to know whether the poverty simulation affects your attitudes about poverty. Reasonable risks and benefits RISKS: Because the major risk of the study is the potential loss of confidentiality, a faculty not involved in the study will remove only the consent form from the manila envelope. If you said yes to participating, your packet will be retained for the study. If you said no, your packet will be marked that it is not to be included in the study. No other risks have been identified related to participating in this study. BENEFITS: The main benefit to you for participating in this study is knowing you have contributed to expanding the body of knowledge available on nursing student’s attitudes toward poverty. Alternative procedures, if applicable There are no alternative procedures for this study. Extent of confidentiality All information obtained about you in this study is strictly confidential unless the law requires disclosure. The results of this study may be used in reports, presentations, and publications, but the researchers will not identify any individual students. Compensation or treatment if injury occurs There are no costs or payments associated with your participation in this study. Who to contact with concerns about study or rights as a study participant In the event that you suffer injury as a result of participation in any research project, you may contact Faculty Member at 123-123-1234 or Chair of the IRB at 321-321-4321, who will be glad to review the matter with you. Voluntary participation; no penalty for not agreeing or discontinuing the study The poverty simulation is a required class activity, but the researchers want your decision about participating in this study to be absolutely voluntary. If you have questions about the study, please ask the researchers before you agree to participate. It is okay for you to say no. Your decision will not affect your participation or grade in the required poverty simulation activity. Your responses will not be linked to your name. Whether de-identified data or specimens will be shared with other researchers The researchers will not share the data with other researchers. Introduction of research activities The researcher begins the informed consent document with several key elements. The informed consent document includes a statement that the prospective participant is being asked to participate in a research study and a description of the purpose of the study, type of data collection, and expected duration of the person’s participation (DHHS, 2018; Santos et al., 2017). Prospective participants also must receive a complete description of the procedures to be followed, such as whether assignment to a group will be random if the study includes an intervention and a control group. The researchers must identify the intervention as being experimental (DHHS, 2018; FDA, 2019b). For example, researchers conducting quantitative and outcome studies need to describe the procedures or mechanisms that will be used to examine, manipulate, or measure the study variables. For qualitative studies, the researcher will describe how data will be collected, such as an interview, and the topics to be discussed or observed. Mixed methods studies will include descriptions of the quantitative and qualitative procedures. In addition, they must inform prospective participants about when the study procedures will be implemented, how many times, and in what setting. Prospective participants must receive a disclosure of alternatives related to their participation in a study. For example, a female hypertensive patient who has uncontrolled blood pressure on a single antihypertensive medication may be recruited for a clinical trial for patients like her who have uncontrolled hypertension on a single drug. The two arms of the trial are following the current EBP guideline of adding a second antihypertensive medication or being prescribed a new experimental antihypertensive medication. She needs to know that, if she decides not to participate, she can continue on her current medication and attend an education program about eating correctly and losing weight. As a prospective participant, the medication plus education is an appropriate, alternative course of treatment about which she must be informed (DHHS, 2018). Research participants also need to know the funding source( s) of a study, such as specific individuals, organizations, or companies (Bonham, 2018). For example, researchers studying the effects of a specific drug must identify any sponsorship by a pharmaceutical company. Description of risks and benefits Prospective participants must be informed about any foreseeable risks or discomforts (physical, emotional, social, or economic) that might result from the study (Bonham, 2018; DHHS, 2018; FDA, 2019b). Female prospective participants need to know whether the study treatment or procedure involves potential risks to them or their fetuses if they are pregnant or become pregnant during the study (DHHS, 2018). For research involving more than minimal risk, prospective participants must be given an explanation as to whether any compensation or medical treatment, or both, would be available if injury should occur. If medical treatments are available, the person obtaining consent must describe the type and extent of the treatments. You should also describe any benefits to the participant or to others that may be reasonably expected from the research. The study might benefit the current participants or might generate knowledge that will provide evidence-based care to patients and families in the future (DHHS, 2018; FDA, 2019b). Most critically, prospective participants want to know how the risks of a study were minimized and the benefits maximized. They need time to compare the potential risks and benefits in the context of their lives so they can determine what is best for them without the researcher’s influence. Assurance of anonymity and confidentiality Prospective participants must be assured their research records, including PHI, will be secured during and following the study and remain confidential (DHHS, 2018). All oral or poster presentations and published papers will report only group findings. The exception may be for qualitative studies when participants’ quotes may be included in a presentation or publication but will not be linked to an identifiable individual. Any limits to confidentiality, such as the researcher’s need to reveal anything the participant reports about ongoing elder abuse, must also be disclosed to the prospective participant before participation begins, if relevant to the study. Depending on the study design, participants’ identities may be anonymous to the researchers, which decreases the potential for bias. For example, an internet survey may allow participants to enter their responses and not include their names. Voluntary and informed participation Despite assessing the capacity of the participant to comprehend the information and providing the consent in the participant’s primary language and at the appropriate reading level, some participants may be confused or have additional questions. As a conscientious researcher, you need to offer to answer any questions that the prospective participants may have during the consent process. Study participants also need an explanation of whom to contact for answers to questions about the research during the conduct of the study and whom to contact in the event of a research-related problem or injury, as well as how to do so (DHHS, 2018). In addition to the researcher who may be contacted, the IRB of the healthcare facility or university IRB to which you are submitting your materials will have specific contact information to include on the consent. A copy of the informed consent should be given to the participant so he or she has this contact information. Voluntary participation is as critical to the consent process as being informed. A noncoercive disclaimer is a statement that participation is voluntary and refusal to participate will involve no penalty or loss of benefits to which the participant is entitled (DHHS, 2018; FDA, 2019b). We do know that participants may agree to participate because they believe their care will be higher quality or they will have improved outcomes (Thakur & Lahiry, 2019). Therapeutic misconception has been documented and may need to be proactively addressed with some participants. For example, CF patients acknowledged that they agreed to participate in research because they believed their care would be better (Bailey & Ladores, 2018). (See previous section for more on therapeutic misconception.) Researchers may pay participants for their time and effort. However, any payment may be coercive to participants with extremely limited financial means (e.g., $ 5 may be coercive to a participant who is hungry). Any financial compensation to prisoners to participate in a study has been viewed as coercive. However, Ravi, Christopher, Filene, Reifeis, and White (2018) conducted a study of the attitudes of prisoners (N = 50) toward financial compensation for being a study participant. The prisoners overwhelmingly indicated that prisoners who are participants in studies should be compensated (74%) and that payment would not keep prisoners from refusing to participate (88%). When determining the amount of compensation for a specific study, factors such as transportation expenses, possible childcare costs, and length of participation should be considered. Astute researchers often seek guidance from community representatives and other experts who are familiar with the study population. When compensation is going to be provided, the information should be included in the consent document. Typically, a small financial payment ($ 10 to $ 30) is seen as noncoercive and appropriate to compensate participants for time and effort related to study participation (Adams & Lawrence, 2019). Subjects may discontinue participation in a study at any time without penalty or loss of benefits, meaning that compensation cannot be dependent on completion of the study. There may be circumstances under which the participant’s involvement in a study may be terminated by the researcher without regard to the participant’s consent (DHHS, 2018). For example, if the intervention being studied becomes potentially dangerous to a participant, you as a researcher have an obligation to discontinue the participant’s involvement in the study. The consent needs to include a general statement about the circumstances that could lead to termination of the entire project, such as safety concerns or unexpected risks. This is especially important in therapeutic research. Consent to incomplete disclosure In some studies, participants experience incomplete disclosure of study information, or are not completely informed of the study purpose, because that knowledge would alter their actions. However, prospective participants must know that certain information is being withheld deliberately. You, the researcher, must ensure that there are no undisclosed risks to the participants that are more than minimal and that their questions are truthfully answered regarding the study. Subjects who are exposed to nondisclosure of information must know when and how they will be debriefed about the study. Subjects are debriefed by informing them of the actual purpose of the study and the results that were obtained (Shamoo & Resnik, 2015). At this point, participants have the option to have their data withdrawn from the study. If the participants experience adverse effects related to the study, you must make every attempt to compensate or alleviate the effects (DHHS, 2018). Documentation of informed consent The standard is that informed consent is presented formally and requires the signature of the participant and a witness. There are lower risk studies, however, in which signatures and/ or written consent can be waived with the approval of the IRB. Waivers of written and signed consent Requirements for written consent or the participants’ signatures on their consent forms may be waived in minimal risk research (DHHS, 2018). For example, if you were using questionnaires to collect low-risk data, obtaining a signed consent form from participants might not be necessary. The participant’s completion of the questionnaire may serve as consent. The top of the questionnaire might contain a statement such as “Your completion of this questionnaire indicates your consent to participate in this study.” In other low-risk studies, data may be collected by mail or online and, after the text of the consent is presented, the participant then signifies consent by completing the questionnaire. Written consent also is waived when the only record linking the participant and the research would be the consent document, and the principal risk is the harm that could result from a breach of confidentiality. The participants must be given the option of signing or not signing a consent form, and the participant’s wishes govern whether the consent form is signed (DHHS, 2018). However, the three elements of consent—information, comprehension, and voluntarism—are essential in all studies (see Fig. 9.4), whether written consent is waived or required. An example of an alteration of the consent process is found in a study with HIV seropositive African Americans (Coleman, 2017). The descriptive correlational study was designed to test a model of factors related to depression and quality of life. In a private room at an HIV clinic, the researcher described the study purpose and other information about the study. Each set of questionnaires was given a unique identifying number, to protect confidentiality. A “waiver of signature was requested for the consent form from the IRB as it was determined the participant’s signature was not needed” (Coleman, 2017, p. 139). In this stigmatized group, confidentiality is especially important. The only link between the data provided and the participants would have been their signatures on the consent form, a valid reason for making this change. Elements of the consent document The written consent document or consent form includes the elements of informed consent required by the DHHS (2018) regulations (see Box 9.8). The IRBs of most healthcare facilities and universities maintain their own templates for the informed consent document with specific requirements, such as detailed headings, suggested wording, and contact information. The participant can read the consent form, or the researcher can read it to the participant; however, the researcher can also explain the study to the participant, using different words, in a conversational manner, which encourages questions. The participant signs the form, and the investigator or research assistant collecting the data witnesses it. This type of consent can be used for minimal-to-moderate-risk studies. All persons signing the consent form must receive a copy. The researcher keeps the original for 3 years in a secure location, such as a locked file cabinet in a locked room. Studies that involve participants with diminished autonomy require a written consent form. If these prospective participants have some comprehension of the study and agree to participate, they must sign the consent form. However, each participant’s legally authorized representative also must sign the form. The representative indicates his or her relationship to the participant under the signature. The written consent form used in a high-risk study often contains the signatures of two witnesses, the researcher, and an additional person. The additional person signing as a witness must not be otherwise connected with the study and is present to observe the informed consent process and to ensure that it adheres to specifications. The best witnesses are research advocates or patient ombudspersons employed by the institution. Sometimes nurses are asked to sign a consent form as a witness for a biomedical study. They must know the study purpose and procedures and the participant’s comprehension of the study before signing the form as a witness. The role of the witness is more important in the consent process if the prospective participant is in awe of the investigator and does not feel free to question the procedures of the study. Short-form written consent document The short-form consent document includes the following statement: “The elements of informed consent required by Section 46.116 have been presented orally to the participant or the participant’s legally authorized representative” (DHHS, 2018, 45 CFR, Section 46.117b). The researcher must develop a written summary of what is to be said to the participant in the oral presentation, and the summary must be approved by an IRB. When the oral presentation is made to the participant or to the participant’s representative, a witness is required. The participant or representative must sign the short-form consent document. The witness must sign both the short form and a copy of the summary, and the person obtaining consent must sign a copy of the summary. Copies of the summary and short form are given to the participant and the witness; the researcher retains the original documents and must keep these documents for 3 years after the end of the study. Short-form written consent documents may be used in studies that present minimal or moderate risk to participants. Recording of the consent process A researcher may choose to document the consent process through audio or video recordings. These methods document what was said to the prospective participant as well as record the participant’s questions and the investigator’s answers. Because recordings can be time consuming and costly, they are rarely used for studies of minimal or moderate risk. If your study is considered high risk, documenting the consent process electronically is recommended. The recording serves as a protection for you and your participants. The researchers and the participant (or representative) will retain a copy of the recording. Authorization for research uses and disclosure The HIPAA Privacy Rule provides individuals the right, as research participants, to authorize covered entities (healthcare provider, health plan, and healthcare clearinghouse) to use or disclose their PHI for research purposes. This authorization is regulated by HIPAA and is separate from the informed consent that is regulated by the DHHS (2018). The authorization of the use of information can be included as part of the consent form, but it is probably best to have two separate forms. The authorization focuses on privacy risks and states how, why, and with whom PHI will be shared. The key ideas required on the authorization form when used for research are included in Box 9.9. BOX 9.9 Requirements for Authorization to Release PHI for Research • Types of PHI to be used, such as medical diagnosis or assessment data, identified in an understandable way • Name of researcher who will use the PHI and affiliated institution • How the PHI will be used in this specific study • Authorization expiration date, which may be the end of the study or “none” if data will become part of a research database or repository • Signature of the participant, legal representative if appropriate, and date From HIPAA Journal. (2018). What is HIPAA authorization? Retrieved from https:// www.hipaajournal.com/ what-is-hipaa-authorization/ Institutional review An institutional review board (IRB) is a committee that reviews research to ensure that all investigators are conducting research ethically. All hospital-based research must be submitted to the hospital’s IRB, which will then determine whether it is high risk, moderate risk, minimal risk, or exempt from review. This is true, as well, of research that does not involve patients. Even though some research clearly falls under the category of “exempt from review” it must, nonetheless, be submitted to the IRB, which then will declare it exempt. Requiring review of all studies is necessary because, in the past, studies that should have been reviewed escaped notice. Universities, hospital corporations, and many managed care centers maintain IRBs to promote the conduct of ethical research and protect the rights of prospective participants at these institutions, as required since 1974. Federal regulations require that the members of an IRB evaluate the study for protection of human participants, including processes for obtaining informed consent. Federal regulations stipulate the membership, functions, and operations of an IRB (DHHS, 2018, 45 CFR, Sections 46.107–46.109). Each IRB has at least five members of various backgrounds (cultural, economic, educational, professional, gender, racial) to promote a complete, scholarly, and fair review of research that is commonly conducted in an institution (Martien & Nelligan, 2018). If an institution regularly reviews studies with participants susceptible to coercion or with impaired cognition, the IRB should include one or more members with knowledge about and experience in working with these individuals. Any IRB member who has a conflict of interest with a research project being reviewed must excuse himself or herself from the review process, except to provide information requested by the IRB. The IRB also must include members who are not affiliated with the institution and whose primary concern is nonscientific, such as an ethicist, a lawyer, or a minister (DHHS, 2018). IRBs in hospitals are often composed of physicians, nurses, lawyers, scientists, clergy, and community laypersons. The revised Common Rule provides a description of the experience and expertise of the IRB (DHHS, 2018): “The IRB shall be sufficiently qualified through the experience and expertise of its members (professional competence), and the diversity of its members, including race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. The IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments (including policies and resources) and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas.” (Section 46.107) A researcher may first develop a research proposal to obtain funding or approval of a faculty committee, if the researcher is a student. After gaining funding and/ or faculty approval, the researcher develops a protocol—a shorter, but detailed description of the proposed study and its methods. The protocol is submitted to the IRB for approval. In addition, the IRB may require a form to gather information specific to the study, such as start and ending dates of the study. The IRB reviews the protocol and form to determine whether the researcher has demonstrated that (1) the benefits of the study outweigh the risks, (2) the risks will be minimized, and (3) the consent process and document are appropriate for the intended participants (Bonham, 2018). The IRB members also protect potential participants by determining the scientific value of the study. The researcher must demonstrate the significance of the research topic and the gap in knowledge that the proposed study will address. If the methods lack rigor or the researcher lacks knowledge and expertise to conduct the proposed study, then the study should not be conducted (Bonham, 2018). For example, a student submitting a protocol will need to document the research experience and professional knowledge of the faculty sponsor relevant to the research topic. Clinical trials and other large multisite studies funded by the NIH must designate a central IRB. A central IRB is that to which the researchers will submit the study for its ethical review. Facilities that comprise the multiple sites of the study will be expected to accept the central IRB’s decision. In the past, each facility’s IRB reviewed the protocol, requiring the researchers to submit the protocol, their specific forms, and an informed consent with their facility’s contact information. Most IRBs were underresourced and burdened by the increasing paperwork required to review and approve a study (Schnipper, 2017). No single IRB had members with sufficient expertise to review studies in every specialty and type of research. As a result, reviews were inconsistent. When one IRB required a change in the methods or consent form, the change had to be reviewed by all the IRBs. Needless to say, the process delayed the implementation of the study. By requiring a central IRB, multisite, federally funded studies will be implemented more quickly. The implementation of review by a central IRB faces some barriers, such as failure to consider the local context in which the study will be implemented at a specific site (Schnipper, 2017). Another barrier to central IRBs is concern about the legal liability of a hospital or clinic when a participant at his or her site experiences an adverse event and there was no local review of the study. Levels of reviews conducted by institutional review boards Federal guidelines identify the levels of reviews required for different types of studies (DHHS, 2018). The functions and operations of an IRB involve the review of research at three different levels of scrutiny: (1) exempt from review, (2) expedited review, and (3) full board review. Researchers cannot determine the level of review their proposed study requires. The IRB chairperson and/ or committee, not the researcher, decides the level of the review. Studies are usually exempt from review if they pose no apparent risks for research participants. Studies usually considered exempt from IRB review, according to federal regulations, are identified in Box 9.10. For example, studies by nurses and other health professionals that have no foreseeable risks or are a mere inconvenience for participants may be identified as exempt from review by the chairperson of the IRB committee. In other states or regions, these same studies may be classified as studies appropriate for expedited reviews. BOX 9.10 Research Qualifying for Exemption From Review 1. Conducted in established or commonly accepted educational settings, involving normal educational practices 2. Involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: • Recorded in such a manner that human participants can be identified, directly or through identifiers • Disclosure of the human participants’ responses could reasonably place the participants at risk of criminal or civil liability • Disclosure of the human participants’ responses could reasonably be damaging to the participants’ financial standing, employability, or reputation 3. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior that is not exempt: • Exempt if human participants are elected or appointed public officials or candidates for public office • Federal statute( s) require( s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. 4. Involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens if publicly available or recorded by the investigator in such a manner that participants cannot be identified, directly or through identifiers 5. Conducted by or participant to the approval of department or agency heads, and which are designed to study, evaluate, or examine the following: • Public benefit or service programs • Procedures for obtaining benefits or services under those programs • Possible changes in or alternatives to those programs or procedures • Possible changes in methods or levels of payment for benefits or services under those programs 6. Taste and food quality evaluation and consumer acceptance studies when: • Wholesome foods without additives are consumed • Food is consumed that contains a food ingredient at or below the level and for a use found to be safe • Food consumed contains an agricultural chemical or environmental contaminant at or below the level found to be safe by the FDA or other federal agency Adapted from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1104 Under expedited IRB review procedures, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. Expedited review procedures can also be used to review minor changes in previously approved research. Studies that have some risks, which are viewed as minimal, are expedited in the review process. Minimal risk means that “probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” (DHHS, 2018, 45 CFR, Section 46.102). In reviewing the research, the reviewers may exercise all of the authorities of the IRB except disapproval of the research. If the reviewer does not believe the research should be approved, the full committee must review the study. Only the full committee can disapprove a study (DHHS, 2018). Box 9.11 identifies research that usually qualifies for expedited review. BOX 9.11 Research Qualifying for Expedited Institutional Review Board Review Expedited review for studies with no more than minimal risk involving: 1. Collection of hair, collection of nail clippings, extraction of deciduous teeth, and extraction of permanent teeth if extraction needed 2. Collection of excreta and external secretions (sweat, saliva, placenta removed at delivery, and amniotic fluid at rupture of the membrane) 3. Recording of data from participants 18 years of age or older using noninvasive procedures routinely used in clinical practice with exception of X-rays 4. Collection of blood samples by venipuncture from healthy, nonpregnant participants 18 years of age or older (amount not > 450 mL in an 8-week period, no more than two times per week) 5. Collection of dental plaque and calculus using accepted prophylactic techniques 6. Voice recordings made for research purposes such as investigations of speech defects 7. Moderate exercise by healthy volunteers 8. The study of existing data, documents, records, pathological specimens, or diagnostic specimens 9. Behavior or characteristics of individuals or groups, with no researcher manipulation. Research will not increase stress of participants. 10. Drugs or devices for which an investigational new drug exemption or an investigational device exemption is not required Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1109 A study involving greater than minimal risk to research participants requires a complete IRB review, also called a full board review. Any study that does not qualify for exempt or expediated review must undergo a full board review. To obtain IRB approval, researchers must ensure that ethical principles are upheld. Risks must be minimized, and those risks must be reasonable when compared to benefits of participation. Consistent with justice, the selection of participants must be fair and equitable. Informed consent must be obtained from each participant or legal representative and documented appropriately. In addition, the researcher must have a plan to monitor data collection, protect privacy, and maintain confidentiality (DHHS, 2018, 45 CFR, Section 46.111). Every research report must indicate that the study had IRB approval and whether the approval was from a university and/ or clinical agency. For example, nurse researchers Kelechi, Mueller, Madisetti, Prentice, and Dooley (2018) conducted a study of cryotherapy for pain relief among patients with chronic venous disease (CVeD). The cryotherapy study was designed as a multicenter randomized controlled trial that compared a 9-month graduated cooling intervention to a placebo control plus usual care among patients with the more severe forms of CVeD. Three wound care centers and an academic medical research center from the south-eastern region of United States (U.S.) participated in the study. The study complied with the Declaration of Helsinki and was approved by the university’s Institutional Review Board for Human Research (IRB). ( Kelechi et al., 2018, p. 3) Informed consent and IRB approval are necessities for conducting ethical research. With revisions to the Common Rule, researchers will want to communicate early with the IRB from which they will be requesting approval. IRBs will be adapting their procedures to be consistent with the revised Common Rule. Research misconduct The goal of research is to generate sound scientific knowledge, which is possible only through honest implementation and reporting of studies. Scientific misconduct has been a known problem since the 1980s. In 1992, the DHHS created the Office of Research Integrity (ORI, n.d.). The ORI was instituted to supervise the implementation of the rules and regulations related to research misconduct and to manage any investigations of misconduct. In this section, terms used to describe scientific misconduct will be defined. Cases of scientific misconduct will be described in health care and nursing followed by how the ORI, journal editors, peer reviewers, and researchers can prevent scientific misconduct. Terms related to scientific misconduct The most current regulations implemented by the ORI (2019b, 2019c) are CFR 42, Parts 50 and 93, Policies of General Applicability. The ORI was responsible for defining important terms used in the identification and management of research misconduct. Research misconduct was defined as “the fabrication, falsification, or plagiarism in processing, performing, or reviewing research, or in reporting research results…. It does not include honest error or differences in opinion” (ORI, 2019b, 42 CFR, Section 93.103). Also from Section 93.103, “fabrication is making up data or results and recording or reporting of them” and “falsification is manipulating research materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record.” Fabrication and falsification of research data are two of the most common acts of research misconduct managed by ORI. Plagiarism is also research misconduct and is defined as “the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit” (ORI, 2019b, 42 CFR, Section 93.103). Examples of scientific misconduct The ORI’s website contains a growing list of persons found to have falsified or fabricated research reports. We have described two completed cases in this section by way of example, but many others are available on the website. In August 2019, Dr. Rahul Agrawal was found to have fabricated data in 59 data files for experiments that were not conducted (ORI, 2019a). Dr. Agrawal was a fellow at the National Cancer Institute at NIH when he fabricated the data. In another case, Brandi Baughman, PhD, acknowledged in 2017 that she had manipulated data for 11 figures in a published paper. At the time, she was a postdoctoral fellow at the University of North Carolina and working on federally funded grants. She signed a letter indicating she had not manipulated data in any other experiments, knowing full well that she and her colleagues had a paper under review in which the findings were based on 14 reused and relabeled Western blot laboratory tests from an unrelated study. The ORI (2018) finding was that she would no longer be eligible to work with a federally funded research team for 2 years. Research misconduct is a growing concern in nursing (Lach, 2019; Ward-Smith, 2016). Asman, Melnikov, Barnoy, and Tabak (2019) surveyed 119 nurses attending nursing education programs and 32 nurses with graduate degrees about scientific misconduct that they had observed. Among these nurses, 15.5% indicated agreement with one or more items about their inclination to fabricate data, and 26.25% indicated agreement with one or more items about their inclination to select or omit data. Fifty nurses (34.2%) had “knowledge of research misconduct in the workplace” (Asman et al., 2019, p. 864). When scientific misconduct is identified, the related publications may be retracted. Al-Ghareeb et al. (2018) conducted a systematic review of 37 years of retractions in nursing and midwifery journals. They found 29 articles in nursing journals had been retracted, with the most common reason being duplicate publication (Al-Ghareeb et al., 2018). Role of the ORI in promoting the conduct of ethical research Currently, the ORI applies federal policies and regulations to protect the integrity of the USPHS’s extramural and intramural research programs. The extramural programs provide funding to research institutions, and the “intramural programs provide funding for research conducted within Federal government facilities” (ORI, n.d.). Box 9.12 contains a summary of the functions of the ORI. BOX 9.12 Functions of the Office of Research Integrity • Developing policies, procedures, and regulations related to responsible conduct of research and to the detection, investigation, and prevention of research misconduct • Monitoring research misconduct investigations • Making recommendations related to findings and consequences of investigations of research misconduct • Assisting the Office of the General Counsel (OGC) to present cases before the DHHS appeals board • Providing technical assistance to institutions responding to allegations of research misconduct • Implementing activities and programs to teach responsible conduct of research, promote research integrity, prevent research misconduct, and improve the handling of allegations of research misconduct • Conducting policy analyses, evaluations, and research to build the knowledge base in research misconduct, research integrity, and prevention and to improve the DHHS research integrity policies and procedures • Administering programs for • Maintaining institutional assurances • Responding to allegations of retaliation against whistleblowers • Approving intramural and extramural policies and procedures • Responding to Freedom of Information Act and Privacy Act requests Summarized from Office of Research Integrity (ORI). (2020). About ORI. Retrieved from https:// ori.hhs.gov/ about-ori To be classified as research misconduct, an action must be intentional and involve a significant departure from acceptable scientific practices for maintaining the integrity of the research record. When an allegation is made, it must be proven by a preponderance of evidence. Institutions that received federal research funding must have policies and procedures for investigating any allegations against one of their researchers (ORI, 2017). The institution in which the misconduct occurred gathers the evidence and determines whether research misconduct has occurred. When research misconduct has been found to have occurred, the actions taken against the researchers or agencies have included disqualification to receive federal funding for a specific length of time or lifetime suspension from receiving funds. Other actions taken may be that the researcher can conduct only supervised research and all data and sources must be certified. All publications reporting the findings of the study in question are corrected or retracted (ORI, 2019b, 42 CFR, Section 93.411). Role of journal editors and researchers in preventing scientific misconduct Editors of journals also have a major role in monitoring and preventing research misconduct in the published literature (World Association of Medical Editors [WAME], n.d.). WAME has identified data falsification, plagiarism, and violations of legal and regulatory requirements as some types of scientific misconduct. (See Chapter 27 for more information on ethical practices for authorship.) Preventing the publication of fraudulent research requires the efforts of authors, coauthors, research coordinators, reviewers of research reports for publication, and editors of professional journals (Al-Ghareeb et al., 2018; Asman et al., 2019; Ward-Smith, 2016). Authors who are primary investigators for research projects must be responsible in their conduct and the conduct of their team members, from data collection through publication of research. Coauthors and coworkers should question and, if necessary, challenge the integrity of a researcher’s claims. Sometimes, well-known scientists’ names have been added to a research publication as coauthors to give it credibility. Individuals should not be listed as coauthors unless they were actively involved in the conduct of the research and preparation of the manuscript (International Council of Medical Journal Editors [ICMJE], 2018). Similarly, supervisors and directors of hospital units should not be included as last author as a “courtesy” for a publication unless they were actively involved in at least one phase of the research. Principal investigators (PIs) in large, funded studies have a role to promote integrity in research and to identify research misconduct activities (Kovach, 2018). They may have delegated implementation of a study to a research coordinator. These individuals are often the ones closest to the actual conduct of the study, during which misconduct often occurs. The PI should monitor the study closely along with the research coordinator to ensure ethical conduct. Peer reviewers have a key role in determining the quality of a manuscript and whether it is publishable. They are considered experts in the field, and their role is to examine research for inconsistencies and inaccuracies. Editors must monitor the peer review process and must be cautious about publishing manuscripts that are at all questionable (ICMJE, 2018). Editors also must have procedures for responding to allegations of research misconduct. They must decide what actions to take if their journal contains an article that has proven to be fraudulent. Usually, fraudulent publications require retraction notations and are not to be cited by authors in future publications. However, Al-Ghareeb et al. (2018) found that the retracted articles in their review had been cited an average of seven times after being retracted. The publication of fraudulent research is a growing concern in medicine and nursing (Ward-Smith, 2016). The shrinking pool of funds available for research and the greater emphasis on research publications for retention in academic settings could lead to a higher incidence of fraudulent publications. Dr. Yoshihiro Sato, a Japanese researcher in prevention of bone fractures, committed one of the biggest frauds in scientific history (Kupferschmidt, 2018). His studies came under scrutiny when one researcher found identical means of body mass indexes for patients in the treatment group and control groups of trials conducted in different populations. Researchers in the same area began to question how his team could recruit several hundreds of patients into studies in just a few months (Else, 2019). Sixty of Sato’s papers have been retracted and his remaining publications are viewed with skepticism. Each researcher is responsible for monitoring the integrity of his or her research protocols, results, and publications. In addition, nursing professionals and journal editors must foster a spirit of intellectual inquiry, mentor prospective scientists regarding the norms for good science, and stress quality, not quantity, in publications (Fierz et al., 2014). Animals as research subjects The use of animals as research participants is a controversial issue of growing interest to nurse researchers. A small but increasing number of nurse scientists are conducting physiological studies that require the use of animals. Many scientists have expressed concerns that the animal welfare movement could threaten the future of health research. For example, a laboratory in Maryland was closed on April 2, 2019, after studying Toxoplasma gondii for 37 years. T. gondii is a foodborne illness that can lead to death. Although not publicly linked, scientists believe the closure was due to animal welfare activists’ protests against the facility (Wadman, 2019). In 2015, the NIH stopped funding studies in which chimpanzees were to be used. NIH has also been advised by lawmakers to continue the reduction in funding for nonhuman primate research by incorporating budget changes in the 2020 US budget (Hou, 2019). Alternative models of investigation have been and continue to be developed, but for now animal research still plays a valuable role in preclinical studies. Studies of new medications and other treatments are based on the findings of preclinical studies done with animals. The use of animals in research is a complicated issue that requires careful scientific and ethical consideration by investigators. From the scientific perspective, Smith, Clutton, Lilley, Hansen, and Brattelid (2018) developed a guideline for researchers that includes formulating the study, initiating dialogue with the animal facility, and ensuring quality control from the beginning of the experiment until its conclusion. Without attention to detail, the findings of laboratory animal experiments may not be reproducible. Multiple sets of regulations protect animals in a research environment. Ceremuga et al. (2017) compared the effects of curcumin on anxiety and depression of rats to the effects of typically used medications for anxiety and depression. This team of nurse researchers implemented a study using rats and noted the regulations they used in protecting the animals. “Fifty-five male Sprague-Dawley rats (Harlan Sprague Dawley Laboratories), each of which weighed between 242 and 298 g, were obtained in 1 shipment…. The animals went through a 14-day adaptation period in a temperature-controlled environment…. The rats were allowed food and water ad libitum. The animals were handled only for the purposes of drug administration, cage cleaning, and obtaining daily weights. All protocols used in this study were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at the US Army Institute of Surgical Research, San Antonio, Texas.” ( Ceremuga et al., 2017, p. 195) Ceremuga et al. (2017) found that curcumin did not have a significant effect on the anxiety and depression of rats. At least five separate sets of regulations exist to protect research animals from mistreatment. Federal government, state governments, independent accreditation organizations, professional societies, and individual institutions work to ensure that research animals are used only when necessary and only under humane conditions. At the federal level, animal research is conducted according to the guidelines of USPHS Policy on Humane Care and Use of Laboratory Animals, which was adopted in 1986 and most recently updated in 2015 (DHHS, 2015b). In addition, more than 1000 institutions in 49 countries have obtained accreditation by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC International, 2019), which demonstrates the commitment of these institutions to ensure the humane treatment of animals in research. Nurse researchers interested in using animals for research must be trained in their care and appropriate use. They will also need to review the guidelines used by their university, other employers, or funders for conducting research with animals. Key points • The ethical conduct of research begins with the identification of the study topic and continues through the publication of the study to ensure that valid evidence is available for practice. • Conducting research ethically requires protection of the human rights of participants. Human rights are claims and demands that have been justified in the eyes of an individual or by the consensus of a group of individuals. The human rights that require protection in research are (1) self-determination, (2) privacy, (3) anonymity or confidentiality, (4) fair treatment, and (5) protection from discomfort and harm. • Two historical documents that have had a strong impact on the conduct of research are the Nuremberg Code and the Declaration of Helsinki. • US federal regulations direct the ethical conduct of research. These regulations include (1) general requirements for informed consent, (2) documentation of informed consent, (3) IRB review of research, (4) exempt and expedited review procedures for certain kinds of research, and (5) criteria for IRB approval of research. • HIPAA has affected research recruitment and data collection since it was implemented in 2003. • The rights of research participants can be protected by balancing benefits and risks of a study, securing informed consent, and submitting the research for institutional review. The responsibility for protection of research participants is borne primarily by the lead or primary researcher. • To balance the benefits and risks of a study, its type, level, and number of risks are examined, and its potential benefits are identified. If possible, risks must be minimized and benefits maximized to achieve the best possible benefit-risk ratio. • The sequencing of the human genome has led to advances in how health and disease can be studied. These advances, however, have raised ethical issues about de-identification of genomic records, the reuse of biological specimens, and the appropriateness of using stem cells and organoids. • Informed consent involves the transmission of essential information, the comprehension of the information, and voluntary consent of the prospective participant. • In institutional review, a committee of peers (IRB) examines each study for ethical concerns. The IRB conducts three levels of review: exempt, expedited, and full board. • Research misconduct includes fabrication, falsification, and plagiarism during the conduct, reporting, or publication of research. The ORI was developed to investigate and manage incidents of research misconduct to protect the integrity of research in all disciplines. • Another current ethical concern is the use of animals as research subjects. The USPHS Policy on Humane Care and Use of Laboratory Animals provides direction along with several other guidelines and regulations on the humane use of animals in research. References Adams K, & Lawrence E. Research methods, statistics, and applications 2nd ed 2019; Sage Thousand Oaks, CA. Advisory Committee on Human Radiation Experiments (ACHRE). Government standards for human experiments The 1960s and 1970s ACHRE Final report (chap. 3) 1995; Retrieved from https:// bioethicsarchive.georgetown.edu/ achre/ final/ chap3. html. Ahalt S, Chute C, Fecho K, Glusman G, Hadlock J, Taylor C.et al:. Clinical data Sources and types, regulatory constraints, applications Clinical and Translational”
