Trust, altruism, and ease of participation in a fully remote, decentralized COVID-19 clinical trial

Clinical trials, while central to evidence-based medicine, are consistently constrained by obstacles in recruitment and retention. These challenges were magnified during the COVID-19 pandemic, when rapid mobilization of research demanded unprecedented participant engagement. While prior work has explored general barriers and facilitators to participation, less is known about how trust, altruism, and procedural design interact to shape engagement in fully remote trials. This study examined how trust in science and institutions, altruistic motivations, and perceived ease of participation shaped engagement and retention in a decentralized COVID-19 treatment trial to identify strategies to optimize recruitment and retention. This research featured a longitudinal qualitative arm within the ACTION trial, a fully remote investigation of azithromycin for mild-to-moderate COVID-19 symptoms. Participants were engaged through semi-structured interviews at two waves: T1 (December 2020–March 2021; n = 19) and T2 (January–February 2022; n = 11). Data were analyzed using immersion–crystallization techniques to identify evolving themes across both phases. Participants' decisions to enroll were primarily driven by altruism and trust in scientific and institutional actors, alongside perceived personal and familial benefit. Ongoing retention was reinforced by the trial's low-burden, user-friendly design and transparent communication processes. Participants identified challenges encountered during trial participation, including discomfort with unfamiliar procedures and apprehension toward novel interventions. Beyond these experiences, they articulated recommendations for future decentralized research, emphasizing proactive outreach strategies, such as targeted digital recruitment campaigns and partnerships with community organizations, alongside timely return of results through automated participant portals that provide interim updates and study milestones. Embedding qualitative methods within decentralized trials offers critical insights into the lived experiences of participants. Findings suggest that trust, altruism, and user-friendly design are central to optimizing engagement and retention. These lessons extend beyond COVID-19 and can inform more equitable, efficient, and participant-centered approaches to clinical research in future public health emergencies.