National Institute for Health and Care Research Global Health Research Centre for Multiple Long-Term Conditions

Implementation framework and study design: This study uses a cluster randomized controlled design in rural primary health centres to test an integrated digital health program for people with multiple long-term conditions. The main outcome is health-related quality of life, measured using the EuroQol five-dimension scale (EQ 5D). This tool asks participants about five areas of daily life mobility, self-care, usual activities, pain or discomfort, and anxiety or depression and includes a visual scale where people rate their overall health. Sample size calculations accounted for clustering at the facility level. The assumptions were a significance level of 0.05, statistical power of 90 percent, a mean score of 74.37 in the control group, a standard deviation of 15.1, a minimum detectable difference of 2.5 points, an intraclass correlation of 0.02, and a 20 percent attrition rate. Based on these parameters, the final sample size is 120 centres with 30 participants in each, giving a total of 3,600 participants. After recruitment, centres will be randomly assigned to either the intervention group or the control group. Participants in the intervention centres will receive the digital health program for 24 months, while those in the control centres will continue with routine care. The trial will be conducted over a 24 month period across selected primary health centres: thirty in Andhra Pradesh, thirty in Rajasthan, thirty in Haryana, and thirty in Nepal. A pilot phase is currently underway in a subset of centres two each in Andhra Pradesh, Rajasthan, and Nepal to refine implementation processes. This includes workflow integration, training delivery, and technical specifications. The intervention package consists of four components: (i) an electronic decision support system to incorporate evidence-based management of multiple long-term conditions into primary health centre workflows; (ii) assisted telemedicine, using both a fixed "hub" model and a portable "backpack" kit, to connect patients and health workers with remote specialists; (iii) a patient-facing mobile application to support self-management through education, reminders, and messaging; and (iv) trained community health champions to strengthen links between the health system and the community.

Co-Design and intervention development: The core intervention components were iteratively co-designed with stakeholders across three sites in India (Jodhpur, Rajasthan; Anakapalli, Andhra Pradesh) and one in Nepal. Over 15 co-design workshops were conducted between December 2024 and early 2026, culminating in a national codesigning workshop in New Delhi. In workshop participants were stratified into stakeholder groups to ensure broad representation: Group A (patients with MLTC and their caregivers/community representatives), Group B (primary healthcare providers, technical experts, and researchers), and Group C (policy makers/district/state officials). Workshops were held in accessible community venues (and online for policy makers) with careful advance mapping and consent of participants. Trained facilitators guided semi-structured discussions using journey mapping, brainstorming, voting/prioritization exercises, and live demonstrations of prototype technologies. These activities elicited user needs and system requirements which directly shaped the intervention package. Group A workshops (patients/caregivers) identified critical user preferences (e.g. trusted provider communication, self-care support, and community champions) and barriers (disappointment with fragmented care, out-of-pocket costs). Group B workshops (providers/experts) yielded practical design recommendations, such as integrating clinical guidelines into workflows, incorporating drug-interaction alerts, and defining standard teleconsultation formats with language and trust considerations. A joint workshop with both Groups A and B validated and prioritized intervention features: for example, "must-have" features included an editable EDSS dashboard, simple app navigation in local languages, offline data entry, and a reliable telemedicine referral pathway. Feedback on the patient-facing application emphasized low-literacy formats (audio/video, SMS/IVR options) and event-triggered reminders. Throughout, emerging insights were documented and fed back into design cycles ("design" and "adapt" phases of the ADAPT framework), ensuring that the EDSS algorithms, telemedicine workflows, and mHealth app reflected local context, language, and health system realities. In summary, the co-design process ensured that the intervention components are grounded in stakeholder experience and health system constraints. The final intervention package consists of an Electronic Decision Support System (EDSS), assisted telemedicine models (facility-based and portable "backpack" models), and a patient-facing mobile application, complemented by trained community champions and strengthened referral pathways. The co-design phase also produced stakeholder engagement structures (e.g. community advisory boards) and preparatory materials (training modules, user manuals) that will underpin implementation. Further, minor refinements to technical specifications (algorithm logic, user interfaces, and data flows) are being informed by ongoing pilot implementation, without altering the core intervention components of the RCT.

Workflow Integration at PHC Level: The EDSS is integrated into routine outpatient workflows, rather than functioning as a parallel system. Nurses and officers are instructed to use the system during normal clinical hours (e.g. during patient intake and consultation). For each patient encounter, PHC staff complete all mandatory fields in the EDSS before submitting the encounter. Usage logs (timestamps of logins, data entries, referral triggers) are captured continuously on the DigiSetu back-end and synchronized daily, creating an audit trail. Supervisors review log data weekly to ensure adherence to protocol. To support these workflows, standard operating procedures (SOPs) have been developed for each task. SOPs detail: (a) Case identification and case-mix classification (how to use the screening tool and record diagnoses); (b) Data collection protocols (guidance on REDCap and EDSS data entry, use of unique patient IDs); (c) Telemedicine workflow (criteria for tele-referral, scheduling process, documentation of consult notes); and (d) Patient app enrolment. These SOPs were co-created with implementers and iteratively refined during pilot workshops. For example, telemedicine SOPs explicitly define "who to refer" (e.g. uncontrolled hypertension or diabetes after 3 medication trials) and "when not to refer" e.g. acute emergencies). All staff nurses and MOs receive printed job aids summarizing key steps for each component (screenshots of EDSS pages, referral algorithms, consent checklists), which are reviewed during training.

