Operational strategies among infectious disease clinical trial sites during pandemics: a scoping review

The aim of this study is to examine documented strategies, challenges, and lessons related to clinical trial site operations during pandemics.

This review focused on seven major pandemics: COVID-19, HIV/AIDS, Ebola, SARS, MERS, H1N1, and Zika. Searches were conducted using PubMed and Embase between September 2024 and February 2025, yielding 7572 unique records. After dual screening, 47 articles met inclusion criteria, with an additional 8 identified through citation searching, for a total of 55. Non-English articles were translated using Google Translate. Data were extracted and thematically analyzed through iterative familiarization, keyword identification, coding, and consensus discussion.

Of the 55 included articles, most originated from the European Region (61%) and the Americas (52%), with additional representation from Africa (19%), the Western Pacific (8%), Eastern Mediterranean (5%), and Southeast Asia (5%). Percentages exceed 100% because several studies reported across multiple regions. Study designs were predominantly descriptive (60%) with fewer randomized controlled trials (22%), observational (18%), and cohort studies (2%). COVID-19 accounted for the majority of articles (58%), followed by HIV/AIDS (20%), Ebola (13%), H1N1 (2%), and Zika (4%); no eligible studies addressed SARS or MERS. Operational themes included policy (73%), resources (55%), networks (53%), infrastructure (47%), technology (45%), study design (31%), and communication (22%). Publications peaked during pandemic years, reflecting intensified research activity. Reported challenges included protocol-practice misalignment, fragmented infrastructure, regulatory bottlenecks, and under-resourced sites. Reported practices included early site engagement in protocol development, streamlined ethics and contracting processes, investment in digital and decentralized infrastructure, and cross-trained staff. Gaps included limited use of adaptive trial designs and insufficient cross-national collaboration.

Clinical trial sites implemented systemic operational changes to sustain research during pandemics. Key lessons include the need to strengthen infrastructure, workforce capacity, and institutional adaptability, and the need to address persistent global inequities. Institutionalizing early site engagement, adaptive designs, and equitable collaboration will be essential to enable timely and resilient clinical research responses in future pandemics.