JMIR Publications

ABSTRACT

Background:

Decentralised and digitally enabled clinical trials (DCTs) have expanded rapidly through telehealth, mobile health applications, wearable sensors, electronic patient-reported outcomes, remote monitoring, and virtual trial infrastructure. Although these approaches promise improved accessibility and reduced participant burden, whether they meet the needs of people with complex health conditions remains uncertain.

Objective:

To examine how decentralised and digitally enabled trial methods align with the needs of complex populations using the Nonadoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework.

Methods:

A systematic review was conducted following PRISMA and registered on the Open Science Framework (10.17605/OSF.IO/AMSRG). PubMed, Scopus, Web of Science, ScienceDirect and CINAHL were searched from January 2000 to March 2026. Eligible studies evaluated decentralised or digitally enabled trial methods in adults with chronic disease or features of clinical complexity older age, frailty, multimorbidity, cognitive impairment, or mental health conditions. Risk of bias was assessed using RoB 2 and ROBINS-I. A JBI convergent integrated mixed-methods synthesis combined deductive NASSS coding with inductive thematic analysis and cross-domain synthesis.

Results:

Sixty-seven studies met the inclusion criteria, predominantly randomised controlled trials alongside non-randomised, feasibility, pragmatic and implementation designs. Most enrolled adults with chronic disease, whereas relatively few specifically recruited older, frail, multimorbid or cognitively impaired participants. Risk of bias was predominantly low to moderate. Harmonised analysis generated 1,904 coded excerpts, with Technology the largest domain (649; 34.1%), followed by Condition (396; 20.8%), Value Proposition (234; 12.3%), Adopter System (209; 11.0%), Organisation (185; 9.7%), Wider System (144; 7.6%) and Embedding and Adaptation over time (87; 4.6%). Twenty-seven studies addressed all seven NASSS domains and 51 addressed at least six, indicating that successful DCTs depend on coordinated technological, behavioural, organisational and system-level mechanisms. In cognitive impairment and mental health, established assessments including the CDR, PHQ-9, PHQ-ADS, MADRS, EPDS and web-based neuropsychological batteries were feasibly captured remotely; however, no included study evaluated remote administration of the MMSE or MoCA, whether clinician-led or automated, providing reference standards for future Composite Digital Cognitive Outcomes derived from wearable sensors, ambient sensing, conversational artificial intelligence, speech and language analysis, and patient-connected outcome measures.

Conclusions:

DCTs can enhance accessibility, engagement, remote monitoring and personalised care when technologies are matched to the clinical, functional, behavioural and cognitive needs of complex populations. However, current provision is not yet sufficiently adapted or validated for people with cognitive impairment and other complex needs. The value of DCTs depends on alignment between technological design, clinical context, participant capability, organisational readiness and wider health-system support, not decentralisation alone. Future trials should prioritise accessible hybrid models, caregiver-supported participation, sustained technical and clinical support, and validation of emerging Composite Digital Cognitive Outcomes against established cognitive reference standards to advance equitable participation and long-term impact. Clinical Trial: N/A