— Burns and Grove’s The Practice of Nursing Research – E-Book: Appraisal, Synthesis, and Generation of Evidence by Jennifer R. Gray, Susan K. Grove
https://a.co/5RD3JMR
“Many factors affected your decision to be a nurse but, for most of you, a key motivation was the desire to help others. Nursing as a profession is firmly based on the ethical principles of respect for persons, beneficence, and justice. These ethical principles that guide clinical practice must also be the standards for the conduct of nursing research (Fowler, 2017). In research, the application of ethics begins with identifying a study topic and continues through publication of the study findings. Ethical research is essential for generating evidence for nursing practice (Lach, 2019), but what does the ethical conduct of research involve? This question has been debated for many years by researchers, politicians, philosophers, lawyers, and even study participants. The debate continues because of the complexity of human rights issues; the focus of research in new, challenging arenas of technology, stem cells, and genomics; the complex ethical codes and regulations governing research; and the various interpretations of these codes and regulations. Unfortunately, specific standards of ethical research were developed in response to historical events in which the rights of participants were egregiously violated or the behavior of research scientists was blatantly dishonest (Grady, 2018). To provide an understanding of the rationale for today’s human participant protection requirements, this chapter begins by reviewing five historical events, and the mandates and regulations for ethical research that were generated as a result of them. In your clinical setting, you are probably familiar with the Health Insurance Portability and Accountability Act (HIPAA) and the necessity of protecting the privacy of a person’s health information (Department of Health and Human Services [DHHS], 2003). HIPAA, which identified the elements of private health information, has had a significant impact on researchers and institutional review boards (IRBs) in universities and healthcare agencies. The chapter also discusses the actions essential for conducting research in an ethical manner through protection of the rights of human participants. This includes making an unbiased assessment of the potential benefits and risks inherent in a study and ensuring that informed consent is obtained properly. The submission of a research proposal for institutional review is also presented. An ethical problem that has received increasing attention since the 1980s is researcher misconduct, also called scientific misconduct. Scientific misconduct is the violation of human rights during a study, including falsifying results or behaving dishonestly when disseminating the findings. Misconduct has occurred during all study phases, including reporting and publication of studies. Many disciplines, including nursing, have experienced episodes of research misconduct that have affected the quality of research evidence generated and disseminated. A discussion of current ethical issues related to research misconduct and to the use of animals in research concludes the chapter. Historical events affecting the development of ethical codes and regulations The ethical conduct of research has been a focus since the 1940s because of mistreatment of human participants in selected studies. Although these are not the only examples of unethical research, five historical experimental projects have been publicized for their unethical treatment of participants and will be described in the order in which the projects began: (1) the syphilis studies in Tuskegee, Alabama (1932–1972); (2) Nazi medical experiments (1941–1946) and resulting trials at Nuremberg; (3) the sexually transmitted infection study in Guatemala (1946–1948); (4) the Willowbrook State School study (1955–1970); and (5) the Jewish Chronic Disease Hospital study (1963–1965). More recent examples are included in the chapter, in relation to specific aspects of research. Although these five projects were biomedical and the primary investigators were physicians, nurses were aware of the research, identified potential participants, delivered treatments to participants, and served as data collectors in all of them. As indicated earlier, these and other incidences of unethical treatment of participants and research misconduct were important catalysts in the formulation of the ethical codes and regulations that direct research today. Tuskegee syphilis study In 1932, the US Public Health Service (USPHS) initiated a study of syphilis in African American men in the small, rural town of Tuskegee, Alabama (Brandt, 1978; Reverby, 2012; Rothman, 1982). The study, which continued for 40 years, was conducted to observe the natural course of syphilis in African American men. The researcher hired an African American nurse, Eunice Rivers, to recruit and retain participants. The research participants were organized into two groups: one group consisted of 400 men who had untreated syphilis, and the other was a control group of approximately 200 men without syphilis. Most of the men who consented to participate in the study were not informed about the purpose and procedures of the research. Some men were unaware that they were participants in a study. Some were subjected to spinal taps and told the procedure was treatment for their “bad blood” (Reverby, 2012), the colloquial term for syphilis and other diseases of the blood. By 1936, the group of men with syphilis experienced more health complications than did the control group. Ten years later, the death rate of the group with syphilis was twice as high as that of the control group. The participants with syphilis were examined periodically but were never administered penicillin, even after it became the standard treatment in the 1940s (Brandt, 1978). These results could have been predicted because untreated syphilis was and is the most damaging of the bacterial venereal diseases, with degeneration occurring from cardiac lesions, brain deterioration, or involvement of other organ systems. The findings of the Tuskegee syphilis study were published beginning in 1936, and additional papers were published every 4 to 6 years. In 1953, Nurse Rivers was the first author on a publication about the study procedures to retain participants (Rivers, Schuman, Simpson, & Olansky, 1953). At least 13 articles were published in medical journals reporting the results of the study. In 1969, the US Centers for Disease Control and Prevention (CDC) reviewed the study and decided that it should continue. In 1972, a story published in the Washington Star about the study sparked public outrage. Only then did the US Department of Health, Education, and Welfare (DHEW) stop the study. An investigation of the Tuskegee study found it to be ethically unjustified. In 1997, President Clinton publicly apologized for the government’s role in this event (Baker, Brawley, & Marks, 2005; Reverby, 2012). Nazi medical experiments From 1933 to 1945, the Third Reich in Europe implemented atrocious, unethical activities, some of which they called research (Steinfels & Levine, 1976). Their goal was to produce a population of racially pure Germans, also known as Aryan. Most notably, the Nazis targeted all Jews for imprisonment and systematic genocide, resulting in millions of deaths. Population growth among the Aryans was encouraged. In contrast, Nazi doctors sterilized people regarded as racial enemies, such as the Jews. In addition, Nazis killed people whom they considered racially impure or disabled, such as persons with mental illness, disabilities, and dementia. Almost 0.25 million Germans who were physically or mentally disabled (Jacobs, 2008) and 300,000 psychiatric patients (Foth, 2013) were killed. These same people were also used as research participants. The medical experiments involved exposing participants to high altitudes, freezing temperatures, malaria, poisons, spotted fever (typhus), new drugs, and unproven surgeries, usually without anesthesia (Steinfels & Levine, 1976). For example, participants were immersed in freezing water to determine how long German pilots could survive if shot down over the North Sea. Identical twins were forced to be participants of experiments in which one would be infected with a disease. Both were later killed for postmortem examination of their organs to determine differences due to the disease. These medical experiments purportedly were conducted to generate knowledge to benefit Aryans at the cost of suffering and death for prisoners in no position to give consent. In addition to the atrocities and coercion, however, the studies were poorly designed and conducted. As a result, little if any useful scientific knowledge was generated. The Nazi experiments violated ethical principles and rights of the research participants. Researchers selected participants on the basis of race, affliction, or sexual orientation, demonstrating an unfair selection process. The participants also had no opportunity to refuse participation; they were prisoners who were coerced or forced to participate. Frequently, study participants were killed during the experiments or sustained permanent physical, mental, and social damage (Levine, 1986; Steinfels & Levine, 1976). The doctors who propagated the mistreatment of human participants were brought to trial, along with other Nazi soldiers and officers, in Nuremberg, Germany, beginning in 1945. Nuremberg code At the conclusion of the trials of Nazi doctors involved in research, the defense presented 10 guidelines for appropriate research with human participants, which collectively became known as the Nuremberg Code (1949). Among the principles were the following: (1) participants’ voluntary consent to participate in research; (2) the right of participants to withdraw from studies; (3) protection of participants from physical and mental suffering, injury, disability, and death during studies; and (4) an assessment of the benefits and risks in a study. The Nuremberg Code (1949) forms the basis for protection for all human participants, regardless of a researcher’s disciplinary affiliation. Declaration of helsinki The members of the World Medical Organization (WMO) were understandably alarmed by the actions of Nazi researchers during World War II. The World Medical Assembly (WMA) of the WMO drafted a document called the Declaration of Helsinki in 1964. The Declaration of Helsinki (WMO, 1996) has subsequently been reviewed and amended, with the last amendment being approved in 2013 (WMA, 2013). The declaration forms the foundation for current research protection practices, such as research ethics committees. A research ethics committee must review proposed human participant research for possible approval; if the study is approved, the committee is responsible for monitoring its methods and outcomes as well as reviewing and approving any alterations in the research plan before such changes are implemented. The declaration also differentiates therapeutic research from nontherapeutic research. Therapeutic research gives the patient an opportunity to receive an experimental treatment that might have beneficial results. Nontherapeutic research is conducted to generate knowledge for a discipline: The results from the study might benefit future patients with similar conditions but will probably not benefit those acting as research participants. Box 9.1 contains several ethical principles from the declaration. The complete document is available from the WMA (2018). BOX 9.1 Key Ideas of the Declaration of Helsinki 1. Well-being of the individual research participant must take precedence over all other interests. 2. Investigators must protect the life, health, privacy, and dignity of research participants. 3. A strong, independent justification must be documented prior to exposing healthy volunteers to risk of harm, merely to gain new scientific information. 4. Extreme care must be taken in making use of placebo-controlled trials, which should be used only in the absence of an existing proven therapy. 5. Clinical trials must focus on improving diagnostic, therapeutic, and prophylactic procedures for patients with selected diseases without exposing participants to any additional risk of serious or irreversible harm. From Declaration of Helsinki. (1964, 2013). WMA declaration of Helsinki—Ethical principles for medical research involving human subjects. Retrieved from https:// www.wma.net/ policies-post/ wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ Worldwide, most institutions in which clinical research is conducted have adopted the Declaration of Helsinki. It has been revised, with the most recent revision increasing protection for vulnerable populations and requiring compensation for participants harmed by research (WMA, 2018). However, neither this document nor the Nuremberg Code has prevented some investigators from conducting unethical research (Beecher, 1966). Remember that the Tuskegee study continued after the Declaration of Helsinki was first released. Guatemala sexually transmitted disease study Beginning in 1946, a USPHS employee, Dr. John C. Cutler, conducted a study in Guatemala in which participants were intentionally exposed to syphilis and other sexually transmitted diseases. The participants were “sex workers, prisoners, mental patients, and soldiers” (Reverby, 2012, p. 8). Initially, participants were to be given penicillin or an arsenic compound (the treatment prior to penicillin) between exposure and infection to determine the prophylactic efficacy of each medication. The records for the study are incomplete, and it is not known how many persons developed an infection, died from the infection, or were harmed by the administered treatment (Reverby, 2012). The researchers suppressed information about their interventions and findings because they anticipated negative publicity due to the unethical nature of the study. After Dr. Cutler left in 1948, the USPHS continued to fund researchers to monitor the research participants and conduct serological testing through 1955 (Presidential Commission for the Study of Bioethical Issues, 2011). In 2010, Reverby (2012) was reviewing the records of researchers who participated in the Tuskegee study and found the papers of Dr. Cutler in which the Guatemala study was described. She shared her discovery with the CDC, and, subsequently, President Obama was informed. A public apology ensued. The Presidential Commission for the Study of Bioethical Issues (2011) investigated and wrote a report confirming the facts of the Guatemala study. Willowbrook study From the mid-1950s to the early 1970s, Dr. Saul Krugman practiced at Willowbrook State School, a large institution for cognitively impaired persons in Brooklyn, New York, and conducted research on hepatitis A infection (Rothman, 1982). The participants, all children, were deliberately infected with the hepatitis A virus. During the 20-year study, Willowbrook closed its doors to new children because of overcrowded conditions. However, the research ward continued to admit new children. To gain a child’s admission to the institution, parents were required to give permission for the child to be a study participant. Hepatitis A affects the liver, producing vomiting, nausea, and tiredness, accompanied by jaundice. The infected children suffered pain and potentially long-term effects. From the late 1950s to early 1970s, Krugman’s research team published several articles describing the study protocol and findings. Beecher (1966) cited the Willowbrook study as an example of unethical research. The investigators defended exposing the children to the virus by citing their own belief that most of the children would have acquired the infection after admission to the institution. They based their belief on the high hepatitis infection rates of children during their first year of living at Willowbrook. The investigators also stressed the benefits that the participants received on the research ward, which were a cleaner environment, better supervision, and a higher nurse-patient ratio (Rothman, 1982). Despite the controversy, this unethical study continued until the early 1970s. Jewish chronic disease hospital study Another highly publicized example of unethical research was a study conducted at the Jewish Chronic Disease Hospital in the 1960s. The USPHS, the American Cancer Society, and Sloan-Kettering Cancer Center funded the study (Nelson-Marten & Rich, 1999). Its purpose was to determine the patients’ rejection responses to live cancer cells. Twenty-two patients were injected with a suspension containing live cancer cells that had been generated from human cancer tissue (Levine, 1986). Most of the patients and their physicians were unaware of the study. An extensive investigation revealed that the patients were not informed they were research participants. They were informed that they were receiving an injection of cells, but the word cancer was omitted (Beecher, 1966). In addition, the Jewish Chronic Disease Hospital’s IRB never reviewed the study. The physician directing the research was an employee of the Sloan-Kettering Institute for Cancer Research, and there was no indication that this institution had reviewed the study (Hershey & Miller, 1976). The study was considered unethical and was terminated, with the lead researcher found to be in violation of the Nuremberg Code (1949) and the Declaration of Helsinki (WMA, 2013). This research had the potential to cause study participants serious or irreversible harm and possibly death, reinforcing the importance of conscientious institutional review and ethical researcher conduct. Early US government research regulations Following World War II, the US government increased funding for research. Federal funding by the National Institutes of Health (NIH) for research grew rapidly from less than $ 1 million in 1945 to over $ 435 million in 1965 (Beecher, 1966). This influx of funds along with newly discovered advances in medical treatment raised the potential for increased numbers of research violations. Dr. Henry Beecher (1966) published a paper with 22 examples of experimental treatments implemented without patient consent, raising concerns that the interests of science could override the interests of the patient. The government recognized the need for additional oversight. This section describes three government regulations that were developed as a result. US department of health, education, and welfare In 1973, the DHEW published its first set of regulations intended to protect human participants (Advisory Committee on Human Radiation Experiments, 1995). Clinical researchers were required to be compliant with the new stricter regulations for human research, with additional regulations to protect persons with limited capacity to consent, such as ill, cognitively impaired, or dying individuals (Levine, 1986). All research proposals involving human participants were required to undergo full institutional review, a task that became overwhelming and greatly prolonged the time required for study approval. Even studies conducted by nurses and other health professionals that involved minimal or no risks to study participants were subjected to full board review. Despite the advancement of the protection of participants’ rights, the government recognized the need for additional strategies to manage the extended time now required for study approval. National commission for the protection of human subjects of biomedical and behavioral research Because of the problems related to the DHEW regulations, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978) was formed. The commission’s charge was to identify basic ethical principles and develop guidelines based on these principles that would underlie the conduct of biomedical and behavioral research involving human participants. The commission developed what is now called the Belmont Report (DHHS, 1979). This report identified three ethical principles as relevant to research involving human participants: respect for persons, beneficence, and justice (Grady, 2018; Thakur & Lahiry, 2019). The principle of respect for persons holds that persons have the right to self-determination and the freedom to participate or not participate in research. The principle of beneficence requires the researcher to do good and avoid causing harm. The principle of justice holds that human participants should be treated fairly (Gravetter & Forzano, 2018). The commission developed ethical research guidelines based on these three principles, made recommendations to the DHHS, and was dissolved in 1978. The three ethical principles that the report identified are still followed for all federally supported research, whether implemented in the United States or internationally. Subsequent to the work of the commission, the DHHS developed federal regulations in 1981 to protect human research participants, which have been revised as needed over the past 35 years (DHHS, 1981). The first of these was the Code of Federal Regulations (CFR), Title 45, Part 46, Protection of Human Subjects, with the most recent edition being available online (DHHS, 2018). Box 9.2 lists the types of research governed by DHHS. An arm of the DHHS is the Federal Drug Administration (FDA), and its research activities are governed by CFR Title 21, Food and Drugs, Part 50, Protection of Human Subjects (FDA, 2019b), and Part 56, Institutional Review Boards (IRBs) (FDA, 2019a). Box 9.3 lists the research covered by the FDA regulations. BOX 9.2 Research Regulated by DHHS: CFR Title 45, Part 46, Protection of Human Subjects 1. Studies conducted by, supported by, or otherwise subject to regulations by any federal department or agency 2. Research conducted in educational and healthcare settings 3. Research involving the use of biophysical measures, educational tests, survey procedures, scales, interview procedures, or observation 4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens. Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5ad32ac566ecdb2466df8f068b6036a27& mc5true& node5pt45.1.46& rgn5div5 BOX 9.3 Research Regulated by the FDA: CFR Title 21, Parts 50 and 56 • Studies that test 1. Drugs for humans 2. Medical devices for human use 3. Biological products for human use 4. Human dietary supplements 5. Electronic healthcare products used with humans • Responsible for the management of new drugs and medical devices Data from U.S. Food and Drug Administration. (2019b). Protection of human subjects. Code of Federal Regulations, Title 21 Food and Drugs, Department of Health and Human Services, Parts 50 and 56. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5d494ea202a7a4e40a8f63306fd8b7142& mc5true& node5pt21.1.50& rgn5div5# se21.1.50_11 The DHHS regulations are known as the Common Rule because they are applicable across multiple DHHS agencies. The DHHS regulations are interpreted and enforced by the Office for Human Research Protection (OHRP), an agency within the DHHS (2016). In addition to providing guidance and regulatory enforcement, the OHRP develops educational programs and materials, and provides advice on ethical and regulatory issues related to biomedical and social-behavioral research. Standards for privacy for research data The concern for privacy of patient information related to the electronic storage and exchange of health information resulted in the privacy regulations known as HIPAA (Bonham, 2018). HIPAA did not require anything that was not required during routine nursing practice before its instigation; however, it addressed both electronic data security and consequences of failure to protect such data. The HIPAA Privacy Rule established the category of protected health information (PHI). The rule allows covered entities, such as health plans, healthcare clearinghouses, and healthcare providers, to use or disclose PHI to others only in certain situations. The Privacy Rule also applies to research that involves the collection of PHI (DHHS & Office for Civil Rights, 2013; HIPAA Journal, 2018). Individuals must provide a signed authorization before their PHI can be used or disclosed for research purposes. This chapter covers these regulations in the sections on protection of human rights, obtaining informed consent, and institutional review of research. Protection of human rights Human rights are justifiable claims and demands that are necessary for the self-respect, dignity, and freedom of choice for an individual (Grady, 2018). Our professional code of ethics, the American Nurses Association (ANA) Code of Ethics for Nurses (ANA, 2015), includes protection for the rights of human participants in biological and behavioral research, founded on the ethical principles of beneficence, nonmaleficence, autonomy, and justice. The human rights that require protection in research are (1) the right to self-determination, (2) the right to privacy, (3) the right to anonymity and confidentiality, (4) the right to fair treatment or justice, and (5) the right to protection from discomfort and harm (ANA, 2015; Fowler, 2017). These rights are described as follows, including situations in which they can be violated. Right to self-determination The right to self-determination is based on the ethical principle of respect for persons. Respect for persons means that humans are capable of self-determination or making their own decisions. Because of this right, humans should be treated as autonomous agents who have the freedom to conduct their lives as they choose without external controls. As a researcher, you treat prospective participants as autonomous agents when you inform them about a proposed study and allow them to choose voluntarily whether to participate (Thakur & Lahiry, 2019). In addition, participants have the right to withdraw from a study at any time without penalty (Grady, 2018). A participant’s right to self-determination can be violated through covert data collection and deception. The right of self-determination may also be threatened when potential research participants are susceptible to coercion or have diminished capacity to make independent decisions. Specific groups who have been identified as being susceptible to coercion needing additional protection include persons of racial/ ethnic minorities, prisoners, pregnant women, fetuses, neonates, and children. Each of these threats and groups requiring additional protection will be described in the following sections. Covert data collection An individual’s right to self-determination can be violated if he or she becomes a research participant without realizing it. Some researchers have exposed persons to experimental treatments without their knowledge, a prime example being the Jewish Chronic Disease Hospital study. With covert data collection, participants are unaware that research data are being collected because the investigator’s study involves collecting data about normal activity or routine health care (Reynolds, 1979). Studies in which observation is used to collect data, such as ethnographic research, are especially challenging because the researcher does not want to interfere with what would normally happen by identifying that observational data are being collected. Covert data collection can occur if participants’ behaviors are public. For example, a researcher could observe and record the number of people walking down a street who are smoking. However, covert data collection is considered unethical when research deals with sensitive aspects of an individual’s behavior, such as illegal conduct, sexual behavior, and drug use. In keeping with the HIPAA Privacy Rule (DHHS & Office for Civil Rights, 2013), PHI data collected in any manner can only be used if there is minimal risk of harm to the participants. This means the use of any type of covertly collected data would be questionable and unethical, and illegal if PHI data were being used or disclosed without prior approval. Deception The use of deception in research also can violate a participant’s right to self-determination. Deception is misinforming participants of the study’s purpose or withholding some information about the study (Gravetter & Forzano, 2018; Kazdin, 2017). A classic example of deception is the Milgram (1963) study, in which participants thought they were administering electric shocks to another person. The participants did not know the person being shocked was a professional actor who pretended to feel pain. Because of participating in this study, some participants experienced severe mental tension, almost to the point of collapse (Algahtani, Bajunaid, & Shirah, 2018; Kazdin, 2017). A researcher developing a study involving deception must be prepared to justify the deception by providing evidence that the benefits of the study are greater than the potential risks (Gravetter & Forzano, 2018; Kazdin, 2017). For example, the researcher must argue that deception is the only way the research question can be answered. The research question must be significant, and the researcher will need to specify how debriefing will occur (Gravetter & Forzano, 2018). After data collection is complete, the researcher provides debriefing of the participant by presenting the complete, accurate purpose of the study with the goal of minimizing the possible negative effects of the study. The debriefing also includes why the deception was deemed necessary (Kazdin, 2017). Covert data collection is passive deception. It may be approved by an IRB in situations in which the research is essential, the data cannot be obtained any other way, and the participants will not be harmed. For an example, on a clinical unit, the researcher may indicate that a study is about the number and type of interruptions that occurred during a nurse’s day. In reality, the researchers are observing the nurses’ compliance with hand hygiene guidelines. Covert direct observation might be approved in such a situation if the results were not going to be linked to individual nurses. In the rare situations in which covert data collection is allowable, participants must be informed of the deception once the study is completed, provided full disclosure of the study activities that were conducted (Gravetter & Forzano, 2018; Kazdin, 2017), and given the opportunity to withdraw their data from the study. Susceptible to coercion Coercion occurs when one person intentionally presents another with an overt threat of harm or the lure of excessive reward to obtain his or her compliance. The older version of the Common Rule (DHHS, 2013) identified specific vulnerable groups, including pregnant women, human fetuses, neonates, children, persons with mental incompetence, and prisoners. Conducting research with members of these groups required additional protection in the conduct of research. The revised Common Rule (DHHS, 2018) does not identify vulnerable populations but describes persons and situations in which persons may be sensitive to coercion or undue influence. The persons sensitive to coercion include some of those who were previously classified as being vulnerable, such as children, prisoners, and persons with diminished decision-making ability. However, persons who are economically or educationally disadvantaged and members of racial and ethnic minorities were included among those susceptible to coercion (DHHS, 2018). This new approach broadens the concept and puts additional responsibility on researchers to consider their inclusion and exclusion criteria and recruitment procedures. However, in many situations, the data needed to determine evidence-based care are dependent on the inclusion of persons who may be sensitive to coercion (Grady, 2018). Subjects may feel coerced to participate in research because they fear that they will suffer harm or discomfort if they do not participate. Students may feel forced to participate in research to protect their grades or prevent negative relationships with the faculty member conducting the research (Boileau, Patenaude, & St-Ong, 2018). Some patients believe that their medical or nursing care will be negatively affected if they do not agree to be research participants, a belief that may be reinforced if a healthcare provider is the one who attempts to recruit them for a study. Therapeutic misconception is the belief that research participation will result in better clinical care (Bailey & Ladores, 2018). Therapeutic misconception has also been defined as participants’ failure to distinguish between the therapeutic relationship between a patient and a healthcare provider and the protocol-driven relationship between a participant and a researcher (McConville, 2017). Despite what the clinician-researcher said about the participant’s care not being based on their consent, persons with cystic fibrosis (CF) believed their care would be better because they participated in research studies (Christofides, Stroud, Tullis, & O’Doherty, 2017). Subjects may feel coerced to participate in studies because the study offers a potential treatment and they have exhausted all other treatment options (Grady, 2018). Other participants believe that they cannot refuse the excessive rewards offered, such as large sums of money, specialized health care, special privileges, and jobs. Another example of coercion is what happened at Willowbrook State School. The school offered a specialized education for children with disabilities. The only way that parents could secure admission was to allow their child to be in the study and deliberately infected with hepatitis. Most nursing studies do not offer excessive rewards to participants. A researcher may offer reasonable payment for time and transportation costs, such as $ 10 to $ 30, or a gift certificate for this amount. When participants have a rare disorder and must travel long distances for data collection, the researcher or sponsor of the study should pay travel and lodging expenses (Gelinas, Crawford, Kelman, & Bierer, 2019). An IRB will evaluate whether a proposed payment is coercive compared to the effort and time required to participate in a study (Grady, 2018). Conducting research ethically requires that persons who are susceptible to coercion have additional protection during the conduct of research (DHHS, 2018). One protective strategy is to have waiting periods between hearing about a study and obtaining informed consent (Grady, 2018). The waiting period allows participants to consult with family and friends or think of questions that they want to ask. Thoughtful planning and open dialogue between researchers and participants can create conditions to ensure informed consent is not coercive. Diminished autonomy Autonomy is the ability to make a voluntary decision based on comprehending information about the study (Kaye, Chongwe, & Sewankambo, 2019). Some persons have diminished autonomy because of legal or mental incompetence, terminal illness, or confinement to an institution (Kazdin, 2017). Persons are said to be incompetent if a qualified healthcare provider judges them to be unable to comprehend and voluntarily decide about participation in a study. Incompetence can be temporary (e.g., substance use), permanent (e.g., intellectual disability), or transitory (e.g., delirium or psychosis). Unconscious patients and those with reduced cognitive abilities are seen as legally incompetent to give informed consent because they lack the ability to comprehend information about a study. The concern is that a person who, for whatever reason, is unable to absorb, retain, and evaluate the information about a study cannot protect themselves from possible harm or make an informed decision about whether to participate in a study. However, without finding ways to ethically obtain informed consent and including them in studies, the evidence upon which to base their safe, quality care will continue to be lacking and not grow (Ho, Downs, Bulsara, Patman, & Hill, 2018). Persons living with psychosis are the logical participants for studies of the safety and efficacy of antipsychotic medications. Nurse researchers conducted a systematic review of 646 clinical trials with participants who had been diagnosed with a psychosis. The purpose of the review was to determine the extent to which the participants were assessed for their capacity to provide informed consent (Weissinger & Ulrich, 2019). They learned that less than 10% of the studies included the capacity to provide informed consent in their inclusion/ exclusion criteria. Only 34 studies (5%) reported using a capacity assessment to determine the ability of potential participants to give consent. Patients with mild to severe dementia or Alzheimer disease may have a compromised capacity to understand the information necessary to giving informed consent. Chester, Clarkson, Davies, Hughes, and Islam (2018) published their study protocol of a pragmatic clinical trial conducted in England comparing caregivers being taught to use memory aids with a person who has early dementia to usual treatment. The researchers elicited input from an advisory group called the Public, Patient, and Carer Reference Group (PPCRG). The process and documents used to recruit potential participants were designed “following guidance from the PPCRG on language and format, to ensure that those with cognitive impairment are fully informed and engaged in the decision to take part” (Chester et al., 2018, p. 4). Using an advisory group such as the PPCRG is a robust strategy for designing appropriate recruitment procedures for any group of persons who may have diminished capacity to provide informed consent. The use of persons with decreased decision-making ability as research participants is more acceptable if several conditions exist. When the research is therapeutic, there is less concern because the participants have the potential to benefit directly from the experimental process (DHHS, 2018). Samples including persons with diminished autonomy are more acceptable when the researcher is recruiting persons with adequate autonomy as well as those with reduced autonomy as participants. Another positive factor is the availability of preclinical and clinical studies that provide evidence upon which to base the assessment of potential risks for participants. Research with persons with diminished decision-making ability is also more acceptable when risk is minimal and the consent process is strictly followed to protect the rights of the prospective participants (DHHS, 2018). Other ways to include persons with diminished capacity in studies is to assess their ability to comprehend using a standard instrument. Ho et al. (2018) recommended that researchers develop relationships with potential participants with diminished capacity and their caregivers, observing the potential participant multiple times prior to obtaining consent from the caregiver or the participant. To assess the capacity of the participant to give consent, they used an assessment tool called the “Three-Item Decisional Questionnaire (3-IDQ) adopted from Palmer et al., 2005” (Ho et al., 2018, p. 94). Another assessment, the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR), was identified as one of the strongest instruments available for assessing an individual’s capacity to give informed consent (Simpson, 2010). The companion tool, the MacArthur Competency Assessment Tool for Treatment (MacCAT-T), has been identified as the gold standard for assessing mental capacity to consent to treatment (Elzakkers, Danner, Grisso, Hoek, & van Elburg, 2018). Evidence has been published for interrater reliability, concurrent validity, and effective use of the tools across a wide range of patients (see Chapter 16) (Elzakkers et al., 2018). For a research study, the persons responsible for recruiting participants and obtaining informed consent would need to be trained in using the MacCAT-CR. Using this instrument or similar tools, researchers can make an objective decision about a participant’s ability to consent to research. If an individual is judged incompetent and incapable of consent, you must seek approval from the prospective participant and his or her legally authorized representative. A legally authorized representative means an individual or a group is authorized under law to consent on behalf of a prospective participant to his or her participation in research. The authorized representative is sometimes called a proxy. The legally authorized representative or proxy may be a spouse or close relative, if the potential participant has not designated a power of attorney. If no spouse or close relative can be accessed, a legal representative can be appointed by the state. Groups needing additional protection The groups identified as susceptible to coercion require additional protection to participate in research. Five groups requiring additional protection are described in this section: prisoners, terminally ill persons, pregnant women, fetuses and neonates, and children. Prisoners. Prisoners have diminished autonomy to consent for research because of their confinement. They may feel coerced to participate in research because they fear harm if they refuse (Midwest Nursing Research Society [MNRS], 2018) or because they desire the benefits of special treatment, monetary gain, or relief from boredom. In the past, prisoners were used for drug studies in which the medications had no health-related benefits and, instead, potential harmful side effects. Current regulations regarding research involving prisoners require that “the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers” and “procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners” (DHHS, 2018, Section 46.305). An IRB that is considering a study that include prisoners must add a prisoner or prisoner representative prior to reviewing the study. When a proposal is reviewed by multiple IRBs, only one of the IRBs must have a member that represents the prisoners. Terminally ill participants. Two factors need to be considered when designing a study with a sample that includes persons with terminal illness: (1) Who will benefit from the research? and (2) Is it ethical to conduct research on individuals who are unlikely to benefit from the study? Participating in research could have greater risks and minimal or no benefits for these participants. In addition, the dying participant’s condition could affect the results, leading to misinterpretation of the findings. Another consideration is persons with terminal illness have limited time remaining in their lives. Is it fair to ask them to spend time on a study instead of spending it with family or engaged in preferred activities? However, unless persons with terminal illness or those receiving palliative care are included in studies, the knowledge base for hospice and palliative care will not grow and be refined (Pereira & Hernández-Marrero, 2019). Some terminally ill individuals are willing participants because they believe that participating in research is a way to contribute to society before they die. Others want to take part in research because they believe that the experimental process may benefit them by slowing their disease process, potentially another example of a therapeutic misconception. Pregnant women and fetuses. Pregnant women have historically been considered vulnerable participants in regard to research (Ballantyne et al., 2017). Policies to include women, including pregnant women, in studies and policies to exclude women due to potential harm to the fetus contradict each other and result in confusion about how women should be recruited for studies (van der Graaf et al., 2018). Federal regulations define pregnancy as encompassing the period of time from implantation until delivery. “A woman is assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery” and the fetus is defined as the “product of conception from implantation until delivery” (DHHS, 2018, 45 CFR Section 46.202). Research conducted with pregnant women can occur only after studies have been done with animals and nonpregnant women to assess the potential risks. Table 9.1 lists the conditions under which a pregnant woman can be included, such as the potential for direct benefit to the woman or the fetus. If a study may benefit only the fetus, the consent of the pregnant woman and father must be obtained. TABLE 9.1 Conditions That Must Be Present for Pregnant Women to Be Included in a Study General Condition Specific Details Knowledge of potential side effects Studies with animals and nonpregnant women have been conducted and results indicated safety of the intervention. Scientifically important information Woman and fetus may benefit from the intervention. If not, risk is minimal. Knowledge cannot be gained any other way. Least possible risk Risk is minimized but study objectives can still be met. Balance of risks and benefits If no potential benefit to either mother or fetus, risk must be minimized. Consent of both parents Required if fetus is only one to benefit from the study. Father’s consent not needed if he is unavailable, incompetent, or pregnancy due to rape or incest. Fully informed Potential impact on the mother or fetus is clear in the consent form, before requesting mother to sign. No incentive or interference to terminate the pregnancy Mother does not receive any inducement to terminate pregnancy. Research staff not involved in any decision to terminate the pregnancy. Viability of the fetus Research staff not involved in any decision about neonate’s viability after delivery. Some researchers did not include pregnant women in their studies because they assumed the women would not want to participate. In New Zealand, Ballantyne et al. (2017) added a qualitative arm to a randomized intervention clinical trial for which the sample was pregnant women. This study was called the Research in Pregnancy Ethics (RIPE) study. “The RIPE study set out to ascertain views of pregnant women about research participation, by conducting semi-structured interviews and then analysing the interview transcripts using inductive thematic analysis ( Braun & Clarke, 2006). Women were recruited from a pool of participants already participating in the PiP [Probiotics in Pregnancy] study.” ( Ballantyne et al., 2017, p. 478) “The main cited benefits of the study by the participants were abstract principles of altruism, playing a valuable civic role and the importance of research. No-one cited personal benefit or gain as a motivation for participating…. The main perceived burdens related to inconvenience and time commitment…. Women wanted to clarify the time commitments and how this would fit into their schedule; they did not want to overcommit given the demands of pregnancy and having a newborn baby.” ( Ballantyne et al., 2017, pp. 479–480) “Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes.” ( Ballantyne et al., 2017, p. 483) Pregnant women should not be excluded from studies unless an increased risk to the woman or the fetus exists. Ballantyne et al. (2017) provided insight for other researchers considering recruiting pregnant women for a study. Neonates. A neonate is defined as a newborn and is further identified as either viable or nonviable on delivery. Viable neonates are able to survive after delivery through the use of technology and other therapies. An additional factor in being considered viable is the ability to maintain a heartbeat and respiration. Nonviable neonates may be living after delivery but will not be able to survive (DHHS, 2018). Neonates are extremely vulnerable and require extra protection to determine their involvement in research. However, research may involve viable neonates, neonates of uncertain viability, and nonviable neonates when the conditions identified in Box 9.4 are met. In addition, for the nonviable neonate, the vital functions of the neonate should not be artificially maintained because of the research, and the research should not terminate the heartbeat or respiration of the neonate (DHHS, 2018). BOX 9.4 Conditions to Be Met for Approval of Research With Neonates • Data available from preclinical and clinical study to assess potential risk to neonates • Potential to provide important biomedical knowledge that cannot be obtained by other means • No additional risk to the neonate • Potential to enhance the probability of the neonate’s survival • Both parents fully informed about the research and give consent • Research team has no part in determining the viability of the neonate Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.hhs.gov/ ohrp/ regulations-and-policy/ regulations/ 45-cfr-46/ index.html Children and adolescents. Children are considered vulnerable in the context of research (Singh, Siddiqi, Parameshwar, & Chandra-Mouli, 2019). However, we need more evidence upon which to base pediatric nursing practice. To develop the necessary evidence, children must be recruited for studies and assent or consent obtained (Crane & Broome, 2017). The distinction between children and adolescents is not clear. The World Health Organization (WHO, 2018) describes adolescents as being the second decade of life. The age of consenting to participate in a study is usually considered to be 18 years of age, but legal and research experts disagree among themselves (Cherry, 2017; Sade, 2017). Unfortunately, the legal definitions of the minor status of a child are statutory and vary among states and even countries. Neurophysical and psychological evidence supports the premise that adolescents lack the cognitive and affective maturity to give consent for themselves. Cherry (2017) identifies three components that comprise meaningful assent or consent for children and adolescents: intellectual development, affective development, and personal agency (Fig. 9.1). The figure is consistent with the findings of Hein, Troost, Lindeboom, Benninga, and Zwaan (2015), who found that age, followed by intelligence, explained the largest portion of the variance in a child’s or adolescent’s competence related to consent to research. Grady et al. (2014) studied the perceptions of assent/ consent among adolescents enrolled in clinical research and their parents. Approximately 40% of the sample believed that the decision for an adolescent to participate should be jointly made by parents and adolescent. Even among adolescent participants in research, however, understanding their rights and grasping the meaning of the study itself has been found to be less than desired (Cherry, 2017). Fig. 9.1Capacity to give meaningful consent. A pie chart representing capacity to give meaningful consent is divided into three sections marked clockwise as affective component, personal agency, and intellectual component. Federal regulations contain two stipulations for obtaining informed consent: The research must be of minimal risk, and both the assent of the child (when capable) and the permission of the parent or guardian must be obtained (DHHS, 2018). Assent means a child’s affirmative agreement to participate in research. Box 9.5 provides an example of an assent form. Permission to participate in a study means that the parent or guardian agrees to the participation of the child or ward in research (DHHS, 2018). If a child does not assent to participate in a study, he or she should not be included as a participant even if the parent or guardian gives permission. For therapeutic research, IRBs can approve studies with children when more than minimal risk is present, provided that potential benefit exists for the child, or when the experimental treatment is similar to usual care and the findings have potential benefit for others. Studies that do not meet these stipulations but have the potential for significant contribution to knowledge that may benefit other children with the same condition can be approved (DDHS, 2018). In all cases, procedures to obtain assent and parental permission must be implemented. BOX 9.5 Sample Assent Form for Children Ages 8 to 12 Years: Weight, Activity, and Eating Habits Before and After Mother-Child Multimedia Intervention Oral explanation We are nurses who want children like you to be strong and have energy to play and go to school. Here at your school, we are doing research on the best ways to teach you and your parents how to eat better and get more exercise using videos and computer games. If you decide to be in the study, we will measure your height and weight in a room with only your mother and the nurse. No one but them will know how much you weigh or how tall you are unless you tell them. We will ask you to answer five questions about what you eat and whether you exercise. Exercise is running, playing games outside, going for a walk, and doing things for fun where you move your body. After that, you and your mom will play a video game on the computer and watch two videos that are less than 5 minutes long. For the next five Tuesdays, we will be here after school. You and your mom will be asked the same five questions, watch two different videos, and play the video game together. We will have snacks for you and your mom to eat each time. On the sixth Tuesday, we will measure how tall you are and how much you weigh. On that day, we will ask you what you liked and didn’t like about the videos and computer games. You can change your mind about being in the study and can stop at any time. To child 1. I want to learn about what to eat to make me strong and have energy. 