A scoping review of randomized controlled trials in the early phase of the COVID-19 pandemic: country-level research response to COVID-19 therapeutics and vaccines

Abstract Backgrounds Clinical trials are central in pandemic preparedness and response (PPR). This scoping review aimed to illustrate the landscape of COVID-19-related randomized controlled trials (RCTs), focusing on the countries’ capacity to conduct and coordinate RCTs, and on the operational features. Methods RCTs on COVID-19 therapeutics and vaccines that were published between November 1, 2019 and November 30, 2021 were identified through EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and CINAHL. Data were collected on study design; intervention; participating countries; responsible party; funding source; and design and operational features, such as platform trial, informed consent, and decentralization. We compared the differences based on whether the study was led by high-income countries (HICs) or low- and middle-income countries (LMICs). Results The final analysis included 328 of the 22,392 screened trials, including 47 multi-country trials, majority of which (46, 97.9%) were led by HICs. Both for therapeutics and vaccines, trials led by HICs enrolled a larger number of study participants than those by LMICs (median 207 vs. 57.5 for therapeutics, and 805 vs. 334 for vaccines). Intervention duplication was observed in 68.6% (81/118) of therapeutic interventions in trials led by HICs and 85.8% (133/155) in those led by LMICs (p-value = 0.001). Of the 42 investigational new drugs trials on therapeutics, 26 and 16 were led by HICs and LMICs, respectively, with a larger proportion led by HICs (odds ratio 2.5, 95% confidence interval 1.3–4.8). Among the 29 platform trials, 28 were led by HICs, all of which focused on therapeutics. Decentralization approaches and consent methods other than the written format were utilized in 15.5% and 19.2% of the trials, respectively. Conclusions Globally, LMICs were under-represented among the published trials during the first two years of the pandemic. Global collaboration and coordination are essential to improve clinical trial ecosystem during health emergencies, and pragmatic approaches and improved design and operational features of clinical trials can strengthen the global clinical trial infrastructure. Clinical trial Not applicable.