Economic Protocol for Mental Health Intervention

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I have attached instructions for this paper. I have no idea what I want to base this paper on which is something I would like the writer to do as well. Perhaps have a discussion with me, i am welcome to ideas. I have also attached what kind of paper the instructor expects.

Merit

Mindfulness-based therapy for people with schizophrenia: randomised control trial and

economic evaluation protocol.

Introduction

Schizophrenia is a neuropsychiatric disorder characterised by the presence of

psychopathological domains, such as delusions, hallucinations, formal thought disorder,

motor abnormalities and negative symptoms (1).

Although this disorder is not particularly frequent, with an estimated prevalence around 1%

(2), it is one of the most disabling conditions according to the Global Burden of Disease

studies (3, 4).

People with schizophrenia not only suffer from symptoms, but also from the consequences of

stigma, neglect and abuse (5, 6). Indeed, people with schizophrenia are less likely to be

employed (7) or have their own house (8), and they die 15–20 years earlier than the general

population (9).

In addition, schizophrenia represents a costly condition for patients, caregivers and the

society. For instance, cost-of-illness systematic reviews have calculated prevalence-based

annual costs for schizophrenia ranging from US$94 million to US$102 billion (2013 US

dollars) (10-12).

Pharmacological treatment is one of the cornerstone of schizophrenia therapeutics (13),

however, noncompliance is a challenging issue (14) and even with adequate adherence, up to

30% of patients experience partial response (15). Psychosocial interventions have been

developed in order to increment treatment compliance, but also to help people to cope with

their symptoms, reduce relapses and increment social functioning (16).

The specific case of cognitive behavioural therapy (CBT) has received special attention in the

literature, being recommended even in patients who are resistant to pharmacological

treatment (17). In addition, some economic evaluations have demonstrated that CBT is a

cost-effective intervention from a health perspective (18-20).

Mindfulness-based therapy (MBT), by contrast, has only recently started to be used to treat

people with psychosis (21). This is an operationalised intervention that includes the

development of cognitive and affect dimensions to embrace internal experiences, rather than

avoid them (22). This intervention includes guided meditation and can be added to cognitive

therapy (23).

Despite initial concerns about the use of meditation in schizophrenia, pilot studies have

demonstrated the feasibility of using MBT for psychosis (24) and clinical trials have shown

that it can alleviate the distress associated with hallucinations and paranoia (25). Two recent

meta-analyses have evaluated the clinical effectiveness of mindfulness-based therapy for

psychosis (26, 27) with favourable results in terms of symptomatology and rehospitalisation

rate.

With this evidence, some people have argued that MBT should be included in the clinical

guidelines, as well as CBT (23). However, until the moment of writing this protocol, no

economic evaluation has been done to probe the cost-effectiveness of such intervention.

Hence, a new randomised trial with an economic evaluation is needed to assess whether MBT

for psychosis represent a valuable therapeutic choice.

Policy question and perspective

This research will answer the policy question about whether it is worthwhile to include MBT

in the package of care of people with schizophrenia.

To make this decision the health service perspective is crucial. Since this protocol is intended

to be applied to the UK setting, the NHS and Personal Social Services perspectives will be

considered according to the NICE recommendations (28).

However, schizophrenia has been proven to impact on many areas of people’s lives (7) and

the evidence has shown that most of costs are indirect costs (11). Hence, a broader

perspective seems more appropriate.

In addition, this research could also be relevant to other policy groups interested in the care of

people with schizophrenia, such as non-governmental organisations (NGO), family and

service-user organisations and research agencies.

Therefore, a societal perspective will be taken, including costs related to health and social

care, but also to productivity losses and costs of informal care.

Productivity losses will be included given that people with schizophrenia have a diminished

ability to work. This is partly due to the symptomatology (cognitive and negative symptoms

(1), but also due to the fact that the first episode of psychosis usually occurs in early

adulthood with a chronic course (29).

Although informal care is not mandatory by NICE, there is substantial evidence on the

impact of schizophrenia in family and caregivers (30) and many of such burden could

eventually implies costs for the NHS, because higher proportion of depression and physical

complaints (31).

Aim

The aim of this study is to assess the clinical and economic value of adding a mindfulness-

based intervention (MBT) to CBT for people with schizophrenia from a societal perspective.

Objectives

1) To compare effectiveness of CBT plus a MBT intervention versus CBT alone on

short- and long-term clinical outcomes in people with schizophrenia from secondary

care settings.

2) To evaluate the cost-effectiveness and cost-utility of adding MBT to CBT for people

with schizophrenia from secondary care settings.

Hypothesis

The addition of MBT to CBT is associated with less symptomatology amongst people with

schizophrenia compared with CBT alone.

CBT with a MBT intervention results in a more cost-effective intervention compared with

CBT alone, for the UK context.

Research methods

Research design

A two-arm, parallel, randomised, controlled trial of MBT plus CBT in comparison with CBT

alone.

Setting

Participants will be recruited from secondary care facilities, either inpatient or community

mental health teams. Specialised services, such as early intervention in psychosis services or

assertive teams will be also included.

Eligibility criteria

Patients aged 18 to 64 years with a diagnosis of schizophrenia-spectrum psychosis according

to the DSM-5 or ICD-11 criteria. This includes schizophrenia, schizophreniform disorder,

delusional disorder and schizoaffective disorder.

Exclusion criteria:

1. Unwillingness to provide informed consent.

2. Intellectual disability defined as an IQ<80.

3. Active comorbidity with substance misuse without treatment.

4. Decompensated physical comorbidity that difficult the interventions.

5. Refusal to psychological therapies.

Intervention

The experimental group will receive MBT according to the procedures developed by Segal et

al (32) and adapted to people with psychosis by Chadwick (24). The rationale for this is its

operationalisation and evidence in previous studies (25, 33). Patients will receive mindfulness

sessions twice a week over a period of 12 weeks led by a trained therapist and will be

encouraged to maintain CD-guided meditation practices at home.

