Effectiveness of peer-group therapy using community based participatory research model on medication adherence among patients of diabetes and/or hypertension: study protocol for a multi-centre cluster randomised trial in rural settings across India (PARTICIPATE study)

Abstract

Background

According to the WHO, more than 50% of patients do not take their medications as prescribed. Nonadherence is caused by several variables, including social and economic factors, issues with the healthcare team and system, problems related to specific diseases, characteristics of those diseases, and their treatments.

Objective

To study the effectiveness of the PARTICIPATE intervention at the community level regarding medication adherence among adults with diabetes and/or hypertension in rural India.

Study design

This is a multicentre cluster randomised trial implemented across 4 blocks (64 villages) of 4 districts in East, West, North, and South India, covering 2880 randomly selected participants. A nested economic evaluation will measure the effectiveness of community-based participatory research (CBPR). The intervention will be delivered by peer educators identified from the community for a duration of 12 months, with the first 6 months followed by monthly sessions for the next 6 months. The control group will continue to receive all aspects of standard care offered by healthcare providers (public or private).

Methods

The measure of drug adherence for hypertension and/or diabetes, as determined by the self-reported Morisky Medication Adherence Scale (MMAS-8) at baseline, midterm, and end, is the study’s outcome variable. The independent variables, namely socio-economic status, number of antihypertensive and/or antidiabetic drugs, their duration, self-perceived health status, systolic and diastolic blood pressure, and/or HbA1c, will be controlled for during the analysis. Secondary outcomes include improvement in health literacy using the All Aspects of Health Literacy Scale (AAHS), clinical outcomes, quality of life using the EURO-QoL (EQ-5D), cost-effectiveness, and return on investment (ROI). Process evaluations will be conducted with a sub-sample of participants to examine engagement in various intervention components. The fidelity of intervention will be monitored using the Normalisation Process Theory framework.

Discussion

To the best of our knowledge, this is the first multi-centre cluster randomised controlled trial in India to assess the effectiveness of the CBPR approach for improving medication adherence among diabetics and hypertensive patients. The results of this study will contribute to the evidence base for scaling up peer-educator models for diabetes and hypertension management in India and similar low- and middle-income countries.

Trial registration

The registration number for this trial is CTRI/2024/01/061939.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-025-09209-7.

Introduction

Background and rationale {6a}

According to the Indian Council of Medical Research (ICMR) State-Level Disease Burden initiative (2017), the percentage of mortality in India attributable to non-communicable diseases (NCDs) rose from 37.9% in 1990 to 61.8% in 2016 [1]. The four major causes of NCD deaths are as follows: coronary heart disease, stroke and hypertension (45%), chronic respiratory disease (22%), cancers (12%), and diabetes (3%) [2]. Despite the fact that drugs work well to treat these diseases, there are several factors that lead to treatment failure. Factors contributing towards treatment failure are unhealthy diet, lack of physical activity, and use of tobacco and alcohol, along with poor treatment adherence [2, 3].

Globally, over 50% of patients do not adhere to their medicines, leading to treatment failure [4]. The WHO defines adherence as the extent to which a person’s behaviour—taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider [4]. Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments [5]. Multiple barriers, such as various socio-cultural and scientific factors, frequently make it difficult for patients to adhere to treatment regimens in the best possible way. These include social and economic factors, the healthcare team and system, disease-related factors, disease features, and disease treatments. If patients’ adherence to treatments is to be improved, the factors associated with these problems must be addressed [4].

Patient-tailored interventions, healthcare professionals trained in adherence, and team building with community and patients’ organisations have been shown to improve adherence [4]. Peer support, an example of team building, can be a critical and effective strategy for health care and sustained behaviour change for people with, or at risk for, chronic diseases and other conditions [4]. Peers can be defined as people sharing similar experiences or backgrounds [6, 7]. The objectives of these support systems are as follows: to promote the exchange of experiences of dealing with a disease and its treatment, to provide comprehensive medical information, and to promote patients’ responsibility for their own care [4].

Numerous studies have been conducted around the world, including in our country, to determine the efficacy of peer group therapy in treating psychiatric disorders, cancers, and infectious diseases like human immunodeficiency virus (HIV) and tuberculosis [8–12].

However, there is a dearth of information regarding the effectiveness of such modalities among diabetic and hypertensive individuals in LMICs. As diabetes and hypertension are highly prevalent in India, adherence to medicines is crucial for bringing down the disease burden.

In a developing country such as India, peer group engagement through the community-based participatory research (CBPR) model can play a crucial role in improving adherence sustainably and affordably manner [13]. CBPR models have also improved health literacy in diabetes and mental health in China and India [13, 14]. As a community health programme, our intervention aims to (i) improve medication adherence in patients with diabetes and/or hypertension, (ii) improve health literacy in patients with diabetes and/or hypertension, (iii) improved clinical outcomes in terms of HbA1cand blood pressure in patients with diabetes and/or hypertension, (iv) improve quality of life among patients with diabetes and/or hypertension, and (v) improve utilisation of healthcare services by patients with diabetes and/or hypertension. We hypothesise that, using a cluster-controlled randomised controlled trial, the intervention, compared to those receiving standard treatment care, will improve medication adherence and health literacy among patients with diabetes and/or hypertension. Measuring the efficiency and implementation process of the intervention will generate valuable insights on how we might sustain the impact of the intervention when delivered to a larger population.

