Integrated Digital Health System With Electronic Decision Support, Assisted Telemedicine and MHeAlth-Supported Self-ManaGement to Improve Health-Related Quality of Life Among Adults With Multiple Long-Term Conditions in Primary Health Centres in India and Nepal: A Cluster Randomised Controlled Trial

Study design and setting:

This study is a cluster randomised controlled trial evaluating an integrated, technology-enabled model of care for people living with multiple long-term conditions (MLTC) in primary health centres (PHCs) in India and Nepal. Whole PHCs, rather than individual participants, are the unit of randomisation: each participating PHC is allocated to either the intervention arm or a usual-care (control) arm, allowing comparison between the two models while limiting contamination.

The trial is being implemented across four sites in India and Nepal: Anakapalli (Andhra Pradesh), Jodhpur (Rajasthan) and Sonipat (Haryana) in India, and Lalitpur , Kathmandu , Bhaktapur , Kavre , Chitwan , Makwanpur , Nuwakot Districts, at Bagmati province in Nepal site covering both rural and urban contexts. Each site includes 30 clusters, participants in intervention clusters receive the programme over a 24-month intervention period, while control clusters continue with routine care. The sample-size calculation allowed for clustering at the facility level, assuming a two-sided significance level of 0.05, 90% power, a mean control-group quality-of-life score of 74.37 (standard deviation 15.1), a minimum detectable difference of 2.5 points, an intracluster correlation coefficient of 0.02, and 20% attrition. On this basis, the required sample is 120 clusters with 30 participants each, giving 3,600 participants in total.

Study phases and progress:

The study was developed in stages. First, a formative phase generated the evidence base, comprising a secondary analysis of MLTC prevalence and patterns by pooling 17 datasets and 2,016,846 participants (approximately two million) from India and Nepal, a case-mix assessment of the conditions presenting at primary care, in-depth interviews with patients, caregivers and health workers, and health facility assessments of readiness to deliver integrated care. The facility assessments covered 40 sub centres and 20 PHCs in India and 37 primary health facilities in Nepal, using standards adapted from the Indian Public Health Standards 2022 and Nepal's Minimum Service Standards 2020.

Second, the findings from the formative phase were brought together with stakeholders through a structured co-design process to develop the intervention. The intervention components were developed iteratively with stakeholders between December 2024 and early 2026. Fourteen co-design workshops were held in total: four at each of the three sites, together with two national-level workshops. The co-design process was guided by the ADAPT framework (Assessment, Decision, Adaptation, Production, and Testing/Implementation), which structured the progression from identifying care gaps to selecting, prioritising, prototyping and testing intervention features. Participants were organised into stakeholder groups to ensure representation: people with MLTC and their caregivers, community representatives; primary health care providers, technical experts and researchers; and policymakers and district or state officials. Patient and caregiver groups identified user preferences, including self-care support, and barriers such as fragmented care and out-of-pocket costs. Provider and expert groups made practical design recommendations, including integrating clinical guidelines into workflows, incorporating drug-interaction alerts, and defining standard teleconsultation formats with attention to language and trust. A joint session validated and prioritised features using the MoSCoW method; prioritised "must-have" features included an editable decision-support dashboard, simple application navigation in local languages, offline data entry, and a reliable telemedicine referral pathway. Feedback on the patient-facing application emphasised low-literacy formats (audio, video and SMS/IVR options) and event-triggered reminders. Emerging insights were documented and fed back through successive design cycles, ensuring that the EDSS algorithms, telemedicine workflows and mobile application reflected local context, language and health-system realities. The co-design phase also established stakeholder-engagement structures and preparatory materials such as training modules and user manuals.

Third stage, co-designed intervention was pilot tested in six PHCs (four in India and two in Nepal) with approximately 180 participants (about 30 per cluster). In pilot, investigators assessed feasibility, usability, acceptability, fidelity, data completeness and implementation processes. The findings were used to refine the workflows, training, study tools and technical specifications, without altering the core intervention components.

The study has now progressed to the main cluster randomised controlled trial. Participant screening, enrolment and baseline assessments commenced on 18 May 2026, and the intervention was initiated in the intervention arm on 13 August 2026.

Intervention components and digital architecture:

The intervention package has three components, delivered on a secure, cloud-enabled platform aligned with national digital health standards.

Electronic Decision Support System (EDSS): Built on the Centre for Chronic Disease Control's DigiSetu platform, the EDSS extends existing modules (hypertension, diabetes and cardiovascular disease) to cover conditions relevant to MLTC, including COPD, asthma, Knee osteoarthritis, backache, mental health conditions (anxiety and depression) and vision and hearing difficulties. Within a structured PHC workflow, nurses enter vital signs, history and laboratory results, and the system generates guideline-based management plans. Medical officers review these plans, override them where clinically indicated, and finalise care. The EDSS provides an at-a-glance dashboard of key diagnoses, pending follow-ups and alerts. It functions as an assistive tool, with clinicians retaining full override authority. Back-end audit trails will be maintained.

Assisted telemedicine: This component connects PHC staff and participants with remote specialists through a facility-based model that provides real-time specialist consultations within the PHC. When a participant needs specialist input or in absence/non availability of PHC medical officer, the trained PHC staff initiates a teleconsultation from the health centre, so the participant can receive expert advice locally without travelling long distances to higher-level facilities.