This group will maintain treatment according to NICE guidelines (34), including

pharmacotherapy, social support and CBT.

Comparator

Patients from the parallel arm will receive treatment according to NICE clinical guidelines

(34) as in the intervention group, but without the mindfulness-based module.

The CBT intervention will be defined as 16 one-to-one based sessions, following a treatment

manual to evaluate links between thoughts, feelings and behaviours (34).

Treatment fidelity

The therapists in the experimental group will complete a form after every session, which will

be assessed by a research team member for treatment fidelity. CBT sessions will be recorded

(in both arms) and will be stochastically evaluated.

Outcomes

The primary outcome will be the change in the Clinical Global Impression-Schizophrenia

(CGI-SCH) (35). The rationale for this is that psychological therapies for schizophrenia have

a focus on how people deal with distressing symptoms, instead of only reducing them (36).

The CGI-SCH scale is applicable by clinicians and it permits evaluate the severity and

general functioning. Psychometric evaluations have demonstrated high reliability and high

correlation with other scales such as GAF and PANSS (35).

The main secondary outcome will be the quality-adjusted life years (QALY). For this study,

the SF-6D instrument will be used. This is an instrument developed by Brazier from the SF-

36 (37). The SF-6D has demonstrated advantages over the EQ-5D specifically in people with

schizophrenia, such as to reflect better the severe nature of the condition, being more

sensitive to change, has a normal distribution and lack of ceiling effect (38).

Other measures

The PANSS (39) will be applied to evaluate more specifically the symptomatology of

schizophrenia and its correlation with CSI-SCH. The Social functioning scale (40) will

evaluate general aspects of recovery.

At baseline, sociodemographic characteristics of participants will be recorded joint with costs

and outcomes measurements. Next assessments with costs evaluation (see forehead) will be

at 3 months (just after the intervention), 6 months and 1 year.

Study procedures

Recruitment and preparation

Patients will be recruited from secondary care facilities from a defined catchment area of

London. Evaluators will be trained in measurement instruments. Inter-rater reliability will be

assessed with practice interviews.

Allocation

Treatment allocation will be generated by an independent computer-derived random sequence

for purposes of concealment. An administrator will inform to patients, key health-workers

and MBT therapists of the allocation by phone.

Blinding

The principal investigator and assessors will be blind to the randomisation status of patients.

This will be maintained by providing instructions to patients, their therapists, clinical teams

and caregivers of no revealing randomisation status. In addition, data will be treated with a

unique identification code to storage and management of the electronic database.

Sample size

The sample size calculations are based on the clinical effectiveness hypothesis.

To detect a mean difference in CGI-SCH of 4 points (which has described as clinically

significant (35)) with a standard deviation (SD) of 4, a two-sided significance level (α) of 5%

and power (1 – β) of 80% would require 17 patients in each arm. However, given the group

modality of the MBT intervention, a cluster effect is likely to be found (41). A new sample

calculation with same means, SD, power and level of significance, but using an intraclass-

correlation of 0.5 and an estimated cluster size of 8 would require 80 participants per

arm.

Both analyses were carried out with STATA 14.2, with commands power and clustersampsi

to sample sizes with and without clustering, respectively.

Estimating a conservative drop-out rate of 30%, is planned to be enrol 104 people in each

arm.

Economic evaluation

Methods

The design for the economic evaluation of the primary outcome will be a cost-effectiveness

analysis. Differences in costs and CGI-SCH scores in both arms will be used to calculate an

incremental cost-effective ratio (ICER) using the following formula (42):

Fig 1. ICER formula for CEA

Where CMBT is the mean costs in the MBT group; CCBT is the mean costs in the control group;

CGIMBT is the mean CGI score in the treatment arm; and CGICBT is the mean CGI score in the

control.

Uncertainty of the ICERs will be simulated by resampling bootstrapping method with 2000

iterations and simulated means for costs and outcomes will be plotted in the cost-

effectiveness plane.

The same process will be applied to the QALYs from the SF-6D, resulting in a cost-utility

analysis of the effect of MBT. This will permit to inform directly to the decision maker with a

generic measure of health gain (42).

Cost-effectiveness acceptability curves will be provided to estimate the probability that the

adding MBT is cost-effective compared with CBT alone (43). The rationale for this are: 1)

Adding a new intervention is likely to be in the northeast quadrant of the cost-effectiveness

plane; 2) There will be uncertainty in the measurement of costs and outcomes; 3) Is unlikely

to find a statistically significant difference between mean costs, given the sample size

calculated (44).

Cost analysis

Identification

In relation to the perspective of the economic evaluation previously mentioned, relevant

resources will be listed for the health system, formal social care, informal social care and

productivity losses.

Direct medical costs will include psychiatric hospitalisation, emergency visits, day-hospital

care, community mental healthcare, medication and general physical care. Hospital- and

community-based staff costs will include those from psychiatrists, GP, nurses and therapists.

Costs of the MBT intervention will be calculated following the people allocated approach

(45). The rationale for this is that groups will be closed at 8 people and every session will run

unless no-one attend. The ratio of direct and indirect time will be extrapolated from a study of

MBT for depression (46).

Costs of formal social care will include supported accommodation and costs of social worker

per hour of contact with patients. Costs of informal care will be calculated based on the

monetary valuation of the time invested by caregivers in assisting the patients (47).