Objectives {7}

Primary objective

1. To assess the effectiveness of community-based participatory research (CBPR) for improving medication adherence in diabetic and/or hypertensive patients in comparison to a control group.

Secondary objective

• (2)To measure the effects of using CBPR for improving medication adherence among diabetes and hypertension patients on individual outcomes such as personal health literacy, quality of life, and service user satisfaction.
• (3)To assess the effects of using CBPR for improving adherence to drugs among diabetes and hypertension patients on implementation outcomes such as acceptability and adoption.
• (4)To assess the cost-effectiveness and return on investment of the intervention (i.e., CBPR for improving medication adherence among diabetes and hypertensive patients).

Trial design {8}

It is a multi-centre cluster randomised controlled trial (MC-CRCT) with a 1:1 allocation ratio. The intervention group participants will receive peer-group therapy sessions on medication adherence using the CBPR model. Participants in the control group will receive standard care offered by private or public healthcare providers. The authors hypothesise that the CBPR model using peer-group therapy sessions is superior to standard care for medication adherence among adult patients with diabetes and/or hypertension.

Methods: participants, interventions and outcomes

Study setting {9}

The intervention will be implemented across four sub-blocks (64 villages) in four districts, spanning the East, West, North, and South zones of India. The implementation will first be conducted in the West zone, which will serve as the coordinating site for the effectiveness study component. It will later be replicated in other zones for the implementation component. In the West zone, the study will be conducted in the Sanwer block of Indore district, Madhya Pradesh state, which has 25 PHCs and 8 CHCs. This district has a population of 3,276,697, comprising 1,699,627 males and 1,577,070 females. The rural population is 848,988, with a literacy rate of 80.87%. Additionally, there are 136,449 people employed in the agricultural sector. Sanwer has a population of 197,835 with 102,874 males and 94,960 females, a rural population of 171,292, and 23,740 people employed in the agricultural sector. In the East Zone, the study will be conducted in the Tigiria block of Cuttack district, Odisha state, which has four primary healthcare centres (PHCs) and two community health centres (CHCs). This block has a population of 76,379, comprising 40,026 males and 36,349 females. The rural population is 66,582, with a literacy rate of approximately 73.2%. Additionally, there are 4049 people employed in the agricultural sector. In the North Zone, the study will be conducted in the Haroli block, Una district, Himachal Pradesh state, with 7 PHCs and 4 CHCs. This block has a population of 112,592, comprising 57,128 males and 55,464 females. It has a rural population of 112,592, a literacy rate of 61%, and 15,074 people employed in the agricultural sector. In the South zone, the study will be conducted in the Pappakudi block of Tirunelveli district, Tamil Nadu, which has 3 PHCs. Pappakudi has a population of 104,380, comprising 51,720 males and 52,660 females. The rural population is 80,333, with a literacy rate of around 69.31%. Additionally, there are 3500 people employed in the agriculture sector.

Eligibility criteria {10}

The study samples will consist of adult community members with diabetes and/or hypertension who are on medications and reside in the target districts and provide informed consent.

Inclusion criteria

• Diagnosed case of diabetes and/or hypertension and are on medication(s).

• Male or female aged 18 years or more.

• Resident of the village during the baseline survey.

• Has no plans to migrate within the next 12 months from the date of intervention initiation.

Exclusion criteria

• Bedridden persons who cannot provide informed consent or are unable to answer the questions

• Pregnant or lactating women

• Persons with a terminal medical condition or with cognitive impairment

Who will take informed consent? {26a}

Written informed consent will be obtained from the study participants by PI/Co-PI or health counsellor. Participants will receive a participant information sheet outlining the rationale for the study, details on interventions, the steps and protocols to be followed throughout the study, potential side effects and risks, benefits, a confidentiality statement, the option to withdraw from the study at any time, and the investigators’ contact information.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

Blood samples will be collected to assess HbA1c among patients with DM and HTN after obtaining consent. These samples will be tested using point-of-care devices and will not be stored. We will request permission for review of participants’ medical records and for the collection of blood samples to assess HbA1c among the patients with type 2 diabetes. But this trial does not involve collecting biological specimens for storage.

Interventions

Explanation for the choice of comparators {6b}

Studies have shown that patient-tailored interventions, involving healthcare professionals trained in adherence and team building with community and patient organisations, have been effective in improving medication adherence among individuals with, or at risk for, chronic diseases and other conditions [15]. Several studies have shown that peer engagement can help improve medication adherence across various conditions like asthma, hypertension, ischemic heart disease, and mental illness [16–18]. However, these studies were primarily conducted in high-income countries and hospital settings. The dearth of information regarding the effectiveness of peer-group therapy among diabetes and hypertensive individuals in LMICs, and high prevalence of these diseases in the Indian context, prompted us to implement this cluster-controlled multicentre study. Utilising community-based participatory research (CBPR) methods for sustained peer group therapy could make a significant contribution to enhancing medication adherence in India affordably and sustainably.

Intervention description {11a}

The implementation will be conducted in four phases, including the intervention of peer group therapy as shown in Fig. 1.

Fig. 1.

Intervention description

Phase 1: planning

The process of developing the intervention started with the initial concepts based on the available literature and interaction with healthcare professionals working in rural areas. The objectives of the interventions included educating patients on adherence and associated challenges, providing daily management help, connecting them to clinical and community resources, and providing ongoing social and emotional support through peer group therapy.