Procedures and delivery workflow: Participants will enrol through a structured visit-based approach at participating primary health centres. During wave 1, trained health workers will screen all adults aged ≥40 years using a standardized eligibility tool to identify individuals with two or more chronic conditions consistent with MLTCs. Eligibility screening will include confirmation of diagnosed conditions and basic demographic information (such as village name, phone number). Individuals meeting eligibility criteria will receive study information and will be invited to provide written informed consent. Wave 2 will serve as the baseline assessment visit and will be conducted after obtaining written informed consent. During this visit, trained research staff will conduct comprehensive baseline evaluations using standardized interviewer administered questionnaire. Data collected will include socio-demographic characteristics, medical history, and behavioural risk factors. Objective clinical measurements will include systolic and diastolic blood pressure and anthropometry (height, weight, and body mass index). Behavioural and patient reported outcomes will be assessed using validated instruments, including diet quality, physical activity, tobacco and alcohol use, depressive symptoms (PHQ-9), anxiety (GAD-7), health-related quality of life (EQ-5D), disability (WHODAS 2.0), frailty measures, self-efficacy, and treatment burden. These baseline measurements will serve as reference values for evaluating changes in predefined clinical, behavioural, and patient-reported outcomes at follow up. Wave 3, Fasting venous blood samples will be collected following standard operating procedures. Laboratory analyses will include glycaemic markers (fasting blood glucose and HbA1c), lipid profile, liver function tests and renal function tests, using standardised protocols to ensure comparability across sites. Participants will receive their test results within approximately 2 to 3 days of sample collection. Results will be provided as a printed report. A trained member of the study team (nurse, CCDC health worker) will explain the results to participants. Participants with abnormal findings will be counselled and referred to the nearest appropriate public health facility (e.g., PHC/CHC/District Hospital) for further evaluation and management as per standard care pathways. In cases of significantly abnormal or critical values, participants will be informed promptly and advised to seek immediate medical care, with the study team facilitating referral where feasible. The duration of intervention up to 12 to 18 months. End line assessments will replicate baseline procedures to enable evaluation of changes over time. Follow up data will be collected using the same standardized instruments and clinical protocols, ensuring consistency across timepoints and study sites.

Training and capacity building: All healthcare providers in intervention PHCs (medical officers, staff nurses, and auxiliary nurse-midwives) will undergo comprehensive training on the intervention components prior to RCT implementation. The training programme consists of a 3-4-day in-person workshop co-facilitated by clinical, public health, and digital health experts. The curriculum was co-developed by a multi-disciplinary Course Advisory Committee (45 members including clinicians, technologists, and community representatives) to cover: MLTC care principles, EDSS operation, telemedicine processes, and patient app overview. Training methods include lectures, interactive demonstrations of EDSS and app mock-ups, hands-on practice in simulation labs, and case scenario role-plays. Pre- and post-tests assess knowledge and confidence. A cascade training model will be employed: initially, "master trainers" (e.g. site investigators, district NCD programme officers) receive intensive instruction, then they train the PHC teams locally. State health authorities are engaged from the outset to embed the training into routine NCD programme capacity building. Custom training manuals and quick-reference job aids (in local languages) were developed and distributed to all trainees. For example, printed flowcharts outline the step-by-step process of a telemedicine consult or patient enrollment in the app. Training attendance and performance are tracked via checklists. In the initial pilot phase, 27 PHC staff (mostly nurses) completed the pilot training with post-training evaluation; similar numbers will be trained in Nepal. Refresher sessions are scheduled at 3 months, supplemented by on-site mentoring visits from research staff. Beyond initial implementation, ongoing capacity building is integrated into the project. Primary Health Centre teams participate in monthly learning sessions with research staff, sharing challenges and solutions. A district-level supervisory structure is in place: each PHC is paired with a mentor (a senior nurse or physician) who conducts quarterly site visits to review fidelity checklists, observe practice, and provid

• Systolic Blood Pressure (SBP) [Срок оценки: Systolic Blood Pressure outcome will be assessed at baseline (recruitment) and at 24 months (endline).]
• Diastolic Blood Pressure (DBP) [Срок оценки: Change in the diastolic blood pressure from baseline to 24-month endline.]
• Glycated Haemoglobin (HbA1c) [Срок оценки: HbA1C outcomes will be assessed at baseline (recruitment) and at 24 months (endline)]
• Fasting Plasma Glucose [Срок оценки: Glycaemic control outcomes will be assessed at baseline (recruitment) and at 24 months (endline).]
• Total cholesterol [Срок оценки: Total cholesterol outcome will be assessed at baseline (recruitment) and at 24 months (endline).]
• Renal function (Estimated glomerular filtration rate) [Срок оценки: Renal function outcome will be assessed at baseline (recruitment) and at 24 months (endline).]
• Liver function (Total Bilirubin) [Срок оценки: Liver function (Total Bilirubin) outcome will be assessed at baseline (recruitment) and at 24 months (endline).]
• Cardiovascular risk [Срок оценки: Cardiovascular risk outcome will be assessed at baseline (recruitment) and at 24 months (endline)]
• Tobacco use [Срок оценки: Changes in tobacco use will be assessed at baseline (recruitment) and at 24 months (endline).]
• Alcohol Consumption [Срок оценки: Changes in alcohol consumption will be assessed at baseline (recruitment) and at 24 months (endline]
• Diet Quality [Срок оценки: Changes in diet quality will be assessed at baseline (recruitment) and at 24 months (endline)]
• Physical Activity [Срок оценки: Changes in the Physical activity will be assessed at baseline and 24 months (endline)]