Measurement

According to recommendations of a taxonomy for resource use measurement (RUM) (48),

this study will calculate resource use in the following way: 1) Source of data: patients and

patient proxies (caregiver or relative); 2) The RUM will be completed by a member of the

research team; 3) It will be administrated in a face-to-face basis; and 4) recorded in an

electronic format following a pre-stabled questionnaire.

The healthcare utilisation will be measured through the Client Socio-demographic and

Service Receipt Inventory (49), which is a recall questionnaire that allow measurement of

health and social care utilisation, specially validated for mental health and with independently

assessment of correlation with computerised records (50). Informal care will be measured by

a face-to-face questionnaire (51) and the productivity losses will be calculated by the World

Health Organization Health and Work Performance Questionnaire (HPQ), a self-report

instrument which estimate the workplace costs of health problems (52).

Valuation

The valuation of health and social care resources will base on published PSSRU unit costs of

Health and Social Care 2016 (53).

To value the informal care provided by caregivers, because the high burden of people caring

schizophrenic patients (54), the wellbeing method shall be used (55).

Finally, the friction cost approach (56) will be used to value the productivity losses, given the

evidence that overestimation by the human capital approach in schizophrenia (57).

Statistical analysis

Analysis will be carried-out with an intention-to-treat basis. This means that data will be

analysed according to initially allocated group, independently of withdrawals (58). Missing

data will treated through the multiple imputation method if they miss at random basis (59). If

such assumption is not satisfied, adjustment and modelling mechanisms will be explored

(60).

To examine successful randomisation, chi-squared and t-test statistics will be used. Baseline

characteristic with the results of statistical test will be presented in tables with 95%

confidence intervals and p-values less than 0.05 will consider significant.

Differences in the mean score of the outcomes and costs will be compared using the t-test

with adjustment by baseline characteristics and costs values.

As a result of the previously mentioned clustering effect, a multilevel analysis will be carried-

out to take into account the differences in therapists’ performance (41).

Several sensitivity analyses will be carried-out to test assumptions in measurements of costs

and outcomes, as well as for loss of follow-up and missing data.

Presentation of the results

Comparison between costs and outcomes will be presented in the form of ICERs (with

resampled estimations) in a cost-effectiveness plane. Cost-effectiveness acceptability curves

with willingness to pay (WTP) ranging between £0 and £35,000 per QALY will permit to the

policy maker take a decision based on the probability of that MBT be cost-effective.

Ethics arrangements and dissemination

Research Ethics Committee approval will be obtained before the start of the project.

All eligible participant will require a written consent to be included in the trial, which will be

conducted according to the Declaration of Helsinki (61).

The results of this research will be published in peer-review journals, anonymised data will

be accessible for sharing for non-commercial aims and it hopes improve the care of people

with schizophrenia.

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Assignment Details

Economic Evaluation in Mental Health Assignment
Write a study protocol outlining proposed methods to be used in an economic evaluation within an area related to your own work. The sections listed below should be used as a guide. Your chosen methods should be justified and appropriately referenced throughout.

The word limit is 2500. You must not go over this word limit or you will only be marked to 2500.

1. Introduction, background, literature review (10 marks)
This section should include an introduction to the disease area, existing interventions, the proposed new intervention, and existing evidence of effectiveness and cost-effectiveness. It should include a discussion of the expected economic impact of the proposed intervention, and thus justification for the proposed economic evaluation.

2. Policy question, decision-maker, perspective (10 marks)
This section should describe the policy context, policy question and decsion-maker, which should determine the method of economic evaluation and the cost and outcome perspectives.

3. Aims and objectives (5 marks)
This section should include an overarching aim, a list of clinical and economic objectives and clearly stated comparators. Aims and objectives should follow from 2 and 3, above.

4. Trial design, subjects, setting (10 marks)
This section should describe and justify the trial design, describe the study subjects and exclusion and inclusion criteria, and describe the study setting, including recruitment and allocation to groups.

5. Sample size (5 marks)
In this section, students should consider the study sample size, demonstrate understanding of the purpose and methods of such calculations, and the issues relevant to economic evaluation. If calculations are not presented, this should be justified and the implications discussed.

6. Identification, measurement and valuation of outcomes (10 marks)
In general, this section should describe and justify the primary clinical outcome measure, any secondary outcome measures and measures to be used in the economic evaluation.

7. Identification of resources (5 marks)
This section should include a description and justification of the methods to be employed to identify relevant resources. It should include an initial list of resources likely to be relevant to the study.

8. Measurement of resources (5 marks)
This section should describe and justify proposed methods for the measurement of resources identified. These methods need to be feasible and cover all resources identified as relevant.

9. Valuation of resources (10 marks)
This section should describe the valuation of all resources to be measured. A variety of methods can be proposed for different resource types and each should be described and justified.

10. Method of economic evaluation (10 marks)
This section should describe, define and justify the method(s) of economic evaluation to be used (cost-effectiveness, cost-utility, cost-benefit analysis etc.).

11. Statistical/sensitivity analysis (5 marks)
This section should describe the proposed statistical approach to (i) differences in cost, (ii) differences in outcome and (iii) the sensitivity of the results to assumptions made.

12. Presentation of results (10 marks)
This section should explain the approach to combining costs and outcomes in order to inform decision making and should include discussion of decision rules and uncertainty. 13. Placing the results in context (5) This section should cover such things as ethical issues, issues of affordability and implementation, and the generalisability of the results.

13. Placing the results in context (5 marks)
This section should cover such things as ethical issues, issues of affordability and implementation, and the generalisability of the results.

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13. Placing the results in context (5 marks)
This section should cover such things as ethical issues, issues of affordability and implementation, and the generalisability of the results.