2. I want to answer questions about what I eat and how much exercise I get. 3. I want to watch videos and play a computer game with my mom. If the child says YES, have him/ her put an “X” here: _______________________ If the child says NO, have him/ her put an “X” here: ________________________ Date: ______________________ Child’s signature: ________________________ Another point of controversy is the age at which a child can assent to a study. A child’s competency to assent is usually governed by age, and research evidence supports the standard of a child over 10 years of age being capable of sufficient understanding to give assent (Crane & Broome, 2017). Children who are developmentally delayed, have a cognitive impairment, suffer an emotional disorder, or are physically ill must be considered on an individual basis. When designing a study in which children will be participants, it is helpful to seek consultation with a child development specialist and the primary IRB to which you will submit the study for approval. Some IRBs have developed assent guidelines or forms specific to their facilities. Assent and permission require that both the child or adolescent and parents be informed about the study. The information shared with the child about the study should be appropriate for the child’s age and culture. In the assenting process, the child must be given developmentally appropriate information on the study purpose, expectations, and benefit-risk ratio (discussed later). Media-enhanced presentations and play activities have been used as a means of providing information about the study. A group of researchers in the Netherlands conducted a participatory study to develop and test comic strips for the purpose of providing information about research participation (Grootens-Wiegers, de Vries, van Beusekom, van Dijck, & van den Broek, 2015). With the input of children at each stage of development, the comic strips evolved and, in their final version, were found to have the potential for increasing children’s knowledge about research. Yeh, Chun, Terrones, and Huang (2017) conducted a randomized controlled trial (RCT) comparing the knowledge of children and their parents about pediatric endoscopy. The intervention group (n = 37 parent-child pairs) obtained information about the procedure by watching a short, animated video and the control group (n = 40 parent-child pairs) received the information by listening to the usual verbal explanation. The 2-minute videos, one for upper endoscopy and the other for lower endoscopy, were developed based on principles of instructional design. Parents and children were interviewed separately and scored on their knowledge of key components of informed consent. The children and parents in the intervention group had significantly higher scores on knowledge of the risks of the procedure and their overall comprehension as compared to the children and parents of the control group. Continued research is needed for development and testing of innovative strategies for providing informed consent information to children and adults. A child who assents to participate in a study should sign the requisite form and be given a copy. To gain assent, the child is “meaningfully involved in the decision-making in a manner that is appropriate for the child’s capacity and age” (WHO, 2018, p. 15). Legally, a nonassenting child can be a research participant if the parents give permission, even if some potential for harm exists. Chwang (2015) argues, however, that including children in a study who have not given assent is every bit as unethical as including nonconsenting adults in a study. A child’s willingness to participate in a study should be reassessed throughout a study, reflecting respect for the child’s autonomy and dignity (Moore, McArthur, & Noble-Carr, 2018). Assent becomes more complex with children from various family dynamics and child characteristics. Oulton et al. (2016) conducted a literature review and an anonymous survey of healthcare professionals involved in pediatric research. Combining the findings of the review and the survey with their own experience of conducting pediatric research, Oulton et al. (2016) developed an algorithm that included child-related factors, family dynamics, and the complexity of the study design as components to consider in obtaining assent. A child-related factor might be a child who is bilingual. In this case, the researchers must determine the most appropriate language to use for the assent process for the child and the process to obtain parental permission. Other children who have no cognitive deficiencies, but are in unusual circumstances, may require the appointment of a legal representative by the legal system. WHO (2018) identifies the need to do this when a child has no living parents, the parents have immigrated and left the child behind, the child lives on the street with no parental supervision, the child who is unaccompanied seeks asylum in the United States, and the child is a member a of child-led household. Children under the age of 18 can give consent for their own participation in research when they have been emancipated by the legal system. In some legal jurisdictions, a girl under the age of 18 who marries is considered an emancipated minor. Other children may have previously be placed in a state’s guardianship (wards of the state). When determining the maturity of a child for the purposes of assent and consent, various professions have different standards by which maturity is assessed (WHO, 2018). Right to privacy Privacy is an individual’s right to determine the time, extent, and general circumstances under which personal information is shared with or withheld from others. This information consists of one’s attitudes, beliefs, behaviors, opinions, and records. The federal government enacted the Privacy Act (1974) to control potential infringement of privacy, related to information collected by the government, or held in federal agencies’ records. The act has four important provisions for the researcher: (1) data collection methods must be strategized so as to protect participants’ privacy, (2) data cannot be gathered from participants without their knowledge, (3) individuals have the right to access their records, and (4) individuals may prevent access by others to existent federal data (DHHS & Office of Civil Rights, 2013). The intent of this act was to prevent the invasion of privacy that occurs when private information is shared without an individual’s knowledge or against his or her will. The HIPAA Privacy Rule expanded the protection of an individual’s privacy, specifically his or her PHI that is individually identifiable, extending the protection to data held by private entities. It described the ways in which those entities covered by the rule can use or disclose this information. “Individually identifiable health information (IIHI) is information that is a subset of health information, including demographic information collected from an individual, and: (1) is created or received by healthcare provider, health plan, or healthcare clearinghouse; and (2) [is] related to past, present, or future physical or mental health or condition of an individual, the provision of health care to an individual, or the past, present, or future payment for the provision of health care to an individual, and that identifies the individual; or with respect to which there is a reasonable basis to believe that the information can be used to identify the individual” (DHHS, 2013, 45 CFR, Section 160.103). According to the HIPAA Privacy Rule, IIHI is PHI that is transmitted by electronic media, maintained in electronic media, or transmitted or maintained in any other form or medium. Thus the HIPAA privacy regulations must be followed when a nurse researcher wants to access data from a covered entity, such as reviewing a patient’s medical record in clinics or hospitals. Ahalt et al. (2019) defined de-identified data sets as having all PHI removed. De-identification consists of removing 18 items from patient records before they are released to other agencies or to researchers. These 18 items include name, contact information, identification numbers, photographs, biometrics, and other elements by which a participant could potentially be identified (Box 9.6). Because de-identification includes removing dates, researchers using de-identified data may not be able to answer some research questions such length of hospital stay and seasonal patterns to diseases (Ahalt et al., 2019). BOX 9.6 18 Elements That Could Be Used to Identify an Individual to Relatives, Employer, or Household Members 1. Names 2. All geographical subdivisions smaller than a state 3. All elements of dates (except year) for dates directly related to an individual 4. Telephone numbers 5. Facsimile numbers 6. Electronic mail (e-mail) addresses 7. Social security numbers 8. Medical record numbers 9. Health plan beneficiary numbers 10. Account numbers 11. Certificate/ license numbers 12. Vehicle identifiers and serial numbers, including license plate numbers 13. Device identifiers and serial numbers 14. Web universal resource locators (URLs) 15. Internet protocol (IP) address numbers 16. Biometric identifiers, including fingerprints and voiceprints 17. Full-face photographic images and any comparable images 18. Any other unique identifying number, characteristic, or code, unless otherwise permitted by the Privacy Rule for De-identification Office for Civil Rights, Department of Health and Human Services (DHHS). (2015). Guidance regarding methods for de-identification of protected health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) privacy rule. Retrieved from https:// www.hhs.gov/ hipaa/ for-professionals/ privacy/ special-topics/ de-identification/ index.html# standard The DHHS (2017) developed the following guidelines to help researchers, healthcare organizations, and healthcare providers determine the conditions under which they can use and disclose IIHI: • The PHI has been de-identified under the HIPAA Privacy Rule. • The data are part of a limited data set, and a data use agreement with the researcher( s) is in place. • The individual who is a potential participant for a study authorizes the researcher to use and disclose his or her PHI. • A waiver or alteration of the authorization requirement is obtained from an IRB or a privacy board. The first two items are discussed in this section of the chapter. The authorization process is discussed in the section on obtaining informed consent, and the waiver or alteration of authorization requirement is covered in the section on institutional review of research. De-identifying protected health information under the privacy rule Covered entities, such as healthcare providers and agencies, can allow researchers access to health information if the information has been de-identified, either by applying statistical methods (expert determination) or removing information (safe harbor) (Fig. 9.2). The covered entity can apply statistical methods that experts agree render the information unidentifiable. The statistical method used for de-identification of the health data must be documented. Safe harbor is certifying that the 18 elements for identification have been removed or revised to ensure the individual is not identified. The covered entity has done what it could to make the information de-identified, but has no information whether the individuals could still be identified (DHHS, 2015a). No matter the method used, you must retain this certification information for 6 years. It is important to note that the element concerning biometrics may be interpreted to include deoxyribonucleic acid (DNA) results and other particularized physiological variants, such as unusual laboratory and histological markers. Fig. 9.2Use of PHI: Two methods of de-identifying data. Source: (Information from the HIPAA Privacy Rule.) H I P P A privacy rule for de-identification methods is categorized into two methods as follows: 1. Expert determination (left): Apply statistical and scientific principles. 2. Safe horror (right): Removal of 18 types of identifiers, and no actual knowledge whether data recipient can identify person. Limited data set and data use agreement Researchers can comply with the privacy standards by accessing a limited data set (LDS) that has been de-identified (Ahalt et al., 2019). A HIPAA-limited data set includes clinical patient-specific data combined with some PHI. Patient authorization is not required to use these data sets for “research, public health, or healthcare operations research” as long as the study is approved by an IRB (Ahalt et al. 2019, p. 329). Under certain conditions, researchers and covered entities (healthcare provider, health plan, and healthcare clearinghouse) may use and disclose an LDS to a researcher for a study, without an individual participant’s authorization or an IRB waiver. These data sets are considered PHI, and the parties involved must have a data use agreement. The data use agreement limits how the data set may be used and how it will be protected, including identification of the researchers who are permitted to use the data set. The researchers receiving the data are not allowed to use or disclose the information in any way that is not permitted by the agreement, is required to protect against the unintended use or disclosure of the information, and must agree not to contact any of the individuals in the LDS (Centers for Medicare & Medicaid Services [CMS], n.d.). Secondary data analysis reuses data collected for a previous study or for other purposes, such as data in clinical or administrative databases (Wickham, 2019). Duncan, Ahmed, Dove, and Maxwell (2019) used secondary data analysis to study the cost of end-of-life (EOL) care for Medicare beneficiaries. They selected a sample (N = 114,028) from the Medicare Limited Data Set to answer their research questions. The data set was also called the Medicare 5% LDS Analytical file or Medicare 5% file. The file had been de-identified as required by HIPAA and comprised of 5% of the Medicare beneficiaries. “For the purpose of understanding cost of care at the EOL, we perform analysis of the Medicare 5% file for the years 2015 and 2016. This file is a random sample of Medicare’s claims for the 2 years, containing experience of approximately 2.9 million patients for each year.“ ( Duncan et al., 2019, p. 706) “Medicare expenditures increase sharply in the last few days of life, particularly for patients who die in hospital. Recent developments in hospice and palliative care offer the possibility of higher quality care at lower cost to Medicare if patients enter hospice earlier. Finding a lower cost site of care that does not jeopardize patients’ wishes is a realistic, worthy goal…. Identifying those who will benefit from intensive care from those in which aggressive care is likely to be futile and burdensome is a challenge for providers, patients, and families.“ ( Duncan et al., 2019, p. 709) The findings of the study conducted by Duncan et al. (2019) provided strategies by which EOL expenditures could be reduced, an important cost savings, without infringing on the desired outcome of a peaceful death. Right to anonymity and confidentiality On the basis of the right to privacy, the research participant has the right to anonymity and the right to assume that all data collected will be kept confidential. Anonymity means that even the researcher cannot link a participant’s identity to that participant’s individual responses (Adams & Lawrence, 2019). For studies that use de-identified health information or data from a limited data set, participants are anonymous to the researchers. In most studies, researchers desire to know the identity of their participants and promise that their identity will be kept confidential. Confidentiality is the researcher’s management of private information shared by a participant that must not be shared with others without the authorization of the participant (Gravetter & Forzano, 2018). Confidentiality is grounded in the premises that patients own their own information, and that only they can decide with whom to share all or part of it (Kazdin, 2017). When information is shared in confidence, the recipient (researcher) has the obligation to maintain confidentiality. Researchers, as professionals, have a duty to maintain confidentiality consistent with their profession’s code of ethics (Gravetter & Forzano, 2018). This section includes breaches in confidentiality that may occur and strategies to maintain confidentiality. Breach of confidentiality A breach of confidentiality can occur when a researcher, by accident or direct action, allows an unauthorized person to gain access to a study’s raw data. Confidentiality can be breached in the reporting or publishing phases of a study, especially in qualitative studies, in which a participant’s identity is revealed by including personal details known to other people (Creswell & Creswell, 2018; Creswell & Poth, 2018). Two other types of research are especially sensitive to breaches in confidentiality. Collecting data through online forums and social media can threaten confidentiality because of the ability to track internet protocol addresses and search the internet participant’s quotes (Hunter et al., 2018). Passive data collection also has ethical issues. Passive data collection is gathering data without the active involvement of the participant (Maher et al., 2019). The data being gathered are linked to specific participants and are generated by wearable devices such as smartphones or electronic pedometers, by global positioning systems, and by e-mails and text messages. Breaches of confidentiality can harm participants psychologically and socially as well as destroy the trust they had in the researcher. Breaches can be especially harmful to a research participant when they involve religious preferences, sexual practices, employment, personal attributes, or opinions that may be considered negative, such as racial prejudices (Gravetter & Forzano, 2018). For example, imagine that you have conducted a study of nurses’ stressful life events and work-related burnout in an acute care hospital. One of the two male participants in the study describes his anxiety disorder. Reporting that one of the male nurses in the study had an anxiety disorder would violate his confidentiality and potentially cause harm. Nurse administrators might be less likely to promote a nurse who has an anxiety disorder. There are legal limits to confidentiality that occur when a participant reveals current drug use or specific intent to harm oneself or others (Gravetter & Forzano, 2018). For example, in a phenomenological study of the experience of parenting a child with development delays, the informed consent document must describe the specific limitations on confidentiality, such as the researcher being obligated to report a mother who reveals harming her child. Maintaining confidentiality includes not allowing health professionals to access data the researcher has gathered about patients in the hospital. Sometimes, family members or close friends will ask to see data collected about a specific research participant. Sharing research data in these circumstances is a breach of confidentiality. When requesting consent for study participation, you should assure the potential participant that you will not share individual information with healthcare professionals, family members, and others in the setting. However, you may elect to share a summary of the study findings with healthcare providers, family members, and other interested parties. Maintaining confidentiality in quantitative research Researchers have a responsibility to protect the identity of participants and to maintain the confidentiality of data collected during a study. You can protect confidentiality by giving each participant a code number. For example, participant Sarah Young might be assigned the code number 001. All of the instruments and forms that Sarah completes and the data you collect about her during the study will be identified with the 001 code number, not her name. To protect participants’ identities, the master list of the participants’ names and their code numbers are kept in a locked file and room, separate from the data collected. You should not attach signed consent forms and authorization documents to instruments or other data collection tools, as this would make it easy for unauthorized persons to readily identify the participants and their responses. Consent forms are appropriately stored with the master list of participants’ names and code numbers. When entering the collected data into a database, code numbers instead of names should be used for identification. Data should be stored in at least two secure places, such as on a separate storage drive, on the researcher’s computer, on web-based or cloud storage, or on a university network. The data files need to be password-protected, and (if possible) have no personal identifiers. Another way to protect anonymity is to have participants generate their own identification codes when data will be collected over time with multiple data points (Lippe, Johnson, & Carter, 2019). The researcher does not have a master list connecting the codes to the participants’ names. You are conducting a study of the role satisfaction of new nurse employees with data collection occurring during the first month, the sixth month, and again at the twelfth month. Each nurse generates an individual code from personal information, such as the first letter of a mother’s name, the first letter of a father’s name, the number of brothers, the number of sisters, and middle initial. Thus the code would be composed of three letters and two numbers, such as BD21M. This code would be used on each form the participant completes. The premise is that the elements of the code do not change, and the participant can generate the same code each time. However, using participant-generated codes has been found to have mixed results. Although the specific components of the ID number were selected for their stability, the participant may not remember, for example, whether they included half-sisters in the number of sisters or whether they used a parent’s legal name or nickname. In quantitative research, the confidentiality of participants’ information must be ensured during the data analysis process. The data collected should undergo group analysis so that an individual cannot be identified by his or her responses. If participants are divided into groups and a group has less than five members, the results for that group should not be reported. For example, a researcher conducts a study with military veterans and collects demographic data. In reporting the results by demographic groups, if only a few women participated, the results by gender should not be reported. In writing the research report, you should describe the findings in such a way that an individual or a group of individuals cannot be identified from their responses. Maintaining confidentiality in qualitative studies Maintaining confidentiality of participants’ data in qualitative studies often requires more effort than in quantitative research. Participants are known to the data collector, so anonymity is not possible (Cypress, 2019). The smaller sample size used in a qualitative study and the depth of detail gathered on each participant requires planning to ensure confidentiality (Morse & Coulehan, 2015). Informed consent documents should contain details about who will have access to the data and how the findings will be reported. In addition, qualitative researchers should communicate to participants that direct quotes from the interview will be included in both professional publications and presentations. Sometimes qualitative participants inappropriately equate confidentiality with secrecy. Researchers should take precautions during data collection and analysis to maintain confidentiality in qualitative studies. The interviews conducted with participants frequently are recorded and later transcribed, so participants’ names should not be mentioned during the recording. Some researchers ask participants to identify pseudonyms by which they will be identified during the interview and on transcripts. Depending on the methods of the study, the researcher may return descriptions of interviews or observations to participants to allow them to correct inaccurate information or remove any information that they do not want included. Participants have the right to know whether anyone other than you will be transcribing interview information or whether other researchers will analyze the data. In addition, participants should be reminded on an ongoing basis that they have the right to withhold information. For other researchers to critically appraise the rigor and credibility of a qualitative study, an audit trail is produced. To continue to protect the participants’ confidentiality, ensure that the audit trail does not contain information linking the demographic characteristics of participants to the qualitative data. When publishing the findings, researchers must respect participants’ privacy as they decide how much detail and editing of private information are necessary to publish a study while maintaining the richness and depth of the participants’ perspectives (Morse & Coulehan, 2015). The researcher may choose to amend biographical details, removing identifiers such as cities, healthcare providers’ names, and healthcare facilities, and use pseudonyms (Cypress, 2019). Right to fair treatment The right to fair treatment is based on the ethical principle of justice. This principle holds that each person should be treated fairly and should receive what he or she is owed. In research, the selection of participants and their assignment to experimental or control group should be made impartially. In addition, their treatment during the course of a study should be fair. Fair selection of subjects As discussed earlier, historically, research was conducted on categories of individuals who were thought to be especially suitable as research participants, such as the poor, uninsured patients, prisoners, slaves, peasants, dying persons, and others who were considered undesirable (Reynolds, 1979). Researchers often treated these participants carelessly and had little regard for the harm and discomfort they experienced. The Nazi medical experiments, the Tuskegee syphilis study, and the Willowbrook study all exemplify unfair participant selection and treatment. In 1986, the NIH implemented a policy requiring the inclusion of women and minorities in federally funded studies. This policy became law in 1993 as part of the NIH Revitalization Act (Office of Research on Women’s Health, 2017). Prior to this, concerns had been raised about the exclusion of women from biomedical studies, especially women of childbearing age. From a scientific standpoint, the concern was that “monthly changes in women’s hormone levels might affect therapeutic interventions and require more complicated designs” (Clayton & Blome, 2018, p. 177). The exclusion of women to avoid harming a fetus or interfering with childbearing also excluded women from the potential benefits of new medications and treatments, for herself and her fetus. The selection of a population and the specific participants to study should be fair so that the risks and benefits of the study are distributed appropriately (Shamoo & Resnick, 2015). Subjects should be selected for reasons directly related to the problem being studied. Too often participants are selected because the researcher has easy access to them. Another concern with participant selection is that some researchers select certain people, possibly friends or patients under their care, to participate because they like them and want them to receive the specific benefits of a study. Other researchers included specific participants in study because they received gifts or money. The Common Rule requires equitable selection of participants (DHHS, 2018). Children, women, minorities, and persons who speak other languages cannot be excluded based solely on their demographic characteristics. Researchers seeking federal funding must describe in their proposals plans to recruit participants from different groups who have been traditionally underrepresented in research. The researchers must remember, if a study poses risk, no demographic group should bear an unfair burden of that risk. Conversely, when a study offers a potential benefit, no demographic group should be deprived of participation solely because of their demographic classification. Random selection of participants can eliminate some of the researcher bias that might influence participant selection. The researcher should make every effort to include fair representation across demographic characteristics, and increased cost is no longer a valid reason for not doing that. For example, the NIH has implemented stricter policies about the inclusion of women in studies and sex being a required variable in animal studies (Clayton & Blome, 2018). The only exception is when a study involves a condition, such as prostate cancer, that only affects men. Proposals for funding must include specific plans for recruiting and maintaining a diverse sample, and federally funded researchers must include demographic characteristics of participants in their annual reports. One of the most challenging tasks of a researcher is recruiting an adequate number of participants who meet the inclusion criteria and comprise a sample that includes female participants and participants from racial and ethnic minorities (Leavy, 2017). The HIPAA Privacy Rule requires that individuals give potential authorization before PHI can be shared with others, unless the researcher has IRB approval to access records for the purpose of screening. The Privacy Rule makes it more difficult for researchers to find participants for their studies; however, researchers are encouraged to work closely with their IRBs and healthcare agencies to ensure fair selection and recruitment of adequate-sized samples. Fair treatment of participants Informed consent is a specific agreement about what inclusion in the study involves and what the role of the researcher will be (Adams & Lawrence, 2019). While conducting a study, you should treat the participants fairly and respect that agreement. If the data collection requires appointments with the participants, be on time for each appointment and terminate the data collection process at the agreed-upon time. You should not change the activities or procedures that a participant is to perform unless you obtain the participant’s consent. The benefits promised the participants should be provided. For example, if you promise a participant a copy of the study findings, you should deliver on your promise when the study is completed. In addition, participants in studies should receive equal benefits, regardless of age, race, and socioeconomic status. When possible, the sample should be representative of the study population and should include participants of various ages, ethnic backgrounds, and socioeconomic levels. Treating participants fairly and respectfully facilitates the data collection process and decreases the likelihood that participants will withdrawal from a study (Clayton & Blome, 2018). Thanking participants is always appropriate; they have given you their time and their honesty. Right to protection from discomfort and harm The right to protection from discomfort and harm is based on the ethical principle of beneficence, which holds that one should do good and, above all, do no harm. Therefore researchers should protect participants from discomfort and harm while ensuring they receive the greatest possible balance of benefits in comparison with harm. Discomfort and harm can be physiological, emotional, social, or economic in nature. This section addresses the level of risk in a study, balancing benefits and risks, and the ethical responsibilities of clinicians to provide the best care possible. Level of risk In his classic text, Reynolds (1979) identified the following five categories of studies based on levels of discomfort and harm: (1) no anticipated effects, (2) temporary discomfort, (3) unusual levels of temporary discomfort, (4) risk of permanent damage, and (5) certainty of permanent damage. Each level is defined in the following discussion. Studies with no anticipated effects are studies without direct involvement of human participants. For example, studies that involve reviewing patients’ records, students’ files, pathology reports, or other documents have no anticipated effect on the participants. In these types of studies, the researcher does not interact directly with research participants. Even in these situations, however, there is a potential risk of invading a participant’s privacy. The HIPAA Privacy Rule requires that the agency providing the health information de-identify the 18 essential elements (see Box 9.6 and Fig. 9.2) that could be used to identify an individual, to promote participants’ privacy during a study. Analysis of variables from a data set that has had the 18 elements removed is usually exempt from IRB review. Participants may experience temporary discomfort in low-risk studies. In these studies, the discomfort encountered is similar to what the participant would experience in his or her daily life and ceases with the termination of the study. Many nursing studies require participants to complete questionnaires or participate in interviews, which usually involve minimal risk. Physical discomforts of such research might be fatigue, headache, or muscle tension. Emotional and social risks might entail the anxiety or embarrassment associated with responding to certain questions. Economic harms may consist of the loss of time spent participating in the study or travel costs to the study site. Most clinical nursing studies examining the impact of a treatment involve minimal risk. For example, your study might involve examining the effects of exercise on the blood glucose levels of patients with noninsulin-dependent diabetes. During the study, you ask the participants to test their blood glucose level one extra time per day. There is discomfort when the blood is obtained and a risk of physical changes that might occur with exercise. The participants might also experience anxiety and fear in association with the additional blood testing, and the testing is an added expense. Diabetic participants in this study would experience similar discomforts in their daily lives, and the discomforts would cease with the termination of the study. Other studies involve unusual levels of temporary discomfort for the participants during the study and after its termination. For example, participants might experience a deep vein thrombosis (DVT), prolonged muscle weakness, joint pain, and dizziness after participating in a study that required them to be confined to bed for 7 days to determine the effects of immobility that severe trauma patients might experience. Studies that require participants to experience failure, extreme fear, or threats to their identity or to act in unnatural ways involve unusual levels of temporary discomfort. In some qualitative studies, participants are asked questions about sensitive topics, which may reopen old emotional wounds or involve reliving traumatic events (Butler, Copnell, & Hall, 2019). For example, asking participants to describe a sexual assault experience could precipitate feelings of extreme fear, anger, and sadness. In studying sensitive topics, you should arrange prior to the study to have appropriate professionals available for referrals should the participants become upset. During the interview, you would need to be vigilant about assessing the participants’ discomfort and refer them for appropriate professional intervention as necessary. If a participant appears upset during a qualitative interview, the researcher should ask questions such as, “Do you want to pause for a moment?” or “Do you want to talk about something else for a while?” or “Do you want to stop this interview?” Some participants will want to stop the interview completely. Others will want to continue despite the discomfort because it is important for them to tell their story. Care must also be taken not to reveal a participant’s identity inadvertently when disseminating the findings, especially when studying sensitive topics (Turcotte-Tremblay & McSween-Cadieux, 2018). Studies with a potential for permanent damage are more likely to involve biomedical researchers than nurse researchers. For example, medical studies of new drugs and surgical procedures have the potential to cause participants permanent physical damage. However, nurses have investigated topics that have the potential to damage participants permanently, emotionally, spiritually, and socially. Studies examining variables such as human immunodeficiency virus (HIV) diagnosis, sexual behavior, child abuse, or drug use have the potential to cause permanent damage to a participant’s personality or reputation. There are also potential economic risks, such as reduced job performance or loss of employment. Studies in which participants will suffer certain permanent damage may be unethical, such as the Nazi medical experiments and the Tuskegee syphilis study. Conducting research that will permanently damage participants is highly questionable and must be scrutinized carefully, regardless of the benefits gained. One exception might be a study that involves participants with a life-threatening disease having the opportunity to have a medical procedure that promises a cure but causes permanent damage to hearing, to peripheral sensation, or to vision. Frequently, in studies that cause permanent damage, other people, not the participants, will receive the benefits of the study. Studies causing permanent damage to participants, without a concomitant gain, violate the Nuremberg Code (1949). Balancing benefits and risks for a study Researchers and reviewers of research must compare the benefits and risks in a study. The comparison is called the benefit-risk ratio. To begin, you must first predict the most likely outcomes of your study based on previous research findings, clinical experience, and theory. What are the benefits and risks, both actual and potential, of these outcomes? As the researcher, your goal is to maximize the benefits and minimize the risks (Fig. 9.3). Fig. 9.3Balancing benefits and risks of a study. A flow diagram for developing a study benefit-risk ratio shows the following steps: 1. Predict the outcomes of the study leading to assess benefits and risks, which collectively lead to benefit-risk ratio to maximize benefits and minimizes risks in the following two ways: a. If benefits are greater than or equal to risks, study is approved. b. If risks outweigh benefits, study is rejected. The probability and magnitude of a study’s potential benefits must be assessed. A research benefit is defined as something of value to the participant whether related to physical health, psychological status, or social gain. Participants may receive the benefit of knowing they have contributed to the acquisition of knowledge for evidence-based practice (EBP). Money and other compensations for participation in research are not benefits but remuneration for research-related inconveniences (DHHS, 2018). In study proposals and informed consent documents, the research benefits are described for the individual participants, participants’ families, and society. The type of research conducted, whether therapeutic or nontherapeutic, affects the potential benefits for the participants. In therapeutic nursing research, the individual participant has the potential to benefit from the procedures of the study, such as skin care, range of motion, touch, emotional support, and pain management strategies. The benefits might include improvement in the participant’s physical condition, which could facilitate emotional and social benefits. The participant also may benefit from the additional attention of and interaction with a healthcare professional. In addition, knowledge generated from the research may expand the participants’ and their families’ understanding of health. The conduct of nontherapeutic nursing research does not benefit the participant directly but is important to generate and refine nursing knowledge for practice. Subjects who understand the lack of therapeutic benefit for them frequently will participate because of altruism and the desire to help others with their condition (Irani & Richmond, 2015). To compare the benefits and risks, you must also assess the type, severity, and number of risks that participants might experience by participating in your study. The risks depend on the purpose of the study and the procedures used to conduct it. Studies can have actual (known) risks and potential risks for participants. As mentioned earlier, participants in a study of the effects of prolonged bed rest have the actual risk of transient muscle weakness and the potential risk of DVT. Some studies contain actual or potential risks for the participants’ families and society. You must determine the likelihood of the risks and take precautions to protect the rights of participants when implementing your study. The benefit-risk ratio is the term given to a comparison of the benefits and risks of a study and is determined on the basis of the maximized benefits and the minimized risks. The researcher attempts to maximize the benefits and minimize the risks by making changes in the study purpose or procedures, or both (Goldstein et al., 2019). If the risks entailed by your study cannot be eliminated or further minimized, you must justify their existence. If the risks outweigh the benefits, the IRB is unlikely to approve the study and you probably need to revise the study or develop a new one. If the benefits equal or outweigh the risks, you can usually justify conducting the study, and an IRB will probably approve it (see Fig. 9.3). Clinical equipoise Clinical equipoise is the responsibility of clinicians to “provide the best possible treatment for their patients” (Gravetter & Forzano, 2018, p. 90). Studies in which participants are randomly assigned to a treatment (intervention) group or control group may threaten the principle of no harm if the control group receives care that is known to be inferior. For example, in a study of patients with heart failure who have had a myocardial infarction (MI), the intervention group receives a new medication that has been shown in animal studies to be effective with fewer side effects; the control group receives an older medication that has some serious side effects. Some participants are not being protected from harm (Gravetter & Forzano, 2018), because the researchers already know that the older drug potentially can cause serious side effects. To maintain equipoise, researchers who compare clinical treatments must either believe them to be relatively equivalent, acknowledge that it is unknown which is best, or indicate professional disagreement about which is best. The informed consent process for a RCT should include benefits and potential harms of both the intervention and control condition (Kotz, Viechtbauer, Spigt, & Crutzen, 2019). Some debate exists about clinical equipoise because it implies the objective of clinical care is the same as the objective of research (Thakur & Lahiry, 2019). For valid findings to be available upon which to base clinical care, studies are needed that randomly assign participants to different groups. Chapter 11 provides information about different types of RCTs that address the issue of equipoise, specifically pragmatic clinical trials and cluster RCTs. Human subject protection in genomics research The Human Genome Project funded by the NIH recognized from the onset the ethical and legal dilemmas of genomic research and allocated 5% of the funding to study these issues (Hammer, 2019). Over $ 300 million has been invested in studying the ethical and legal issues within genomic research. The funded studies made it “evident that a delicate balance exists between major genomics scientific progress and the challenge of maintaining the ethical tenets of autonomy, beneficence, non-maleficence, and justice” (Hammer, 2019, p. 94). Several highly publicized cases have increased awareness as well as fear among the public. In 1951, Henrietta Lacks, an African American woman, only 31 years of age, was diagnosed with