Overview of Phase IV Clinical Trials Targeting COVID-19: Status Report of Studies Registered on the ClinicalTrials.gov Platform

Abstract

Introduction: Phase IV trials evaluate drugs' efficacy, safety, and tolerability in a real-world setting, which may provide evidence related to the safety of approved drugs. This study aimed to characterize the phase IV clinical trials registered at ClinicalTrials.gov targeting COVID-19 and reflect on future needs for post-marketing clinical trials. Methods: A descriptive cross-sectional study was performed in the ClinitalTrials.gov database with phase IV clinical trials addressed to COVID-19. The search was carried out on March 23rd, 2021, considering search filters for this disease. Results: A total of 146 protocols were retrieved through a structured search. The results showed the need to promote new, blinded, and larger sample-size phase IV clinical trials. 93.9% of the clinical trials were funded by individuals, universities, and organizations (category "other" funders), and 56.8% were open-label. America and Europe played a more critical role in phase IV clinical trials, with the former leading with 58 trials spread across five countries and the latter with 38 trials in 17 countries. More than two-thirds of the trials (69.8%) included 500 participants. Conclusions: For the observed period, phase IV clinical trials registered in the ClinicalTrials.gov were dominated by short-term follow-up, open-label designs, small sample sizes, funded mainly by individuals, universities, and organizations, and centered mainly in America and Europe. The methodological features of future studies should be emphasized, namely adequate sample sizes, for which appropriate funding for the implementation of these studies is paramount.