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Distinction

A UK based randomised control trial (RCT) of a specialised

online cognitive behavioural therapy for depression in a HIV

positive population (HIVCBT): An economic evaluation

Introduction

HIV is associated with a heightened risk of mental health difficulties(1, 2) and depression

has been acknowledged as the most prominent mental health conditions within this

population(3-7). Prevalence of depression within HIV+ populations fall between 0-80%(6)

and has been linked to adverse outcomes including medication non-adherence(8) and

advanced disease development (9). Due to advances in antiretroviral therapy, HIV+

individuals now have a longer life expectancy(10), therefore alleviating depression may

further improve long-term health outcomes within HIV+ populations.

Depression within HIV+ populations has significant cost implications including, increased use

of provision and medical costs(11). In the UK, 12-18% of expenditure in chronic conditions is

allied to mental health problems, currently £8-13 billion(12). Hence, reduced depression

symptomology within chronic conditions may improve cost outcomes.

Cognitive-behavior focused interventions have been found to be effective within HIV+

populations(6). Extensive research demonstrates cognitive behavioural therapies (CBT) to

be successful(13) and cost-effective(14). Computerised CBT, using fewer resources than

traditional (e.g. practitioner time)(15), has emerged due to technological advances, and has

been found to be again both successful (15) and cost-effective within some settings(16, 17).

Computerised CBT may be an alternative or complimentary treatment for depression within

HIV+ populations and thus aid in reducing the cost burden associated with such co-

morbidities. There is a dearth of literature exploring computerised CBT within HIV+

populations, particularly with regards to economic outcomes. A recent protocol outlines a

study investigating the impact of computerised CBT in HIV populations however, no

economic outcomes are to be investigated(18). This protocol will explore the economic

outcomes of a similar type of intervention, adapted for use within a UK HIV population.

This study will be developed within the UK, to inform decision making regarding resource

allocation and treatment options for depression within HIV+ populations and will aim to

inform both the National Institute for Health and Care Excellence (NICE)(19) as well as

patients and healthcare providers. A health and social care (HSC inclusive of National Health

Service) perspective will be adopted to adhere to guidance from NICE (19), informing a cost-

utility analysis (CUA). Additionally, cost-effectiveness analysis (CEA) will be undertaken from

a patient perspective to inform treatment decision making and clinical care for patients and

healthcare providers(20).

An economic evaluation alongside a RCT will be used to assess the costs and outcomes(20)

associated with HIVCBT together with treatment as usual, comparative to treatment as

usual alone (TAU) within a HIV+ population over 12-months. The objectives will be to

compare the effectiveness and cost-effectiveness of the HIVCBT intervention and the TAU

control group, to estimate and assess differences in cost between the HIVCBT and TAU

groups from a HSC and patient perspective, to estimate and explore differences in health

related outcomes between the HIVCBT and TAU groups from a HSC (quality-adjusted life

years; QALY)(21) and patient perspective (Patient health questionnaire measure of

depression; PHQ-9)(22), and to estimate cost-effectiveness at different willingness-to-pay

(WTP) values (20).

Methods

Trial design

An economic evaluation will be conducted alongside a multi-site RCT (individual level) aimed

at exploring the effectiveness and cost-effectiveness of HIVCBT for HIV+ individuals

identified as having depression. An RCT trial design was chosen to maximise the available

information for decision makers(23).

Participants will be recruited from 16 primary care outlets within four UK geographical

counties and will be randomised equally (stratified by geographical location and sex; as

there is a higher proportion HIV+ males comparative to females within the UK)(2) to receive

HIVCBT or TAU. Nine weekly self-led internet-based CBT sessions with a HIV care

component within each session and one face-to-face psychologist-led motivational

interview session at week 4/5, will be included within the HIVCBT intervention. Data will be

collected at baseline, 6 and 12 months. A single-blind study will be conducted as

researchers will be masked from participants’ treatment allocation.

Eligible participants must give consent, be over age 18, be diagnosed as HIV+, be newly

diagnosed as having major depressive disorder (identified by PHQ-9 score ≥10)(22), have

access to a device with internet connection and be fluent in the English language. If

participants were currently suicidal or had been suicidal 6 months prior to the study, or did

not have capacity to consent they were excluded from the trial.

Sample size

A sample size of approximately 100 participants in each trial arm will be used. This figure is

based on exploratory studies of computerised CBT comparative to TAU(16, 18, 24, 25). A

normal distribution was assumed. An estimation was used as a pragmatic RCT, with a

sample size based on economic outcomes (i.e. a net monetary benefit above zero)(26), was

not deemed practical as larger sample sizes are required to detect significant economic

outcomes(27), raising issues regarding feasibility, ethics and funding(20). Furthermore, a

sample size estimate based on the primary clinical outcome (a PHQ-9 score reduced by five

points(22); the estimated minimal clinical relevant difference(28)) was too small and would

not allow for adequate extrapolation of results(29, 30).

Outcomes

As a HSC perspective will be adopted, the QALY, the NICE preferred outcome(19), will be

used as a measure of intervention effectiveness within the CUA. The QALY is a standardized

comparable outcome incorporating quantity and quality of life over time that can be used

across differing settings and disease areas(21).

Based on NICE guidance, the EQ-5D-5L, a standardised health related quality of life

measure(31), will be used to assess utility to inform calculations of the QALY(19). The EQ-

5D-5L measures five health domains (self-care, mobility, usual activities, pain and

discomfort, depression and anxiety) across 5 levels and has been found to be a valid and

sensitive measure of depression(31), and has been shown to be valid within HIV+

populations(32), thus suitable for the current trial. The EQ-5D-5L provides health state

values based on valuations from the general populations (UK)(33), which can be used to

identify deviation in utility value and thus calculate the QALY, which measures the

favorability of differing states of health on a scale of 1; best health state to 0; representing

death(34, 35). Utility value difference at baseline, 6 and 12 months will be used to calculate

the QALY(36).