cervical cancer. She was admitted to the hospital for the standard treatment at the time (Jones, 1997). The specimens collected were taken to the laboratory of a scientist named Dr. Gey. Dr. Gey was trying to identify and reproduce a cell line for research purposes (Jones, 1997). When Mrs. Lacks’s cells continued to multiply, Dr. Gey developed methods to produce even more and generously provided the cell line to other researchers free of charge. These researchers, building on Dr. Gey’s research, developed a cell line from those especially hardy tumor cells, which were successfully used in research (Bledsoe & Grizzle, 2013; Skloot, 2010). Highly effective treatments, such as the polio vaccine and in vitro fertilization (IVF), were developed using the cell line and were extremely profitable for the researchers and their institutions. Literally billions of dollars were made by selling the cell line to other researchers (McEwen, Boyer, & Sun, 2013). Mrs. Lacks died never knowing her tumor cells were used for research, and her family only learned of her contribution to science in 2010. In 1990, researchers began collecting blood specimens of members of an isolated Native American Indian tribe, the Havasupai, who lived in the Grand Canyon (Caplan & Moreno, 2011). Diabetes mellitus was a devastating disease among the tribe, and researchers proposed a study to identify genetic clues of disease susceptibility. However, the researchers used the blood specimens to study other topics (McEwen et al., 2013). The publications from the subsequent studies linked schizophrenia to the tribe’s DNA and contradicted the tribe’s story of their origin. The tribe sued Arizona State University, the employer of the original researcher, and was awarded a financial settlement in 2010. In addition, tribal leaders were given the remaining blood samples to be disposed of in a culturally appropriate way. Several ethical issues in genomics research have not been resolved. The following section will include issues with de-identification of data, additional studies being conducted with specimens already collected, participants withdrawing from a study, and return of information to the research participant if beneficial to the participant. The second section will identify ethical issues about specific methods such as use of embryonic tissue. Ethical issues related to genomic specimens By its very nature, genomic data cannot be completely de-identified (Quinn & Quinn, 2018; Terry, 2015). Genomic data could be combined with data from publicly available demographic databases and be re-identified. The likelihood of linking genomic data to an individual (re-identification) has increased because genome-wide sequencing and large samples have increased the size of databases, computer processing speeds have dramatically increased, and personal data are available through public internet sources (Quinn & Quinn, 2018). Despite this issue, genomic data that have been de-identified (18 elements removed) can be used by researchers without the notification or authorization of the participants. Without links to individuals, the research is considered nonhuman research (Bledsoe, Russell-Einhorn, & Grizzle, 2018) and not subject to regulation by the Common Rule. Genomic data are being generated from the body tissues and fluids that are left over after specimens are removed during clinical care. For example, a patient has a lung biopsy. The tissue is examined to determine the presence and types of abnormal cells. Not all of the tissue is used, however, and is saved on paraffin blocks. Archival tissue and fluids have been de-identified, studied, and resulted in dramatic and rapid advances in scientific knowledge, including targeted cancer treatments, improved immunotherapy, and genome sequencing of abnormal tissues (Bledsoe et al., 2018). The issues of whether identified information will be used for future studies was directly addressed in the revised Common Rule (DHHS, 2018). The new rule includes a new type of consent, called broad consent. Broad consent asks the patient or potential study participant for permission to store, maintain, and use for future studies private information and biological specimens that are identifiable. Box 9.7 contains the required elements of broad consent. Broad consent addresses whether any profits from commercial processes developed based on participant’s biospecimen will be shared with the participant, a statement developed because of the case of Mrs. Lack. BOX 9.7 Required Elements of Broad Consent • Potential risks and discomforts • Possible benefits • Extent to which private information will be kept confidential • Participation is voluntary • Refusal to participate involves no harm or loss of benefits • May stop participation at any time • Specimens and information (identifiable and nonidentifiable) may result in commercial products and process • Whether participant will share any profits • Whether whole genome sequencing is planned From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. Voluntary participation in research and the possibility of withdrawing are hallmark characteristics of informed consent (Capron, 2018). When biospecimens have been de-identified, withdrawing from a study becomes problematic. How does a researcher delete or remove a participant’s data if the data have been de-identified? Researchers must consider this possibility when planning the study. One strategy would be to delay de-identification until data collection is complete. Another would be to de-identify the data over the course of the study but retain a code number linking the data to the participant until the study is completed. Another pressing question is what happens if the researcher’s results include information that would benefit the participants directly? For example, the researchers are studying genetic characteristics of de-identified biospecimens from 20,000 adults who have osteoarthritis and are 61 to 79 years old. They incidentally find that 3% of the 11,000 women in the study have a breast cancer gene (BRCA) mutation that is associated with an inherited predisposition to breast cancer. Should the researchers re-identify the 330 specimens with the mutation and inform the women of their results? The ethical principles of beneficence, respect of persons, and justice would support a decision to re-identify the specimens (Bledsoe et al., 2018). However, the researchers need to balance the decision with whether the original study can be completed if funding is diverted to identifying the women and whether harm would occur to women who are informed but do not have breast cancer (Bledsoe et al., 2018). Relative to harm, the researchers would need to know that Black are underrepresented in genetic testing, which means the evidence linking BRCA mutations and breast cancer among Black women is weaker than it is for White women. Therefore the researchers would be less confident about notifying Black women about a BRCA mutation (Gehlert & Mozersky, 2018). Research teams will need to discuss these issues prior to initiating a study using biospecimens. The revised Common Rule does not require re-identification but does require that a broad consent includes what the researchers would do if this situation occurred (see Box 9.7). Ethical issues with specific types of genomic research Advanced practice nurses, nurse educators, and nurse administrators are likely to confront the genomic ethical issues in their work. Warren (2016) calls for nurses to be leaders in the policy debate about stem cell and genomic research. Nurse leaders cannot be leaders in the research and policy without understanding physiological and ethical challenges, such as the moral status of embryos and organoids. Specially trained nurses are being utilized to implement the stem cell therapies in clinical trials (Perrin et al., 2018). Stem cells continue to be a controversial source of genetic material and will be discussed first. Much of the related controversy is based on the source of the cells. Ethical issues with embryos are related to the views of researchers and funders on abortion and human cloning. Organoids are produced from stem cells for research and raise some new questions about ethical use of cerebral organoids. Stem cell research We begin with a few definitions of key terms because the ethical issues are hard to understand without understanding these terms. Stem cells are human cells that can reproduce themselves or can develop into specialized cells of other types, such as blood cells or muscle cells. Stem cells have been derived from somatic cells of adults and umbilical cord blood of infants (Johnston & Zacharias, 2019). Somatic cells are any cell in the body except those cells used for reproduction, specifically any cells except sperm and eggs. Pluripotent cells are master cells and can make cells for any layer of the body. They are important because the cells they produce as they divide are used for tissue repair in the body. Scientific advances have allowed the identification or creation of stem cells from four sources: adult cells, fetal cells, embryos, and reprogrammed human cells. The ethical issues vary based on the source of the cells. For example, stem cells generated from somatic adult and child cells pose no major ethical issues for the majority of the US population. The adults involved can give informed consent to the use their cells, and parents can give consent for use of their infant’s blood. Using the cells from aborted fetuses has been more troublesome because of strong opinions about the morality of terminating a pregnancy. The revised code addresses this issue directly by removing researchers from the decision about the termination of pregnancy and not allowing them to offer any compensation for a woman having an abortion in exchange for use of the fetal tissue (DHHS, 2018). Federal funding is available for research with stem cells generated from fetal tissues or cells; however, researchers involved in fetal stem cell research need to be aware of state regulations because five states have legal bans on using fetal cells (Johnston & Zacharias, 2019). Stem cells can be extracted from preimplantation human embryos that are 4 to 7 days old because each cell has the potential to develop into all types of human cells. These stem cells are called human embryonic stem cells (hEScs). Based on initial research results, hEScs have the therapeutic potential to repair damaged human organs (Johnston & Zacharias, 2019). The opposition is great, however, because extracting the cells results in the death of the embryo, an embryo that is considered by some to be a potential human being to which ethical principles apply (Hostiuc et al., 2019). The embryos may come from IVF. Reproductive cells that were initially harvested for a future pregnancy may be donated by parents who no longer need them for that purpose. This means of generating hEScs is more acceptable on ethical grounds, because the embryos would have been destroyed anyway (Johnston & Zacharias, 2019). However, the number of donated embryos and the lack of cultural diversity of the embryos do not meet the needs of science. hEScs can be produced by cloning using a process called somatic cell nuclear transfer (SCNT). SCNT can produce embryos from which stem cells are derived, stem cells that are used for research or therapeutic purposes (Johnston & Zacharias, 2019). The embryos are destroyed after the stem cells are removed, making it ethically unacceptable to some. The hEScs derived from cloned embryo stem cells also have the potential to cause an undesired immune response or abnormal cells in a recipient (Prentice, 2019). Beginning in 1973, federal funding was not available to study embryos, hEScs, and cloned embryos. Stem cell research continued, however, funded by states, individuals, and foundations. In 1998, a change occurred in federal funding. Once the stem cells were created, federal funds were available to conduct research using the cells (Johnston & Zacharias, 2019). The specifics of funding have varied according to which US president is in office. Stem cell research has become a major political issue, with debate around which ethical principle is stronger: beneficence, nonmaleficence, or respect for persons. Beneficence supports funding and encouraging stem cell research because of its great potential in improving the health of many people suffering with diseases (Warren, 2016). Nonmaleficence supports maintaining the restrictions on any research that produces embryos that will be destroyed. When an individual views an embryo as a human life, respect for persons also supports maintaining the restrictions on destroying embryos produced for research. Induced pluripotent stem cells (iPScs) are “human somatic cells reprogrammed to develop into nearly every human cell type, and are believed to be functionally very similar or identical to embryonic stem cells” (Johnston & Zacharias, 2019, p. 1311). Ethical and legal oppositions to iPScs have been less than the opposition to hEScs. Although iPScs have some potential for negative side effects, such as immune responses and abnormal cell growth, published studies using iPScs have increased in number and are outpacing published studies with hEScs (Prentice, 2019). In 2009, the NIH released Guidelines for Human Stem Cell Research (DHHS, 2009). Other guidelines have been released by the National Academies of Science (2005) and the International Society for Stem Cell Research, with the latest revision published in 2016. Nurse researchers who are working in stem cell research will want to be familiar with these guidelines and any relevant state laws, the ethical views of other members of the research team, and the IRBs overseeing the research. Cerebral organoids Organoids are three-dimensional structures created from stem cells to mimic functions of organs (Hostiuc et al., 2019). The organs for which organoids have been generated include the retina, intestines, liver, pancreas, testes, thyroid, heart, kidneys, lungs, and brain (Hostiuc et al., 2019; Lavazza & Massimini, 2018). These miniature organs are different from human organs in that they are less complex and may not exhibit all the desired functions of the full-size organ (Lavazza & Massimini, 2018). However, the similarities to human organs have made organoids an increasingly valuable resource for biomedical research. Cerebral organoids are being used to study autism, Parkinson disease, microcephaly, and traumatic brain injury. Because human embryonic stem cells are used to make organoids, some researchers would argue against organoids on the same ethical basis as other embryonic research. However, organoids can be generated from iPScs or hEScs, with the source potentially being the deciding factor in the ethics of creating organoids (see previous section). Beyond the source of the stem cells, the functions of cerebral organoids are beginning to raise new ethical issues. Research related to developing cerebral organoids has resulted in highly complex structures with neurons specific to each of the six layers of the cortex and others that have been shown to stimulate muscle contractions (Hostiuc et al., 2019). These highly complex cerebral organoids replicate the functions of the brain in an embryo a few months old (Hostiuc et al., 2019). The complexity of these structures gives rise to questions about the extent to which cerebral organoids should be considered human: How long will it be before these tissues are conscious and sentient (Lavazza & Massimini, 2018)? At what point in their development should the ethical principles of human research apply to cerebral organoids? Sancar (2018) reported an interview with Dr. Madeline Lancaster, the scientist whose cultures began to produce the three-dimensional structures that led to the development of organoids. Dr. Lancaster argues that cerebral organoids will not progress to the point of being conscious and sentient. Research conducted with cerebral organoids will continue to be an area of knowledge to monitor. These and other organoid-related ethical questions are likely to generate lively debate in the coming years. Informed consent Obtaining informed consent from human participants is essential for the conduct of ethical research in the United States (DHHS, 2018) and in other countries. Informing is the transmission of essential ideas and content from the researcher to the prospective participant. Consent is the prospective participant’s agreement, after assimilating essential information, to participate in a study as a participant. The phenomenon of informed consent was formally defined in the first principle of the Nuremberg Code as follows: “the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the participant matter involved, as to enable him to make an understanding and enlightened decision” (Nuremberg Code, 1949, p. 181). The definition of informed consent from the Nuremberg Code provides a basis for the discussion of consent in all subsequent research codes and has wide acceptance in the research community. Informed consent can only occur when the prospective participant is mentally competent and able to comprehend that information, the researcher discloses essential information, and the prospective participant has the freedom to volunteer to participate (Fig. 9.4) (Thakur & Lahiry, 2019). Fig. 9.4 displays the informed consent process as the related components of information, comprehension, and voluntarism. Informed consent does not meet ethical standards or legal requirements unless all three components are present. Fig. 9.4Components of informed consent: information, comprehension, and voluntarism. A cyclic flow diagram shows voluntarism, information, and comprehension connected to each other. Facilitating comprehension Persons with a cognitive impairment may participate in research studies when another person can act on their behalf. To the degree that they are capable, persons with cognitive impairment should have the opportunity to choose whether to participate in research. Previously in this chapter, we discussed persons with limited capacity due to cognitive impairment, psychosis, and dementia. With careful accommodations, a study’s participants may include persons with cognitive impairment (Forster & Borasky, 2018), a diagnosis of psychosis (Weissinger & Ulrich, 2019), or dementia (Chester et al., 2018). To enhance the comprehension of all prospective participants, professional jargon in the consent document needs to be replaced by everyday language. The language of the consent document should be adapted to the expected participants. Healthcare facilities may require that the researcher make the consent form available in the most common languages spoken by their patients. Depending on the geographic area, the consent form may need to be translated into Vietnamese, French, Spanish, or another language. For example, when some of the potential participants are Spanish speakers, the researchers should provide the consent and written instruments in Spanish. However, translating the consent into Castilian Spanish is not helpful if the population is primarily from Central America. Translation of instruments is a complex process, and we recommend the book on measurement by Waltz, Strickland, and Lenz (2017) as a reference (also see Chapter 17). The reading level of the consent should be adjusted for the expected participants. The recommended reading level for informed consent documents is an eighth-grade reading level (Tamariz et al., 2019). Gehlert and Mozersky (2018) report that half of the US population has a reading level below the eighth grade. When it is likely that some participants may have limited reading ability, the researcher may read the consent aloud to all participants to avoid embarrassment. When study information is not comprehended, there is no informed consent. This section describes the information that must be included in the consent document or oral consent and the methods of documenting consent. Another way to improve comprehension is to provide the consent information in multiple modes and assess the participants’ comprehension. Lindsley (2019) conducted a quality improvement initiative that began by assessing the research participants’ knowledge of a study to which they had consented to participate. Their knowledge gaps were used as the basis for questions to use in assessing comprehension and developing a multimodal presentation with the required elements of informed consent. The text of the presentation was reduced to a sixth-grade reading level. The presentation was delivered on a touchscreen tablet. Adult volunteers were randomized to receive standard or multimodal format of consent. The comprehension of all participants was assessed. The comprehension of those participants who viewed the multimodal presentation was significantly higher than the comprehension of participants who received the standard method of consent (Lindsley, 2019). Earlier in the chapter, we identified the benefits of using visual and oral methods to enhance comprehension in children and their parents, but Lindsley’s results indicated a multimodal approach is appropriate for adults, too. Information essential for consent Informed consent requires the researcher to disclose specific information to each prospective participant. In addition to the elements that are required by federal regulations (Box 9.8), the IRB or institution where the study will be conducted may have additional elements that they require (DHHS, 2018). Typical examples of the additional elements required by some IRBs are the anticipated number of participants, whether individual clinically relevant data will be returned to participants, and the conditions under which a person’s participation in the study would be terminated by the researcher. Table 9.2 provides the required elements with examples of the corresponding information from a consent document. BOX 9.8 Required Elements of Informed Consent • Statement that the study is research • Purpose of the study • Expected time the participant will be involved • Procedures involved and which are experimental • Reasonable risks and benefits • Alternative procedures, if applicable • Extent of confidentiality • Compensation or treatment if injury occurs • Who to contact with concerns about study or rights as a study participant • Voluntary participation; no penalty for not agreeing or discontinuing the study • Whether de-identified data or specimens will be shared with other researchers • Additional information to include as applicable • Any procedures that would hurt the fetus if a woman is pregnant • Circumstances under which participation could be terminated by researchers • Any costs related to being in the study • Consequences of withdrawal and orderly termination of withdrawing • New research findings might influence participant’s decision to participate • Approximate number of participants in the study • De-identified biospecimens may be used for commercial profit • Whether and how participant’s clinically relevant results will be shared with participant • Whether biospecimens will undergo whole genome sequencing From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. TABLE 9.2 Informed Consent Language for a Descriptive Comparative Study Required Element Example Statement that the study is research You are being asked to participate in a research study about nursing students’ attitudes toward poverty. Purpose of the study The purpose of the study is to compare junior and senior nursing students’ attitudes toward poverty before and after a poverty simulation. Expected time the participant will be involved The Attitudes Toward Poverty Short-Form Scale (ATPS) takes 5 to 10 minutes to complete. Procedures involved and which are experimental The poverty simulation is a required class activity. You will be asked to complete the ATPS before and after the simulation. The researchers want to know whether the poverty simulation affects your attitudes about poverty. Reasonable risks and benefits RISKS: Because the major risk of the study is the potential loss of confidentiality, a faculty not involved in the study will remove only the consent form from the manila envelope. If you said yes to participating, your packet will be retained for the study. If you said no, your packet will be marked that it is not to be included in the study. No other risks have been identified related to participating in this study. BENEFITS: The main benefit to you for participating in this study is knowing you have contributed to expanding the body of knowledge available on nursing student’s attitudes toward poverty. Alternative procedures, if applicable There are no alternative procedures for this study. Extent of confidentiality All information obtained about you in this study is strictly confidential unless the law requires disclosure. The results of this study may be used in reports, presentations, and publications, but the researchers will not identify any individual students. Compensation or treatment if injury occurs There are no costs or payments associated with your participation in this study. Who to contact with concerns about study or rights as a study participant In the event that you suffer injury as a result of participation in any research project, you may contact Faculty Member at 123-123-1234 or Chair of the IRB at 321-321-4321, who will be glad to review the matter with you. Voluntary participation; no penalty for not agreeing or discontinuing the study The poverty simulation is a required class activity, but the researchers want your decision about participating in this study to be absolutely voluntary. If you have questions about the study, please ask the researchers before you agree to participate. It is okay for you to say no. Your decision will not affect your participation or grade in the required poverty simulation activity. Your responses will not be linked to your name. Whether de-identified data or specimens will be shared with other researchers The researchers will not share the data with other researchers. Introduction of research activities The researcher begins the informed consent document with several key elements. The informed consent document includes a statement that the prospective participant is being asked to participate in a research study and a description of the purpose of the study, type of data collection, and expected duration of the person’s participation (DHHS, 2018; Santos et al., 2017). Prospective participants also must receive a complete description of the procedures to be followed, such as whether assignment to a group will be random if the study includes an intervention and a control group. The researchers must identify the intervention as being experimental (DHHS, 2018; FDA, 2019b). For example, researchers conducting quantitative and outcome studies need to describe the procedures or mechanisms that will be used to examine, manipulate, or measure the study variables. For qualitative studies, the researcher will describe how data will be collected, such as an interview, and the topics to be discussed or observed. Mixed methods studies will include descriptions of the quantitative and qualitative procedures. In addition, they must inform prospective participants about when the study procedures will be implemented, how many times, and in what setting. Prospective participants must receive a disclosure of alternatives related to their participation in a study. For example, a female hypertensive patient who has uncontrolled blood pressure on a single antihypertensive medication may be recruited for a clinical trial for patients like her who have uncontrolled hypertension on a single drug. The two arms of the trial are following the current EBP guideline of adding a second antihypertensive medication or being prescribed a new experimental antihypertensive medication. She needs to know that, if she decides not to participate, she can continue on her current medication and attend an education program about eating correctly and losing weight. As a prospective participant, the medication plus education is an appropriate, alternative course of treatment about which she must be informed (DHHS, 2018). Research participants also need to know the funding source( s) of a study, such as specific individuals, organizations, or companies (Bonham, 2018). For example, researchers studying the effects of a specific drug must identify any sponsorship by a pharmaceutical company. Description of risks and benefits Prospective participants must be informed about any foreseeable risks or discomforts (physical, emotional, social, or economic) that might result from the study (Bonham, 2018; DHHS, 2018; FDA, 2019b). Female prospective participants need to know whether the study treatment or procedure involves potential risks to them or their fetuses if they are pregnant or become pregnant during the study (DHHS, 2018). For research involving more than minimal risk, prospective participants must be given an explanation as to whether any compensation or medical treatment, or both, would be available if injury should occur. If medical treatments are available, the person obtaining consent must describe the type and extent of the treatments. You should also describe any benefits to the participant or to others that may be reasonably expected from the research. The study might benefit the current participants or might generate knowledge that will provide evidence-based care to patients and families in the future (DHHS, 2018; FDA, 2019b). Most critically, prospective participants want to know how the risks of a study were minimized and the benefits maximized. They need time to compare the potential risks and benefits in the context of their lives so they can determine what is best for them without the researcher’s influence. Assurance of anonymity and confidentiality Prospective participants must be assured their research records, including PHI, will be secured during and following the study and remain confidential (DHHS, 2018). All oral or poster presentations and published papers will report only group findings. The exception may be for qualitative studies when participants’ quotes may be included in a presentation or publication but will not be linked to an identifiable individual. Any limits to confidentiality, such as the researcher’s need to reveal anything the participant reports about ongoing elder abuse, must also be disclosed to the prospective participant before participation begins, if relevant to the study. Depending on the study design, participants’ identities may be anonymous to the researchers, which decreases the potential for bias. For example, an internet survey may allow participants to enter their responses and not include their names. Voluntary and informed participation Despite assessing the capacity of the participant to comprehend the information and providing the consent in the participant’s primary language and at the appropriate reading level, some participants may be confused or have additional questions. As a conscientious researcher, you need to offer to answer any questions that the prospective participants may have during the consent process. Study participants also need an explanation of whom to contact for answers to questions about the research during the conduct of the study and whom to contact in the event of a research-related problem or injury, as well as how to do so (DHHS, 2018). In addition to the researcher who may be contacted, the IRB of the healthcare facility or university IRB to which you are submitting your materials will have specific contact information to include on the consent. A copy of the informed consent should be given to the participant so he or she has this contact information. Voluntary participation is as critical to the consent process as being informed. A noncoercive disclaimer is a statement that participation is voluntary and refusal to participate will involve no penalty or loss of benefits to which the participant is entitled (DHHS, 2018; FDA, 2019b). We do know that participants may agree to participate because they believe their care will be higher quality or they will have improved outcomes (Thakur & Lahiry, 2019). Therapeutic misconception has been documented and may need to be proactively addressed with some participants. For example, CF patients acknowledged that they agreed to participate in research because they believed their care would be better (Bailey & Ladores, 2018). (See previous section for more on therapeutic misconception.) Researchers may pay participants for their time and effort. However, any payment may be coercive to participants with extremely limited financial means (e.g., $ 5 may be coercive to a participant who is hungry). Any financial compensation to prisoners to participate in a study has been viewed as coercive. However, Ravi, Christopher, Filene, Reifeis, and White (2018) conducted a study of the attitudes of prisoners (N = 50) toward financial compensation for being a study participant. The prisoners overwhelmingly indicated that prisoners who are participants in studies should be compensated (74%) and that payment would not keep prisoners from refusing to participate (88%). When determining the amount of compensation for a specific study, factors such as transportation expenses, possible childcare costs, and length of participation should be considered. Astute researchers often seek guidance from community representatives and other experts who are familiar with the study population. When compensation is going to be provided, the information should be included in the consent document. Typically, a small financial payment ($ 10 to $ 30) is seen as noncoercive and appropriate to compensate participants for time and effort related to study participation (Adams & Lawrence, 2019). Subjects may discontinue participation in a study at any time without penalty or loss of benefits, meaning that compensation cannot be dependent on completion of the study. There may be circumstances under which the participant’s involvement in a study may be terminated by the researcher without regard to the participant’s consent (DHHS, 2018). For example, if the intervention being studied becomes potentially dangerous to a participant, you as a researcher have an obligation to discontinue the participant’s involvement in the study. The consent needs to include a general statement about the circumstances that could lead to termination of the entire project, such as safety concerns or unexpected risks. This is especially important in therapeutic research. Consent to incomplete disclosure In some studies, participants experience incomplete disclosure of study information, or are not completely informed of the study purpose, because that knowledge would alter their actions. However, prospective participants must know that certain information is being withheld deliberately. You, the researcher, must ensure that there are no undisclosed risks to the participants that are more than minimal and that their questions are truthfully answered regarding the study. Subjects who are exposed to nondisclosure of information must know when and how they will be debriefed about the study. Subjects are debriefed by informing them of the actual purpose of the study and the results that were obtained (Shamoo & Resnik, 2015). At this point, participants have the option to have their data withdrawn from the study. If the participants experience adverse effects related to the study, you must make every attempt to compensate or alleviate the effects (DHHS, 2018). Documentation of informed consent The standard is that informed consent is presented formally and requires the signature of the participant and a witness. There are lower risk studies, however, in which signatures and/ or written consent can be waived with the approval of the IRB. Waivers of written and signed consent Requirements for written consent or the participants’ signatures on their consent forms may be waived in minimal risk research (DHHS, 2018). For example, if you were using questionnaires to collect low-risk data, obtaining a signed consent form from participants might not be necessary. The participant’s completion of the questionnaire may serve as consent. The top of the questionnaire might contain a statement such as “Your completion of this questionnaire indicates your consent to participate in this study.” In other low-risk studies, data may be collected by mail or online and, after the text of the consent is presented, the participant then signifies consent by completing the questionnaire. Written consent also is waived when the only record linking the participant and the research would be the consent document, and the principal risk is the harm that could result from a breach of confidentiality. The participants must be given the option of signing or not signing a consent form, and the participant’s wishes govern whether the consent form is signed (DHHS, 2018). However, the three elements of consent—information, comprehension, and voluntarism—are essential in all studies (see Fig. 9.4), whether written consent is waived or required. An example of an alteration of the consent process is found in a study with HIV seropositive African Americans (Coleman, 2017). The descriptive correlational study was designed to test a model of factors related to depression and quality of life. In a private room at an HIV clinic, the researcher described the study purpose and other information about the study. Each set of questionnaires was given a unique identifying number, to protect confidentiality. A “waiver of signature was requested for the consent form from the IRB as it was determined the participant’s signature was not needed” (Coleman, 2017, p. 139). In this stigmatized group, confidentiality is especially important. The only link between the data provided and the participants would have been their signatures on the consent form, a valid reason for making this change. Elements of the consent document The written consent document or consent form includes the elements of informed consent required by the DHHS (2018) regulations (see Box 9.8). The IRBs of most healthcare facilities and universities maintain their own templates for the informed consent document with specific requirements, such as detailed headings, suggested wording, and contact information. The participant can read the consent form, or the researcher can read it to the participant; however, the researcher can also explain the study to the participant, using different words, in a conversational manner, which encourages questions. The participant signs the form, and the investigator or research assistant collecting the data witnesses it. This type of consent can be used for minimal-to-moderate-risk studies. All persons signing the consent form must receive a copy. The researcher keeps the original for 3 years in a secure location, such as a locked file cabinet in a locked room. Studies that involve participants with diminished autonomy require a written consent form. If these prospective participants have some comprehension of the study and agree to participate, they must sign the consent form. However, each participant’s legally authorized representative also must sign the form. The representative indicates his or her relationship to the participant under the signature. The written consent form used in a high-risk study often contains the signatures of two witnesses, the researcher, and an additional person. The additional person signing as a witness must not be otherwise connected with the study and is present to observe the informed consent process and to ensure that it adheres to specifications. The best witnesses are research advocates or patient ombudspersons employed by the institution. Sometimes nurses are asked to sign a consent form as a witness for a biomedical study. They must know the study purpose and procedures and the participant’s comprehension of the study before signing the form as a witness. The role of the witness is more important in the consent process if the prospective participant is in awe of the investigator and does not feel free to question the procedures of the study. Short-form written consent document The short-form consent document includes the following statement: “The elements of informed consent required by Section 46.116 have been presented orally to the participant or the participant’s legally authorized representative” (DHHS, 2018, 45 CFR, Section 46.117b). The researcher must develop a written summary of what is to be said to the participant in the oral presentation, and the summary must be approved by an IRB. When the oral presentation is made to the participant or to the participant’s representative, a witness is required. The participant or representative must sign the short-form consent document. The witness must sign both the short form and a copy of the summary, and the person obtaining consent must sign a copy of the summary. Copies of the summary and short form are given to the participant and the witness; the researcher retains the original documents and must keep these documents for 3 years after the end of the study. Short-form written consent documents may be used in studies that present minimal or moderate risk to participants. Recording of the consent process A researcher may choose to document the consent process through audio or video recordings. These methods document what was said to the prospective participant as well as record the participant’s questions and the investigator’s answers. Because recordings can be time consuming and costly, they are rarely used for studies of minimal or moderate risk. If your study is considered high risk, documenting the consent process electronically is recommended. The recording serves as a protection for you and your participants. The researchers and the participant (or representative) will retain a copy of the recording. Authorization for research uses and disclosure The HIPAA Privacy Rule provides individuals the right, as research participants, to authorize covered entities (healthcare provider, health plan, and healthcare clearinghouse) to use or disclose their PHI for research purposes. This authorization is regulated by HIPAA and is separate from the informed consent that is regulated by the DHHS (2018). The authorization of the use of information can be included as part of the consent form, but it is probably best to have two separate forms. The authorization focuses on privacy risks and states how, why, and with whom PHI will be shared. The key ideas required on the authorization form when used for research are included in Box 9.9. BOX 9.9 Requirements for Authorization to Release PHI for Research • Types of PHI to be used, such as medical diagnosis or assessment data, identified in an understandable way • Name of researcher who will use the PHI and affiliated institution • How the PHI will be used in this specific study • Authorization expiration date, which may be the end of the study or “none” if data will become part of a research database or repository • Signature of the participant, legal representative if appropriate, and date From HIPAA Journal. (2018). What is HIPAA authorization? Retrieved from https:// www.hipaajournal.com/ what-is-hipaa-authorization/ Institutional review An institutional review board (IRB) is a committee that reviews research to ensure that all investigators are conducting research ethically. All hospital-based research must be submitted to the hospital’s IRB, which will then determine whether it is high risk, moderate risk, minimal risk, or exempt from review. This is true, as well, of research that does not involve patients. Even though some research clearly falls under the category of “exempt from review” it must, nonetheless, be submitted to the IRB, which then will declare it exempt. Requiring review of all studies is necessary because, in the past, studies that should have been reviewed escaped notice. Universities, hospital corporations, and many managed care centers maintain IRBs to promote the conduct of ethical research and protect the rights of prospective participants at these institutions, as required since 1974. Federal regulations require that the members of an IRB evaluate the study for protection of human participants, including processes for obtaining informed consent. Federal regulations stipulate the membership, functions, and operations of an IRB (DHHS, 2018, 45 CFR, Sections 46.107–46.109). Each IRB has at least five members of various backgrounds (cultural, economic, educational, professional, gender, racial) to promote a complete, scholarly, and fair review of research that is commonly conducted in an institution (Martien & Nelligan, 2018). If an institution regularly reviews studies with participants susceptible to coercion or with impaired cognition, the IRB should include one or more members with knowledge about and experience in working with these individuals. Any IRB member who has a conflict of interest with a research project being reviewed must excuse himself or herself from the review process, except to provide information requested by the IRB. The IRB also must include members who are not affiliated with the institution and whose primary concern is nonscientific, such as an ethicist, a lawyer, or a minister (DHHS, 2018). IRBs in hospitals are often composed of physicians, nurses, lawyers, scientists, clergy, and community laypersons. The revised Common Rule provides a description of the experience and expertise of the IRB (DHHS, 2018): “The IRB shall be sufficiently qualified through the experience and expertise of its members (professional competence), and the diversity of its members, including race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. The IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments (including policies and resources) and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas.” (Section 46.107) A researcher may first develop a research proposal to obtain funding or approval of a faculty committee, if the researcher is a student. After gaining funding and/ or faculty approval, the researcher develops a protocol—a shorter, but detailed description of the proposed study and its methods. The protocol is submitted to the IRB for approval. In addition, the IRB may require a form to gather information specific to the study, such as start and ending dates of the study. The IRB reviews the protocol and form to determine whether the researcher has demonstrated that (1) the benefits of the study outweigh the risks, (2) the risks will be minimized, and (3) the consent process and document are appropriate for the intended participants (Bonham, 2018). The IRB members also protect potential participants by determining the scientific value of the study. The researcher must demonstrate the significance of the research topic and the gap in knowledge that the proposed study will address. If the methods lack rigor or the researcher lacks knowledge and expertise to conduct the proposed study, then the study should not be conducted (Bonham, 2018). For example, a student submitting a protocol will need to document the research experience and professional knowledge of the faculty sponsor relevant to the research topic. Clinical trials and other large multisite studies funded by the NIH must designate a central IRB. A central IRB is that to which the researchers will submit the study for its ethical review. Facilities that comprise the multiple sites of the study will be expected to accept the central IRB’s decision. In the past, each facility’s IRB reviewed the protocol, requiring the researchers to submit the protocol, their specific forms, and an informed consent with their facility’s contact information. Most IRBs were underresourced and burdened by the increasing paperwork required to review and approve a study (Schnipper, 2017). No single IRB had members with sufficient expertise to review studies in every specialty and type of research. As a result, reviews were inconsistent. When one IRB required a change in the methods or consent form, the change had to be reviewed by all the IRBs. Needless to say, the process delayed the implementation of the study. By requiring a central IRB, multisite, federally funded studies will be implemented more quickly. The implementation of review by a central IRB faces some barriers, such as failure to consider the local context in which the study will be implemented at a specific site (Schnipper, 2017). Another barrier to central IRBs is concern about the legal liability of a hospital or clinic when a participant at his or her site experiences an adverse event and there was no local review of the study. Levels of reviews conducted by institutional review boards Federal guidelines identify the levels of reviews required for different types of studies (DHHS, 2018). The functions and operations of an IRB involve the review of research at three different levels of scrutiny: (1) exempt from review, (2) expedited review, and (3) full board review. Researchers cannot determine the level of review their proposed study requires. The IRB chairperson and/ or committee, not the researcher, decides the level of the review. Studies are usually exempt from review if they pose no apparent risks for research participants. Studies usually considered exempt from IRB review, according to federal regulations, are identified in Box 9.10. For example, studies by nurses and other health professionals that have no foreseeable risks or are a mere inconvenience for participants may be identified as exempt from review by the chairperson of the IRB committee. In other states or regions, these same studies may be classified as studies appropriate for expedited reviews. BOX 9.10 Research Qualifying for Exemption From Review 1. Conducted in established or commonly accepted educational settings, involving normal educational practices 2. Involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: • Recorded in such a manner that human participants can be identified, directly or through identifiers • Disclosure of the human participants’ responses could reasonably place the participants at risk of criminal or civil liability • Disclosure of the human participants’ responses could reasonably be damaging to the participants’ financial standing, employability, or reputation 3. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior that is not exempt: • Exempt if human participants are elected or appointed public officials or candidates for public office • Federal statute( s) require( s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. 4. Involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens if publicly available or recorded by the investigator in such a manner that participants cannot be identified, directly or through identifiers 5. Conducted by or participant to the approval of department or agency heads, and which are designed to study, evaluate, or examine the following: • Public benefit or service programs • Procedures for obtaining benefits or services under those programs • Possible changes in or alternatives to those programs or procedures • Possible changes in methods or levels of payment for benefits or services under those programs 6. Taste and food quality evaluation and consumer acceptance studies when: • Wholesome foods without additives are consumed • Food is consumed that contains a food ingredient at or below the level and for a use found to be safe • Food consumed contains an agricultural chemical or environmental contaminant at or below the level found to be safe by the FDA or other federal agency Adapted from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1104 Under expedited IRB review procedures, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. Expedited review procedures can also be used to review minor changes in previously approved research. Studies that have some risks, which are viewed as minimal, are expedited in the review process. Minimal risk means that “probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” (DHHS, 2018, 45 CFR, Section 46.102). In reviewing the research, the reviewers may exercise all of the authorities of the IRB except disapproval of the research. If the reviewer does not believe the research should be approved, the full committee must review the study. Only the full committee can disapprove a study (DHHS, 2018). Box 9.11 identifies research that usually qualifies for expedited review. BOX 9.11 Research Qualifying for Expedited Institutional Review Board Review Expedited review for studies with no more than minimal risk involving: 1. Collection of hair, collection of nail clippings, extraction of deciduous teeth, and extraction of permanent teeth if extraction needed 2. Collection of excreta and external secretions (sweat, saliva, placenta removed at delivery, and amniotic fluid at rupture of the membrane) 3. Recording of data from participants 18 years of age or older using noninvasive procedures routinely used in clinical practice with exception of X-rays 4. Collection of blood samples by venipuncture from healthy, nonpregnant participants 18 years of age or older (amount not > 450 mL in an 8-week period, no more than two times per week) 5. Collection of dental plaque and calculus using accepted prophylactic techniques 6. Voice recordings made for research purposes such as investigations of speech defects 7. Moderate exercise by healthy volunteers 8. The study of existing data, documents, records, pathological specimens, or diagnostic specimens 9. Behavior or characteristics of individuals or groups, with no researcher manipulation. Research will not increase stress of participants. 10. Drugs or devices for which an investigational new drug exemption or an investigational device exemption is not required Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1109 A study involving greater than minimal risk to research participants requires a complete IRB review, also called a full board review. Any study that does not qualify for exempt or expediated review must undergo a full board review. To obtain IRB approval, researchers must ensure that ethical principles are upheld. Risks must be minimized, and those risks must be reasonable when compared to benefits of participation. Consistent with justice, the selection of participants must be fair and equitable. Informed consent must be obtained from each participant or legal representative and documented appropriately. In addition, the researcher must have a plan to monitor data collection, protect privacy, and maintain confidentiality (DHHS, 2018, 45 CFR, Section 46.111). Every research report must indicate that the study had IRB approval and whether the approval was from a university and/ or clinical agency. For example, nurse researchers Kelechi, Mueller, Madisetti, Prentice, and Dooley (2018) conducted a study of cryotherapy for pain relief among patients with chronic venous disease (CVeD). The cryotherapy study was designed as a multicenter randomized controlled trial that compared a 9-month graduated cooling intervention to a placebo control plus usual care among patients with the more severe forms of CVeD. Three wound care centers and an academic medical research center from the south-eastern region of United States (U.S.) participated in the study. The study complied with the Declaration of Helsinki and was approved by the university’s Institutional Review Board for Human Research (IRB). ( Kelechi et al., 2018, p. 3) Informed consent and IRB approval are necessities for conducting ethical research. With revisions to the Common Rule, researchers will want to communicate early with the IRB from which they will be requesting approval. IRBs will be adapting their procedures to be consistent with the revised Common Rule. Research misconduct The goal of research is to generate sound scientific knowledge, which is possible only through honest implementation and reporting of studies. Scientific misconduct has been a known problem since the 1980s. In 1992, the DHHS created the Office of Research Integrity (ORI, n.d.). The ORI was instituted to supervise the implementation of the rules and regulations related to research misconduct and to manage any investigations of misconduct. In this section, terms used to describe scientific misconduct will be defined. Cases of scientific misconduct will be described in health care and nursing followed by how the ORI, journal editors, peer reviewers, and researchers can prevent scientific misconduct. Terms related to scientific misconduct The most current regulations implemented by the ORI (2019b, 2019c) are CFR 42, Parts 50 and 93, Policies of General Applicability. The ORI was responsible for defining important terms used in the identification and management of research misconduct. Research misconduct was defined as “the fabrication, falsification, or plagiarism in processing, performing, or reviewing research, or in reporting research results…. It does not include honest error or differences in opinion” (ORI, 2019b, 42 CFR, Section 93.103). Also from Section 93.103, “fabrication is making up data or results and recording or reporting of them” and “falsification is manipulating research materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record.” Fabrication and falsification of research data are two of the most common acts of research misconduct managed by ORI. Plagiarism is also research misconduct and is defined as “the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit” (ORI, 2019b, 42 CFR, Section 93.103). Examples of scientific misconduct The ORI’s website contains a growing list of persons found to have falsified or fabricated research reports. We have described two completed cases in this section by way of example, but many others are available on the website. In August 2019, Dr. Rahul Agrawal was found to have fabricated data in 59 data files for experiments that were not conducted (ORI, 2019a). Dr. Agrawal was a fellow at the National Cancer Institute at NIH when he fabricated the data. In another case, Brandi Baughman, PhD, acknowledged in 2017 that she had manipulated data for 11 figures in a published paper. At the time, she was a postdoctoral fellow at the University of North Carolina and working on federally funded grants. She signed a letter indicating she had not manipulated data in any other experiments, knowing full well that she and her colleagues had a paper under review in which the findings were based on 14 reused and relabeled Western blot laboratory tests from an unrelated study. The ORI (2018) finding was that she would no longer be eligible to work with a federally funded research team for 2 years. Research misconduct is a growing concern in nursing (Lach, 2019; Ward-Smith, 2016). Asman, Melnikov, Barnoy, and Tabak (2019) surveyed 119 nurses attending nursing education programs and 32 nurses with graduate degrees about scientific misconduct that they had observed. Among these nurses, 15.5% indicated agreement with one or more items about their inclination to fabricate data, and 26.25% indicated agreement with one or more items about their inclination to select or omit data. Fifty nurses (34.2%) had “knowledge of research misconduct in the workplace” (Asman et al., 2019, p. 864). When scientific misconduct is identified, the related publications may be retracted. Al-Ghareeb et al. (2018) conducted a systematic review of 37 years of retractions in nursing and midwifery journals. They found 29 articles in nursing journals had been retracted, with the most common reason being duplicate publication (Al-Ghareeb et al., 2018). Role of the ORI in promoting the conduct of ethical research Currently, the ORI applies federal policies and regulations to protect the integrity of the USPHS’s extramural and intramural research programs. The extramural programs provide funding to research institutions, and the “intramural programs provide funding for research conducted within Federal government facilities” (ORI, n.d.). Box 9.12 contains a summary of the functions of the ORI. BOX 9.12 Functions of the Office of Research Integrity • Developing policies, procedures, and regulations related to responsible conduct of research and to the detection, investigation, and prevention of research misconduct • Monitoring research misconduct investigations • Making recommendations related to findings and consequences of investigations of research misconduct • Assisting the Office of the General Counsel (OGC) to present cases before the DHHS appeals board • Providing technical assistance to institutions responding to allegations of research misconduct • Implementing activities and programs to teach responsible conduct of research, promote research integrity, prevent research misconduct, and improve the handling of allegations of research misconduct • Conducting policy analyses, evaluations, and research to build the knowledge base in research misconduct, research integrity, and prevention and to improve the DHHS research integrity policies and procedures • Administering programs for • Maintaining institutional assurances • Responding to allegations of retaliation against whistleblowers • Approving intramural and extramural policies and procedures • Responding to Freedom of Information Act and Privacy Act requests Summarized from Office of Research Integrity (ORI). (2020). About ORI. Retrieved from https:// ori.hhs.gov/ about-ori To be classified as research misconduct, an action must be intentional and involve a significant departure from acceptable scientific practices for maintaining the integrity of the research record. When an allegation is made, it must be proven by a preponderance of evidence. Institutions that received federal research funding must have policies and procedures for investigating any allegations against one of their researchers (ORI, 2017). The institution in which the misconduct occurred gathers the evidence and determines whether research misconduct has occurred. When research misconduct has been found to have occurred, the actions taken against the researchers or agencies have included disqualification to receive federal funding for a specific length of time or lifetime suspension from receiving funds. Other actions taken may be that the researcher can conduct only supervised research and all data and sources must be certified. All publications reporting the findings of the study in question are corrected or retracted (ORI, 2019b, 42 CFR, Section 93.411). Role of journal editors and researchers in preventing scientific misconduct Editors of journals also have a major role in monitoring and preventing research misconduct in the published literature (World Association of Medical Editors [WAME], n.d.). WAME has identified data falsification, plagiarism, and violations of legal and regulatory requirements as some types of scientific misconduct. (See Chapter 27 for more information on ethical practices for authorship.) Preventing the publication of fraudulent research requires the efforts of authors, coauthors, research coordinators, reviewers of research reports for publication, and editors of professional journals (Al-Ghareeb et al., 2018; Asman et al., 2019; Ward-Smith, 2016). Authors who are primary investigators for research projects must be responsible in their conduct and the conduct of their team members, from data collection through publication of research. Coauthors and coworkers should question and, if necessary, challenge the integrity of a researcher’s claims. Sometimes, well-known scientists’ names have been added to a research publication as coauthors to give it credibility. Individuals should not be listed as coauthors unless they were actively involved in the conduct of the research and preparation of the manuscript (International Council of Medical Journal Editors [ICMJE], 2018). Similarly, supervisors and directors of hospital units should not be included as last author as a “courtesy” for a publication unless they were actively involved in at least one phase of the research. Principal investigators (PIs) in large, funded studies have a role to promote integrity in research and to identify research misconduct activities (Kovach, 2018). They may have delegated implementation of a study to a research coordinator. These individuals are often the ones closest to the actual conduct of the study, during which misconduct often occurs. The PI should monitor the study closely along with the research coordinator to ensure ethical conduct. Peer reviewers have a key role in determining the quality of a manuscript and whether it is publishable. They are considered experts in the field, and their role is to examine research for inconsistencies and inaccuracies. Editors must monitor the peer review process and must be cautious about publishing manuscripts that are at all questionable (ICMJE, 2018). Editors also must have procedures for responding to allegations of research misconduct. They must decide what actions to take if their journal contains an article that has proven to be fraudulent. Usually, fraudulent publications require retraction notations and are not to be cited by authors in future publications. However, Al-Ghareeb et al. (2018) found that the retracted articles in their review had been cited an average of seven times after being retracted. The publication of fraudulent research is a growing concern in medicine and nursing (Ward-Smith, 2016). The shrinking pool of funds available for research and the greater emphasis on research publications for retention in academic settings could lead to a higher incidence of fraudulent publications. Dr. Yoshihiro Sato, a Japanese researcher in prevention of bone fractures, committed one of the biggest frauds in scientific history (Kupferschmidt, 2018). His studies came under scrutiny when one researcher found identical means of body mass indexes for patients in the treatment group and control groups of trials conducted in different populations. Researchers in the same area began to question how his team could recruit several hundreds of patients into studies in just a few months (Else, 2019). Sixty of Sato’s papers have been retracted and his remaining publications are viewed with skepticism. Each researcher is responsible for monitoring the integrity of his or her research protocols, results, and publications. In addition, nursing professionals and journal editors must foster a spirit of intellectual inquiry, mentor prospective scientists regarding the norms for good science, and stress quality, not quantity, in publications (Fierz et al., 2014). Animals as research subjects The use of animals as research participants is a controversial issue of growing interest to nurse researchers. A small but increasing number of nurse scientists are conducting physiological studies that require the use of animals. Many scientists have expressed concerns that the animal welfare movement could threaten the future of health research. For example, a laboratory in Maryland was closed on April 2, 2019, after studying Toxoplasma gondii for 37 years. T. gondii is a foodborne illness that can lead to death. Although not publicly linked, scientists believe the closure was due to animal welfare activists’ protests against the facility (Wadman, 2019). In 2015, the NIH stopped funding studies in which chimpanzees were to be used. NIH has also been advised by lawmakers to continue the reduction in funding for nonhuman primate research by incorporating budget changes in the 2020 US budget (Hou, 2019). Alternative models of investigation have been and continue to be developed, but for now animal research still plays a valuable role in preclinical studies. Studies of new medications and other treatments are based on the findings of preclinical studies done with animals. The use of animals in research is a complicated issue that requires careful scientific and ethical consideration by investigators. From the scientific perspective, Smith, Clutton, Lilley, Hansen, and Brattelid (2018) developed a guideline for researchers that includes formulating the study, initiating dialogue with the animal facility, and ensuring quality control from the beginning of the experiment until its conclusion. Without attention to detail, the findings of laboratory animal experiments may not be reproducible. Multiple sets of regulations protect animals in a research environment. Ceremuga et al. (2017) compared the effects of curcumin on anxiety and depression of rats to the effects of typically used medications for anxiety and depression. This team of nurse researchers implemented a study using rats and noted the regulations they used in protecting the animals. “Fifty-five male Sprague-Dawley rats (Harlan Sprague Dawley Laboratories), each of which weighed between 242 and 298 g, were obtained in 1 shipment…. The animals went through a 14-day adaptation period in a temperature-controlled environment…. The rats were allowed food and water ad libitum. The animals were handled only for the purposes of drug administration, cage cleaning, and obtaining daily weights. All protocols used in this study were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at the US Army Institute of Surgical Research, San Antonio, Texas.” ( Ceremuga et al., 2017, p. 195) Ceremuga et al. (2017) found that curcumin did not have a significant effect on the anxiety and depression of rats. At least five separate sets of regulations exist to protect research animals from mistreatment. Federal government, state governments, independent accreditation organizations, professional societies, and individual institutions work to ensure that research animals are used only when necessary and only under humane conditions. At the federal level, animal research is conducted according to the guidelines of USPHS Policy on Humane Care and Use of Laboratory Animals, which was adopted in 1986 and most recently updated in 2015 (DHHS, 2015b). In addition, more than 1000 institutions in 49 countries have obtained accreditation by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC International, 2019), which demonstrates the commitment of these institutions to ensure the humane treatment of animals in research. Nurse researchers interested in using animals for research must be trained in their care and appropriate use. They will also need to review the guidelines used by their university, other employers, or funders for conducting research with animals. Key points • The ethical conduct of research begins with the identification of the study topic and continues through the publication of the study to ensure that valid evidence is available for practice. • Conducting research ethically requires protection of the human rights of participants. Human rights are claims and demands that have been justified in the eyes of an individual or by the consensus of a group of individuals. The human rights that require protection in research are (1) self-determination, (2) privacy, (3) anonymity or confidentiality, (4) fair treatment, and (5) protection from discomfort and harm. • Two historical documents that have had a strong impact on the conduct of research are the Nuremberg Code and the Declaration of Helsinki. • US federal regulations direct the ethical conduct of research. These regulations include (1) general requirements for informed consent, (2) documentation of informed consent, (3) IRB review of research, (4) exempt and expedited review procedures for certain kinds of research, and (5) criteria for IRB approval of research. • HIPAA has affected research recruitment and data collection since it was implemented in 2003. • The rights of research participants can be protected by balancing benefits and risks of a study, securing informed consent, and submitting the research for institutional review. The responsibility for protection of research participants is borne primarily by the lead or primary researcher. • To balance the benefits and risks of a study, its type, level, and number of risks are examined, and its potential benefits are identified. If possible, risks must be minimized and benefits maximized to achieve the best possible benefit-risk ratio. • The sequencing of the human genome has led to advances in how health and disease can be studied. These advances, however, have raised ethical issues about de-identification of genomic records, the reuse of biological specimens, and the appropriateness of using stem cells and organoids. • Informed consent involves the transmission of essential information, the comprehension of the information, and voluntary consent of the prospective participant. • In institutional review, a committee of peers (IRB) examines each study for ethical concerns. The IRB conducts three levels of review: exempt, expedited, and full board. • Research misconduct includes fabrication, falsification, and plagiarism during the conduct, reporting, or publication of research. The ORI was developed to investigate and manage incidents of research misconduct to protect the integrity of research in all disciplines. • Another current ethical concern is the use of animals as research subjects. The USPHS Policy on Humane Care and Use of Laboratory Animals provides direction along with several other guidelines and regulations on the humane use of animals in research. References Adams K, & Lawrence E. Research methods, statistics, and applications 2nd ed 2019; Sage Thousand Oaks, CA. Advisory Committee on Human Radiation Experiments (ACHRE). Government standards for human experiments The 1960s and 1970s ACHRE Final report (chap. 3) 1995; Retrieved from https:// bioethicsarchive.georgetown.edu/ achre/ final/ chap3. html. Ahalt S, Chute C, Fecho K, Glusman G, Hadlock J, Taylor C.et al:. Clinical data Sources and types, regulatory constraints, applications Clinical and Translational”
— Burns and Grove’s The Practice of Nursing Research – E-Book: Appraisal, Synthesis, and Generation of Evidence by Jennifer R. Gray, Susan K. Grove
https://a.co/5RD3JMR
“Many factors affected your decision to be a nurse but, for most of you, a key motivation was the desire to help others. Nursing as a profession is firmly based on the ethical principles of respect for persons, beneficence, and justice. These ethical principles that guide clinical practice must also be the standards for the conduct of nursing research (Fowler, 2017). In research, the application of ethics begins with identifying a study topic and continues through publication of the study findings. Ethical research is essential for generating evidence for nursing practice (Lach, 2019), but what does the ethical conduct of research involve? This question has been debated for many years by researchers, politicians, philosophers, lawyers, and even study participants. The debate continues because of the complexity of human rights issues; the focus of research in new, challenging arenas of technology, stem cells, and genomics; the complex ethical codes and regulations governing research; and the various interpretations of these codes and regulations. Unfortunately, specific standards of ethical research were developed in response to historical events in which the rights of participants were egregiously violated or the behavior of research scientists was blatantly dishonest (Grady, 2018). To provide an understanding of the rationale for today’s human participant protection requirements, this chapter begins by reviewing five historical events, and the mandates and regulations for ethical research that were generated as a result of them. In your clinical setting, you are probably familiar with the Health Insurance Portability and Accountability Act (HIPAA) and the necessity of protecting the privacy of a person’s health information (Department of Health and Human Services [DHHS], 2003). HIPAA, which identified the elements of private health information, has had a significant impact on researchers and institutional review boards (IRBs) in universities and healthcare agencies. The chapter also discusses the actions essential for conducting research in an ethical manner through protection of the rights of human participants. This includes making an unbiased assessment of the potential benefits and risks inherent in a study and ensuring that informed consent is obtained properly. The submission of a research proposal for institutional review is also presented. An ethical problem that has received increasing attention since the 1980s is researcher misconduct, also called scientific misconduct. Scientific misconduct is the violation of human rights during a study, including falsifying results or behaving dishonestly when disseminating the findings. Misconduct has occurred during all study phases, including reporting and publication of studies. Many disciplines, including nursing, have experienced episodes of research misconduct that have affected the quality of research evidence generated and disseminated. A discussion of current ethical issues related to research misconduct and to the use of animals in research concludes the chapter. Historical events affecting the development of ethical codes and regulations The ethical conduct of research has been a focus since the 1940s because of mistreatment of human participants in selected studies. Although these are not the only examples of unethical research, five historical experimental projects have been publicized for their unethical treatment of participants and will be described in the order in which the projects began: (1) the syphilis studies in Tuskegee, Alabama (1932–1972); (2) Nazi medical experiments (1941–1946) and resulting trials at Nuremberg; (3) the sexually transmitted infection study in Guatemala (1946–1948); (4) the Willowbrook State School study (1955–1970); and (5) the Jewish Chronic Disease Hospital study (1963–1965). More recent examples are included in the chapter, in relation to specific aspects of research. Although these five projects were biomedical and the primary investigators were physicians, nurses were aware of the research, identified potential participants, delivered treatments to participants, and served as data collectors in all of them. As indicated earlier, these and other incidences of unethical treatment of participants and research misconduct were important catalysts in the formulation of the ethical codes and regulations that direct research today. Tuskegee syphilis study In 1932, the US Public Health Service (USPHS) initiated a study of syphilis in African American men in the small, rural town of Tuskegee, Alabama (Brandt, 1978; Reverby, 2012; Rothman, 1982). The study, which continued for 40 years, was conducted to observe the natural course of syphilis in African American men. The researcher hired an African American nurse, Eunice Rivers, to recruit and retain participants. The research participants were organized into two groups: one group consisted of 400 men who had untreated syphilis, and the other was a control group of approximately 200 men without syphilis. Most of the men who consented to participate in the study were not informed about the purpose and procedures of the research. Some men were unaware that they were participants in a study. Some were subjected to spinal taps and told the procedure was treatment for their “bad blood” (Reverby, 2012), the colloquial term for syphilis and other diseases of the blood. By 1936, the group of men with syphilis experienced more health complications than did the control group. Ten years later, the death rate of the group with syphilis was twice as high as that of the control group. The participants with syphilis were examined periodically but were never administered penicillin, even after it became the standard treatment in the 1940s (Brandt, 1978). These results could have been predicted because untreated syphilis was and is the most damaging of the bacterial venereal diseases, with degeneration occurring from cardiac lesions, brain deterioration, or involvement of other organ systems. The findings of the Tuskegee syphilis study were published beginning in 1936, and additional papers were published every 4 to 6 years. In 1953, Nurse Rivers was the first author on a publication about the study procedures to retain participants (Rivers, Schuman, Simpson, & Olansky, 1953). At least 13 articles were published in medical journals reporting the results of the study. In 1969, the US Centers for Disease Control and Prevention (CDC) reviewed the study and decided that it should continue. In 1972, a story published in the Washington Star about the study sparked public outrage. Only then did the US Department of Health, Education, and Welfare (DHEW) stop the study. An investigation of the Tuskegee study found it to be ethically unjustified. In 1997, President Clinton publicly apologized for the government’s role in this event (Baker, Brawley, & Marks, 2005; Reverby, 2012). Nazi medical experiments From 1933 to 1945, the Third Reich in Europe implemented atrocious, unethical activities, some of which they called research (Steinfels & Levine, 1976). Their goal was to produce a population of racially pure Germans, also known as Aryan. Most notably, the Nazis targeted all Jews for imprisonment and systematic genocide, resulting in millions of deaths. Population growth among the Aryans was encouraged. In contrast, Nazi doctors sterilized people regarded as racial enemies, such as the Jews. In addition, Nazis killed people whom they considered racially impure or disabled, such as persons with mental illness, disabilities, and dementia. Almost 0.25 million Germans who were physically or mentally disabled (Jacobs, 2008) and 300,000 psychiatric patients (Foth, 2013) were killed. These same people were also used as research participants. The medical experiments involved exposing participants to high altitudes, freezing temperatures, malaria, poisons, spotted fever (typhus), new drugs, and unproven surgeries, usually without anesthesia (Steinfels & Levine, 1976). For example, participants were immersed in freezing water to determine how long German pilots could survive if shot down over the North Sea. Identical twins were forced to be participants of experiments in which one would be infected with a disease. Both were later killed for postmortem examination of their organs to determine differences due to the disease. These medical experiments purportedly were conducted to generate knowledge to benefit Aryans at the cost of suffering and death for prisoners in no position to give consent. In addition to the atrocities and coercion, however, the studies were poorly designed and conducted. As a result, little if any useful scientific knowledge was generated. The Nazi experiments violated ethical principles and rights of the research participants. Researchers selected participants on the basis of race, affliction, or sexual orientation, demonstrating an unfair selection process. The participants also had no opportunity to refuse participation; they were prisoners who were coerced or forced to participate. Frequently, study participants were killed during the experiments or sustained permanent physical, mental, and social damage (Levine, 1986; Steinfels & Levine, 1976). The doctors who propagated the mistreatment of human participants were brought to trial, along with other Nazi soldiers and officers, in Nuremberg, Germany, beginning in 1945. Nuremberg code At the conclusion of the trials of Nazi doctors involved in research, the defense presented 10 guidelines for appropriate research with human participants, which collectively became known as the Nuremberg Code (1949). Among the principles were the following: (1) participants’ voluntary consent to participate in research; (2) the right of participants to withdraw from studies; (3) protection of participants from physical and mental suffering, injury, disability, and death during studies; and (4) an assessment of the benefits and risks in a study. The Nuremberg Code (1949) forms the basis for protection for all human participants, regardless of a researcher’s disciplinary affiliation. Declaration of helsinki The members of the World Medical Organization (WMO) were understandably alarmed by the actions of Nazi researchers during World War II. The World Medical Assembly (WMA) of the WMO drafted a document called the Declaration of Helsinki in 1964. The Declaration of Helsinki (WMO, 1996) has subsequently been reviewed and amended, with the last amendment being approved in 2013 (WMA, 2013). The declaration forms the foundation for current research protection practices, such as research ethics committees. A research ethics committee must review proposed human participant research for possible approval; if the study is approved, the committee is responsible for monitoring its methods and outcomes as well as reviewing and approving any alterations in the research plan before such changes are implemented. The declaration also differentiates therapeutic research from nontherapeutic research. Therapeutic research gives the patient an opportunity to receive an experimental treatment that might have beneficial results. Nontherapeutic research is conducted to generate knowledge for a discipline: The results from the study might benefit future patients with similar conditions but will probably not benefit those acting as research participants. Box 9.1 contains several ethical principles from the declaration. The complete document is available from the WMA (2018). BOX 9.1 Key Ideas of the Declaration of Helsinki 1. Well-being of the individual research participant must take precedence over all other interests. 2. Investigators must protect the life, health, privacy, and dignity of research participants. 3. A strong, independent justification must be documented prior to exposing healthy volunteers to risk of harm, merely to gain new scientific information. 4. Extreme care must be taken in making use of placebo-controlled trials, which should be used only in the absence of an existing proven therapy. 5. Clinical trials must focus on improving diagnostic, therapeutic, and prophylactic procedures for patients with selected diseases without exposing participants to any additional risk of serious or irreversible harm. From Declaration of Helsinki. (1964, 2013). WMA declaration of Helsinki—Ethical principles for medical research involving human subjects. Retrieved from https:// www.wma.net/ policies-post/ wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ Worldwide, most institutions in which clinical research is conducted have adopted the Declaration of Helsinki. It has been revised, with the most recent revision increasing protection for vulnerable populations and requiring compensation for participants harmed by research (WMA, 2018). However, neither this document nor the Nuremberg Code has prevented some investigators from conducting unethical research (Beecher, 1966). Remember that the Tuskegee study continued after the Declaration of Helsinki was first released. Guatemala sexually transmitted disease study Beginning in 1946, a USPHS employee, Dr. John C. Cutler, conducted a study in Guatemala in which participants were intentionally exposed to syphilis and other sexually transmitted diseases. The participants were “sex workers, prisoners, mental patients, and soldiers” (Reverby, 2012, p. 8). Initially, participants were to be given penicillin or an arsenic compound (the treatment prior to penicillin) between exposure and infection to determine the prophylactic efficacy of each medication. The records for the study are incomplete, and it is not known how many persons developed an infection, died from the infection, or were harmed by the administered treatment (Reverby, 2012). The researchers suppressed information about their interventions and findings because they anticipated negative publicity due to the unethical nature of the study. After Dr. Cutler left in 1948, the USPHS continued to fund researchers to monitor the research participants and conduct serological testing through 1955 (Presidential Commission for the Study of Bioethical Issues, 2011). In 2010, Reverby (2012) was reviewing the records of researchers who participated in the Tuskegee study and found the papers of Dr. Cutler in which the Guatemala study was described. She shared her discovery with the CDC, and, subsequently, President Obama was informed. A public apology ensued. The Presidential Commission for the Study of Bioethical Issues (2011) investigated and wrote a report confirming the facts of the Guatemala study. Willowbrook study From the mid-1950s to the early 1970s, Dr. Saul Krugman practiced at Willowbrook State School, a large institution for cognitively impaired persons in Brooklyn, New York, and conducted research on hepatitis A infection (Rothman, 1982). The participants, all children, were deliberately infected with the hepatitis A virus. During the 20-year study, Willowbrook closed its doors to new children because of overcrowded conditions. However, the research ward continued to admit new children. To gain a child’s admission to the institution, parents were required to give permission for the child to be a study participant. Hepatitis A affects the liver, producing vomiting, nausea, and tiredness, accompanied by jaundice. The infected children suffered pain and potentially long-term effects. From the late 1950s to early 1970s, Krugman’s research team published several articles describing the study protocol and findings. Beecher (1966) cited the Willowbrook study as an example of unethical research. The investigators defended exposing the children to the virus by citing their own belief that most of the children would have acquired the infection after admission to the institution. They based their belief on the high hepatitis infection rates of children during their first year of living at Willowbrook. The investigators also stressed the benefits that the participants received on the research ward, which were a cleaner environment, better supervision, and a higher nurse-patient ratio (Rothman, 1982). Despite the controversy, this unethical study continued until the early 1970s. Jewish chronic disease hospital study Another highly publicized example of unethical research was a study conducted at the Jewish Chronic Disease Hospital in the 1960s. The USPHS, the American Cancer Society, and Sloan-Kettering Cancer Center funded the study (Nelson-Marten & Rich, 1999). Its purpose was to determine the patients’ rejection responses to live cancer cells. Twenty-two patients were injected with a suspension containing live cancer cells that had been generated from human cancer tissue (Levine, 1986). Most of the patients and their physicians were unaware of the study. An extensive investigation revealed that the patients were not informed they were research participants. They were informed that they were receiving an injection of cells, but the word cancer was omitted (Beecher, 1966). In addition, the Jewish Chronic Disease Hospital’s IRB never reviewed the study. The physician directing the research was an employee of the Sloan-Kettering Institute for Cancer Research, and there was no indication that this institution had reviewed the study (Hershey & Miller, 1976). The study was considered unethical and was terminated, with the lead researcher found to be in violation of the Nuremberg Code (1949) and the Declaration of Helsinki (WMA, 2013). This research had the potential to cause study participants serious or irreversible harm and possibly death, reinforcing the importance of conscientious institutional review and ethical researcher conduct. Early US government research regulations Following World War II, the US government increased funding for research. Federal funding by the National Institutes of Health (NIH) for research grew rapidly from less than $ 1 million in 1945 to over $ 435 million in 1965 (Beecher, 1966). This influx of funds along with newly discovered advances in medical treatment raised the potential for increased numbers of research violations. Dr. Henry Beecher (1966) published a paper with 22 examples of experimental treatments implemented without patient consent, raising concerns that the interests of science could override the interests of the patient. The government recognized the need for additional oversight. This section describes three government regulations that were developed as a result. US department of health, education, and welfare In 1973, the DHEW published its first set of regulations intended to protect human participants (Advisory Committee on Human Radiation Experiments, 1995). Clinical researchers were required to be compliant with the new stricter regulations for human research, with additional regulations to protect persons with limited capacity to consent, such as ill, cognitively impaired, or dying individuals (Levine, 1986). All research proposals involving human participants were required to undergo full institutional review, a task that became overwhelming and greatly prolonged the time required for study approval. Even studies conducted by nurses and other health professionals that involved minimal or no risks to study participants were subjected to full board review. Despite the advancement of the protection of participants’ rights, the government recognized the need for additional strategies to manage the extended time now required for study approval. National commission for the protection of human subjects of biomedical and behavioral research Because of the problems related to the DHEW regulations, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1978) was formed. The commission’s charge was to identify basic ethical principles and develop guidelines based on these principles that would underlie the conduct of biomedical and behavioral research involving human participants. The commission developed what is now called the Belmont Report (DHHS, 1979). This report identified three ethical principles as relevant to research involving human participants: respect for persons, beneficence, and justice (Grady, 2018; Thakur & Lahiry, 2019). The principle of respect for persons holds that persons have the right to self-determination and the freedom to participate or not participate in research. The principle of beneficence requires the researcher to do good and avoid causing harm. The principle of justice holds that human participants should be treated fairly (Gravetter & Forzano, 2018). The commission developed ethical research guidelines based on these three principles, made recommendations to the DHHS, and was dissolved in 1978. The three ethical principles that the report identified are still followed for all federally supported research, whether implemented in the United States or internationally. Subsequent to the work of the commission, the DHHS developed federal regulations in 1981 to protect human research participants, which have been revised as needed over the past 35 years (DHHS, 1981). The first of these was the Code of Federal Regulations (CFR), Title 45, Part 46, Protection of Human Subjects, with the most recent edition being available online (DHHS, 2018). Box 9.2 lists the types of research governed by DHHS. An arm of the DHHS is the Federal Drug Administration (FDA), and its research activities are governed by CFR Title 21, Food and Drugs, Part 50, Protection of Human Subjects (FDA, 2019b), and Part 56, Institutional Review Boards (IRBs) (FDA, 2019a). Box 9.3 lists the research covered by the FDA regulations. BOX 9.2 Research Regulated by DHHS: CFR Title 45, Part 46, Protection of Human Subjects 1. Studies conducted by, supported by, or otherwise subject to regulations by any federal department or agency 2. Research conducted in educational and healthcare settings 3. Research involving the use of biophysical measures, educational tests, survey procedures, scales, interview procedures, or observation 4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens. Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5ad32ac566ecdb2466df8f068b6036a27& mc5true& node5pt45.1.46& rgn5div5 BOX 9.3 Research Regulated by the FDA: CFR Title 21, Parts 50 and 56 • Studies that test 1. Drugs for humans 2. Medical devices for human use 3. Biological products for human use 4. Human dietary supplements 5. Electronic healthcare products used with humans • Responsible for the management of new drugs and medical devices Data from U.S. Food and Drug Administration. (2019b). Protection of human subjects. Code of Federal Regulations, Title 21 Food and Drugs, Department of Health and Human Services, Parts 50 and 56. Retrieved from https:// www.ecfr.gov/ cgi-bin/ text-idx? SID5d494ea202a7a4e40a8f63306fd8b7142& mc5true& node5pt21.1.50& rgn5div5# se21.1.50_11 The DHHS regulations are known as the Common Rule because they are applicable across multiple DHHS agencies. The DHHS regulations are interpreted and enforced by the Office for Human Research Protection (OHRP), an agency within the DHHS (2016). In addition to providing guidance and regulatory enforcement, the OHRP develops educational programs and materials, and provides advice on ethical and regulatory issues related to biomedical and social-behavioral research. Standards for privacy for research data The concern for privacy of patient information related to the electronic storage and exchange of health information resulted in the privacy regulations known as HIPAA (Bonham, 2018). HIPAA did not require anything that was not required during routine nursing practice before its instigation; however, it addressed both electronic data security and consequences of failure to protect such data. The HIPAA Privacy Rule established the category of protected health information (PHI). The rule allows covered entities, such as health plans, healthcare clearinghouses, and healthcare providers, to use or disclose PHI to others only in certain situations. The Privacy Rule also applies to research that involves the collection of PHI (DHHS & Office for Civil Rights, 2013; HIPAA Journal, 2018). Individuals must provide a signed authorization before their PHI can be used or disclosed for research purposes. This chapter covers these regulations in the sections on protection of human rights, obtaining informed consent, and institutional review of research. Protection of human rights Human rights are justifiable claims and demands that are necessary for the self-respect, dignity, and freedom of choice for an individual (Grady, 2018). Our professional code of ethics, the American Nurses Association (ANA) Code of Ethics for Nurses (ANA, 2015), includes protection for the rights of human participants in biological and behavioral research, founded on the ethical principles of beneficence, nonmaleficence, autonomy, and justice. The human rights that require protection in research are (1) the right to self-determination, (2) the right to privacy, (3) the right to anonymity and confidentiality, (4) the right to fair treatment or justice, and (5) the right to protection from discomfort and harm (ANA, 2015; Fowler, 2017). These rights are described as follows, including situations in which they can be violated. Right to self-determination The right to self-determination is based on the ethical principle of respect for persons. Respect for persons means that humans are capable of self-determination or making their own decisions. Because of this right, humans should be treated as autonomous agents who have the freedom to conduct their lives as they choose without external controls. As a researcher, you treat prospective participants as autonomous agents when you inform them about a proposed study and allow them to choose voluntarily whether to participate (Thakur & Lahiry, 2019). In addition, participants have the right to withdraw from a study at any time without penalty (Grady, 2018). A participant’s right to self-determination can be violated through covert data collection and deception. The right of self-determination may also be threatened when potential research participants are susceptible to coercion or have diminished capacity to make independent decisions. Specific groups who have been identified as being susceptible to coercion needing additional protection include persons of racial/ ethnic minorities, prisoners, pregnant women, fetuses, neonates, and children. Each of these threats and groups requiring additional protection will be described in the following sections. Covert data collection An individual’s right to self-determination can be violated if he or she becomes a research participant without realizing it. Some researchers have exposed persons to experimental treatments without their knowledge, a prime example being the Jewish Chronic Disease Hospital study. With covert data collection, participants are unaware that research data are being collected because the investigator’s study involves collecting data about normal activity or routine health care (Reynolds, 1979). Studies in which observation is used to collect data, such as ethnographic research, are especially challenging because the researcher does not want to interfere with what would normally happen by identifying that observational data are being collected. Covert data collection can occur if participants’ behaviors are public. For example, a researcher could observe and record the number of people walking down a street who are smoking. However, covert data collection is considered unethical when research deals with sensitive aspects of an individual’s behavior, such as illegal conduct, sexual behavior, and drug use. In keeping with the HIPAA Privacy Rule (DHHS & Office for Civil Rights, 2013), PHI data collected in any manner can only be used if there is minimal risk of harm to the participants. This means the use of any type of covertly collected data would be questionable and unethical, and illegal if PHI data were being used or disclosed without prior approval. Deception The use of deception in research also can violate a participant’s right to self-determination. Deception is misinforming participants of the study’s purpose or withholding some information about the study (Gravetter & Forzano, 2018; Kazdin, 2017). A classic example of deception is the Milgram (1963) study, in which participants thought they were administering electric shocks to another person. The participants did not know the person being shocked was a professional actor who pretended to feel pain. Because of participating in this study, some participants experienced severe mental tension, almost to the point of collapse (Algahtani, Bajunaid, & Shirah, 2018; Kazdin, 2017). A researcher developing a study involving deception must be prepared to justify the deception by providing evidence that the benefits of the study are greater than the potential risks (Gravetter & Forzano, 2018; Kazdin, 2017). For example, the researcher must argue that deception is the only way the research question can be answered. The research question must be significant, and the researcher will need to specify how debriefing will occur (Gravetter & Forzano, 2018). After data collection is complete, the researcher provides debriefing of the participant by presenting the complete, accurate purpose of the study with the goal of minimizing the possible negative effects of the study. The debriefing also includes why the deception was deemed necessary (Kazdin, 2017). Covert data collection is passive deception. It may be approved by an IRB in situations in which the research is essential, the data cannot be obtained any other way, and the participants will not be harmed. For an example, on a clinical unit, the researcher may indicate that a study is about the number and type of interruptions that occurred during a nurse’s day. In reality, the researchers are observing the nurses’ compliance with hand hygiene guidelines. Covert direct observation might be approved in such a situation if the results were not going to be linked to individual nurses. In the rare situations in which covert data collection is allowable, participants must be informed of the deception once the study is completed, provided full disclosure of the study activities that were conducted (Gravetter & Forzano, 2018; Kazdin, 2017), and given the opportunity to withdraw their data from the study. Susceptible to coercion Coercion occurs when one person intentionally presents another with an overt threat of harm or the lure of excessive reward to obtain his or her compliance. The older version of the Common Rule (DHHS, 2013) identified specific vulnerable groups, including pregnant women, human fetuses, neonates, children, persons with mental incompetence, and prisoners. Conducting research with members of these groups required additional protection in the conduct of research. The revised Common Rule (DHHS, 2018) does not identify vulnerable populations but describes persons and situations in which persons may be sensitive to coercion or undue influence. The persons sensitive to coercion include some of those who were previously classified as being vulnerable, such as children, prisoners, and persons with diminished decision-making ability. However, persons who are economically or educationally disadvantaged and members of racial and ethnic minorities were included among those susceptible to coercion (DHHS, 2018). This new approach broadens the concept and puts additional responsibility on researchers to consider their inclusion and exclusion criteria and recruitment procedures. However, in many situations, the data needed to determine evidence-based care are dependent on the inclusion of persons who may be sensitive to coercion (Grady, 2018). Subjects may feel coerced to participate in research because they fear that they will suffer harm or discomfort if they do not participate. Students may feel forced to participate in research to protect their grades or prevent negative relationships with the faculty member conducting the research (Boileau, Patenaude, & St-Ong, 2018). Some patients believe that their medical or nursing care will be negatively affected if they do not agree to be research participants, a belief that may be reinforced if a healthcare provider is the one who attempts to recruit them for a study. Therapeutic misconception is the belief that research participation will result in better clinical care (Bailey & Ladores, 2018). Therapeutic misconception has also been defined as participants’ failure to distinguish between the therapeutic relationship between a patient and a healthcare provider and the protocol-driven relationship between a participant and a researcher (McConville, 2017). Despite what the clinician-researcher said about the participant’s care not being based on their consent, persons with cystic fibrosis (CF) believed their care would be better because they participated in research studies (Christofides, Stroud, Tullis, & O’Doherty, 2017). Subjects may feel coerced to participate in studies because the study offers a potential treatment and they have exhausted all other treatment options (Grady, 2018). Other participants believe that they cannot refuse the excessive rewards offered, such as large sums of money, specialized health care, special privileges, and jobs. Another example of coercion is what happened at Willowbrook State School. The school offered a specialized education for children with disabilities. The only way that parents could secure admission was to allow their child to be in the study and deliberately infected with hepatitis. Most nursing studies do not offer excessive rewards to participants. A researcher may offer reasonable payment for time and transportation costs, such as $ 10 to $ 30, or a gift certificate for this amount. When participants have a rare disorder and must travel long distances for data collection, the researcher or sponsor of the study should pay travel and lodging expenses (Gelinas, Crawford, Kelman, & Bierer, 2019). An IRB will evaluate whether a proposed payment is coercive compared to the effort and time required to participate in a study (Grady, 2018). Conducting research ethically requires that persons who are susceptible to coercion have additional protection during the conduct of research (DHHS, 2018). One protective strategy is to have waiting periods between hearing about a study and obtaining informed consent (Grady, 2018). The waiting period allows participants to consult with family and friends or think of questions that they want to ask. Thoughtful planning and open dialogue between researchers and participants can create conditions to ensure informed consent is not coercive. Diminished autonomy Autonomy is the ability to make a voluntary decision based on comprehending information about the study (Kaye, Chongwe, & Sewankambo, 2019). Some persons have diminished autonomy because of legal or mental incompetence, terminal illness, or confinement to an institution (Kazdin, 2017). Persons are said to be incompetent if a qualified healthcare provider judges them to be unable to comprehend and voluntarily decide about participation in a study. Incompetence can be temporary (e.g., substance use), permanent (e.g., intellectual disability), or transitory (e.g., delirium or psychosis). Unconscious patients and those with reduced cognitive abilities are seen as legally incompetent to give informed consent because they lack the ability to comprehend information about a study. The concern is that a person who, for whatever reason, is unable to absorb, retain, and evaluate the information about a study cannot protect themselves from possible harm or make an informed decision about whether to participate in a study. However, without finding ways to ethically obtain informed consent and including them in studies, the evidence upon which to base their safe, quality care will continue to be lacking and not grow (Ho, Downs, Bulsara, Patman, & Hill, 2018). Persons living with psychosis are the logical participants for studies of the safety and efficacy of antipsychotic medications. Nurse researchers conducted a systematic review of 646 clinical trials with participants who had been diagnosed with a psychosis. The purpose of the review was to determine the extent to which the participants were assessed for their capacity to provide informed consent (Weissinger & Ulrich, 2019). They learned that less than 10% of the studies included the capacity to provide informed consent in their inclusion/ exclusion criteria. Only 34 studies (5%) reported using a capacity assessment to determine the ability of potential participants to give consent. Patients with mild to severe dementia or Alzheimer disease may have a compromised capacity to understand the information necessary to giving informed consent. Chester, Clarkson, Davies, Hughes, and Islam (2018) published their study protocol of a pragmatic clinical trial conducted in England comparing caregivers being taught to use memory aids with a person who has early dementia to usual treatment. The researchers elicited input from an advisory group called the Public, Patient, and Carer Reference Group (PPCRG). The process and documents used to recruit potential participants were designed “following guidance from the PPCRG on language and format, to ensure that those with cognitive impairment are fully informed and engaged in the decision to take part” (Chester et al., 2018, p. 4). Using an advisory group such as the PPCRG is a robust strategy for designing appropriate recruitment procedures for any group of persons who may have diminished capacity to provide informed consent. The use of persons with decreased decision-making ability as research participants is more acceptable if several conditions exist. When the research is therapeutic, there is less concern because the participants have the potential to benefit directly from the experimental process (DHHS, 2018). Samples including persons with diminished autonomy are more acceptable when the researcher is recruiting persons with adequate autonomy as well as those with reduced autonomy as participants. Another positive factor is the availability of preclinical and clinical studies that provide evidence upon which to base the assessment of potential risks for participants. Research with persons with diminished decision-making ability is also more acceptable when risk is minimal and the consent process is strictly followed to protect the rights of the prospective participants (DHHS, 2018). Other ways to include persons with diminished capacity in studies is to assess their ability to comprehend using a standard instrument. Ho et al. (2018) recommended that researchers develop relationships with potential participants with diminished capacity and their caregivers, observing the potential participant multiple times prior to obtaining consent from the caregiver or the participant. To assess the capacity of the participant to give consent, they used an assessment tool called the “Three-Item Decisional Questionnaire (3-IDQ) adopted from Palmer et al., 2005” (Ho et al., 2018, p. 94). Another assessment, the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR), was identified as one of the strongest instruments available for assessing an individual’s capacity to give informed consent (Simpson, 2010). The companion tool, the MacArthur Competency Assessment Tool for Treatment (MacCAT-T), has been identified as the gold standard for assessing mental capacity to consent to treatment (Elzakkers, Danner, Grisso, Hoek, & van Elburg, 2018). Evidence has been published for interrater reliability, concurrent validity, and effective use of the tools across a wide range of patients (see Chapter 16) (Elzakkers et al., 2018). For a research study, the persons responsible for recruiting participants and obtaining informed consent would need to be trained in using the MacCAT-CR. Using this instrument or similar tools, researchers can make an objective decision about a participant’s ability to consent to research. If an individual is judged incompetent and incapable of consent, you must seek approval from the prospective participant and his or her legally authorized representative. A legally authorized representative means an individual or a group is authorized under law to consent on behalf of a prospective participant to his or her participation in research. The authorized representative is sometimes called a proxy. The legally authorized representative or proxy may be a spouse or close relative, if the potential participant has not designated a power of attorney. If no spouse or close relative can be accessed, a legal representative can be appointed by the state. Groups needing additional protection The groups identified as susceptible to coercion require additional protection to participate in research. Five groups requiring additional protection are described in this section: prisoners, terminally ill persons, pregnant women, fetuses and neonates, and children. Prisoners. Prisoners have diminished autonomy to consent for research because of their confinement. They may feel coerced to participate in research because they fear harm if they refuse (Midwest Nursing Research Society [MNRS], 2018) or because they desire the benefits of special treatment, monetary gain, or relief from boredom. In the past, prisoners were used for drug studies in which the medications had no health-related benefits and, instead, potential harmful side effects. Current regulations regarding research involving prisoners require that “the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers” and “procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners” (DHHS, 2018, Section 46.305). An IRB that is considering a study that include prisoners must add a prisoner or prisoner representative prior to reviewing the study. When a proposal is reviewed by multiple IRBs, only one of the IRBs must have a member that represents the prisoners. Terminally ill participants. Two factors need to be considered when designing a study with a sample that includes persons with terminal illness: (1) Who will benefit from the research? and (2) Is it ethical to conduct research on individuals who are unlikely to benefit from the study? Participating in research could have greater risks and minimal or no benefits for these participants. In addition, the dying participant’s condition could affect the results, leading to misinterpretation of the findings. Another consideration is persons with terminal illness have limited time remaining in their lives. Is it fair to ask them to spend time on a study instead of spending it with family or engaged in preferred activities? However, unless persons with terminal illness or those receiving palliative care are included in studies, the knowledge base for hospice and palliative care will not grow and be refined (Pereira & Hernández-Marrero, 2019). Some terminally ill individuals are willing participants because they believe that participating in research is a way to contribute to society before they die. Others want to take part in research because they believe that the experimental process may benefit them by slowing their disease process, potentially another example of a therapeutic misconception. Pregnant women and fetuses. Pregnant women have historically been considered vulnerable participants in regard to research (Ballantyne et al., 2017). Policies to include women, including pregnant women, in studies and policies to exclude women due to potential harm to the fetus contradict each other and result in confusion about how women should be recruited for studies (van der Graaf et al., 2018). Federal regulations define pregnancy as encompassing the period of time from implantation until delivery. “A woman is assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery” and the fetus is defined as the “product of conception from implantation until delivery” (DHHS, 2018, 45 CFR Section 46.202). Research conducted with pregnant women can occur only after studies have been done with animals and nonpregnant women to assess the potential risks. Table 9.1 lists the conditions under which a pregnant woman can be included, such as the potential for direct benefit to the woman or the fetus. If a study may benefit only the fetus, the consent of the pregnant woman and father must be obtained. TABLE 9.1 Conditions That Must Be Present for Pregnant Women to Be Included in a Study General Condition Specific Details Knowledge of potential side effects Studies with animals and nonpregnant women have been conducted and results indicated safety of the intervention. Scientifically important information Woman and fetus may benefit from the intervention. If not, risk is minimal. Knowledge cannot be gained any other way. Least possible risk Risk is minimized but study objectives can still be met. Balance of risks and benefits If no potential benefit to either mother or fetus, risk must be minimized. Consent of both parents Required if fetus is only one to benefit from the study. Father’s consent not needed if he is unavailable, incompetent, or pregnancy due to rape or incest. Fully informed Potential impact on the mother or fetus is clear in the consent form, before requesting mother to sign. No incentive or interference to terminate the pregnancy Mother does not receive any inducement to terminate pregnancy. Research staff not involved in any decision to terminate the pregnancy. Viability of the fetus Research staff not involved in any decision about neonate’s viability after delivery. Some researchers did not include pregnant women in their studies because they assumed the women would not want to participate. In New Zealand, Ballantyne et al. (2017) added a qualitative arm to a randomized intervention clinical trial for which the sample was pregnant women. This study was called the Research in Pregnancy Ethics (RIPE) study. “The RIPE study set out to ascertain views of pregnant women about research participation, by conducting semi-structured interviews and then analysing the interview transcripts using inductive thematic analysis ( Braun & Clarke, 2006). Women were recruited from a pool of participants already participating in the PiP [Probiotics in Pregnancy] study.” ( Ballantyne et al., 2017, p. 478) “The main cited benefits of the study by the participants were abstract principles of altruism, playing a valuable civic role and the importance of research. No-one cited personal benefit or gain as a motivation for participating…. The main perceived burdens related to inconvenience and time commitment…. Women wanted to clarify the time commitments and how this would fit into their schedule; they did not want to overcommit given the demands of pregnancy and having a newborn baby.” ( Ballantyne et al., 2017, pp. 479–480) “Our results show that at least some pregnant women recognise the value and importance of research during pregnancy. The women we interviewed were deeply invested in the research process and outcomes.” ( Ballantyne et al., 2017, p. 483) Pregnant women should not be excluded from studies unless an increased risk to the woman or the fetus exists. Ballantyne et al. (2017) provided insight for other researchers considering recruiting pregnant women for a study. Neonates. A neonate is defined as a newborn and is further identified as either viable or nonviable on delivery. Viable neonates are able to survive after delivery through the use of technology and other therapies. An additional factor in being considered viable is the ability to maintain a heartbeat and respiration. Nonviable neonates may be living after delivery but will not be able to survive (DHHS, 2018). Neonates are extremely vulnerable and require extra protection to determine their involvement in research. However, research may involve viable neonates, neonates of uncertain viability, and nonviable neonates when the conditions identified in Box 9.4 are met. In addition, for the nonviable neonate, the vital functions of the neonate should not be artificially maintained because of the research, and the research should not terminate the heartbeat or respiration of the neonate (DHHS, 2018). BOX 9.4 Conditions to Be Met for Approval of Research With Neonates • Data available from preclinical and clinical study to assess potential risk to neonates • Potential to provide important biomedical knowledge that cannot be obtained by other means • No additional risk to the neonate • Potential to enhance the probability of the neonate’s survival • Both parents fully informed about the research and give consent • Research team has no part in determining the viability of the neonate Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human subjects. Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, Part 46. Retrieved from https:// www.hhs.gov/ ohrp/ regulations-and-policy/ regulations/ 45-cfr-46/ index.html Children and adolescents. Children are considered vulnerable in the context of research (Singh, Siddiqi, Parameshwar, & Chandra-Mouli, 2019). However, we need more evidence upon which to base pediatric nursing practice. To develop the necessary evidence, children must be recruited for studies and assent or consent obtained (Crane & Broome, 2017). The distinction between children and adolescents is not clear. The World Health Organization (WHO, 2018) describes adolescents as being the second decade of life. The age of consenting to participate in a study is usually considered to be 18 years of age, but legal and research experts disagree among themselves (Cherry, 2017; Sade, 2017). Unfortunately, the legal definitions of the minor status of a child are statutory and vary among states and even countries. Neurophysical and psychological evidence supports the premise that adolescents lack the cognitive and affective maturity to give consent for themselves. Cherry (2017) identifies three components that comprise meaningful assent or consent for children and adolescents: intellectual development, affective development, and personal agency (Fig. 9.1). The figure is consistent with the findings of Hein, Troost, Lindeboom, Benninga, and Zwaan (2015), who found that age, followed by intelligence, explained the largest portion of the variance in a child’s or adolescent’s competence related to consent to research. Grady et al. (2014) studied the perceptions of assent/ consent among adolescents enrolled in clinical research and their parents. Approximately 40% of the sample believed that the decision for an adolescent to participate should be jointly made by parents and adolescent. Even among adolescent participants in research, however, understanding their rights and grasping the meaning of the study itself has been found to be less than desired (Cherry, 2017). Fig. 9.1Capacity to give meaningful consent. A pie chart representing capacity to give meaningful consent is divided into three sections marked clockwise as affective component, personal agency, and intellectual component. Federal regulations contain two stipulations for obtaining informed consent: The research must be of minimal risk, and both the assent of the child (when capable) and the permission of the parent or guardian must be obtained (DHHS, 2018). Assent means a child’s affirmative agreement to participate in research. Box 9.5 provides an example of an assent form. Permission to participate in a study means that the parent or guardian agrees to the participation of the child or ward in research (DHHS, 2018). If a child does not assent to participate in a study, he or she should not be included as a participant even if the parent or guardian gives permission. For therapeutic research, IRBs can approve studies with children when more than minimal risk is present, provided that potential benefit exists for the child, or when the experimental treatment is similar to usual care and the findings have potential benefit for others. Studies that do not meet these stipulations but have the potential for significant contribution to knowledge that may benefit other children with the same condition can be approved (DDHS, 2018). In all cases, procedures to obtain assent and parental permission must be implemented. BOX 9.5 Sample Assent Form for Children Ages 8 to 12 Years: Weight, Activity, and Eating Habits Before and After Mother-Child Multimedia Intervention Oral explanation We are nurses who want children like you to be strong and have energy to play and go to school. Here at your school, we are doing research on the best ways to teach you and your parents how to eat better and get more exercise using videos and computer games. If you decide to be in the study, we will measure your height and weight in a room with only your mother and the nurse. No one but them will know how much you weigh or how tall you are unless you tell them. We will ask you to answer five questions about what you eat and whether you exercise. Exercise is running, playing games outside, going for a walk, and doing things for fun where you move your body. After that, you and your mom will play a video game on the computer and watch two videos that are less than 5 minutes long. For the next five Tuesdays, we will be here after school. You and your mom will be asked the same five questions, watch two different videos, and play the video game together. We will have snacks for you and your mom to eat each time. On the sixth Tuesday, we will measure how tall you are and how much you weigh. On that day, we will ask you what you liked and didn’t like about the videos and computer games. You can change your mind about being in the study and can stop at any time. To child 1. I want to learn about what to eat to make me strong and have energy. 2. I want to answer questions about what I eat and how much exercise I get. 3. I want to watch videos and play a computer game with my mom. If the child says YES, have him/ her put an “X” here: _______________________ If the child says NO, have him/ her put an “X” here: ________________________ Date: ______________________ Child’s signature: ________________________ Another point of controversy is the age at which a child can assent to a study. A child’s competency to assent is usually governed by age, and research evidence supports the standard of a child over 10 years of age being capable of sufficient understanding to give assent (Crane & Broome, 2017). Children who are developmentally delayed, have a cognitive impairment, suffer an emotional disorder, or are physically ill must be considered on an individual basis. When designing a study in which children will be participants, it is helpful to seek consultation with a child development specialist and the primary IRB to which you will submit the study for approval. Some IRBs have developed assent guidelines or forms specific to their facilities. Assent and permission require that both the child or adolescent and parents be informed about the study. The information shared with the child about the study should be appropriate for the child’s age and culture. In the assenting process, the child must be given developmentally appropriate information on the study purpose, expectations, and benefit-risk ratio (discussed later). Media-enhanced presentations and play activities have been used as a means of providing information about the study. A group of researchers in the Netherlands conducted a participatory study to develop and test comic strips for the purpose of providing information about research participation (Grootens-Wiegers, de Vries, van Beusekom, van Dijck, & van den Broek, 2015). With the input of children at each stage of development, the comic strips evolved and, in their final version, were found to have the potential for increasing children’s knowledge about research. Yeh, Chun, Terrones, and Huang (2017) conducted a randomized controlled trial (RCT) comparing the knowledge of children and their parents about pediatric endoscopy. The intervention group (n = 37 parent-child pairs) obtained information about the procedure by watching a short, animated video and the control group (n = 40 parent-child pairs) received the information by listening to the usual verbal explanation. The 2-minute videos, one for upper endoscopy and the other for lower endoscopy, were developed based on principles of instructional design. Parents and children were interviewed separately and scored on their knowledge of key components of informed consent. The children and parents in the intervention group had significantly higher scores on knowledge of the risks of the procedure and their overall comprehension as compared to the children and parents of the control group. Continued research is needed for development and testing of innovative strategies for providing informed consent information to children and adults. A child who assents to participate in a study should sign the requisite form and be given a copy. To gain assent, the child is “meaningfully involved in the decision-making in a manner that is appropriate for the child’s capacity and age” (WHO, 2018, p. 15). Legally, a nonassenting child can be a research participant if the parents give permission, even if some potential for harm exists. Chwang (2015) argues, however, that including children in a study who have not given assent is every bit as unethical as including nonconsenting adults in a study. A child’s willingness to participate in a study should be reassessed throughout a study, reflecting respect for the child’s autonomy and dignity (Moore, McArthur, & Noble-Carr, 2018). Assent becomes more complex with children from various family dynamics and child characteristics. Oulton et al. (2016) conducted a literature review and an anonymous survey of healthcare professionals involved in pediatric research. Combining the findings of the review and the survey with their own experience of conducting pediatric research, Oulton et al. (2016) developed an algorithm that included child-related factors, family dynamics, and the complexity of the study design as components to consider in obtaining assent. A child-related factor might be a child who is bilingual. In this case, the researchers must determine the most appropriate language to use for the assent process for the child and the process to obtain parental permission. Other children who have no cognitive deficiencies, but are in unusual circumstances, may require the appointment of a legal representative by the legal system. WHO (2018) identifies the need to do this when a child has no living parents, the parents have immigrated and left the child behind, the child lives on the street with no parental supervision, the child who is unaccompanied seeks asylum in the United States, and the child is a member a of child-led household. Children under the age of 18 can give consent for their own participation in research when they have been emancipated by the legal system. In some legal jurisdictions, a girl under the age of 18 who marries is considered an emancipated minor. Other children may have previously be placed in a state’s guardianship (wards of the state). When determining the maturity of a child for the purposes of assent and consent, various professions have different standards by which maturity is assessed (WHO, 2018). Right to privacy Privacy is an individual’s right to determine the time, extent, and general circumstances under which personal information is shared with or withheld from others. This information consists of one’s attitudes, beliefs, behaviors, opinions, and records. The federal government enacted the Privacy Act (1974) to control potential infringement of privacy, related to information collected by the government, or held in federal agencies’ records. The act has four important provisions for the researcher: (1) data collection methods must be strategized so as to protect participants’ privacy, (2) data cannot be gathered from participants without their knowledge, (3) individuals have the right to access their records, and (4) individuals may prevent access by others to existent federal data (DHHS & Office of Civil Rights, 2013). The intent of this act was to prevent the invasion of privacy that occurs when private information is shared without an individual’s knowledge or against his or her will. The HIPAA Privacy Rule expanded the protection of an individual’s privacy, specifically his or her PHI that is individually identifiable, extending the protection to data held by private entities. It described the ways in which those entities covered by the rule can use or disclose this information. “Individually identifiable health information (IIHI) is information that is a subset of health information, including demographic information collected from an individual, and: (1) is created or received by healthcare provider, health plan, or healthcare clearinghouse; and (2) [is] related to past, present, or future physical or mental health or condition of an individual, the provision of health care to an individual, or the past, present, or future payment for the provision of health care to an individual, and that identifies the individual; or with respect to which there is a reasonable basis to believe that the information can be used to identify the individual” (DHHS, 2013, 45 CFR, Section 160.103). According to the HIPAA Privacy Rule, IIHI is PHI that is transmitted by electronic media, maintained in electronic media, or transmitted or maintained in any other form or medium. Thus the HIPAA privacy regulations must be followed when a nurse researcher wants to access data from a covered entity, such as reviewing a patient’s medical record in clinics or hospitals. Ahalt et al. (2019) defined de-identified data sets as having all PHI removed. De-identification consists of removing 18 items from patient records before they are released to other agencies or to researchers. These 18 items include name, contact information, identification numbers, photographs, biometrics, and other elements by which a participant could potentially be identified (Box 9.6). Because de-identification includes removing dates, researchers using de-identified data may not be able to answer some research questions such length of hospital stay and seasonal patterns to diseases (Ahalt et al., 2019). BOX 9.6 18 Elements That Could Be Used to Identify an Individual to Relatives, Employer, or Household Members 1. Names 2. All geographical subdivisions smaller than a state 3. All elements of dates (except year) for dates directly related to an individual 4. Telephone numbers 5. Facsimile numbers 6. Electronic mail (e-mail) addresses 7. Social security numbers 8. Medical record numbers 9. Health plan beneficiary numbers 10. Account numbers 11. Certificate/ license numbers 12. Vehicle identifiers and serial numbers, including license plate numbers 13. Device identifiers and serial numbers 14. Web universal resource locators (URLs) 15. Internet protocol (IP) address numbers 16. Biometric identifiers, including fingerprints and voiceprints 17. Full-face photographic images and any comparable images 18. Any other unique identifying number, characteristic, or code, unless otherwise permitted by the Privacy Rule for De-identification Office for Civil Rights, Department of Health and Human Services (DHHS). (2015). Guidance regarding methods for de-identification of protected health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) privacy rule. Retrieved from https:// www.hhs.gov/ hipaa/ for-professionals/ privacy/ special-topics/ de-identification/ index.html# standard The DHHS (2017) developed the following guidelines to help researchers, healthcare organizations, and healthcare providers determine the conditions under which they can use and disclose IIHI: • The PHI has been de-identified under the HIPAA Privacy Rule. • The data are part of a limited data set, and a data use agreement with the researcher( s) is in place. • The individual who is a potential participant for a study authorizes the researcher to use and disclose his or her PHI. • A waiver or alteration of the authorization requirement is obtained from an IRB or a privacy board. The first two items are discussed in this section of the chapter. The authorization process is discussed in the section on obtaining informed consent, and the waiver or alteration of authorization requirement is covered in the section on institutional review of research. De-identifying protected health information under the privacy rule Covered entities, such as healthcare providers and agencies, can allow researchers access to health information if the information has been de-identified, either by applying statistical methods (expert determination) or removing information (safe harbor) (Fig. 9.2). The covered entity can apply statistical methods that experts agree render the information unidentifiable. The statistical method used for de-identification of the health data must be documented. Safe harbor is certifying that the 18 elements for identification have been removed or revised to ensure the individual is not identified. The covered entity has done what it could to make the information de-identified, but has no information whether the individuals could still be identified (DHHS, 2015a). No matter the method used, you must retain this certification information for 6 years. It is important to note that the element concerning biometrics may be interpreted to include deoxyribonucleic acid (DNA) results and other particularized physiological variants, such as unusual laboratory and histological markers. Fig. 9.2Use of PHI: Two methods of de-identifying data. Source: (Information from the HIPAA Privacy Rule.) H I P P A privacy rule for de-identification methods is categorized into two methods as follows: 1. Expert determination (left): Apply statistical and scientific principles. 2. Safe horror (right): Removal of 18 types of identifiers, and no actual knowledge whether data recipient can identify person. Limited data set and data use agreement Researchers can comply with the privacy standards by accessing a limited data set (LDS) that has been de-identified (Ahalt et al., 2019). A HIPAA-limited data set includes clinical patient-specific data combined with some PHI. Patient authorization is not required to use these data sets for “research, public health, or healthcare operations research” as long as the study is approved by an IRB (Ahalt et al. 2019, p. 329). Under certain conditions, researchers and covered entities (healthcare provider, health plan, and healthcare clearinghouse) may use and disclose an LDS to a researcher for a study, without an individual participant’s authorization or an IRB waiver. These data sets are considered PHI, and the parties involved must have a data use agreement. The data use agreement limits how the data set may be used and how it will be protected, including identification of the researchers who are permitted to use the data set. The researchers receiving the data are not allowed to use or disclose the information in any way that is not permitted by the agreement, is required to protect against the unintended use or disclosure of the information, and must agree not to contact any of the individuals in the LDS (Centers for Medicare & Medicaid Services [CMS], n.d.). Secondary data analysis reuses data collected for a previous study or for other purposes, such as data in clinical or administrative databases (Wickham, 2019). Duncan, Ahmed, Dove, and Maxwell (2019) used secondary data analysis to study the cost of end-of-life (EOL) care for Medicare beneficiaries. They selected a sample (N = 114,028) from the Medicare Limited Data Set to answer their research questions. The data set was also called the Medicare 5% LDS Analytical file or Medicare 5% file. The file had been de-identified as required by HIPAA and comprised of 5% of the Medicare beneficiaries. “For the purpose of understanding cost of care at the EOL, we perform analysis of the Medicare 5% file for the years 2015 and 2016. This file is a random sample of Medicare’s claims for the 2 years, containing experience of approximately 2.9 million patients for each year.“ ( Duncan et al., 2019, p. 706) “Medicare expenditures increase sharply in the last few days of life, particularly for patients who die in hospital. Recent developments in hospice and palliative care offer the possibility of higher quality care at lower cost to Medicare if patients enter hospice earlier. Finding a lower cost site of care that does not jeopardize patients’ wishes is a realistic, worthy goal…. Identifying those who will benefit from intensive care from those in which aggressive care is likely to be futile and burdensome is a challenge for providers, patients, and families.