• ◦ Development of peer group therapy sessions and education materials—There will be eighteen face-to-face sessions, twice a month for the first 6 months and then once a month for the following 6 months. The agenda of these sessions are WHO adherence principles, barriers, methods for overcoming such challenges, and providing daily management help. These sessions will be categorised under five modules which are understanding disease- and medication-related information, information about disease and medication, tackling misinformation, concept of adherence, and institutionalising the intervention on a long-term basis. Each session will start with re-cap of the previous session and questions on adherence/NCDs followed by delivery of content for the day using teach-back technique. The last session of each module will be goal setting and learnings. Intermediate feedback will be collected from the participants and learning from them will be incorporated in future sessions. Details of eighteen face-to-face sessions are included in Appendix 2.

• ◦ Advocacy meetings—Line listing of villages will be done and selected villages will be stratified based on population cut-off of 2500. These villages will be randomised into intervention and control clusters as shown in Fig. 2.

Fig. 2.

Flowchart

To identify the eligible participants and peer educator from each cluster, a meeting will be organised with the head of the villages and the responsible NCD clinic. Under the National Programme for prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS), Government of India has established NCD clinics for the screening, management, counselling, and other aspects of non-communicable disease management. These clinics at the community health centre level maintain individual diagnosis, treatment, and referral records on the patient chronic disease card, with verbal and pictorial advice for the patient. Patients who are all eligible for the study will have their information collected from NCD clinics. Peer educators will be selected from the community. These clinics will be used for intervention implementation site.

• ◦ Selection and training of team—Our team will consist of principal investigator (PI), co-principal investigators (Co-PI), health counsellor (trained psychologist/clinical pharmacologist/clinical pharmacist), and project coordinator along with a peer educator from the community. Health counsellor and project coordinator will be recruited and trained by the PI and Co-PIs. Health counsellor will deliver the intervention initially and project coordinator will assist the training programmes and meetings, supporting health counsellor and record keeping. Peer educator will be recruited by the investigators on the advice of village head and NCD clinic in-charge. He should be a member of community with an interest in health care and community, willingness to learn, and leadership qualities. A strong commitment to work in the community was identified as an important criteria for the selection of all the team members.

Phase 2: baseline evaluation and implementation of intervention at the coordinating site

In Phase 2, the study will be implemented at the coordinating site (SAMC & PGI, Indore) after obtaining the ethics committee approval. Written informed consent will be obtained from the study participants by the PI/Co-PI or a health counsellor. Participants will receive a participant information sheet (PIS) outlining the rationale for the study, details on interventions, the steps and protocols to be followed throughout the study, potential side effects and risks, benefits, a confidentiality statement, the option to withdraw from the study at any time, and the investigators’ contact information. The baseline survey will be done at the T0 visit, which will include questionnaires to assess the degree of adherence, health literacy, and quality of life. It will be performed by trained health counsellor who have undergone training. Questions will be explained to each participant to familiarise them with the contents. Instructions for filling them out will be provided, and the responses will be recorded. Special instructions would be given not to ask or consult a colleague while answering the questionnaire. After completion of the baseline survey at all clusters, the intervention will be implemented in the intervention clusters for 12 months. All the participants in both intervention and control arm will be permitted to used standard treatment for diabetes and hypertension. For the 1 st 6 months, sessions will be given twice a month, followed by once a month for the next 6 months. The control group (waitlist group) will receive the intervention after completing the 12-month session in the intervention group. This will not be included for data analysis. Table 1 presents the time point for intervention implementation, as per the SPIRIT reporting guidelines [19]. Mid-term evaluation will be done at T7 and T13 sessions.

Table 1.

Timepoint for the intervention implementation

Phase 3: interim analysis and implementation of intervention at collaborative sites

An interim analysis will be conducted after 9 months of intervention at the coordinating site to facilitate the early identification of treatment effectiveness. A final analysis will be conducted at the end of the 12-month intervention period. If the analysis yields the expected result (an 8% difference in clinical outcomes between the intervention and control groups), the study will be implemented at other collaborating sites, like the coordinating site. The coordinating site team will train the PI and Co-PIs from collaborating sites. A workshop will be conducted at the coordinating site for this training.

If the community trial does not demonstrate treatment effectiveness after the 12-month follow-up, key steps will be taken. These include exploring potential confounders such as adherence issues or patient characteristics, re-assessing how the intervention was delivered and its fidelity, examining biases from participants and researchers, and checking whether the follow-up period was sufficient or if there was participant loss. Qualitative data from process evaluations will help identify implementation challenges. Based on discussions with partner sites, appropriate modifications will be made to support implementation at other locations.

Phase 4: data analysis and publications

After the completion of the study at all the collaborating sites, data will be compiled at the coordinating site. They will be analysed and submitted to the ICMR. The study’s results will be published in a peer-reviewed journal and shared with the participants.

Criteria for discontinuing or modifying allocated interventions {11b}

This is not applicable as the intervention is aimed at improving medication adherence, so there will be no special criteria for discontinuing or modifying the allocated intervention. All the participants are permitted to use standard care treatment for diabetes or hypertension.

Strategies to improve adherence to interventions {11c}

The intervention is designed to enhance medication adherence in individuals with diabetes and/or hypertension, as assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8) [16]. Adherence to interventions will be ensured through the selection of peers from the community. Research team members (PI and Co-PI of coordinating site) will be conducting multiple visits to ensure intervention fidelity. Process evaluations will be conducted in conjunction with the intervention through interviews with treating doctors, programme staff, peer educators, and target beneficiaries at regular intervals during the intervention. The analysis of these interviews will be used by programme staff to improve adherence to interventions.