Depression score (PHQ-9)(22),will be used as the primary clinical outcome for the CEA to

inform a patient perspective. The PHQ-9, scored from 0-27, is a reliable measure sensitive to

varying levels of depression(22).

Resources

Treatment and use of provision for HIV+ individuals is complex and multifaceted(37). As

such, focus groups with both service users and heath care experts, the groups exposed most

to resource use, will be undertaken to identify relevant resources from both a HSC

perspective and a patient perspective. Previous literature will supplement this process(20).

Relevant HSC resources are likely are to include: general practitioner, psychologist, nurses

(either practice based or psychiatric), HIV specialist doctor, social workers, training,

specialised clinic (HIV), accident and emergency, overheads, community care. Relevant

resources from a patient perspective are likely to include: patient out-of-pocket expenditure

(i.e. travel costs) and private treatment (mental health).

Intervention focused resources will be identified using focus groups, inclusive of software

developers, clinical experts and patient groups and will be supplemented by the literature.

Intervention relevant resources are likely to include: development costs (programming and

project management), implementation costs; psychologist, overheads, software support,

maintenance and internet usage(38).

Support and service use information for each participant will be measured using the Client

Service Receipt Inventory (CSRI)(39); a self-report questionnaire completed by participants.

The use of the CSRI is appropriate as the questionnaire is a valid measure of care

component and service usage, thus relevant to the HSC perspective being adopted. The CSRI

will be adapted to include all identified resources from both a HSC and a patient

perspective, and will measure both duration and frequency of resource use (including

intervention use)(39). Due to the complex disease trajectory of HIV, HIV+ groups often use

multiple care outlets and therefore it would not be feasible to conduct record searches for

each healthcare outlet used. The CSRI is therefore the most appropriate measure.(40) The

complexity of HIV may result in difficulty attributing service use, as such, detailed

information will be collected and expert opinion will be used to assess service attribution.

Total costs relating to each perspective (HSC/patient) will be obtained from multiplying

costs (per unit) by the duration and incidence of each service and support use. Publically

available records; Department of Health’s NHS reference costs 2015- 2016(41) and Unit Cost

of Health and Social Care 2016 (PSSRU)(42), will be used to establish HSC services and

alternative service costs inclusive of professionals’ salaries, respectively. Median costs will

be used to obtain average valuations of appropriate overheads and salaries. Patient

expenditure and private services (from a patient perspective) will be based on market

value(20).

Development and execution costs associated with the internet-based intervention will be

obtained from the software developer and costs of development will be apportioned to the

projected software lifespan(38). Internet usage costs will be based on market value. These

costs will be supplemented by incidence and duration data to be obtained from the CSRI to

establish contact time with a psychologist within the intervention. The PSSRU will be used to

obtain psychologists training requirements and per hour contact costs(42) and the

Department of Health’s NHS reference costs 2015- 2016 will be used to obtain costs of

overheads(41).

Economic evaluation

Both CEA and CUA are to be used to assess cost-effectiveness as different outcome

measures of effectiveness based on differing perspectives are to be used. Cost-effectiveness

will be explored by means of comparing additional health improvements (QALY gain in the

CUA and five-point improvement in PHQ-9 score(22, 28) in the CEA) to additional costs.(20)

CEA involves assessing and comparing the costs and outcomes of differing treatment

trajectories (20). A CEA will be undertaken, to assess costs and outcomes in the HIVCBT

group comparative to the TAU group. CEA uses a disease specific (natural) outcome(20)

here, PHQ-9 score(22), and is deemed appropriate in this instance as the CEA is to be

undertaken to inform patient choice regarding treatment of depression within a HIV+

population and thus a measure of clinical effectiveness (i.e. the primary clinical outcome) is

required.

CEA does not however explore opportunity costs in relation to alternative treatments and

therefore to inform decision making bodies’ (i.e. NICE) resource allocation a generic

measure is required(19, 20). Hence, a CUA, based on NICE guidance, will be undertaken

from a HSC perspective(19). CUA aims to determine cost in relation to utilities in trajectories

of treatment action and uses a general health improvement measure (QALY) that can be

used comparatively across different disease areas and settings(21). Here, CUA will be used

to assess the costs associated with gaining a single QALY in the HIVCBT group comparative

to TAU group. This will allow for opportunity costs based on the notion of implementing

treatments to be assessed at differing WTP values(20).

Statistical/sensitivity analysis

All analysis will be completed on an intention to treat basis(43). Differences in cost between

HIVCBT and TAU alone and outcome (QALY and PHQ-9 score) between the trial arms, will be

estimated using multiple regression analysis(44). Potential confounders will be adjusted for

including, baseline characteristics, recruitment site (i.e. to account for clustering effects e.g.

therapist) baseline costs and repeated measures.

Non-parametric bootstrapping (5000 times) will be used to address uncertainty by

establishing 95% confidence intervals for the net monetary benefit approach to establish

cost effectiveness acceptability curves (below)(26, 45, 46). To further address uncertainty,

multiple one-way sensitivity analyses will be undertaken to increasing the robustness of

results. These will explore variations in parameters including differing salaries and training

costs for the psychologist in the intervention, missing data (costs and outcomes) will also be

imputed (using a multiple imputation method) (47) and compared to complete data to

explore the impact of alternative assumptions on cost-effectiveness.

