Design
We employ a stepped wedge cluster randomized controlled trial, with a nested health economic evaluation to assess the return on investment of the intervention for the funder and policymakers from state of Gujarat.
The stepped wedge design was chosen for evaluating the scale-up of Atmiyata intervention as it allows for random allocation of the time at which clusters receive an intervention (15), and all clusters receive the intervention before the trial ends which is ethically appropriate. In the present SW-CRCT delivery of the Atmiyata intervention is delivered in a staggered manner to account for practical and logistic constraints. Logistically, it is not feasible to deliver the intervention in all clusters same time and stepwise implementation gives enough preparation time for the implementation team. Additionally, the staggered implementation of the intervention over time periods provide greater depth of analysis than a simple pre-post cluster randomized controlled trial design.
There are 56 primary health centers (PHCs) in Mehsana, and each PHC is considered as unit of clustering in this study. All villages served by a PHC are included for roll out of the intervention in staggered manner. We created 4 groups (A, B, C and D) of 14 PHCs each. The clusters are created according to geographical location to help reduce the probability of contamination between clusters. Thus, PHCs in Cluster A are farther from B and PHCs in Cluster C are farther than D. The duration of each period is 5 months to accommodate for baseline and 3 months follow-up data collection. [Figure 1 and 2]
This study uses a repeated cross-sectional design as outcome data is be derived from different participants at each period. All four groups start at baseline in the control phase and are exposed to the intervention at regular time interval of five months. [Figure 1 and 2]
Setting
The study takes place in Mehsana district located in Western India in the state of Gujarat. Mehsana is primarily a rural district, with a population of 1.52 million people, of which approximately one million are above 18 years. The district is divided into 10 blocks/ sub districts with a total of 645 villages and 316,536 rural households (16). Almost half (45.4%) of Mehsana’s rural population has a low standard of living as per the Standard of Living Index. Most residents (53%) are employed in the agricultural sector. The rural population of Mehsana district is economically disadvantaged since agriculture is not always a viable occupation given uncertain climatic events (16). In terms of health services, Mehsana has 56 PHCs, 11 Community Health Centers and 1 District Hospital staffed by 2 psychiatrists, along with District Mental Health Program (DMHP). Mental health care is primarily delivered by psychiatrists at the District Hospital, the psychiatrists also visit Community Health Centers as part of DMHP, primarily focused on SMD. The hospital has in-patient and out-patient services for persons with mental illness, and limited psychosocial support services.
Participants
The study sample consists of adult community members with common mental disorders (i.e. anxiety and depression) residing in Mehsana.
Inclusion Criteria:
- Persons aged 18 years or more and less than 65 years of age
- A score of 3 or above on the General Health Questionnaire (GHQ-12), indicating case with common mental disorders
Exclusion criteria:
- Persons who cannot give or refuse informed consent to participate in the study
- Persons with a terminal medical condition
- Persons who have suicidal ideation or plans for suicide at baseline interview
Primary outcome
The primary outcome measure is symptomatic improvement as measured by General Health Questionnaire- 12 (GHQ-12) (17) from baseline to 3-month follow-up and at 8-month follow-up to look at any new or sustained effects of the intervention on symptoms. The GHQ is a widely used screening tool with reliable sensitivity for assessing CMD (18). GHQ-12 is a dichotomous 12-item questionnaire. Each item is rated on a 4-point scale, with possible responses being "less than usual," "no more than usual," "rather more than usual," or "much more than usual." We used a bimodal scoring method, whereby "less than usual" and "no more than usual" is scored as 0 point, and "rather more than usual" and "much more than usual” is scored as 1 (17).GHQ-12 scores will be analyzed as both continuous (ranging from 0 to 12) and categorical outcomes (case defined as 3 and above score on GHQ scale; non-case as less than 3 score on GHQ scale).
Secondary outcomes
Secondary outcome measures are assessed at baseline, 3 months, and 8 months after the start of the intervention.
Quality of life (QOL): Improvement in quality of life of persons with CMDs will be assessed using the validated Gujarati version of EURO Quality of life 5D (EQ-5D) (19).The EQ-5D’s descriptive system is a preference-based Health Related Quality of Life measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression measured at 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Lower score indicates better quality of life (19).