Patient-facing mobile application and care coordination through Care Mitras: The application supports self-management and is linked with the EDSS. This linkage makes the care plan and prescription generated during clinical visits available directly to the participant. The application displays the participant's current medications, care plan and scheduled follow-up dates, and aligns reminders with the instructions recorded in the EDSS. It also connects with the national ABHA Health ID to import health records securely and provides symptom tracking and a library of lifestyle and adherence content. Following co-design feedback, content is provided in low-literacy, audio-visual formats in local languages, with notifications triggered around clinic visits, medication changes and scheduled follow-ups rather than continuously. For participants without smartphones, SMS and interactive voice response reminders are used, with caregivers and frontline workers engaged to relay key messages. Care Mitras are trained, facility-based members of the study team who support participants throughout their care pathway. They help participants use the digital tools, encourage treatment adherence and attendance at follow-up visits, arrange telemedicine consultations at the PHC, and act as a trusted link between participants and the primary healthcare team.

Cluster randomised controlled trial The trial involves participant screening, enrolment and baseline assessment, followed by cluster randomisation into intervention and control arms, intervention implementation, and subsequent midline and endline assessments.

Trained health workers screen attendees visiting PHCs using a standardised eligibility tool to determine whether they meet the study inclusion criteria, including age (40 years and above) and the presence of at least two of the listed long-term conditions. Eligible individuals receive study information and provide written informed consent. After consent, a baseline assessment visit will be scheduled to collects socio-demographic, medical-history and behavioural information, together with objective clinical measurements, using standardised, interviewer-administered instruments. Fasting venous blood samples are collected under standard operating procedures for glycaemic, lipid, renal and liver markers, with comparable protocols across sites. Participants receive a printed results report within approximately two to three days, explained by a trained study team member; those with abnormal findings are counselled and referred to the nearest appropriate public facility, and critical values are communicated promptly with referral support. After the 24-month intervention period, end-line assessments replicate baseline procedures, using the same instruments and protocols, to enable evaluation of change over time. All outcomes are assessed at baseline and repeated at midline and endline, enabling comparison of change between the intervention and control arms.

The primary outcome is the change in health-related quality of life, measured using the EuroQol five-dimension visual analogue scale (EQ-5D VAS). The EQ-5D captures five dimensions of daily life: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. It also includes a visual analogue scale on which participants rate their overall health from 0 to 100. The change in the mean EQ-5D VAS score between the intervention and control arms is the principal measure of effectiveness.

The secondary outcomes includes clinical and cardio renal metabolic, behavioural, psychosocial and functional, and health-system and economic domains, measured with standardised instruments and laboratory methods applied consistently across sites.

Clinical and cardio renal metabolic outcomes: Blood pressure control is assessed using validated digital blood-pressure monitors. Glycaemic control is assessed using fasting blood glucose and glycated haemoglobin (HbA1c), with HbA1c analysed from EDTA samples using high-performance liquid chromatography certified to the National Glycohemoglobin Standardization Program (NGSP) and Glucose Oxidase-Peroxidase method, for fasting glucose. The lipid profile comprises total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides; these are measured using standardised enzymatic assays. Renal function is assessed using serum creatinine measured by methods traceable to isotope-dilution mass spectrometry, and liver function is assessed using standard biochemical assays. Body mass index is calculated from measured height and weight. A composite cardiovascular disease risk score is derived using an established algorithm incorporating age, blood pressure, antihypertensive treatment status, fasting glucose, lipid profile and tobacco use.

Behavioural outcomes: Tobacco use, alcohol consumption, diet and physical activity are assessed using instruments from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) study.

Psychosocial, mental-health and functional outcomes: Psychosocial, mental-health and functional outcomes: Health-related quality of life across physical and mental domains is also measured using the twelve-item Short Form Health Survey (SF-12), complementing the EQ-5D. Depressive symptoms are measured using the Patient Health Questionnaire (PHQ-9), and anxiety is measured using the Generalised Anxiety Disorder scale (GAD-7). Disability and functioning are assessed using the twelve-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). Frailty is assessed using the Fried Frailty Phenotype scale. Self-efficacy for managing chronic disease is assessed using the six-item Self-Efficacy for Managing Chronic Disease scale (SEMCD-6).

Health-system and economic outcomes: Healthcare utilisation, treatment burden and economic burden are measured using structured instruments adapted from previously validated tools. These measurements will inform a cost-effectiveness analysis of the intervention.

The cluster randomised controlled trial (cRCT) commenced on 18 May 2026 with participant screening, enrolment and baseline assessments. Following completion of baseline assessments, clusters were randomised to the intervention and control groups. The intervention was initiated in the intervention group on 13 August 2026. Midline assessments are planned for August 2027, followed by end-line assessments to evaluate implementation progress, measure health outcomes and assess intervention effectiveness.

Quality assurance and Process evaluation:

Quality is monitored in real time throughout implementation. At each site, a designated study coordinator checks enrolment logs and EDSS entries each week to confirm completeness, while monthly central monitoring audits the data by cross-checking records between REDCap and the EDSS to identify missing or inconsistent entries. A process evaluation runs alongside the trial to understand how the intervention is delivered in practice, rather than only whether it is effective. It assesses the reach, dose, fidelity and acceptability of the intervention. This includes examining how consistently the EDSS, telemedicine and patient application are used and how closely delivery follows the intended workflows. The evaluation draws on system-usage logs, fidelity checklists, supervision records and qualitative interviews with participants and providers. These findings will help interpret the trial results, identify the barriers to and enablers of implementation, and inform future scale-up.

Data Management:

Study data are managed on a common data platform that links the three digital components through a single unique participant identifier. Baseline and survey data are entered into REDCap, clinical visit and prescription data are captured in the EDSS on the DigiSetu platform, and patient-application usage data are recorded automatically; linking these through the shared identifier enables longitudinal follow-up, avoids duplicate entry, and supports unified monitoring and analysis. All data are held on secure, access-controlled systems with audit trails, and recruitment and retention are monitored monthly.