Results

Incremental cost effectiveness ratios (ICER) for the CEA are to be calculated as difference in

mean cost (patient perspective) between the HIVCBT and TAU trial arms divided by the

difference in mean depression score (PHQ-9)(22) between the trial arms to establish cost

per five-point reduction in depression score. The ICER for the CUA are to be calculated as

the difference in mean cost (HSC perspective) between the HIVCBT and TAU trial arms

divided by the difference in mean QALY(21) between the trial arms to establish cost per

additional QALY(20).

CEA

𝐼𝐶𝐸𝑅 =
𝐻𝐼𝑉𝐶𝐵𝑇 𝑐𝑜𝑠𝑡𝑠 (𝑝𝑎𝑡𝑖𝑒𝑛𝑡 𝑝𝑒𝑟𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒) − 𝑇𝐴𝑈 𝑐𝑜𝑠𝑡𝑠 (𝑝𝑎𝑡𝑖𝑒𝑛𝑡 𝑝𝑒𝑟𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒)

𝐻𝐼𝑉𝐶𝐵𝑇 𝑚𝑒𝑎𝑛 𝑃𝐻𝑄9 𝑠𝑐𝑜𝑟𝑒 − 𝑇𝐴𝑈 𝑚𝑒𝑎𝑛 𝑃𝐻𝑄9 𝑠𝑐𝑜𝑟𝑒

CUA

𝐼𝐶𝐸𝑅 =
𝐻𝐼𝑉𝐶𝐵𝑇 𝑐𝑜𝑠𝑡𝑠 (𝐻𝑆𝐶 𝑝𝑒𝑟𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒) − 𝑇𝐴𝑈 𝑐𝑜𝑠𝑡𝑠 (𝐻𝑆𝐶 𝑝𝑒𝑟𝑠𝑝𝑒𝑐𝑡𝑖𝑣𝑒)

𝐻𝐼𝑉𝐶𝐵𝑇 𝑚𝑒𝑎𝑛 𝑄𝐴𝐿𝑌 − 𝑇𝐴𝑈 𝑚𝑒𝑎𝑛 𝑄𝐴𝐿𝑌

Cost-effectiveness planes will be formed to establish any dominance as well as explore

uncertainty and variation in estimates of cost-effectiveness using 95% confidence intervals

established from non-parametric bootstrapping(46), (also used to inform the net monetary

benefit approach [NMB]).

The NMB will be used in both the CUA and CEA to combine both costs and outcomes within

a single scale and establish cost-effectiveness. The NMB multiplies willingness-to-pay () by

the difference in outcomes (i.e. mean PHQ-9 score(22) in the CEA and mean QALY in the

CUA) between each trial arm (HIVCBT vs. TAU) and from this total subtracts the difference in

costs between each trial arm (HIVCBT vs. TAU). If the resulting value is greater than zero,

then the intervention will be considered cost-effective(26).

Based on this data, cost-effectiveness acceptability curves (CEAC) can be produced to

provide an overview of value(26) and calculate the likelihood that HIVCBT is cost-effective at

differing WTP values (48). Cost-effective points plotted in the CEAC are derived from the

cost-effectiveness plane (excluding the NE quadrant)(49). WTP values between £0-50,000

will be investigated so to incorporate the ceiling ratio of £20000-30000 recommended by

NICE (19) for a single QALY gain.

Results in context

An economic evaluation of specialised computerised CBT within a HIV+ population has not

been conducted previously. This trial aims to inform patient groups, providers of healthcare

and policy makers. Some considerations should be noted. Based online, HIVCBT has the

potential for extensive implementation and may be a useful alternative or collaborative care

approach for HIV+ individuals using minimal resources(50). However, adaptations may be

required to implement the intervention across cultures.

Ethically it is not deemed as appropriate to deny HIVCBT to the TAU group. Hence, this

group will be offered HIVCBT alongside their TAU at both 6 and 12-month follow-up. Data

will be excluded from the analysis accordingly(51).

While cost-effectiveness will be explored, affordability will not directly be assessed. Budgets

constrain policy makers, and while cost-effective, interventions may be unaffordable.

Further study could incorporate ‘affordability curves’ to provide data on both cost-

effectiveness and affordability to better inform policy makers and other potential

stakeholders(52).

A pragmatic RCT was not undertaken and as such this study will only present estimates of

cost-effectiveness(23, 27). A larger sample size is required to establish confidence in cost-

effectiveness estimates(27). Further research, (e.g. conducting a decision analytic model)

would also allow for the generalisability of the CUA/CEA across differing settings(53).

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Family-based psychosocial intervention for returning child soldiers in Central African

Republic: a randomised control trial with economic evaluation

Background

The 2007 Paris Principles(1) defines “a child associated with an armed force or armed group”

(CAFFAG) as “any person below 18 years of age who is or who has been recruited or used by

an armed force or armed group in any capacity, including but not limited to children, boys,

and girls used as fighters, cooks, porters, messengers, spies, or for sexual purposes. It does

not only refer to a child who is taking or has taken a direct part in hostilities.” These

CAAFAG, also known as child soldiers(2) , witness and experience a range of traumatising

events in combat, causing child soldiers who have been released to have very low emotional

well-being: child soldiers suffer from a variety of mental illnesses including posttraumatic

stress disorder, depression, and anxiety(3). This state of health makes returning home a very

disorienting experience for these soldiers and it is extremely important for their families and

communities to accept and support them through this time of change. However, the

children’s homes are usually within conflict zones, and their families and community

members have also been traumatised and disoriented. Lack of education and preparedness,

fear, spirituality, and recognised behavioural differences in the child (e.g. hostility, anger,

unable to handle situations without violence(4)) create stigmatising attitudes and behaviours

amongst family members and the community(5) hindering successful reintegration of these

children. Research has shown that child soldiers who are supported by their family upon

their return are more likely to be socially reintegrated and have higher emotional well-being

than those stigmatised and rejected, and, lack of social support has been shown to increase

risk for PTSD, anxiety, and depression(6). Also, it’s been reported(4) that PTSD in returned

child soldiers are vulnerable to viewing the world as “good versus bad,” encouraging violent

behaviour and reactions outside of fighting and in their communities, potentially leading to

increased contact with criminal justice system. Humanitarian aids have guidelines(1) to

support their staff in the reintegration and reunification process, but are consistently met

with the challenges listed above. A family-based psychosocial intervention could support

psychosocial adjustment(7), decrease the risk of mental illness and encourage reintegration

of child soldiers cross-culturally, but no policy is currently in place to allow automatic use of

such a tool.