Relevant concomitant care permitted or prohibited during the trial {11d}

Concomitant care permitted are medicines and other cares that patients’ doctors provide to treat their hypertension and diabetes or any other associated illness.

Provisions for post-trial care {30}

This is a non-pharmacological intervention; therefore, there are no specific post-trial care provisions.

Outcomes {12}

Primary, secondary and other outcomes

The primary outcome is the medication adherence of patients with diabetes and/or hypertension as measured by the Morisky Medication Adherence Scale (MMAS-8) at baseline, midterm, and endline [20].

The secondary outcomes include personal health literacy improvements due to the intervention measured using All Aspects of Health Literacy Scale (AAHLS) based on the conceptual causal model linking health literacy to health outcomes as documented in Paasche-Orlow& Wolf (2007) (Annexure I) [21, 22]. Other secondary outcomes include improvement in clinical outcomes measured in terms of HbA1c and blood pressure in patients with diabetes and/or hypertension in both the groups, costs of intervention, cost-consequence based on the observed results within the trial period, and cost-effectiveness analysis where differences between groups in the trial will be extrapolated to the longer term where appropriate. Exploratory outcomes included quality of life using a validated version of the EURO Quality of life-5D (EQ-5D) in the local language of the target sub-districts [23, 24], user satisfaction with the intervention will be assessed using a validated version in the local language of the Patient Satisfaction Questionnaire Short-Form (PSQ-18) [25], and fidelity of intervention will be monitored using the Normalisation Process Theory framework [26].

Participant timeline {13}

Sample size {14}

The required sample size will be determined by focusing on the primary objective of this trial, which is to evaluate the effect of peer group therapy on medical adherence in individuals with diabetes and hypertension in rural India. The sample size was calculated using the parameters of the study published by Amer et al. [27] and Abdullah et al. [28] on hypertensive and diabetic medication adherence populations, respectively [27, 28]. R software version 4.1.3 was used for the sample size calculation. Proportion of hypertension and Type-II diabetes medication adherence among 18 years and above was 57.3 and 53.4%, respectively, in the control group [29]. Sample sizes of 1088 in control group and 1088 in intervention group, which were obtained by sampling 32 (m) clusters with 34 subjects each in control group and 32 clusters with 34 subjects each in intervention group, achieve 90% power (β) and 5% (α) (one sided) significance level, allowing for intra-cluster correlation (ICC) 0.02 (ρ) to detect a difference between the intervention and control group proportions of 8% [pI = 61.4%] through the formula: [22–24]

$$n_c=\frac{\left(1,+,\left(m,-,1\right),\rho \right){\left(Z_{\frac{\alpha }{2}},+,Z_{\beta }\right)}^2}{{\left({\text{p}}_{\text{I}},-,{\text{p}}_{\text{C}}\right)}^2}\left[{\text{p}}_{\text{I}},\left(1,-,{\text{p}}_{\text{I}}\right),+,{\text{p}}_{\text{C}},({1-\text{p}}_{\text{C}})\right]$$

Considering the 20% loss to follow-up, we anticipated the final sample size of ~ 2880 from 4 participating centres, i.e., 360 per group and per centre to complete sample size.

• Total number of clusters in Control group= 32 [Village [4]X Population Group [2]X Centre [4]] = Total number of clusters Intervention group

• Total participants per cluster in Control group per centre= 360 [i.e., 45 from each of Village [8]] = Total participants per cluster in Intervention group

• Total participants= 2880 [720 × 4 Centres]

Recruitment {15}

The Principal Investigator (PI) and Co-Principal Investigator (Co-PI) in charge of implementation will meet with the village heads of the target villages and the NCD clinic staff. Patients who are all eligible for the study will have their information collected. We will only enrol patients who agree to participate in the trial.

Assignment of interventions: allocation

Sequence generation {16a}

Allocation of intervention and sequence generation will be conducted as follows. Codes will be randomly assigned to the two interventions (CBPR and control groups) namely A and B. In the next step, a randomisation list will be generated using the RANDOM ALLOC software. Four centres will be randomised into 2 study groups (A and B). Each centre will be allocated random numbers ranging from 1 to 4 using computer random number generators. Following randomisation, participants and caregivers will be aware of whether they are in an intervention village or a control village. Participants who fulfil the eligibility criteria and sign the informed consent will be included in the study.

Concealment mechanism {16b}

Due to the nature of the intervention (peer-group), blinding is not possible for this trial. However, study site allocation will be conducted only after completing the baseline assessment and obtaining agreements with participating sites. A centralised online computer-generated system (Sealed Envelope) will conceal allocation for the study. The allocation sequence is provided to the PI/Co-PI at each site via this secure system. Once participants are randomised to a treatment arm, the PI/Co-PI in charge of implementation will meet with the village heads and the NCD clinic staff. Patients who are all eligible for the study will have their information collected, and those patients who agree to participate in the trial will be included. The system has restricted access to the allocation, which is assigned only to specific personnel, i.e., the unblinded statistician. All other study personnel involved in the direct conduct of the study and participants are completely blinded to the randomisation system. It will not be possible for the study team to determine treatment allocation using laboratory data during the trial period.

Implementation {16c}

A statistician who will be unaware of the group assignment will randomly select villages for each stratum using a computer-generated random number and also assign random treatment allocation. The enrolment will be done by the Co-PI, and the Co-PI will assign the village as it is a cluster randomised trial.