Psychiatric symptoms: Improvement in psychiatric symptoms will be assessed using a validated Gujarati version of Self report questionnaire (SRQ). SRQ is a scale developed by the World Health Organization to screen for psychiatric disturbances for developing countries consisting of 20 questions which are scored 1= yes and 0=no indicating presence and absence of the symptom in past one month. SRQ is a continuous scale; responses are calculated as total score ranging from 0 to 20 with lower scores indicates better recovery of symptoms (20).
Disability: Reduction of disability and reduction in number of days unable to work and improvement in productivity will be assessed using validated Gujarati version of WHO-DAS-12. WHODAS-12 is useful for brief assessment of overall functioning it assesses difficulties due to health conditions. The scale uses 12 items, 5-point rating scale from none, mild moderate to severe and extreme. Responses are calculated as total score ranging from to 12 to 60 (21)
Depression and anxiety symptoms: Improvements in depression symptoms will be assessed using a validated Gujarati version of Patient Health Questionnaire (PHQ-9). PHQ-9 total scores range from 0 to 27 (22). Improvements in anxiety scores will be assessed by using a validated Gujarati version of Generalized Anxiety Disorder (GAD-7). GAD-7 total scores range from 0 -21 (23).
Social Participation: Increase in social participation will be assessed using the Social Participation Scale (SPS). The SPS is an 18-item interview-based instrument which measures perceived problems in major domains of life. The scale allows quantification of participation restrictions experienced by people affected by disability or other stigmatized conditions. The 18 items are rated on a 5-point scale ranging from 0 (no problem) to 5 (large problem). Responses are calculated as total score ranging from 0 to 90 (24).
Service User Satisfaction: User-satisfaction with the intervention will be assessed using a validated Gujarati version of the Client Satisfaction Questionnaire (CSQ) (25) at baseline and 8-month follow-up. The CSQ is an 8-item scale assessing client satisfaction with care/treatment received. The scoring uses a 4-point rating scale and is scored by summing the individual scores to produce a range of 8 to 32, with higher scores indicating greater satisfaction with care (25).
Economic Evaluation
The most common measure of efficiency in the health sector is cost-effectiveness analysis (CEA) which measures only health related benefits and expresses these in natural unit such as lives saved, or symptoms reduced. However, return of investment (ROI) analysis expresses all the benefits in monetary terms. Expressing both the costs and the full range of benefits of an intervention in the same units (money) has the distinct advantage of making investment decisions very straightforward (25). If the money value of benefits of an intervention is larger than the cost of the intervention, it is a sound investment. Return of investment analysis will be conducted for the Atmiyata intervention.
Costs will be calculated using both government and societal perspective (26). Costs will be presented in two categories: (1) total cost of the intervention; (2) treatment cost of CMDs. Treatment costs will be presented under three headings: direct medical cost, direct non-medical cost and indirect cost and these will be presented in different time zones: at baseline, at 3 months and at 8 months. Benefits will be presented in terms of improved health, functioning, participation, productivity, increased saving and investment, reduced informal care giving and health and welfare services.
Intervention condition
The Atmiyata intervention has been described extensively elsewhere (13). Briefly, Atmiyata is a complex intervention involving two-tiers of community volunteers for identification and support to people in distress and with symptoms of common mental disorders. The first tier consists of community volunteers called Atmiyata Mitras who are from different caste and religion-based sections of the village, trained to identify persons with mental distress. The second tier is Atmiyata Champions (CH), who are important community members (e.g. former teachers, community leaders) that possess leadership and communication skills, and are well-known and approachable in their village. Champions are trained to identify and counsel persons with significant mental distress, including the ones referred by Mitras. Given the social barriers based on caste, gender, religion, the identification and support by Champions and Mitras ensure equitable reach and improves coverage of the intervention across the entire village.
In the Atmiyata pilot intervention, Champions and Mitras were trained by the project team. In the Atmiyata Gujarat program, where the target population is substantially larger, Champions are identified and trained by Community Facilitators (CF) who typically have a master’s degree in social work or related fields, are locally based and aware of community dynamics. Facilitators first map their allotted villages, then identify and recruit the Champions, followed by providing training and ongoing support to Champions. The CFs are recruited, trained and mentored by Project Managers (PM). Each Project Manager supports 7-8 Community Facilitators. Each CF supports 40-50 Champions (1 per 1000 population), and each Champion has 4-5 Mitras. Principal Investigator (PI) monitor and support the project managers. [Figure 3]
Mitras receive 4 hours of training from the Champions at the village. Champions receive 40 hours of training over 3 weeks, at a central location in the block or village area. Project Managers and Community Facilitators receive 55 hours of training over 5 weeks, with additional 8-hour sessions on how to be a master-trainer. The methodology of the training is interactive, reflective and participatory.