Policy context, target audience, perspective

A recent peace deal in the Central African Republic (CAR) has enabled the release of

hundreds of children since May of 2015(8), and along with retracing these children to their

homes, UNICEF, with support from public sector partners (i.e. the U.N.), has been working

feverishly to promote reintegration. To help facilitate successful reintegration while using

the research base above, this study would like to explore the usefulness and cost of a

family-based psychosocial intervention for recently reunited child soldiers and families.

From the perspective of services provided by the public sector of humanitarian aids and the

criminal justice system, and with consideration of funding from the charity UNICEF, is a

caregiver-child family-based psychosocial intervention program for returning child soldiers

preferable to the current, non-existent family-based psychosocial intervention program?

Aims and objectives

This economic evaluation will examine the effects and cost-effectiveness of a caregiver-child

family-based psychosocial intervention program to strengthen families and support positive

reintegration of returning child soldiers. A randomised control trial design will be used to

compare the effectiveness and cost-effectiveness of this intervention with that of routine

practice, which currently stands as non-existent. The evaluation will compare the monetary

costs and effects of the 4-week intervention with the effects of the control (no intervention)

on the child soldier’s emotional well-being, rate of social integration, and amount of

interaction with the criminal justice system.

Trial design

A two-armed, clustered, pragmatic randomised control trial (RCT) will be performed. After

receiving approval from UNICEF, this study will recruit through the matches made in the

tracing process. Consent will be obtained from both the child and caregiver. Participants will

be groups of similar demographics (village, gender, and age group) and we will use a

computer generated sequence to randomly assign groups to the intervention or control(9).

To reduce selection bias, the person recruiting participants will be concealed from

treatment allocation and the person allocating the group assignment will have no previous

interaction with the participants.

Setting

The setting will take place in communities throughout CAR. The initial release of over 300

child soldiers happened in the town of Bambari in 2015(8). We will begin recruitment with

the matched families of those children.

Participants

A participant involves one child soldier and his or her caregiver. This study will include

children that fit within the definition of a child soldier given by the 2007 Paris Principles,

referenced above. Children will have served at least one month in armed forces(6) abducted

by the armed forces. Accounting for any possible intended disagreement during

intervention, we will exclude children who had volunteered to be in armed forces will be

excluded. The caregiver is defined as having full responsibility/guardianship of the child and

will only be included as such. A final exclusion factor for both caregiver and child will be the

result of any psychosis symptoms present or show severe substance abuse based on results

of an initial psychological screening.

Intervention

This intervention will be run similarly to that of a pilot study(10) recently run on children and

their caregivers living in conflict zones. Measures will be collected pre-intervention, post-

intervention (4 weeks), and at a 3-month follow-up. This is a group-based psychosocial

intervention. It consists of 2-hour blocks, three times a week for four weeks. It will consist of

seven chapters of training including: 1) Psychoeducation, 2) Relaxation Techniques(11), 3)

creative problem-solving techniques to tackle big family issues that may arise, 4)

interpersonal communication, 5) community-based conflict resolution methods, 6) effective

parenting and child contribution, and 7) a summary of learned practices. A trained

teacher/group leader will run each group.

According to established good practice(12) measures and materials not currently in CAR’s

official languages, French or Sangho, will go through a process of translation and adaptation

before commencing the study, ensuring coherency with language and local cultural

definitions. Accounting for the illiteracy rates in CAR(13), it’s possible some participants may

not be able to read. Therefore, research assistants will be prepared to read questions from

the measures in the official languages.

Sample size

Data on mental illness interventions and reintegration processes for child soldiers in CAR is

scarce, and general family-based interventions are yet to be verified in similar populations

around the world(7). However, the pilot study, which we are basing our intervention from,

worked with a conflict affected population and although not child soldiers, these children

witnessed traumatizing events such as torture and massacre. If we use this as a comparison,

we can adapt the means of both groups from the depression/anxiety outcome from this

study in a power sample calculation(14). The calculation predicted a sample size of 116 to be

significant to the true population for this study.

Identification, measurement and valuation of outcomes

The primary clinical outcome for this study will be lower internalising symptomology in the

intervention arm. Secondary outcomes will include less conduct problems, higher pro-social

behaviour, more social integration, and less interaction with the criminal justice system for

those in the intervention arm. The African Youth Psychosocial Assessment Instrument

(AYPA)(15) is an African based, validated questionnaire(16), and will be used to measure

internalising symptoms, conduct problems, and pro-social behaviour. Due to cultural

differences, past research has relied on creating a local measure for community

reintegration(6),therefore our study will create a local 11-question measure for integration.

Interaction with the criminal justice system will be measured through self-report and

interview from both the child and guardian, and short interviews will be conducted with

local community members. The World Health Organization Quality Of Life-Spirituality,

Religiousness and Personal Beliefs Field-Test Instrument (WHOQOL-SRPB)(17) is based off of

(and used in tandem with) the original WHOQOL-100(18) but includes a domain to analyse

the religious and spiritual influences on cultures’ perspectives. This will be used to collect a

generic quality of life measure to be used in for the statistical analysis of this economic

evaluation.

