Digital health technology use in clinical trials of rare diseases: a systematic review

Background

Rare disease clinical trials face unique challenges, resulting in low enrollment and limited retention. Digital health technologies (DHTs), when applied through a patientcentric lens, offer promising solutions to these challenges by enhancing data collection efficiency, improving patient engagement, and supporting long-term health care.

Methods

This study investigates DHT application in clinical studies across the ten moststudied rare diseases and was registered with PROSPERO (registration number: CRD420251088025). Up to June 26 2024, a total of 262 studies were identified through ClinicalTrials.gov, the International Clinical Trials Registry Platform, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science. DHT applications were classified into patient recruitment, digital treatment, data monitoring and collection, outcome assessment, remote follow-up, and long-term care management based on scenarios and functionalities.

Results

Among all DHT applications, data monitoring and collection was the most prevalent (31.3%), serving primarily to enable continuous tracking of physiological parameters relevant to specific rare disease conditions. Digital treatment is featured in 57 studies (21.8%), most commonly as digital physiotherapy. A notable increase in DHT adoption is observed from 2017–2020 to 2021–2024 across nearly all ten diseases. Between 2021 and 2024, cystic fibrosis shows the highest proportion of DHT-enabled trials relative to all studies conducted for that disease (29.7%).

Conclusions

Our findings reveal a growing trend toward digital integration in rare disease trials to support decentralized, scalable, and patient-centered research models. We propose a “4A” conceptual framework—Accessibility, Agility, Awareness, and Adaptability to accelerate therapeutic development and expand access to care for these underserved rare disease populations.