Assignment of interventions: blinding

Who will be blinded {17a}

Data analysts (biostatisticians) will be blinded. The patients, their caregivers, and outcome assessors are not blinded.

Procedure for unblinding if needed {17b}

In this study, the patients, their caregivers, and outcome assessors will not be blinded. Only the data analyst will be blinded. The data analyst will be unblinded if there are any outlier biochemical values that require immediate action so that the patient can be informed.

Data collection and management

Plans for assessment and collection of outcomes {18a}

The primary outcome is the improvement in medication adherence in diabetes and/or hypertension as measured using the eight-item Morisky Medication Adherence Scale (MMAS-8) [16]. The MMAS-8 consists of eight questions, first seven items having a dichotomous answer (yes/no) that indicates adherence or non-adherent behaviour. For Indore site, MMAS-8 Hindi version would be used. For the sites in Odisha and Tamil Nadu, translation versions of the MMAS-8 tool will be used, adhering to ISPOR best practices guidelines [24].

Personal health literacy improvements due to the intervention will be measured using All Aspects of Health Literacy Scale (AAHLS) [21, 30].

Improvement in clinical outcomes will be measured in terms of HbA1c and blood pressure in patients with diabetes and/or hypertension in both the groups. HbA1c and blood pressure will be measured at baseline and will be compared from midline and endline measurements. For HbA1c measurement, 5 ml of blood will be collected from participants by venipuncture after taking consent in EDTA tube. Samples will be carried to analysis centre in icepack (2–8 °C) and will be analysed in Trivitron nano H5 machine using High Performance Liquid Chromatography (HPLC) technique. Calibration of the instrument will be as per the manufacturer’s guidelines and lab quality assurance. Blood pressure measurements will be taken using a digital sphygmomanometer and will be recorded according to the guidelines of the Centres for Disease Control and Prevention (CDC). Calibration of the instrument will be as per the manufacturer’s guidelines. Improvement in quality of life among persons with diabetes and/or hypertension will be assessed using a validated version of the EURO Quality of life-5D (EQ-5D) in the local language of the target sub-districts. The EQ-5D’s descriptive system is a preference-based Health Related Quality of Life (HRQoL) 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. A lower score indicates a better quality of life [20].

User satisfaction with the intervention will be assessed using a validated version in the local language of the Patient Satisfaction Questionnaire Short-Form (PSQ-18) [25]. The PSQ-18 contains 18 times tapping each of the seven dimensions of satisfaction with medical care measured by the PSQ-III: general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with doctor, and accessibility and convenience. Subjects have five options when answering each question: Strongly agree, Agree, Uncertain, Disagree, and Strongly Disagree, with 1–5 points for each answer, where 5 mean the highest satisfaction [25].

Process evaluation will use questionnaires, interviews, and focus groups to understand participants' experiences, discrepancies between expected and observed outcomes, intervention influence, sustainability, contamination, and unexpected events. Questionnaires will gather participant opinions. Interviews and focus groups will explore engagement, barriers, facilitators, implementation, and experiences. All will be audio-recorded and transcribed.

Throughout the intervention, fidelity will be monitored using the Normalisation Process Theory Framework. Observations across clusters will assess if the intervention was delivered as expected and received by attendees. During observations, a case report form will be completed, combining an ‘adherence measure’ to capture delivery mode (dose, duration, content) and resource use (materials, activities).

Plans to promote participant retention and complete follow-up {18b}

All efforts will be made to retain all participants in the study. Due to the institutions providing medical and clinical care in the respective study sites, there is a good rapport with the study group, local self-government, and frontline health workers. Loss to follow-up may result from migration to their children’s places of living, death, or other reasons. The characteristics of patients who drop out will be recorded and compared to those of patients who remain in the study.

Data management {19}

All the PIs and Co-PIs, along with data entry operators, will have access to the research data. All qualitative and quantitative data will be stored in both paper and electronic formats. The paper copies and documents will be stored in closed cabinets at the individual sites, under lock and key, and will have limited access to the data management team. The electronic data will be stored on the cloud using a separate Google Drive account for this research, with access restricted to the data management team only. Audit trails of ongoing decisions, including revisions to existing codes and emergent codes, will be maintained for all interviews. Quality of data will be ensured at every step by the site data operators, PIs, and Co-PIs. Strict confidentiality will be maintained throughout the handling of the data. The data will be stored for a period of 5 years. The results generated by this research will be freely shared with the public and the research community through research publications.

Confidentiality {27}

Confidentiality of the participants will be ensured during recruitment of the participants, data collection, during transcription, data analysis, and during dissemination of research results. It will be done by assigning unique ID to the participants while recruitment and coding them during analysis. This will be stored confidentially before, during, and after the trial.

Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

For HbA1c measurement, 5 ml of blood will be collected from participants by venipuncture after taking consent in EDTA tube. Samples will be carried to the analysis centre in an icepack (2–8 °C) and will be analysed in the Trivitron nano H5 machine using the High-Performance Liquid Chromatography (HPLC) technique. The blood samples will not be stored in the current trial.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

Dichotomous outcomes will be compared between the intervention and control groups using a chi-square test. Continuous outcomes will be compared between intervention and control using a t-test or a non-parametric test, and for more than two groups’ comparison, an ANOVA test/Kruskal test, and a post hoc test for within-group’s comparison. After more than 2 follow-up repeated measures, an ANOVA test/Friedman test will be applied. A pre- and post-interventional comparison will be performed using a paired t-test/Wilcoxon signed-rank test.