Identification, measurement, and valuation of resources

This table represents all identified resources with methods for measuring and valuing those

resources. Literature supporting the chosen methods and available resources are

referenced within.

Type of Resource

Identified

Method for Measuring Resource Valuation of Resource

Staff:

Teachers/Group leaders

for 8 session

intervention

– Documented hours of direct

contact with the group

– Records and diaries for any

indirect time spent on

materials

– Reference to current

UNICEF salaries for staff

members. Wages/salary

per teacher will be

divided by hours of

contact worked per

week to give a final

value of cost per hour.

– Per literature(19), client-

related time will be

calculated using the

ratio of direct and

indirect

Training of staff:

Trainers, facility,

materials

– Document hours of

contact the trainer spent

teaching staff.

– Hours spent at facility for

training

– Unit prices for materials

– Reference to

organization

supplying the

intervention

materials and trainer

for unit prices(20).

– Divide the annual

overhead cost of the

facility by hours

spent for unit price

per hour

Intervention materials:

“Relaxation Technique”

scripts, cinema clips,

extra supplies (pencils,

paper, etc.), tablet for

cinema

clips

– Count for number of

scripts needed for each

participant/group (some

may be shared), purchase

of one set of cinema clips,

final participant

involvement for number of

pencils/paper, and one

tablet

– Trauma-Focused CBT

website for price of

scripts(11)

– Provider’s listed

price for cinema

clips

– Local store unit

prices for extra

supplies

– Unit price for tablet

at local supplier

Facility:

Space for therapy

– Document number of

hours spent at facility

during intervention

– Account for any extra

furniture that may need to

be purchased

– Annual overhead

and capital price for

facility divided by

amount of hours

spent in the space

for unit price per

hour(19)

– Local supplier for

unit costs for extra

furniture

Criminal Justice System:

Contact

– Self-report from child

– Interview/report from

guardian

– Interview/report from

community members

– Price/reports of

costs(19) from

criminal justice

system (hourly wage

of officer, any time

spent in cell)

– Consequence

valuation(19): Cost of

property loss and

lost production time

if crime was a

robbery from local

store

Method of economic evaluation

This study must accommodate for a more generic form of comparison between treatments

(intervention arm vs. control), therefore a cost-utility analysis will be performed. Quality of

life years (QALY) measured through the EQ-5D(21) is the most preferable incremental unit of

health gain used in order to quantitatively compare benefits produced by the interventions

with monetary costs of the interventions. Unfortunately, the validated EQ-5D is not

applicable to this complex population, and therefore a strict conversion to the well-known

QALY is impossible. However, the WHOQOL-SPRB collects and measures the respondents

perceived quality of life, and higher scores represent a higher quality of life for each of the

five main domains: physical, psychological, level of independence, social relationships, and

environment. So, after calculating mean scores for both arms, we will use the algorithm

provided in the measure manual, then convert scores to a 0-100 rating, divide each score by

100, and produce scores (associated with time of intervention and standardised to a year)

that fit onto a QALY-like cardinal scale of 0 (bad health) to 1 (best health)(22) This will allow

for an incremental unit of intervention effects (or benefits) to compare with monetary costs

in order to statistically quantify a monetary amount for combined cost-effectiveness.

Statistical/sensitivity analysis

The study will use an incremental cost effectiveness ratio (ICER)(23) to define a monetary

amount for each QALY-like unit of benefit gained as represented in the following equation:

Cost of the intervention (Ca) [MINUS] cost of control (Cb) (this case, $0)

[DIVIDED BY]

Difference in the psychological domain scores for the intervention (Ea) [MINUS] Difference in

the psychological domain scores for the control (Eb)

An estimation process of non-parametric bootstrapping will be used in order to report an

accurate confidence interval (CI) of 95%(24) to represent any uncertainty in the cost-

effectiveness results computed by the ICER. We chose non-parametric bootstrapping as it is

widely applied in cost-effectiveness analyses, to allow for computational resampling of the

original data to develop an “empirical estimate of the sampling distribution of the ICER.”(24)

Presentation of results

Although we offer a unit of cost per benefit gained, there is no current threshold to denote

a willingness-to-pay for a QALY-like unit offered by the government in CAR, creating

uncertainty of how this cost-effectiveness result will place on a larger scale. UNICEF has a

working budget (fluctuating with donations) for humanitarian aid in CAR(25), but this is for all

causes, and with the influx of released child soldiers to support, it is difficult to define a

worthy threshold. We hope this cost-utility analysis will be useful for decision-makers as the

situation progresses. Variability of individual Reponses to treatment must be accounted for

when preparing the decision(24). Also, the parameters offered above (with a standardised life

year) is based upon the assumption that the treatment will have lasting effects outside of

the time observed. It is unknown when the conflict will desist, and this brings further

uncertainty to how well the benefits of the treatment will intervene with on-going stress.

Time-horizons should also be considered. It is uncertain what environment and priority

changes this conflict zone might bring, and the possibility of a sudden change in available

funds and staff due to reallocation for an emergency (i.e. mass bombing requiring mass

population first aid) could affect the intervention process.

Placing the results in context

As mentioned above, UNICEF may not be able to afford this intervention due to limited

funds currently allocated for expenses in CAR, lack of strict funds for child soldier

reintegration, fluctuating amounts dependent on donations, and uncertainty of future

disasters that may absorb funds and staff being used for child soldier reintegration. These

results are also not generalizable to the international population of child soldiers because of

the varying response to intervention being related to cultural standards (i.e. Nepali soldiers’

reintegration success also depends on their caste(6)).

References

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