The Champions are trained on: (i) how to identify persons with CMD and provide evidence-based 4-6 counselling sessions (3); (ii) how to ‘narrow-cast’ four films scripted and filmed for Atmiyata project and dubbed in local language, to the community. These films are approximately 10 minutes long and based on social needs or risky behaviours such as unemployment, familial conflict, domestic violence, and alcoholism; (28) (iii) make referrals to the public health system for common and severe mental disorders, and (iv) enable access to social benefits for persons in distress.
The 4-6 counselling sessions by CH involves three evidence-based techniques: active listening, behavior activation and problem-solving techniques which have been used in other similar task sharing programs (29,30). The training includes basic skills of empathy, non-judgemental behaviour, rapport building, verbal and non-verbal communication, creating a safe environment to build skills for ‘active listening’. Behaviour activation enables the person with distress to be aware of the activities he/she has been avoiding and the reasons for doing so, and explore thoughts and feelings associated with the same, and to begin engaging in day to day activities. Problem solving techniques are used for a positive orientation towards the problem which enables viewing problems as solvable, and as opportunities to learn and change.
Adverse events
Attempted suicide / Self harm and Suicide are considered as an adverse event. The protocol for reporting and record of adverse event will be developed and research team will be trained on the same. The report of any adverse event will be submitted to ethics committee within 15 days of occurrence.
Comparison condition
Participants from PHCs in the control arm receive Enhanced Usual Care (EUC). The EUC protocol will be delivered to each participant in the comparison group who scored 3 and above on GHQ-12. EUC provides information on the impact of of distress on their physical and mental health and relevant information of accessible and available public mental health care services, including services by District Mental Health Program (DMHP), and helplines for mental health support and for domestic violence in and around Mehsana.
The EUC makes provisions for providing active support to participants who are in crisis. A crisis is defined as the participant revealing a recent self-harm attempt or expressing thoughts of self- harm during data collection. The participants will be encouraged to seek help immediately and the data collectors will inform the family member or a friend after seeking the consent from the participant.
Sample size and power calculations
A trained lay health worker led intervention study conducted in India had reported a risk difference of 12% at follow up between intervention and control arm for recovery of CMD patients (31,32). The sample size for this SW-CRCT has been calculated to detect a 13% difference in CMD cases at 3-month follow-up using GHQ-12 as a categorical measure between intervention (58% improved) and control groups (45% improved).The targeted sample size for the SW-CRCT has been planned taking into account an intra-cluster correlation coefficient (ICC=0.1), expected effect size (13%), number of steps (t=4), number of clusters randomized in each step (k=14), average cluster size (m=4) and the desired power (80%) of the study and alpha of 0.05. This translates to 1120 participants, i.e., approximately 56 individuals per cluster per period. [Figure 4] The sample size was calculated using “stepped wedge” function of STATA 14 (33).
Randomization and treatment allocation
The unit of randomization is the PHC. The administrative organization of primary health care in Gujarat ensures that inter-PHC movement of people for health care was minimal and avoids contamination of the intervention. Typically, a PHC in Gujarat covers a population of 25000-30000 across 12-13 villages. The 56 PHCs are assigned to four parallel groups (Cluster A, B, C D) 14 PHCs in each. Although the PHCs are the unit of randomization, participants will not be recruited from the PHC attenders but from the villages served by the PHC to ensure recruitment of a community sample of persons with CMD.
We employed several blinding and procedures to minimize bias. First, to minimize contamination that might arise due to the intervention and control village members meeting and potentially discussing the intervention, clusters will be geographically dispersed. Second, the data collection team is separate from intervention team and blind to the treatment status. Third, the training and re-training of the data collection team.
Recruitment
For control arm, a screening list will be generated from electoral roll of the district using systematic random sampling method with pre-decided random start and random interval, with every nth number from the pool being selected. The prevalence of CMD is 4%-8% as per National Mental Health Survey, India (34). To prepare a screening list of participants, we considered a minimum prevalence of 4%. There was a possibility of 25% of participants may not be present during screening. Taking in account these factors, a screening list of 1800 participants was created to achieve the target sample size of 56 cases in each period and each group of PHC clusters.