“ ( Duncan et al., 2019, p. 709) The findings of the study conducted by Duncan et al. (2019) provided strategies by which EOL expenditures could be reduced, an important cost savings, without infringing on the desired outcome of a peaceful death. Right to anonymity and confidentiality On the basis of the right to privacy, the research participant has the right to anonymity and the right to assume that all data collected will be kept confidential. Anonymity means that even the researcher cannot link a participant’s identity to that participant’s individual responses (Adams & Lawrence, 2019). For studies that use de-identified health information or data from a limited data set, participants are anonymous to the researchers. In most studies, researchers desire to know the identity of their participants and promise that their identity will be kept confidential. Confidentiality is the researcher’s management of private information shared by a participant that must not be shared with others without the authorization of the participant (Gravetter & Forzano, 2018). Confidentiality is grounded in the premises that patients own their own information, and that only they can decide with whom to share all or part of it (Kazdin, 2017). When information is shared in confidence, the recipient (researcher) has the obligation to maintain confidentiality. Researchers, as professionals, have a duty to maintain confidentiality consistent with their profession’s code of ethics (Gravetter & Forzano, 2018). This section includes breaches in confidentiality that may occur and strategies to maintain confidentiality. Breach of confidentiality A breach of confidentiality can occur when a researcher, by accident or direct action, allows an unauthorized person to gain access to a study’s raw data. Confidentiality can be breached in the reporting or publishing phases of a study, especially in qualitative studies, in which a participant’s identity is revealed by including personal details known to other people (Creswell & Creswell, 2018; Creswell & Poth, 2018). Two other types of research are especially sensitive to breaches in confidentiality. Collecting data through online forums and social media can threaten confidentiality because of the ability to track internet protocol addresses and search the internet participant’s quotes (Hunter et al., 2018). Passive data collection also has ethical issues. Passive data collection is gathering data without the active involvement of the participant (Maher et al., 2019). The data being gathered are linked to specific participants and are generated by wearable devices such as smartphones or electronic pedometers, by global positioning systems, and by e-mails and text messages. Breaches of confidentiality can harm participants psychologically and socially as well as destroy the trust they had in the researcher. Breaches can be especially harmful to a research participant when they involve religious preferences, sexual practices, employment, personal attributes, or opinions that may be considered negative, such as racial prejudices (Gravetter & Forzano, 2018). For example, imagine that you have conducted a study of nurses’ stressful life events and work-related burnout in an acute care hospital. One of the two male participants in the study describes his anxiety disorder. Reporting that one of the male nurses in the study had an anxiety disorder would violate his confidentiality and potentially cause harm. Nurse administrators might be less likely to promote a nurse who has an anxiety disorder. There are legal limits to confidentiality that occur when a participant reveals current drug use or specific intent to harm oneself or others (Gravetter & Forzano, 2018). For example, in a phenomenological study of the experience of parenting a child with development delays, the informed consent document must describe the specific limitations on confidentiality, such as the researcher being obligated to report a mother who reveals harming her child. Maintaining confidentiality includes not allowing health professionals to access data the researcher has gathered about patients in the hospital. Sometimes, family members or close friends will ask to see data collected about a specific research participant. Sharing research data in these circumstances is a breach of confidentiality. When requesting consent for study participation, you should assure the potential participant that you will not share individual information with healthcare professionals, family members, and others in the setting. However, you may elect to share a summary of the study findings with healthcare providers, family members, and other interested parties. Maintaining confidentiality in quantitative research Researchers have a responsibility to protect the identity of participants and to maintain the confidentiality of data collected during a study. You can protect confidentiality by giving each participant a code number. For example, participant Sarah Young might be assigned the code number 001. All of the instruments and forms that Sarah completes and the data you collect about her during the study will be identified with the 001 code number, not her name. To protect participants’ identities, the master list of the participants’ names and their code numbers are kept in a locked file and room, separate from the data collected. You should not attach signed consent forms and authorization documents to instruments or other data collection tools, as this would make it easy for unauthorized persons to readily identify the participants and their responses. Consent forms are appropriately stored with the master list of participants’ names and code numbers. When entering the collected data into a database, code numbers instead of names should be used for identification. Data should be stored in at least two secure places, such as on a separate storage drive, on the researcher’s computer, on web-based or cloud storage, or on a university network. The data files need to be password-protected, and (if possible) have no personal identifiers. Another way to protect anonymity is to have participants generate their own identification codes when data will be collected over time with multiple data points (Lippe, Johnson, & Carter, 2019). The researcher does not have a master list connecting the codes to the participants’ names. You are conducting a study of the role satisfaction of new nurse employees with data collection occurring during the first month, the sixth month, and again at the twelfth month. Each nurse generates an individual code from personal information, such as the first letter of a mother’s name, the first letter of a father’s name, the number of brothers, the number of sisters, and middle initial. Thus the code would be composed of three letters and two numbers, such as BD21M. This code would be used on each form the participant completes. The premise is that the elements of the code do not change, and the participant can generate the same code each time. However, using participant-generated codes has been found to have mixed results. Although the specific components of the ID number were selected for their stability, the participant may not remember, for example, whether they included half-sisters in the number of sisters or whether they used a parent’s legal name or nickname. In quantitative research, the confidentiality of participants’ information must be ensured during the data analysis process. The data collected should undergo group analysis so that an individual cannot be identified by his or her responses. If participants are divided into groups and a group has less than five members, the results for that group should not be reported. For example, a researcher conducts a study with military veterans and collects demographic data. In reporting the results by demographic groups, if only a few women participated, the results by gender should not be reported. In writing the research report, you should describe the findings in such a way that an individual or a group of individuals cannot be identified from their responses. Maintaining confidentiality in qualitative studies Maintaining confidentiality of participants’ data in qualitative studies often requires more effort than in quantitative research. Participants are known to the data collector, so anonymity is not possible (Cypress, 2019). The smaller sample size used in a qualitative study and the depth of detail gathered on each participant requires planning to ensure confidentiality (Morse & Coulehan, 2015). Informed consent documents should contain details about who will have access to the data and how the findings will be reported. In addition, qualitative researchers should communicate to participants that direct quotes from the interview will be included in both professional publications and presentations. Sometimes qualitative participants inappropriately equate confidentiality with secrecy. Researchers should take precautions during data collection and analysis to maintain confidentiality in qualitative studies. The interviews conducted with participants frequently are recorded and later transcribed, so participants’ names should not be mentioned during the recording. Some researchers ask participants to identify pseudonyms by which they will be identified during the interview and on transcripts. Depending on the methods of the study, the researcher may return descriptions of interviews or observations to participants to allow them to correct inaccurate information or remove any information that they do not want included. Participants have the right to know whether anyone other than you will be transcribing interview information or whether other researchers will analyze the data. In addition, participants should be reminded on an ongoing basis that they have the right to withhold information. For other researchers to critically appraise the rigor and credibility of a qualitative study, an audit trail is produced. To continue to protect the participants’ confidentiality, ensure that the audit trail does not contain information linking the demographic characteristics of participants to the qualitative data. When publishing the findings, researchers must respect participants’ privacy as they decide how much detail and editing of private information are necessary to publish a study while maintaining the richness and depth of the participants’ perspectives (Morse & Coulehan, 2015). The researcher may choose to amend biographical details, removing identifiers such as cities, healthcare providers’ names, and healthcare facilities, and use pseudonyms (Cypress, 2019). Right to fair treatment The right to fair treatment is based on the ethical principle of justice. This principle holds that each person should be treated fairly and should receive what he or she is owed. In research, the selection of participants and their assignment to experimental or control group should be made impartially. In addition, their treatment during the course of a study should be fair. Fair selection of subjects As discussed earlier, historically, research was conducted on categories of individuals who were thought to be especially suitable as research participants, such as the poor, uninsured patients, prisoners, slaves, peasants, dying persons, and others who were considered undesirable (Reynolds, 1979). Researchers often treated these participants carelessly and had little regard for the harm and discomfort they experienced. The Nazi medical experiments, the Tuskegee syphilis study, and the Willowbrook study all exemplify unfair participant selection and treatment. In 1986, the NIH implemented a policy requiring the inclusion of women and minorities in federally funded studies. This policy became law in 1993 as part of the NIH Revitalization Act (Office of Research on Women’s Health, 2017). Prior to this, concerns had been raised about the exclusion of women from biomedical studies, especially women of childbearing age. From a scientific standpoint, the concern was that “monthly changes in women’s hormone levels might affect therapeutic interventions and require more complicated designs” (Clayton & Blome, 2018, p. 177). The exclusion of women to avoid harming a fetus or interfering with childbearing also excluded women from the potential benefits of new medications and treatments, for herself and her fetus. The selection of a population and the specific participants to study should be fair so that the risks and benefits of the study are distributed appropriately (Shamoo & Resnick, 2015). Subjects should be selected for reasons directly related to the problem being studied. Too often participants are selected because the researcher has easy access to them. Another concern with participant selection is that some researchers select certain people, possibly friends or patients under their care, to participate because they like them and want them to receive the specific benefits of a study. Other researchers included specific participants in study because they received gifts or money. The Common Rule requires equitable selection of participants (DHHS, 2018). Children, women, minorities, and persons who speak other languages cannot be excluded based solely on their demographic characteristics. Researchers seeking federal funding must describe in their proposals plans to recruit participants from different groups who have been traditionally underrepresented in research. The researchers must remember, if a study poses risk, no demographic group should bear an unfair burden of that risk. Conversely, when a study offers a potential benefit, no demographic group should be deprived of participation solely because of their demographic classification. Random selection of participants can eliminate some of the researcher bias that might influence participant selection. The researcher should make every effort to include fair representation across demographic characteristics, and increased cost is no longer a valid reason for not doing that. For example, the NIH has implemented stricter policies about the inclusion of women in studies and sex being a required variable in animal studies (Clayton & Blome, 2018). The only exception is when a study involves a condition, such as prostate cancer, that only affects men. Proposals for funding must include specific plans for recruiting and maintaining a diverse sample, and federally funded researchers must include demographic characteristics of participants in their annual reports. One of the most challenging tasks of a researcher is recruiting an adequate number of participants who meet the inclusion criteria and comprise a sample that includes female participants and participants from racial and ethnic minorities (Leavy, 2017). The HIPAA Privacy Rule requires that individuals give potential authorization before PHI can be shared with others, unless the researcher has IRB approval to access records for the purpose of screening. The Privacy Rule makes it more difficult for researchers to find participants for their studies; however, researchers are encouraged to work closely with their IRBs and healthcare agencies to ensure fair selection and recruitment of adequate-sized samples. Fair treatment of participants Informed consent is a specific agreement about what inclusion in the study involves and what the role of the researcher will be (Adams & Lawrence, 2019). While conducting a study, you should treat the participants fairly and respect that agreement. If the data collection requires appointments with the participants, be on time for each appointment and terminate the data collection process at the agreed-upon time. You should not change the activities or procedures that a participant is to perform unless you obtain the participant’s consent. The benefits promised the participants should be provided. For example, if you promise a participant a copy of the study findings, you should deliver on your promise when the study is completed. In addition, participants in studies should receive equal benefits, regardless of age, race, and socioeconomic status. When possible, the sample should be representative of the study population and should include participants of various ages, ethnic backgrounds, and socioeconomic levels. Treating participants fairly and respectfully facilitates the data collection process and decreases the likelihood that participants will withdrawal from a study (Clayton & Blome, 2018). Thanking participants is always appropriate; they have given you their time and their honesty. Right to protection from discomfort and harm The right to protection from discomfort and harm is based on the ethical principle of beneficence, which holds that one should do good and, above all, do no harm. Therefore researchers should protect participants from discomfort and harm while ensuring they receive the greatest possible balance of benefits in comparison with harm. Discomfort and harm can be physiological, emotional, social, or economic in nature. This section addresses the level of risk in a study, balancing benefits and risks, and the ethical responsibilities of clinicians to provide the best care possible. Level of risk In his classic text, Reynolds (1979) identified the following five categories of studies based on levels of discomfort and harm: (1) no anticipated effects, (2) temporary discomfort, (3) unusual levels of temporary discomfort, (4) risk of permanent damage, and (5) certainty of permanent damage. Each level is defined in the following discussion. Studies with no anticipated effects are studies without direct involvement of human participants. For example, studies that involve reviewing patients’ records, students’ files, pathology reports, or other documents have no anticipated effect on the participants. In these types of studies, the researcher does not interact directly with research participants. Even in these situations, however, there is a potential risk of invading a participant’s privacy. The HIPAA Privacy Rule requires that the agency providing the health information de-identify the 18 essential elements (see Box 9.6 and Fig. 9.2) that could be used to identify an individual, to promote participants’ privacy during a study. Analysis of variables from a data set that has had the 18 elements removed is usually exempt from IRB review. Participants may experience temporary discomfort in low-risk studies. In these studies, the discomfort encountered is similar to what the participant would experience in his or her daily life and ceases with the termination of the study. Many nursing studies require participants to complete questionnaires or participate in interviews, which usually involve minimal risk. Physical discomforts of such research might be fatigue, headache, or muscle tension. Emotional and social risks might entail the anxiety or embarrassment associated with responding to certain questions. Economic harms may consist of the loss of time spent participating in the study or travel costs to the study site. Most clinical nursing studies examining the impact of a treatment involve minimal risk. For example, your study might involve examining the effects of exercise on the blood glucose levels of patients with noninsulin-dependent diabetes. During the study, you ask the participants to test their blood glucose level one extra time per day. There is discomfort when the blood is obtained and a risk of physical changes that might occur with exercise. The participants might also experience anxiety and fear in association with the additional blood testing, and the testing is an added expense. Diabetic participants in this study would experience similar discomforts in their daily lives, and the discomforts would cease with the termination of the study. Other studies involve unusual levels of temporary discomfort for the participants during the study and after its termination. For example, participants might experience a deep vein thrombosis (DVT), prolonged muscle weakness, joint pain, and dizziness after participating in a study that required them to be confined to bed for 7 days to determine the effects of immobility that severe trauma patients might experience. Studies that require participants to experience failure, extreme fear, or threats to their identity or to act in unnatural ways involve unusual levels of temporary discomfort. In some qualitative studies, participants are asked questions about sensitive topics, which may reopen old emotional wounds or involve reliving traumatic events (Butler, Copnell, & Hall, 2019). For example, asking participants to describe a sexual assault experience could precipitate feelings of extreme fear, anger, and sadness. In studying sensitive topics, you should arrange prior to the study to have appropriate professionals available for referrals should the participants become upset. During the interview, you would need to be vigilant about assessing the participants’ discomfort and refer them for appropriate professional intervention as necessary. If a participant appears upset during a qualitative interview, the researcher should ask questions such as, “Do you want to pause for a moment?” or “Do you want to talk about something else for a while?” or “Do you want to stop this interview?” Some participants will want to stop the interview completely. Others will want to continue despite the discomfort because it is important for them to tell their story. Care must also be taken not to reveal a participant’s identity inadvertently when disseminating the findings, especially when studying sensitive topics (Turcotte-Tremblay & McSween-Cadieux, 2018). Studies with a potential for permanent damage are more likely to involve biomedical researchers than nurse researchers. For example, medical studies of new drugs and surgical procedures have the potential to cause participants permanent physical damage. However, nurses have investigated topics that have the potential to damage participants permanently, emotionally, spiritually, and socially. Studies examining variables such as human immunodeficiency virus (HIV) diagnosis, sexual behavior, child abuse, or drug use have the potential to cause permanent damage to a participant’s personality or reputation. There are also potential economic risks, such as reduced job performance or loss of employment. Studies in which participants will suffer certain permanent damage may be unethical, such as the Nazi medical experiments and the Tuskegee syphilis study. Conducting research that will permanently damage participants is highly questionable and must be scrutinized carefully, regardless of the benefits gained. One exception might be a study that involves participants with a life-threatening disease having the opportunity to have a medical procedure that promises a cure but causes permanent damage to hearing, to peripheral sensation, or to vision. Frequently, in studies that cause permanent damage, other people, not the participants, will receive the benefits of the study. Studies causing permanent damage to participants, without a concomitant gain, violate the Nuremberg Code (1949). Balancing benefits and risks for a study Researchers and reviewers of research must compare the benefits and risks in a study. The comparison is called the benefit-risk ratio. To begin, you must first predict the most likely outcomes of your study based on previous research findings, clinical experience, and theory. What are the benefits and risks, both actual and potential, of these outcomes? As the researcher, your goal is to maximize the benefits and minimize the risks (Fig. 9.3). Fig. 9.3Balancing benefits and risks of a study. A flow diagram for developing a study benefit-risk ratio shows the following steps: 1. Predict the outcomes of the study leading to assess benefits and risks, which collectively lead to benefit-risk ratio to maximize benefits and minimizes risks in the following two ways: a. If benefits are greater than or equal to risks, study is approved. b. If risks outweigh benefits, study is rejected. The probability and magnitude of a study’s potential benefits must be assessed. A research benefit is defined as something of value to the participant whether related to physical health, psychological status, or social gain. Participants may receive the benefit of knowing they have contributed to the acquisition of knowledge for evidence-based practice (EBP). Money and other compensations for participation in research are not benefits but remuneration for research-related inconveniences (DHHS, 2018). In study proposals and informed consent documents, the research benefits are described for the individual participants, participants’ families, and society. The type of research conducted, whether therapeutic or nontherapeutic, affects the potential benefits for the participants. In therapeutic nursing research, the individual participant has the potential to benefit from the procedures of the study, such as skin care, range of motion, touch, emotional support, and pain management strategies. The benefits might include improvement in the participant’s physical condition, which could facilitate emotional and social benefits. The participant also may benefit from the additional attention of and interaction with a healthcare professional. In addition, knowledge generated from the research may expand the participants’ and their families’ understanding of health. The conduct of nontherapeutic nursing research does not benefit the participant directly but is important to generate and refine nursing knowledge for practice. Subjects who understand the lack of therapeutic benefit for them frequently will participate because of altruism and the desire to help others with their condition (Irani & Richmond, 2015). To compare the benefits and risks, you must also assess the type, severity, and number of risks that participants might experience by participating in your study. The risks depend on the purpose of the study and the procedures used to conduct it. Studies can have actual (known) risks and potential risks for participants. As mentioned earlier, participants in a study of the effects of prolonged bed rest have the actual risk of transient muscle weakness and the potential risk of DVT. Some studies contain actual or potential risks for the participants’ families and society. You must determine the likelihood of the risks and take precautions to protect the rights of participants when implementing your study. The benefit-risk ratio is the term given to a comparison of the benefits and risks of a study and is determined on the basis of the maximized benefits and the minimized risks. The researcher attempts to maximize the benefits and minimize the risks by making changes in the study purpose or procedures, or both (Goldstein et al., 2019). If the risks entailed by your study cannot be eliminated or further minimized, you must justify their existence. If the risks outweigh the benefits, the IRB is unlikely to approve the study and you probably need to revise the study or develop a new one. If the benefits equal or outweigh the risks, you can usually justify conducting the study, and an IRB will probably approve it (see Fig. 9.3). Clinical equipoise Clinical equipoise is the responsibility of clinicians to “provide the best possible treatment for their patients” (Gravetter & Forzano, 2018, p. 90). Studies in which participants are randomly assigned to a treatment (intervention) group or control group may threaten the principle of no harm if the control group receives care that is known to be inferior. For example, in a study of patients with heart failure who have had a myocardial infarction (MI), the intervention group receives a new medication that has been shown in animal studies to be effective with fewer side effects; the control group receives an older medication that has some serious side effects. Some participants are not being protected from harm (Gravetter & Forzano, 2018), because the researchers already know that the older drug potentially can cause serious side effects. To maintain equipoise, researchers who compare clinical treatments must either believe them to be relatively equivalent, acknowledge that it is unknown which is best, or indicate professional disagreement about which is best. The informed consent process for a RCT should include benefits and potential harms of both the intervention and control condition (Kotz, Viechtbauer, Spigt, & Crutzen, 2019). Some debate exists about clinical equipoise because it implies the objective of clinical care is the same as the objective of research (Thakur & Lahiry, 2019). For valid findings to be available upon which to base clinical care, studies are needed that randomly assign participants to different groups. Chapter 11 provides information about different types of RCTs that address the issue of equipoise, specifically pragmatic clinical trials and cluster RCTs. Human subject protection in genomics research The Human Genome Project funded by the NIH recognized from the onset the ethical and legal dilemmas of genomic research and allocated 5% of the funding to study these issues (Hammer, 2019). Over $ 300 million has been invested in studying the ethical and legal issues within genomic research. The funded studies made it “evident that a delicate balance exists between major genomics scientific progress and the challenge of maintaining the ethical tenets of autonomy, beneficence, non-maleficence, and justice” (Hammer, 2019, p. 94). Several highly publicized cases have increased awareness as well as fear among the public. In 1951, Henrietta Lacks, an African American woman, only 31 years of age, was diagnosed with cervical cancer. She was admitted to the hospital for the standard treatment at the time (Jones, 1997). The specimens collected were taken to the laboratory of a scientist named Dr. Gey. Dr. Gey was trying to identify and reproduce a cell line for research purposes (Jones, 1997). When Mrs. Lacks’s cells continued to multiply, Dr. Gey developed methods to produce even more and generously provided the cell line to other researchers free of charge. These researchers, building on Dr. Gey’s research, developed a cell line from those especially hardy tumor cells, which were successfully used in research (Bledsoe & Grizzle, 2013; Skloot, 2010). Highly effective treatments, such as the polio vaccine and in vitro fertilization (IVF), were developed using the cell line and were extremely profitable for the researchers and their institutions. Literally billions of dollars were made by selling the cell line to other researchers (McEwen, Boyer, & Sun, 2013). Mrs. Lacks died never knowing her tumor cells were used for research, and her family only learned of her contribution to science in 2010. In 1990, researchers began collecting blood specimens of members of an isolated Native American Indian tribe, the Havasupai, who lived in the Grand Canyon (Caplan & Moreno, 2011). Diabetes mellitus was a devastating disease among the tribe, and researchers proposed a study to identify genetic clues of disease susceptibility. However, the researchers used the blood specimens to study other topics (McEwen et al., 2013). The publications from the subsequent studies linked schizophrenia to the tribe’s DNA and contradicted the tribe’s story of their origin. The tribe sued Arizona State University, the employer of the original researcher, and was awarded a financial settlement in 2010. In addition, tribal leaders were given the remaining blood samples to be disposed of in a culturally appropriate way. Several ethical issues in genomics research have not been resolved. The following section will include issues with de-identification of data, additional studies being conducted with specimens already collected, participants withdrawing from a study, and return of information to the research participant if beneficial to the participant. The second section will identify ethical issues about specific methods such as use of embryonic tissue. Ethical issues related to genomic specimens By its very nature, genomic data cannot be completely de-identified (Quinn & Quinn, 2018; Terry, 2015). Genomic data could be combined with data from publicly available demographic databases and be re-identified. The likelihood of linking genomic data to an individual (re-identification) has increased because genome-wide sequencing and large samples have increased the size of databases, computer processing speeds have dramatically increased, and personal data are available through public internet sources (Quinn & Quinn, 2018). Despite this issue, genomic data that have been de-identified (18 elements removed) can be used by researchers without the notification or authorization of the participants. Without links to individuals, the research is considered nonhuman research (Bledsoe, Russell-Einhorn, & Grizzle, 2018) and not subject to regulation by the Common Rule. Genomic data are being generated from the body tissues and fluids that are left over after specimens are removed during clinical care. For example, a patient has a lung biopsy. The tissue is examined to determine the presence and types of abnormal cells. Not all of the tissue is used, however, and is saved on paraffin blocks. Archival tissue and fluids have been de-identified, studied, and resulted in dramatic and rapid advances in scientific knowledge, including targeted cancer treatments, improved immunotherapy, and genome sequencing of abnormal tissues (Bledsoe et al., 2018). The issues of whether identified information will be used for future studies was directly addressed in the revised Common Rule (DHHS, 2018). The new rule includes a new type of consent, called broad consent. Broad consent asks the patient or potential study participant for permission to store, maintain, and use for future studies private information and biological specimens that are identifiable. Box 9.7 contains the required elements of broad consent. Broad consent addresses whether any profits from commercial processes developed based on participant’s biospecimen will be shared with the participant, a statement developed because of the case of Mrs. Lack. BOX 9.7 Required Elements of Broad Consent • Potential risks and discomforts • Possible benefits • Extent to which private information will be kept confidential • Participation is voluntary • Refusal to participate involves no harm or loss of benefits • May stop participation at any time • Specimens and information (identifiable and nonidentifiable) may result in commercial products and process • Whether participant will share any profits • Whether whole genome sequencing is planned From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. Voluntary participation in research and the possibility of withdrawing are hallmark characteristics of informed consent (Capron, 2018). When biospecimens have been de-identified, withdrawing from a study becomes problematic. How does a researcher delete or remove a participant’s data if the data have been de-identified? Researchers must consider this possibility when planning the study. One strategy would be to delay de-identification until data collection is complete. Another would be to de-identify the data over the course of the study but retain a code number linking the data to the participant until the study is completed. Another pressing question is what happens if the researcher’s results include information that would benefit the participants directly? For example, the researchers are studying genetic characteristics of de-identified biospecimens from 20,000 adults who have osteoarthritis and are 61 to 79 years old. They incidentally find that 3% of the 11,000 women in the study have a breast cancer gene (BRCA) mutation that is associated with an inherited predisposition to breast cancer. Should the researchers re-identify the 330 specimens with the mutation and inform the women of their results? The ethical principles of beneficence, respect of persons, and justice would support a decision to re-identify the specimens (Bledsoe et al., 2018). However, the researchers need to balance the decision with whether the original study can be completed if funding is diverted to identifying the women and whether harm would occur to women who are informed but do not have breast cancer (Bledsoe et al., 2018). Relative to harm, the researchers would need to know that Black are underrepresented in genetic testing, which means the evidence linking BRCA mutations and breast cancer among Black women is weaker than it is for White women. Therefore the researchers would be less confident about notifying Black women about a BRCA mutation (Gehlert & Mozersky, 2018). Research teams will need to discuss these issues prior to initiating a study using biospecimens. The revised Common Rule does not require re-identification but does require that a broad consent includes what the researchers would do if this situation occurred (see Box 9.7). Ethical issues with specific types of genomic research Advanced practice nurses, nurse educators, and nurse administrators are likely to confront the genomic ethical issues in their work. Warren (2016) calls for nurses to be leaders in the policy debate about stem cell and genomic research. Nurse leaders cannot be leaders in the research and policy without understanding physiological and ethical challenges, such as the moral status of embryos and organoids. Specially trained nurses are being utilized to implement the stem cell therapies in clinical trials (Perrin et al., 2018). Stem cells continue to be a controversial source of genetic material and will be discussed first. Much of the related controversy is based on the source of the cells. Ethical issues with embryos are related to the views of researchers and funders on abortion and human cloning. Organoids are produced from stem cells for research and raise some new questions about ethical use of cerebral organoids. Stem cell research We begin with a few definitions of key terms because the ethical issues are hard to understand without understanding these terms. Stem cells are human cells that can reproduce themselves or can develop into specialized cells of other types, such as blood cells or muscle cells. Stem cells have been derived from somatic cells of adults and umbilical cord blood of infants (Johnston & Zacharias, 2019). Somatic cells are any cell in the body except those cells used for reproduction, specifically any cells except sperm and eggs. Pluripotent cells are master cells and can make cells for any layer of the body. They are important because the cells they produce as they divide are used for tissue repair in the body. Scientific advances have allowed the identification or creation of stem cells from four sources: adult cells, fetal cells, embryos, and reprogrammed human cells. The ethical issues vary based on the source of the cells. For example, stem cells generated from somatic adult and child cells pose no major ethical issues for the majority of the US population. The adults involved can give informed consent to the use their cells, and parents can give consent for use of their infant’s blood. Using the cells from aborted fetuses has been more troublesome because of strong opinions about the morality of terminating a pregnancy. The revised code addresses this issue directly by removing researchers from the decision about the termination of pregnancy and not allowing them to offer any compensation for a woman having an abortion in exchange for use of the fetal tissue (DHHS, 2018). Federal funding is available for research with stem cells generated from fetal tissues or cells; however, researchers involved in fetal stem cell research need to be aware of state regulations because five states have legal bans on using fetal cells (Johnston & Zacharias, 2019). Stem cells can be extracted from preimplantation human embryos that are 4 to 7 days old because each cell has the potential to develop into all types of human cells. These stem cells are called human embryonic stem cells (hEScs). Based on initial research results, hEScs have the therapeutic potential to repair damaged human organs (Johnston & Zacharias, 2019). The opposition is great, however, because extracting the cells results in the death of the embryo, an embryo that is considered by some to be a potential human being to which ethical principles apply (Hostiuc et al., 2019). The embryos may come from IVF. Reproductive cells that were initially harvested for a future pregnancy may be donated by parents who no longer need them for that purpose. This means of generating hEScs is more acceptable on ethical grounds, because the embryos would have been destroyed anyway (Johnston & Zacharias, 2019). However, the number of donated embryos and the lack of cultural diversity of the embryos do not meet the needs of science. hEScs can be produced by cloning using a process called somatic cell nuclear transfer (SCNT). SCNT can produce embryos from which stem cells are derived, stem cells that are used for research or therapeutic purposes (Johnston & Zacharias, 2019). The embryos are destroyed after the stem cells are removed, making it ethically unacceptable to some. The hEScs derived from cloned embryo stem cells also have the potential to cause an undesired immune response or abnormal cells in a recipient (Prentice, 2019). Beginning in 1973, federal funding was not available to study embryos, hEScs, and cloned embryos. Stem cell research continued, however, funded by states, individuals, and foundations. In 1998, a change occurred in federal funding. Once the stem cells were created, federal funds were available to conduct research using the cells (Johnston & Zacharias, 2019). The specifics of funding have varied according to which US president is in office. Stem cell research has become a major political issue, with debate around which ethical principle is stronger: beneficence, nonmaleficence, or respect for persons. Beneficence supports funding and encouraging stem cell research because of its great potential in improving the health of many people suffering with diseases (Warren, 2016). Nonmaleficence supports maintaining the restrictions on any research that produces embryos that will be destroyed. When an individual views an embryo as a human life, respect for persons also supports maintaining the restrictions on destroying embryos produced for research. Induced pluripotent stem cells (iPScs) are “human somatic cells reprogrammed to develop into nearly every human cell type, and are believed to be functionally very similar or identical to embryonic stem cells” (Johnston & Zacharias, 2019, p. 1311). Ethical and legal oppositions to iPScs have been less than the opposition to hEScs. Although iPScs have some potential for negative side effects, such as immune responses and abnormal cell growth, published studies using iPScs have increased in number and are outpacing published studies with hEScs (Prentice, 2019). In 2009, the NIH released Guidelines for Human Stem Cell Research (DHHS, 2009). Other guidelines have been released by the National Academies of Science (2005) and the International Society for Stem Cell Research, with the latest revision published in 2016. Nurse researchers who are working in stem cell research will want to be familiar with these guidelines and any relevant state laws, the ethical views of other members of the research team, and the IRBs overseeing the research. Cerebral organoids Organoids are three-dimensional structures created from stem cells to mimic functions of organs (Hostiuc et al., 2019). The organs for which organoids have been generated include the retina, intestines, liver, pancreas, testes, thyroid, heart, kidneys, lungs, and brain (Hostiuc et al., 2019; Lavazza & Massimini, 2018). These miniature organs are different from human organs in that they are less complex and may not exhibit all the desired functions of the full-size organ (Lavazza & Massimini, 2018). However, the similarities to human organs have made organoids an increasingly valuable resource for biomedical research. Cerebral organoids are being used to study autism, Parkinson disease, microcephaly, and traumatic brain injury. Because human embryonic stem cells are used to make organoids, some researchers would argue against organoids on the same ethical basis as other embryonic research. However, organoids can be generated from iPScs or hEScs, with the source potentially being the deciding factor in the ethics of creating organoids (see previous section). Beyond the source of the stem cells, the functions of cerebral organoids are beginning to raise new ethical issues. Research related to developing cerebral organoids has resulted in highly complex structures with neurons specific to each of the six layers of the cortex and others that have been shown to stimulate muscle contractions (Hostiuc et al., 2019). These highly complex cerebral organoids replicate the functions of the brain in an embryo a few months old (Hostiuc et al., 2019). The complexity of these structures gives rise to questions about the extent to which cerebral organoids should be considered human: How long will it be before these tissues are conscious and sentient (Lavazza & Massimini, 2018)? At what point in their development should the ethical principles of human research apply to cerebral organoids? Sancar (2018) reported an interview with Dr. Madeline Lancaster, the scientist whose cultures began to produce the three-dimensional structures that led to the development of organoids. Dr. Lancaster argues that cerebral organoids will not progress to the point of being conscious and sentient. Research conducted with cerebral organoids will continue to be an area of knowledge to monitor. These and other organoid-related ethical questions are likely to generate lively debate in the coming years. Informed consent Obtaining informed consent from human participants is essential for the conduct of ethical research in the United States (DHHS, 2018) and in other countries. Informing is the transmission of essential ideas and content from the researcher to the prospective participant. Consent is the prospective participant’s agreement, after assimilating essential information, to participate in a study as a participant. The phenomenon of informed consent was formally defined in the first principle of the Nuremberg Code as follows: “the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the participant matter involved, as to enable him to make an understanding and enlightened decision” (Nuremberg Code, 1949, p. 181). The definition of informed consent from the Nuremberg Code provides a basis for the discussion of consent in all subsequent research codes and has wide acceptance in the research community. Informed consent can only occur when the prospective participant is mentally competent and able to comprehend that information, the researcher discloses essential information, and the prospective participant has the freedom to volunteer to participate (Fig. 9.4) (Thakur & Lahiry, 2019). Fig. 9.4 displays the informed consent process as the related components of information, comprehension, and voluntarism. Informed consent does not meet ethical standards or legal requirements unless all three components are present. Fig. 9.4Components of informed consent: information, comprehension, and voluntarism. A cyclic flow diagram shows voluntarism, information, and comprehension connected to each other. Facilitating comprehension Persons with a cognitive impairment may participate in research studies when another person can act on their behalf. To the degree that they are capable, persons with cognitive impairment should have the opportunity to choose whether to participate in research. Previously in this chapter, we discussed persons with limited capacity due to cognitive impairment, psychosis, and dementia. With careful accommodations, a study’s participants may include persons with cognitive impairment (Forster & Borasky, 2018), a diagnosis of psychosis (Weissinger & Ulrich, 2019), or dementia (Chester et al., 2018). To enhance the comprehension of all prospective participants, professional jargon in the consent document needs to be replaced by everyday language. The language of the consent document should be adapted to the expected participants. Healthcare facilities may require that the researcher make the consent form available in the most common languages spoken by their patients. Depending on the geographic area, the consent form may need to be translated into Vietnamese, French, Spanish, or another language. For example, when some of the potential participants are Spanish speakers, the researchers should provide the consent and written instruments in Spanish. However, translating the consent into Castilian Spanish is not helpful if the population is primarily from Central America. Translation of instruments is a complex process, and we recommend the book on measurement by Waltz, Strickland, and Lenz (2017) as a reference (also see Chapter 17). The reading level of the consent should be adjusted for the expected participants. The recommended reading level for informed consent documents is an eighth-grade reading level (Tamariz et al., 2019). Gehlert and Mozersky (2018) report that half of the US population has a reading level below the eighth grade. When it is likely that some participants may have limited reading ability, the researcher may read the consent aloud to all participants to avoid embarrassment. When study information is not comprehended, there is no informed consent. This section describes the information that must be included in the consent document or oral consent and the methods of documenting consent. Another way to improve comprehension is to provide the consent information in multiple modes and assess the participants’ comprehension. Lindsley (2019) conducted a quality improvement initiative that began by assessing the research participants’ knowledge of a study to which they had consented to participate. Their knowledge gaps were used as the basis for questions to use in assessing comprehension and developing a multimodal presentation with the required elements of informed consent. The text of the presentation was reduced to a sixth-grade reading level. The presentation was delivered on a touchscreen tablet. Adult volunteers were randomized to receive standard or multimodal format of consent. The comprehension of all participants was assessed. The comprehension of those participants who viewed the multimodal presentation was significantly higher than the comprehension of participants who received the standard method of consent (Lindsley, 2019). Earlier in the chapter, we identified the benefits of using visual and oral methods to enhance comprehension in children and their parents, but Lindsley’s results indicated a multimodal approach is appropriate for adults, too. Information essential for consent Informed consent requires the researcher to disclose specific information to each prospective participant. In addition to the elements that are required by federal regulations (Box 9.8), the IRB or institution where the study will be conducted may have additional elements that they require (DHHS, 2018). Typical examples of the additional elements required by some IRBs are the anticipated number of participants, whether individual clinically relevant data will be returned to participants, and the conditions under which a person’s participation in the study would be terminated by the researcher. Table 9.2 provides the required elements with examples of the corresponding information from a consent document. BOX 9.8 Required Elements of Informed Consent • Statement that the study is research • Purpose of the study • Expected time the participant will be involved • Procedures involved and which are experimental • Reasonable risks and benefits • Alternative procedures, if applicable • Extent of confidentiality • Compensation or treatment if injury occurs • Who to contact with concerns about study or rights as a study participant • Voluntary participation; no penalty for not agreeing or discontinuing the study • Whether de-identified data or specimens will be shared with other researchers • Additional information to include as applicable • Any procedures that would hurt the fetus if a woman is pregnant • Circumstances under which participation could be terminated by researchers • Any costs related to being in the study • Consequences of withdrawal and orderly termination of withdrawing • New research findings might influence participant’s decision to participate • Approximate number of participants in the study • De-identified biospecimens may be used for commercial profit • Whether and how participant’s clinically relevant results will be shared with participant • Whether biospecimens will undergo whole genome sequencing From Department of Health and Human Services (DHHS). (2018). Basic HHS policy for protection of human subjects. Code of Federal Regulations, Sub-Part A of 45, Part 46. TABLE 9.2 Informed Consent Language for a Descriptive Comparative Study Required Element Example Statement that the study is research You are being asked to participate in a research study about nursing students’ attitudes toward poverty. Purpose of the study The purpose of the study is to compare junior and senior nursing students’ attitudes toward poverty before and after a poverty simulation. Expected time the participant will be involved The Attitudes Toward Poverty Short-Form Scale (ATPS) takes 5 to 10 minutes to complete. Procedures involved and which are experimental The poverty simulation is a required class activity. You will be asked to complete the ATPS before and after the simulation. The researchers want to know whether the poverty simulation affects your attitudes about poverty. Reasonable risks and benefits RISKS: Because the major risk of the study is the potential loss of confidentiality, a faculty not involved in the study will remove only the consent form from the manila envelope. If you said yes to participating, your packet will be retained for the study. If you said no, your packet will be marked that it is not to be included in the study. No other risks have been identified related to participating in this study. BENEFITS: The main benefit to you for participating in this study is knowing you have contributed to expanding the body of knowledge available on nursing student’s attitudes toward poverty. Alternative procedures, if applicable There are no alternative procedures for this study. Extent of confidentiality All information obtained about you in this study is strictly confidential unless the law requires disclosure. The results of this study may be used in reports, presentations, and publications, but the researchers will