Decentralized clinical trials: A comprehensive analysis of trends, technologies, and global challenges

Decentralized clinical trials (DCTs), particularly in the U.S., gained substantial attention during the COVID-19 pandemic, enabling trial activities to be conducted from participants' homes or local healthcare facilities despite restrictions and lockdowns. Regardless of the growth in interest, many facets of the DCT landscape remain unexplored or nascent in their development. This study aims to explore the key characteristics and development of the U.S.-registered DCT landscape, adoption patterns across various clinical contexts, and the role of digital technologies. We analyzed 1370 decentralized trials from ClinicalTrials.gov, collected using a broad DCT-keyword search. The data were screened and coded manually, and analyzed descriptively for temporal trends, purpose of decentralization, intervention type, geographic representation, and digitalization. Our findings align with previous reports of a growing, heterogeneous landscape of DCTs, with behavioral interventions appearing more suitable for decentralization than other types of interventions. Notably, most DCTs still focus on evaluating decentralized methods rather than merely implementing them in their investigations. Often, studies integrate digital tools either as the interventions themselves or to enable the digital delivery of study activities. Although the trial registry used is U.S.-based, and a U.S. partner is part of more than 50% of the studies identified, many trials are done in multiple countries or countries outside of the U.S. (42%). Among these trials, the data revealed considerable differences, with digitalized DCTs in this sample concentrated in high-income countries. Despite rapid growth in DCTs, our findings suggest the presence of a field in development, very much focused on establishing a methodological foundation. To unlock the potential of DCTs locally and globally, four critical areas demand further attention: digital equity, regulatory frameworks for diverse technologies, establishment of methodological validation processes, and further research on barriers to implementation.