In the intervention arm, when a Champion identifies a person, who in their opinion has CMD and who they intend to provide 4-6 counselling sessions, to they will inform their CF who will then inform the project manager who will create a caseload list of cases for each Champion. The sample will be drawn from the caseload list using computer generated random method the intervention arm. Participants will be screened in each Cluster using GHQ-12 (score of 3 and above). This process will continue till we achieve target sample size of 56 cases. The data is collected by the data collection team (trained researchers) which collected data from control arm. By this sampling method, we will able to identify the specificity of identification of people with CMD by Champions.
Data collection
Written Informed consent will be sought from all participants prior to data collection. For the participant who is not literate, a thumb impression and signature of the witness will be taken on the consent form. Data will be collected by trained researchers in two stages using paper pencil method. In the first stage, demographic data along with GHQ-12 is collected through a paper-based questionnaire, which takes approximately 15 minutes to complete. The researchers would score the GHQ based on the scoring sheet, if the respondent had a score of 3 or more, secondary outcome data is collected at same time. The questionnaire for secondary outcome data takes 40-45 minutes to complete. Data collectors are trained to allocate a unique identification code to all the participants to conceal personal identifiable information.
Data management
The study will have ongoing quality assurance procedures including mandatory training and refresher training sessions for staff involved in data collection. The project manager will conduct periodic on-site monitoring visits to check quality of data collection. The project manager will ensure completeness and legibility of the data prior to data entry and will be responsible for storing all the data. Designated data entry person will be trained for specific entry guidelines to avoid erroneous data entry. All the entered data will be shared with statistician for analysis by the project manager. Statistician will collate the data, maintained database and reviewed data quality in terms of numbers, consistency and completeness.
Several strategies will be adopted to achieveadequate participant enrolment which include three telephonic follow-up calls for persons who are not available during in-person visits, two reminders for follow-up visits, rescheduling visits as per convenience of community members. Recruitment, follow-up rates and missing data will be discussed at monthly team review meetings between project manager and data collectors.
Data storage, security and confidentiality
Study data will be anonymized using unique study identification (ID) codes for participants, which will be matched to the physical copy of consent form and then entered in the study database. Only the consent form will include personal-identifiable details. A code sheet linking participant’s personal identifiable information will be linked to the unique study ID code. Data will be stored on a password-protected external hard drive periodically as a back-up. All consent forms and data forms will be kept confidential and stored in a locked cabinet at the site office in Mehsana, accessible only to the principal investigator (PI) and project manager. After the study is over, the data will be stored in the sealed cabinet for period as per Indian regulations. The data in excel sheet formats will be stored in an open access repository.
Data monitoring
We will form an advisory/mentor committee consisting of researchers, academician, ethicist to monitor the implementation and research. We will meet with the committee once in 6 months to present the data and the committee makes a visit to the site too to monitor the progress. The adverse event will be reported to the committee. The committee will help the team from development of the protocol to the implementation and conduct of the trial.
Statistical analysis
Baseline characteristics will be summarized using counts (percentages) for categorical variables and means (SD) for continuous variables. Analysis will be based on intention to treat principle. The participants will be analyzed in the group that the cluster was assigned to at each time point.
The analysis plan is based on the Hussey and Hughes model for analysis of cross-sectional SW-CRCT designs (15). Generalized Linear Mixed Model (GLMM) will be used to determine the size and direction of the difference between the control and intervention arms for the primary and secondary outcomes. The estimated intervention effect will be reported as the mean outcome difference for continuous variables and Odds Ratio for categorical variables between intervention and control group assuming a constant treatment effect over time. Estimates of the difference and 95% CIs will be calculated. To take time effect into account, all the analysis will be adjusted for time (periods) of the intervention and for clusters. Period (time) and intervention (counseling sessions) will be specified as fixed effects and clusters as random effect. Analysis will be adjusted for baseline covariates if required. The analytical plan does not include any interim analyses.
Two broad model extensions (35), random cluster by period effect and random cluster by treatment effect will be used for secondary analysis. Secondary analysis will also investigate an interaction effect between intervention and time and interaction effect between cluster and time. Additional analyses of the primary outcome will be conducted controlling for demographic variables if required. Statistical analyses will be carried out using STATA version 14 (33).
Economic evaluation analysis
All data will be analysed in Microsoft excel. The ratio of costs and benefits will be calculated and will be presented as ROI. This will inform whether Atmiyata intervention is a sound investment. Apart from that the study will provide economic burden of CMD in Mehsana district. We will present this information to funders and policy makers and in turn we will able to scale Atmiyata intervention in other districts of India.