not identify any individual students. Compensation or treatment if injury occurs There are no costs or payments associated with your participation in this study. Who to contact with concerns about study or rights as a study participant In the event that you suffer injury as a result of participation in any research project, you may contact Faculty Member at 123-123-1234 or Chair of the IRB at 321-321-4321, who will be glad to review the matter with you. Voluntary participation; no penalty for not agreeing or discontinuing the study The poverty simulation is a required class activity, but the researchers want your decision about participating in this study to be absolutely voluntary. If you have questions about the study, please ask the researchers before you agree to participate. It is okay for you to say no. Your decision will not affect your participation or grade in the required poverty simulation activity. Your responses will not be linked to your name. Whether de-identified data or specimens will be shared with other researchers The researchers will not share the data with other researchers. Introduction of research activities The researcher begins the informed consent document with several key elements. The informed consent document includes a statement that the prospective participant is being asked to participate in a research study and a description of the purpose of the study, type of data collection, and expected duration of the person’s participation (DHHS, 2018; Santos et al., 2017). Prospective participants also must receive a complete description of the procedures to be followed, such as whether assignment to a group will be random if the study includes an intervention and a control group. The researchers must identify the intervention as being experimental (DHHS, 2018; FDA, 2019b). For example, researchers conducting quantitative and outcome studies need to describe the procedures or mechanisms that will be used to examine, manipulate, or measure the study variables. For qualitative studies, the researcher will describe how data will be collected, such as an interview, and the topics to be discussed or observed. Mixed methods studies will include descriptions of the quantitative and qualitative procedures. In addition, they must inform prospective participants about when the study procedures will be implemented, how many times, and in what setting. Prospective participants must receive a disclosure of alternatives related to their participation in a study. For example, a female hypertensive patient who has uncontrolled blood pressure on a single antihypertensive medication may be recruited for a clinical trial for patients like her who have uncontrolled hypertension on a single drug. The two arms of the trial are following the current EBP guideline of adding a second antihypertensive medication or being prescribed a new experimental antihypertensive medication. She needs to know that, if she decides not to participate, she can continue on her current medication and attend an education program about eating correctly and losing weight. As a prospective participant, the medication plus education is an appropriate, alternative course of treatment about which she must be informed (DHHS, 2018). Research participants also need to know the funding source( s) of a study, such as specific individuals, organizations, or companies (Bonham, 2018). For example, researchers studying the effects of a specific drug must identify any sponsorship by a pharmaceutical company. Description of risks and benefits Prospective participants must be informed about any foreseeable risks or discomforts (physical, emotional, social, or economic) that might result from the study (Bonham, 2018; DHHS, 2018; FDA, 2019b). Female prospective participants need to know whether the study treatment or procedure involves potential risks to them or their fetuses if they are pregnant or become pregnant during the study (DHHS, 2018). For research involving more than minimal risk, prospective participants must be given an explanation as to whether any compensation or medical treatment, or both, would be available if injury should occur. If medical treatments are available, the person obtaining consent must describe the type and extent of the treatments. You should also describe any benefits to the participant or to others that may be reasonably expected from the research. The study might benefit the current participants or might generate knowledge that will provide evidence-based care to patients and families in the future (DHHS, 2018; FDA, 2019b). Most critically, prospective participants want to know how the risks of a study were minimized and the benefits maximized. They need time to compare the potential risks and benefits in the context of their lives so they can determine what is best for them without the researcher’s influence. Assurance of anonymity and confidentiality Prospective participants must be assured their research records, including PHI, will be secured during and following the study and remain confidential (DHHS, 2018). All oral or poster presentations and published papers will report only group findings. The exception may be for qualitative studies when participants’ quotes may be included in a presentation or publication but will not be linked to an identifiable individual. Any limits to confidentiality, such as the researcher’s need to reveal anything the participant reports about ongoing elder abuse, must also be disclosed to the prospective participant before participation begins, if relevant to the study. Depending on the study design, participants’ identities may be anonymous to the researchers, which decreases the potential for bias. For example, an internet survey may allow participants to enter their responses and not include their names. Voluntary and informed participation Despite assessing the capacity of the participant to comprehend the information and providing the consent in the participant’s primary language and at the appropriate reading level, some participants may be confused or have additional questions. As a conscientious researcher, you need to offer to answer any questions that the prospective participants may have during the consent process. Study participants also need an explanation of whom to contact for answers to questions about the research during the conduct of the study and whom to contact in the event of a research-related problem or injury, as well as how to do so (DHHS, 2018). In addition to the researcher who may be contacted, the IRB of the healthcare facility or university IRB to which you are submitting your materials will have specific contact information to include on the consent. A copy of the informed consent should be given to the participant so he or she has this contact information. Voluntary participation is as critical to the consent process as being informed. A noncoercive disclaimer is a statement that participation is voluntary and refusal to participate will involve no penalty or loss of benefits to which the participant is entitled (DHHS, 2018; FDA, 2019b). We do know that participants may agree to participate because they believe their care will be higher quality or they will have improved outcomes (Thakur & Lahiry, 2019). Therapeutic misconception has been documented and may need to be proactively addressed with some participants. For example, CF patients acknowledged that they agreed to participate in research because they believed their care would be better (Bailey & Ladores, 2018). (See previous section for more on therapeutic misconception.) Researchers may pay participants for their time and effort. However, any payment may be coercive to participants with extremely limited financial means (e.g., $ 5 may be coercive to a participant who is hungry). Any financial compensation to prisoners to participate in a study has been viewed as coercive. However, Ravi, Christopher, Filene, Reifeis, and White (2018) conducted a study of the attitudes of prisoners (N = 50) toward financial compensation for being a study participant. The prisoners overwhelmingly indicated that prisoners who are participants in studies should be compensated (74%) and that payment would not keep prisoners from refusing to participate (88%). When determining the amount of compensation for a specific study, factors such as transportation expenses, possible childcare costs, and length of participation should be considered. Astute researchers often seek guidance from community representatives and other experts who are familiar with the study population. When compensation is going to be provided, the information should be included in the consent document. Typically, a small financial payment ($ 10 to $ 30) is seen as noncoercive and appropriate to compensate participants for time and effort related to study participation (Adams & Lawrence, 2019). Subjects may discontinue participation in a study at any time without penalty or loss of benefits, meaning that compensation cannot be dependent on completion of the study. There may be circumstances under which the participant’s involvement in a study may be terminated by the researcher without regard to the participant’s consent (DHHS, 2018). For example, if the intervention being studied becomes potentially dangerous to a participant, you as a researcher have an obligation to discontinue the participant’s involvement in the study. The consent needs to include a general statement about the circumstances that could lead to termination of the entire project, such as safety concerns or unexpected risks. This is especially important in therapeutic research. Consent to incomplete disclosure In some studies, participants experience incomplete disclosure of study information, or are not completely informed of the study purpose, because that knowledge would alter their actions. However, prospective participants must know that certain information is being withheld deliberately. You, the researcher, must ensure that there are no undisclosed risks to the participants that are more than minimal and that their questions are truthfully answered regarding the study. Subjects who are exposed to nondisclosure of information must know when and how they will be debriefed about the study. Subjects are debriefed by informing them of the actual purpose of the study and the results that were obtained (Shamoo & Resnik, 2015). At this point, participants have the option to have their data withdrawn from the study. If the participants experience adverse effects related to the study, you must make every attempt to compensate or alleviate the effects (DHHS, 2018). Documentation of informed consent The standard is that informed consent is presented formally and requires the signature of the participant and a witness. There are lower risk studies, however, in which signatures and/ or written consent can be waived with the approval of the IRB. Waivers of written and signed consent Requirements for written consent or the participants’ signatures on their consent forms may be waived in minimal risk research (DHHS, 2018). For example, if you were using questionnaires to collect low-risk data, obtaining a signed consent form from participants might not be necessary. The participant’s completion of the questionnaire may serve as consent. The top of the questionnaire might contain a statement such as “Your completion of this questionnaire indicates your consent to participate in this study.” In other low-risk studies, data may be collected by mail or online and, after the text of the consent is presented, the participant then signifies consent by completing the questionnaire. Written consent also is waived when the only record linking the participant and the research would be the consent document, and the principal risk is the harm that could result from a breach of confidentiality. The participants must be given the option of signing or not signing a consent form, and the participant’s wishes govern whether the consent form is signed (DHHS, 2018). However, the three elements of consent—information, comprehension, and voluntarism—are essential in all studies (see Fig. 9.4), whether written consent is waived or required. An example of an alteration of the consent process is found in a study with HIV seropositive African Americans (Coleman, 2017). The descriptive correlational study was designed to test a model of factors related to depression and quality of life. In a private room at an HIV clinic, the researcher described the study purpose and other information about the study. Each set of questionnaires was given a unique identifying number, to protect confidentiality. A “waiver of signature was requested for the consent form from the IRB as it was determined the participant’s signature was not needed” (Coleman, 2017, p. 139). In this stigmatized group, confidentiality is especially important. The only link between the data provided and the participants would have been their signatures on the consent form, a valid reason for making this change. Elements of the consent document The written consent document or consent form includes the elements of informed consent required by the DHHS (2018) regulations (see Box 9.8). The IRBs of most healthcare facilities and universities maintain their own templates for the informed consent document with specific requirements, such as detailed headings, suggested wording, and contact information. The participant can read the consent form, or the researcher can read it to the participant; however, the researcher can also explain the study to the participant, using different words, in a conversational manner, which encourages questions. The participant signs the form, and the investigator or research assistant collecting the data witnesses it. This type of consent can be used for minimal-to-moderate-risk studies. All persons signing the consent form must receive a copy. The researcher keeps the original for 3 years in a secure location, such as a locked file cabinet in a locked room. Studies that involve participants with diminished autonomy require a written consent form. If these prospective participants have some comprehension of the study and agree to participate, they must sign the consent form. However, each participant’s legally authorized representative also must sign the form. The representative indicates his or her relationship to the participant under the signature. The written consent form used in a high-risk study often contains the signatures of two witnesses, the researcher, and an additional person. The additional person signing as a witness must not be otherwise connected with the study and is present to observe the informed consent process and to ensure that it adheres to specifications. The best witnesses are research advocates or patient ombudspersons employed by the institution. Sometimes nurses are asked to sign a consent form as a witness for a biomedical study. They must know the study purpose and procedures and the participant’s comprehension of the study before signing the form as a witness. The role of the witness is more important in the consent process if the prospective participant is in awe of the investigator and does not feel free to question the procedures of the study. Short-form written consent document The short-form consent document includes the following statement: “The elements of informed consent required by Section 46.116 have been presented orally to the participant or the participant’s legally authorized representative” (DHHS, 2018, 45 CFR, Section 46.117b). The researcher must develop a written summary of what is to be said to the participant in the oral presentation, and the summary must be approved by an IRB. When the oral presentation is made to the participant or to the participant’s representative, a witness is required. The participant or representative must sign the short-form consent document. The witness must sign both the short form and a copy of the summary, and the person obtaining consent must sign a copy of the summary. Copies of the summary and short form are given to the participant and the witness; the researcher retains the original documents and must keep these documents for 3 years after the end of the study. Short-form written consent documents may be used in studies that present minimal or moderate risk to participants. Recording of the consent process A researcher may choose to document the consent process through audio or video recordings. These methods document what was said to the prospective participant as well as record the participant’s questions and the investigator’s answers. Because recordings can be time consuming and costly, they are rarely used for studies of minimal or moderate risk. If your study is considered high risk, documenting the consent process electronically is recommended. The recording serves as a protection for you and your participants. The researchers and the participant (or representative) will retain a copy of the recording. Authorization for research uses and disclosure The HIPAA Privacy Rule provides individuals the right, as research participants, to authorize covered entities (healthcare provider, health plan, and healthcare clearinghouse) to use or disclose their PHI for research purposes. This authorization is regulated by HIPAA and is separate from the informed consent that is regulated by the DHHS (2018). The authorization of the use of information can be included as part of the consent form, but it is probably best to have two separate forms. The authorization focuses on privacy risks and states how, why, and with whom PHI will be shared. The key ideas required on the authorization form when used for research are included in Box 9.9. BOX 9.9 Requirements for Authorization to Release PHI for Research • Types of PHI to be used, such as medical diagnosis or assessment data, identified in an understandable way • Name of researcher who will use the PHI and affiliated institution • How the PHI will be used in this specific study • Authorization expiration date, which may be the end of the study or “none” if data will become part of a research database or repository • Signature of the participant, legal representative if appropriate, and date From HIPAA Journal. (2018). What is HIPAA authorization? Retrieved from https:// www.hipaajournal.com/ what-is-hipaa-authorization/ Institutional review An institutional review board (IRB) is a committee that reviews research to ensure that all investigators are conducting research ethically. All hospital-based research must be submitted to the hospital’s IRB, which will then determine whether it is high risk, moderate risk, minimal risk, or exempt from review. This is true, as well, of research that does not involve patients. Even though some research clearly falls under the category of “exempt from review” it must, nonetheless, be submitted to the IRB, which then will declare it exempt. Requiring review of all studies is necessary because, in the past, studies that should have been reviewed escaped notice. Universities, hospital corporations, and many managed care centers maintain IRBs to promote the conduct of ethical research and protect the rights of prospective participants at these institutions, as required since 1974. Federal regulations require that the members of an IRB evaluate the study for protection of human participants, including processes for obtaining informed consent. Federal regulations stipulate the membership, functions, and operations of an IRB (DHHS, 2018, 45 CFR, Sections 46.107–46.109). Each IRB has at least five members of various backgrounds (cultural, economic, educational, professional, gender, racial) to promote a complete, scholarly, and fair review of research that is commonly conducted in an institution (Martien & Nelligan, 2018). If an institution regularly reviews studies with participants susceptible to coercion or with impaired cognition, the IRB should include one or more members with knowledge about and experience in working with these individuals. Any IRB member who has a conflict of interest with a research project being reviewed must excuse himself or herself from the review process, except to provide information requested by the IRB. The IRB also must include members who are not affiliated with the institution and whose primary concern is nonscientific, such as an ethicist, a lawyer, or a minister (DHHS, 2018). IRBs in hospitals are often composed of physicians, nurses, lawyers, scientists, clergy, and community laypersons. The revised Common Rule provides a description of the experience and expertise of the IRB (DHHS, 2018): “The IRB shall be sufficiently qualified through the experience and expertise of its members (professional competence), and the diversity of its members, including race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. The IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments (including policies and resources) and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas.” (Section 46.107) A researcher may first develop a research proposal to obtain funding or approval of a faculty committee, if the researcher is a student. After gaining funding and/ or faculty approval, the researcher develops a protocol—a shorter, but detailed description of the proposed study and its methods. The protocol is submitted to the IRB for approval. In addition, the IRB may require a form to gather information specific to the study, such as start and ending dates of the study. The IRB reviews the protocol and form to determine whether the researcher has demonstrated that (1) the benefits of the study outweigh the risks, (2) the risks will be minimized, and (3) the consent process and document are appropriate for the intended participants (Bonham, 2018). The IRB members also protect potential participants by determining the scientific value of the study. The researcher must demonstrate the significance of the research topic and the gap in knowledge that the proposed study will address. If the methods lack rigor or the researcher lacks knowledge and expertise to conduct the proposed study, then the study should not be conducted (Bonham, 2018). For example, a student submitting a protocol will need to document the research experience and professional knowledge of the faculty sponsor relevant to the research topic. Clinical trials and other large multisite studies funded by the NIH must designate a central IRB. A central IRB is that to which the researchers will submit the study for its ethical review. Facilities that comprise the multiple sites of the study will be expected to accept the central IRB’s decision. In the past, each facility’s IRB reviewed the protocol, requiring the researchers to submit the protocol, their specific forms, and an informed consent with their facility’s contact information. Most IRBs were underresourced and burdened by the increasing paperwork required to review and approve a study (Schnipper, 2017). No single IRB had members with sufficient expertise to review studies in every specialty and type of research. As a result, reviews were inconsistent. When one IRB required a change in the methods or consent form, the change had to be reviewed by all the IRBs. Needless to say, the process delayed the implementation of the study. By requiring a central IRB, multisite, federally funded studies will be implemented more quickly. The implementation of review by a central IRB faces some barriers, such as failure to consider the local context in which the study will be implemented at a specific site (Schnipper, 2017). Another barrier to central IRBs is concern about the legal liability of a hospital or clinic when a participant at his or her site experiences an adverse event and there was no local review of the study. Levels of reviews conducted by institutional review boards Federal guidelines identify the levels of reviews required for different types of studies (DHHS, 2018). The functions and operations of an IRB involve the review of research at three different levels of scrutiny: (1) exempt from review, (2) expedited review, and (3) full board review. Researchers cannot determine the level of review their proposed study requires. The IRB chairperson and/ or committee, not the researcher, decides the level of the review. Studies are usually exempt from review if they pose no apparent risks for research participants. Studies usually considered exempt from IRB review, according to federal regulations, are identified in Box 9.10. For example, studies by nurses and other health professionals that have no foreseeable risks or are a mere inconvenience for participants may be identified as exempt from review by the chairperson of the IRB committee. In other states or regions, these same studies may be classified as studies appropriate for expedited reviews. BOX 9.10 Research Qualifying for Exemption From Review 1. Conducted in established or commonly accepted educational settings, involving normal educational practices 2. Involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: • Recorded in such a manner that human participants can be identified, directly or through identifiers • Disclosure of the human participants’ responses could reasonably place the participants at risk of criminal or civil liability • Disclosure of the human participants’ responses could reasonably be damaging to the participants’ financial standing, employability, or reputation 3. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior that is not exempt: • Exempt if human participants are elected or appointed public officials or candidates for public office • Federal statute( s) require( s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. 4. Involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens if publicly available or recorded by the investigator in such a manner that participants cannot be identified, directly or through identifiers 5. Conducted by or participant to the approval of department or agency heads, and which are designed to study, evaluate, or examine the following: • Public benefit or service programs • Procedures for obtaining benefits or services under those programs • Possible changes in or alternatives to those programs or procedures • Possible changes in methods or levels of payment for benefits or services under those programs 6. Taste and food quality evaluation and consumer acceptance studies when: • Wholesome foods without additives are consumed • Food is consumed that contains a food ingredient at or below the level and for a use found to be safe • Food consumed contains an agricultural chemical or environmental contaminant at or below the level found to be safe by the FDA or other federal agency Adapted from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1104 Under expedited IRB review procedures, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. Expedited review procedures can also be used to review minor changes in previously approved research. Studies that have some risks, which are viewed as minimal, are expedited in the review process. Minimal risk means that “probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests” (DHHS, 2018, 45 CFR, Section 46.102). In reviewing the research, the reviewers may exercise all of the authorities of the IRB except disapproval of the research. If the reviewer does not believe the research should be approved, the full committee must review the study. Only the full committee can disapprove a study (DHHS, 2018). Box 9.11 identifies research that usually qualifies for expedited review. BOX 9.11 Research Qualifying for Expedited Institutional Review Board Review Expedited review for studies with no more than minimal risk involving: 1. Collection of hair, collection of nail clippings, extraction of deciduous teeth, and extraction of permanent teeth if extraction needed 2. Collection of excreta and external secretions (sweat, saliva, placenta removed at delivery, and amniotic fluid at rupture of the membrane) 3. Recording of data from participants 18 years of age or older using noninvasive procedures routinely used in clinical practice with exception of X-rays 4. Collection of blood samples by venipuncture from healthy, nonpregnant participants 18 years of age or older (amount not > 450 mL in an 8-week period, no more than two times per week) 5. Collection of dental plaque and calculus using accepted prophylactic techniques 6. Voice recordings made for research purposes such as investigations of speech defects 7. Moderate exercise by healthy volunteers 8. The study of existing data, documents, records, pathological specimens, or diagnostic specimens 9. Behavior or characteristics of individuals or groups, with no researcher manipulation. Research will not increase stress of participants. 10. Drugs or devices for which an investigational new drug exemption or an investigational device exemption is not required Summarized from Department of Health and Human Services (DHHS). (2018). Protection of human participants. Code of Federal Regulations, Title 45, Part 46. Retrieved from https:// www.ecfr.gov/ cgi-bin/ retrieveECFR? gp5& SID583cd09e1c0f5c6937cd9d7513160fc3f& pitd520180719& n5pt45.1.46& r5PART& ty5HTML# se45.1.46_1109 A study involving greater than minimal risk to research participants requires a complete IRB review, also called a full board review. Any study that does not qualify for exempt or expediated review must undergo a full board review. To obtain IRB approval, researchers must ensure that ethical principles are upheld. Risks must be minimized, and those risks must be reasonable when compared to benefits of participation. Consistent with justice, the selection of participants must be fair and equitable. Informed consent must be obtained from each participant or legal representative and documented appropriately. In addition, the researcher must have a plan to monitor data collection, protect privacy, and maintain confidentiality (DHHS, 2018, 45 CFR, Section 46.111). Every research report must indicate that the study had IRB approval and whether the approval was from a university and/ or clinical agency. For example, nurse researchers Kelechi, Mueller, Madisetti, Prentice, and Dooley (2018) conducted a study of cryotherapy for pain relief among patients with chronic venous disease (CVeD). The cryotherapy study was designed as a multicenter randomized controlled trial that compared a 9-month graduated cooling intervention to a placebo control plus usual care among patients with the more severe forms of CVeD. Three wound care centers and an academic medical research center from the south-eastern region of United States (U.S.) participated in the study. The study complied with the Declaration of Helsinki and was approved by the university’s Institutional Review Board for Human Research (IRB). ( Kelechi et al., 2018, p. 3) Informed consent and IRB approval are necessities for conducting ethical research. With revisions to the Common Rule, researchers will want to communicate early with the IRB from which they will be requesting approval. IRBs will be adapting their procedures to be consistent with the revised Common Rule. Research misconduct The goal of research is to generate sound scientific knowledge, which is possible only through honest implementation and reporting of studies. Scientific misconduct has been a known problem since the 1980s. In 1992, the DHHS created the Office of Research Integrity (ORI, n.d.). The ORI was instituted to supervise the implementation of the rules and regulations related to research misconduct and to manage any investigations of misconduct. In this section, terms used to describe scientific misconduct will be defined. Cases of scientific misconduct will be described in health care and nursing followed by how the ORI, journal editors, peer reviewers, and researchers can prevent scientific misconduct. Terms related to scientific misconduct The most current regulations implemented by the ORI (2019b, 2019c) are CFR 42, Parts 50 and 93, Policies of General Applicability. The ORI was responsible for defining important terms used in the identification and management of research misconduct. Research misconduct was defined as “the fabrication, falsification, or plagiarism in processing, performing, or reviewing research, or in reporting research results…. It does not include honest error or differences in opinion” (ORI, 2019b, 42 CFR, Section 93.103). Also from Section 93.103, “fabrication is making up data or results and recording or reporting of them” and “falsification is manipulating research materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record.” Fabrication and falsification of research data are two of the most common acts of research misconduct managed by ORI. Plagiarism is also research misconduct and is defined as “the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit” (ORI, 2019b, 42 CFR, Section 93.103). Examples of scientific misconduct The ORI’s website contains a growing list of persons found to have falsified or fabricated research reports. We have described two completed cases in this section by way of example, but many others are available on the website. In August 2019, Dr. Rahul Agrawal was found to have fabricated data in 59 data files for experiments that were not conducted (ORI, 2019a). Dr. Agrawal was a fellow at the National Cancer Institute at NIH when he fabricated the data. In another case, Brandi Baughman, PhD, acknowledged in 2017 that she had manipulated data for 11 figures in a published paper. At the time, she was a postdoctoral fellow at the University of North Carolina and working on federally funded grants. She signed a letter indicating she had not manipulated data in any other experiments, knowing full well that she and her colleagues had a paper under review in which the findings were based on 14 reused and relabeled Western blot laboratory tests from an unrelated study. The ORI (2018) finding was that she would no longer be eligible to work with a federally funded research team for 2 years. Research misconduct is a growing concern in nursing (Lach, 2019; Ward-Smith, 2016). Asman, Melnikov, Barnoy, and Tabak (2019) surveyed 119 nurses attending nursing education programs and 32 nurses with graduate degrees about scientific misconduct that they had observed. Among these nurses, 15.5% indicated agreement with one or more items about their inclination to fabricate data, and 26.25% indicated agreement with one or more items about their inclination to select or omit data. Fifty nurses (34.2%) had “knowledge of research misconduct in the workplace” (Asman et al., 2019, p. 864). When scientific misconduct is identified, the related publications may be retracted. Al-Ghareeb et al. (2018) conducted a systematic review of 37 years of retractions in nursing and midwifery journals. They found 29 articles in nursing journals had been retracted, with the most common reason being duplicate publication (Al-Ghareeb et al., 2018). Role of the ORI in promoting the conduct of ethical research Currently, the ORI applies federal policies and regulations to protect the integrity of the USPHS’s extramural and intramural research programs. The extramural programs provide funding to research institutions, and the “intramural programs provide funding for research conducted within Federal government facilities” (ORI, n.d.). Box 9.12 contains a summary of the functions of the ORI. BOX 9.12 Functions of the Office of Research Integrity • Developing policies, procedures, and regulations related to responsible conduct of research and to the detection, investigation, and prevention of research misconduct • Monitoring research misconduct investigations • Making recommendations related to findings and consequences of investigations of research misconduct • Assisting the Office of the General Counsel (OGC) to present cases before the DHHS appeals board • Providing technical assistance to institutions responding to allegations of research misconduct • Implementing activities and programs to teach responsible conduct of research, promote research integrity, prevent research misconduct, and improve the handling of allegations of research misconduct • Conducting policy analyses, evaluations, and research to build the knowledge base in research misconduct, research integrity, and prevention and to improve the DHHS research integrity policies and procedures • Administering programs for • Maintaining institutional assurances • Responding to allegations of retaliation against whistleblowers • Approving intramural and extramural policies and procedures • Responding to Freedom of Information Act and Privacy Act requests Summarized from Office of Research Integrity (ORI). (2020). About ORI. Retrieved from https:// ori.hhs.gov/ about-ori To be classified as research misconduct, an action must be intentional and involve a significant departure from acceptable scientific practices for maintaining the integrity of the research record. When an allegation is made, it must be proven by a preponderance of evidence. Institutions that received federal research funding must have policies and procedures for investigating any allegations against one of their researchers (ORI, 2017). The institution in which the misconduct occurred gathers the evidence and determines whether research misconduct has occurred. When research misconduct has been found to have occurred, the actions taken against the researchers or agencies have included disqualification to receive federal funding for a specific length of time or lifetime suspension from receiving funds. Other actions taken may be that the researcher can conduct only supervised research and all data and sources must be certified. All publications reporting the findings of the study in question are corrected or retracted (ORI, 2019b, 42 CFR, Section 93.411). Role of journal editors and researchers in preventing scientific misconduct Editors of journals also have a major role in monitoring and preventing research misconduct in the published literature (World Association of Medical Editors [WAME], n.d.). WAME has identified data falsification, plagiarism, and violations of legal and regulatory requirements as some types of scientific misconduct. (See Chapter 27 for more information on ethical practices for authorship.) Preventing the publication of fraudulent research requires the efforts of authors, coauthors, research coordinators, reviewers of research reports for publication, and editors of professional journals (Al-Ghareeb et al., 2018; Asman et al., 2019; Ward-Smith, 2016). Authors who are primary investigators for research projects must be responsible in their conduct and the conduct of their team members, from data collection through publication of research. Coauthors and coworkers should question and, if necessary, challenge the integrity of a researcher’s claims. Sometimes, well-known scientists’ names have been added to a research publication as coauthors to give it credibility. Individuals should not be listed as coauthors unless they were actively involved in the conduct of the research and preparation of the manuscript (International Council of Medical Journal Editors [ICMJE], 2018). Similarly, supervisors and directors of hospital units should not be included as last author as a “courtesy” for a publication unless they were actively involved in at least one phase of the research. Principal investigators (PIs) in large, funded studies have a role to promote integrity in research and to identify research misconduct activities (Kovach, 2018). They may have delegated implementation of a study to a research coordinator. These individuals are often the ones closest to the actual conduct of the study, during which misconduct often occurs. The PI should monitor the study closely along with the research coordinator to ensure ethical conduct. Peer reviewers have a key role in determining the quality of a manuscript and whether it is publishable. They are considered experts in the field, and their role is to examine research for inconsistencies and inaccuracies. Editors must monitor the peer review process and must be cautious about publishing manuscripts that are at all questionable (ICMJE, 2018). Editors also must have procedures for responding to allegations of research misconduct. They must decide what actions to take if their journal contains an article that has proven to be fraudulent. Usually, fraudulent publications require retraction notations and are not to be cited by authors in future publications. However, Al-Ghareeb et al. (2018) found that the retracted articles in their review had been cited an average of seven times after being retracted. The publication of fraudulent research is a growing concern in medicine and nursing (Ward-Smith, 2016). The shrinking pool of funds available for research and the greater emphasis on research publications for retention in academic settings could lead to a higher incidence of fraudulent publications. Dr. Yoshihiro Sato, a Japanese researcher in prevention of bone fractures, committed one of the biggest frauds in scientific history (Kupferschmidt, 2018). His studies came under scrutiny when one researcher found identical means of body mass indexes for patients in the treatment group and control groups of trials conducted in different populations. Researchers in the same area began to question how his team could recruit several hundreds of patients into studies in just a few months (Else, 2019). Sixty of Sato’s papers have been retracted and his remaining publications are viewed with skepticism. Each researcher is responsible for monitoring the integrity of his or her research protocols, results, and publications. In addition, nursing professionals and journal editors must foster a spirit of intellectual inquiry, mentor prospective scientists regarding the norms for good science, and stress quality, not quantity, in publications (Fierz et al., 2014). Animals as research subjects The use of animals as research participants is a controversial issue of growing interest to nurse researchers. A small but increasing number of nurse scientists are conducting physiological studies that require the use of animals. Many scientists have expressed concerns that the animal welfare movement could threaten the future of health research. For example, a laboratory in Maryland was closed on April 2, 2019, after studying Toxoplasma gondii for 37 years. T. gondii is a foodborne illness that can lead to death. Although not publicly linked, scientists believe the closure was due to animal welfare activists’ protests against the facility (Wadman, 2019). In 2015, the NIH stopped funding studies in which chimpanzees were to be used. NIH has also been advised by lawmakers to continue the reduction in funding for nonhuman primate research by incorporating budget changes in the 2020 US budget (Hou, 2019). Alternative models of investigation have been and continue to be developed, but for now animal research still plays a valuable role in preclinical studies. Studies of new medications and other treatments are based on the findings of preclinical studies done with animals. The use of animals in research is a complicated issue that requires careful scientific and ethical consideration by investigators. From the scientific perspective, Smith, Clutton, Lilley, Hansen, and Brattelid (2018) developed a guideline for researchers that includes formulating the study, initiating dialogue with the animal facility, and ensuring quality control from the beginning of the experiment until its conclusion. Without attention to detail, the findings of laboratory animal experiments may not be reproducible. Multiple sets of regulations protect animals in a research environment. Ceremuga et al. (2017) compared the effects of curcumin on anxiety and depression of rats to the effects of typically used medications for anxiety and depression. This team of nurse researchers implemented a study using rats and noted the regulations they used in protecting the animals. “Fifty-five male Sprague-Dawley rats (Harlan Sprague Dawley Laboratories), each of which weighed between 242 and 298 g, were obtained in 1 shipment…. The animals went through a 14-day adaptation period in a temperature-controlled environment…. The rats were allowed food and water ad libitum. The animals were handled only for the purposes of drug administration, cage cleaning, and obtaining daily weights. All protocols used in this study were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at the US Army Institute of Surgical Research, San Antonio, Texas.” ( Ceremuga et al., 2017, p. 195) Ceremuga et al. (2017) found that curcumin did not have a significant effect on the anxiety and depression of rats. At least five separate sets of regulations exist to protect research animals from mistreatment. Federal government, state governments, independent accreditation organizations, professional societies, and individual institutions work to ensure that research animals are used only when necessary and only under humane conditions. At the federal level, animal research is conducted according to the guidelines of USPHS Policy on Humane Care and Use of Laboratory Animals, which was adopted in 1986 and most recently updated in 2015 (DHHS, 2015b). In addition, more than 1000 institutions in 49 countries have obtained accreditation by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC International, 2019), which demonstrates the commitment of these institutions to ensure the humane treatment of animals in research. Nurse researchers interested in using animals for research must be trained in their care and appropriate use. They will also need to review the guidelines used by their university, other employers, or funders for conducting research with animals. Key points • The ethical conduct of research begins with the identification of the study topic and continues through the publication of the study to ensure that valid evidence is available for practice. • Conducting research ethically requires protection of the human rights of participants. Human rights are claims and demands that have been justified in the eyes of an individual or by the consensus of a group of individuals. The human rights that require protection in research are (1) self-determination, (2) privacy, (3) anonymity or confidentiality, (4) fair treatment, and (5) protection from discomfort and harm. • Two historical documents that have had a strong impact on the conduct of research are the Nuremberg Code and the Declaration of Helsinki. • US federal regulations direct the ethical conduct of research. These regulations include (1) general requirements for informed consent, (2) documentation of informed consent, (3) IRB review of research, (4) exempt and expedited review procedures for certain kinds of research, and (5) criteria for IRB approval of research. • HIPAA has affected research recruitment and data collection since it was implemented in 2003. • The rights of research participants can be protected by balancing benefits and risks of a study, securing informed consent, and submitting the research for institutional review. The responsibility for protection of research participants is borne primarily by the lead or primary researcher. • To balance the benefits and risks of a study, its type, level, and number of risks are examined, and its potential benefits are identified. If possible, risks must be minimized and benefits maximized to achieve the best possible benefit-risk ratio. • The sequencing of the human genome has led to advances in how health and disease can be studied. These advances, however, have raised ethical issues about de-identification of genomic records, the reuse of biological specimens, and the appropriateness of using stem cells and organoids. • Informed consent involves the transmission of essential information, the comprehension of the information, and voluntary consent of the prospective participant. • In institutional review, a committee of peers (IRB) examines each study for ethical concerns. The IRB conducts three levels of review: exempt, expedited, and full board. • Research misconduct includes fabrication, falsification, and plagiarism during the conduct, reporting, or publication of research. The ORI was developed to investigate and manage incidents of research misconduct to protect the integrity of research in all disciplines. • Another current ethical concern is the use of animals as research subjects. The USPHS Policy on Humane Care and Use of Laboratory Animals provides direction along with several other guidelines and regulations on the humane use of animals in research. References Adams K, & Lawrence E. Research methods, statistics, and applications 2nd ed 2019; Sage Thousand Oaks, CA. Advisory Committee on Human Radiation Experiments (ACHRE). Government standards for human experiments The 1960s and 1970s ACHRE Final report (chap. 3) 1995; Retrieved from https:// bioethicsarchive.georgetown.edu/ achre/ final/ chap3. html. Ahalt S, Chute C, Fecho K, Glusman G, Hadlock J, Taylor C.et al:. Clinical data Sources and types, regulatory constraints, applications Clinical and Translational”
— Burns and Grove’s The Practice of Nursing Research – E-Book: Appraisal, Synthesis, and Generation of Evidence by Jennifer R. Gray, Susan K. Grove
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