Multilevel modeling (linear or logistic, as appropriate) will be used to compare the primary outcome (pre-intervention to post-intervention data) between groups, while adjusting for potential covariates (age, sex, and comorbidities) and secondary outcomes (blood pressure, random blood sugar, HbA1c levels, and quality of life).

For MMAS-8, scores range between 0 and 8, where scores below 6 indicate weak medication adherence, scores between 6 and 8 indicate average medication adherence and scores of 8 indicate strong medication adherence [16]. When the MMAS-8 score is dichotomised (e.g., high adherence vs. low adherence, a multilevel logistic regression model will be used to compare adherence between groups while accounting for clustering within the data [31–33]. The Model includes [31]:

• ◦ Level 1 (individual level): This includes patient-level factors such as age, gender, socioeconomic status, or duration of illness.

• ◦ Level 2 (cluster level): This includes higher-level factors such as clinics or regions, if the patients are nested within these settings.

When the MMAS-8 score is treated as a continuous variable (ranging from 0 to 8), a multilevel linear regression model is appropriate for analysing adherence [20, 34, 35]. The model includes:

• ◦ Level 1 (individual level): Continuous MMAS-8 scores are modeled at the patient level with covariates such as age, income, or comorbidities.

• ◦ Level 2 (cluster level): Clinics, doctors, or geographic regions where patients are nested are treated as higher-level units, introducing random intercepts (or slopes, if needed).

By using multilevel modeling, we can effectively compare adherence outcomes while accounting for the hierarchical structure of the data (e.g., patients nested within clinics), making the estimates more reliable and appropriately controlling for between-group variability.

Questionnaire data from the qualitative interviews will be summarised using frequency counts and means (+/− SD) where appropriate.

Interim analyses {21b}

An interim analysis will be done at the 9th month of intervention at the coordinating site. Since the risk associated with the intervention (CBPR method) is minimal or nonexistent, interim analysis and stopping guidelines have not been prescribed by the ethics committee; therefore, there will be no stopping guidelines.

Methods for additional analyses (e.g., subgroup analyses) {20b}

Subgroup analysis will not be carried out. However, for the primary and secondary outcome variables, covariates such as age, sex, and comorbidities will be considered as potential confounders in the mixed-effect model analysis.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

Nonadherence will be managed through an intention-to-treat analysis. If any missing data arise due to the longitudinal nature of the study, imputations using Markov Chain Monte Carlo (MCMC) will be considered for addressing missing data problems. A mixed-methods analysis will be regarded as an intention-to-treat analysis. Additionally, depending on the percentage of missing data and the assumption about data missingness in the study variables, an appropriate missing data imputation technique will be employed.

Plans to give access to the full protocol, participant-level data and statistical code {31c}

Full protocol can be given. The full dataset can be given with the permission of the participating institutions and the ICMR.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {5d}

Principal Investigators and Co-PIs will form a project management unit (PMU). They will meet monthly online to discuss the project’s progress, and the PI will report quarterly to the oversight steering committee. Recruitment, follow-up rates, and missing data will be discussed at monthly review meetings between the data manager and field data collectors. The oversight steering committee will comprise senior members from various institutions, including the Dean or heads of collaborating institutions, who are not directly involved in the project. Their objective is to ensure that the PI gets the strategic support for all the activities of the research project.

Composition of the data monitoring committee, its role and reporting structure {21a}

The PI will be conducting all aspects of data collection and management. All participants will be given a unique study Participation Identification Number (PIN). Data will be entered under this identification number onto the laptop of the PI that will be controlled with a unique username and password. Once data entry is complete, the database will be locked prior to any trial analysis. Following consent, identifiable (consented participants only) data linked to the PIN will be held locally at the research office in a locked filing cabinet. After completion of the study, the identification, screening, and enrolment logs will be securely archived at the research office for 5 years, unless otherwise advised by the university.

Adverse event reporting and harms {22}

As this study measures adherence to an intervention, no adverse events, serious adverse events, or harms from the intervention are anticipated. We will consider adverse events as stopping treatment altogether or any adverse events arising due to the medications. A protocol for reporting and recording of adverse events is provided in the Additional file. The data manager and PI will train all team members on proper identification, recording, and reporting of adverse events. All adverse events will be tracked in accordance with the protocol and reported to the Institutional Ethics Committee within 15 days of occurrence, as well as to the District Health Authority and the Trial Steering Committee. Trial deviations will be reported to the ethical committee. Harms reporting in the final publication will be conducted as per the CONSORT Harms 2022 statement [36].

Frequency and plans for auditing trial conduct {23}

The meetings of the Project management group, Trial Steering group, independent data monitoring, and Ethics Committee will also serve to audit the trial periodically.

Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}

Before the start and at the start, there have been some minor modifications which has been updated to the ethical committee and subsequently uploaded in the CTRI.

Dissemination plans {31a}

The results of the study will be published in standard peer-review journals with authorship as per ICMJE (2023) and CRediT recommendations. Social media and Stakeholder workshops will be used to disseminate the findings. A plain-language summary will be shared with all participants.

Discussion

This cluster-randomised, multi-centric trial will be one of the unique studies that will benefit the community by increasing drug adherence for chronic conditions using the CBPR model. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence.

The trial will employ a Type 2 hybrid effectiveness-implementation design, with the effectiveness study conducted in the West zone of the country and the implementation to be replicated in the other three zones of India, in areas with diverse cultures and beliefs, which will enhance the model’s generalizability. It will make the evidence applicable to India and South Asia, as well as similar contexts. A hybrid type 2 design has a dual focus on the clinical intervention and implementation-related factors. In hybrid Type 2 designs, it is essential to have an explicitly described implementation strategy that is considered plausible in the real world. Hybrid type 2 designs always require explicit measurement of implementation outcomes (e.g., adoption, fidelity), and it is essential to distinguish between the intervention components and the implementation strategy components [37, 38]. Stepped wedge designs involve implementing an intervention over time in a staggered manner, typically involving cluster randomisation, with the collection of observations during a baseline period, and then randomly assigning clusters to receive the intervention at regular intervals [39].

There are significant expected implementation challenges to note. First, the trial involves working with the primary clinics providing NCD screening and detection services, and building an effective partnership with the state government of each state where the project will be implemented will be crucial for its success. Second, medication nonadherence for patients with chronic diseases is extremely common, with 40–50% of patients prescribed medications for the management of diabetes and hypertension [40]. There exist treatment-related barriers, such as treatment complexity, side effects (or fear of side effects), inconvenience, cost, and time, and other barriers such as poor practitioner-patient relationship, aspects of which are beyond the scope of the intervention [41, 42].

If successful, the medication adherence intervention, utilising minimal technology and low financial investment, has the potential to establish evidence-based practice for improving medication adherence in diabetes and hypertension in India, as well as in similar developing countries. The use of CBPR has the potential to improve health literacy among the target populations thus making the study sustainable beyond the project period. The examination of implementation processes throughout the trial will also help in preparing a roadmap for policymakers and researchers to implement and scale up medication adherence interventions in diabetes and hypertension, as well as potentially other non-communicable diseases, in various settings.

Trial status

The current protocol is version 6.0, dated February 28, 2024. The recruitment began on April 01, 2024, and was completed by March 31, 2025, at the coordinating site. For the collaborating site, recruitment will start on April 1, 2025, with an end date of March 31, 2026.

The protocol submission has been delayed due to unavoidable circumstances, including changes in the trial registry and adverse weather conditions.

Abbreviations

ANOVA

Analysis of Variance

CBPR

Community-based participatory research

CDC

Centres for Disease Control and Prevention

Co-PI

Co-principal investigators

CRediT

Contributor Roles Taxonomy

CTRI

Clinical Trials Registry of India

EDTA

Ethylenediaminetetraacetic acid

HIV

Human immunodeficiency virus

HPLC

High Performance Liquid Chromatography

ICER

Incremental Cost-Effectiveness Ratio

ICMJE

International Committee of Medical Journal Editors

ICMR

Indian Council of Medical Research

ISPOR

International Society for Pharmacoeconomics and Outcomes Research

MCMC

Markov Chain Monte Carlo

MMAS 8

Morisky Medication Adherence Scale 8

MRHRU

Model rural health research unit

NCD

Non-communicable diseases

NP-NCD

National Programme for Non-Communicable Diseases

PI

Principal Investigator

QALY

Quality Adjusted Life Year

SD

Standard Deviation

WHO

World Health Organization

Appendix 1

Causal pathways between limited health literacy and health outcomes

Source: Paasche-Orlow and Wolf [22]. Reprinted by permission from PNG Publications, American Journal of Health Behavior, www.ajhb.org.

Appendix 2

Table 2.

Details of intervention sessions

Each session will be structured as follow:
• Re-cap of the previous session· Content for the session • Teach back technique/Feedback • Goal setting for the next session
Session Zero (T0): Creating the peer group, Informed consent, Base line assessment
Module1: Patient’s perspective of disease and medications
Sessions1,2,3 (T1, T2, T3)
• Rapport establishment following CBPR model for understanding patients’ disease and medication experiences, effectiveness, and side effects of the medicines, and barriers to adhering to medications, and • Goal setting for the next session
Module2: Knowledge transfer of disease and medications
• Sessions4, 5,6 (T4, T5, T6) • Knowledge transfer of disease, medications and its adherence to the participants, strategies to overcome barriers for medication adherence. To educate about diet, lifestyle, and exercise. • Goal setting for the next session
Session7: Midterm evaluation (T7)
Module 3: Introduction of peer educator
• Sessions8 (T8)
Module 4: Reality orientation and sensitization program in collaboration with Peer educator and role of social support
• Sessions9,10, 11, 12 (T9, T10, T11, T12)
Session13: Midterm evaluation (T13)
Module5: Institutionalization of interventions
• Session14,15,16.17 (T14, T15, T16, T17)
Session18: Final evaluation (T18)
Session number	Aim	Content	Delivery strategy
T1	To establish rapport Goal setting for the next session	Ice breaking by general introductions of the participants with each other Inform participants about the purpose and procedure of the whole intervention Give one plan to each participant & ask them to adhere tothe care regimen for the patients	Active listening Introduction of group anthem Feedbac
T2	To understand the participant’s medication experiences, effectiveness and side effects of the drugs To identify the misconception related to medication Goal setting for the next session	Ask patients on disease-and medication-related information and misinformation (if any),including the name, dosage, frequency, and timing, purpose of each medication potential side effects, and special administration considerations.	Active listening Group anthem Feedback
T3	To interact with each participant based on feedback from the previous session Discussion about treatment burden and barriers to medication adherence Goal setting for the next session	Encourage patients to express their feelings and barriers to their medication adherence	Active listening Group anthem Feedback
T4	To educate patients about disease and their medication Discuss about the role and importance of medication adherence Goal setting for the next session	Discuss about the symptoms, causes, management of hypertension and Diabetes Empower patients with knowledge about the importance of medication adherence and the consequences of nonadherence using Linkert scale	Active listening and teach back technique Story telling with Linkert scale Group anthem Feedback
T5	Discuss the strategies to overcome barriers for medication adherence Goal setting for the next session	Set goals and help make an individualized adherence improvement plan based on patients’ expectations and preferences. Ask patients to select three skills they want to learn to improve health	Active listening Group anthem Feedback
T6	To educate the participants about diet, lifestyle, and exercise Goal setting for the next session	Discuss the dietary habit of all participants, ask their favourite foodDiscuss about healthy food, exercise, and self-careAsk the participant to get their plant in thenext session	Active listening and Teach back technique using Poster Group anthem Feedback
T7	Mid-term evaluation	Participants will be asked to fill questionnaires. Inspect the plant that how participants take care of the plant and adhere to care	1.MMAS-8 questionnaire 2. EQ-5D questionnaire 3. AAHLS questionnaire 4. PSQ-8 questionnaire
T8	Introduction of peer educator Discuss the role of social support Goal setting for the next session	Aware them about the role and importance of social support Explore social support networks inthe management of hypertension and self-care.	Teach-back and Active listening Group anthem Feedback
T9	Strengthening social support network in collaboration with peer educator Goal setting for the next session	Peer educator will make a list of local resources and share with the participants (e. g, medical care institutions, and psychological support organizations).	Mobilizing social support Group anthem Feedback
T10	Reality orientation programme in the collaboration with peer educator Goal setting for the next session	Session will be started with the motivation speech by the peer educator and followed by the movie prepared by health care professionals	Movie Group anthem Feedback
T11	Community sensitization programme in collaboration with peer educator Goal setting for the next session	Participant with poorest compliance acts as a doctorand participants with good compliance will be asked by the peer educator to act as patients. Reflection of the experienceand summary of the Role-playing by the participants	Role play Group anthem Feedback
T12	Strengthening group cohesiveness and bond with in self-help group Goal setting for the next session	Peer educator and health care professional will plan a trip of the village with the participants Ask the participant to get their plant in the next session	Cooking & shopping with participant in their local market and farm visit Group anthem Feedback
T13	Mid-term evaluation	Participants will be asked to fill questionnaires. Inspect the plant that how participants take care of the plant and adhere to care	1.MMAS-8 questionnaire 2. EQ-5D questionnaire 3. AAHLS questionnaire 4. PSQ-8 questionnaire
T14	Awareness building and reinforcement by the peer educator	Peer educator will deliver a session on all the aspects of hypertension and diabetes	Peer educator session Group anthem Feedback
T15	Health focused fun game activity conducted by peer educator in the presence of health professionals	Playing the game in which participants must put a capsule shaped ball into a mouth shaped box in 3 attempts	Fun game Health line race Group anthem Feedback
T16	Assessment of the knowledge gain by the participants during the previous sessions by peer educator in the presence of health professionals	The cards with pictures of different food items given to the participants. They have to sort out the healthy food card in the green colour box and the unhealthy food in the red colour box Ask the participant toget their plant in the next session	Food sorting game Group anthem Feedback
T17	To know the experience of the participants of the intervention	Each participant will share their experience with the peer group Inspect the plant that how participants take care of the plant and adhere to care	Sharing session Group anthem Feedback
T18	Final evaluation	Participants will be asked to fill questionnaires.	1.MMAS-8 questionnaire 2. EQ-5D questionnaire 3. AAHLS questionnaire 4. PSQ-8 questionnaire

Authors’ contributions

PR is the Chief Investigator; conceived the study, led the proposal and protocol development and acquired funding, Methodology, Writing-Original Draft Preparation, Review & Editing. AJ—Design of intervention, development of the proposal, acquired funding, Methodology, Writing-Original Draft Preparation, Review & Editing. HG & VV are involved as statisticians and will conduct the statistical and qualitative analyses. Writing-Review & Editing. DK, AB, SM, TR, SKR, MJ, ACPR, SK, KS and BU will be responsible for implementing intervention at collaborating sites. Writing-Review & Editing. JC & TA are attached to ICMR and are research managers to the project, Writing- Review & Editing. DJ is lead methodologist for the trial design, and economic evaluation, Writing—Original Draft Preparation, Review & Editing. All authors read and approved the final manuscript.

Funding

This is a ICMR-funded research protocol under National task force on Safe and Rational Use of Medicine. Protocol ID is 2023–20019, version 6 dated 28/02/2024. JC & TA is employed with ICMR who have funded the study. JC & TA have contributed to protocol development and agreement to the final manuscript. The funding institution had no other role in the development of this protocol.

Data availability

The investigators will have access to the final data set. There are no contractual agreements that limit access to investigators. The investigators in the field collect the data, and the data will be entered in the RedCap software. Any data required to support the protocol can be supplied on request.

Declarations

Ethics approval and consent to participate

Ethics committee approval has been obtained from the Institutional Ethics Committee of Sri Aurobindo Medical College & PGI, Indore, for protocol version 6, dated 28 February 2024. Written, informed consent to participate will be obtained from all participants.

Consent for publication

Informed consent has been obtained, and the model consent form can be made available. No identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results.

Competing interests

The authors declare that there are no competing interests.