EXPLORING THE IMPACT OF RANDOMIZED CONTROLLED TRIALS EVALUATING COVID-19 THERAPEUTICS ON CLINICAL PRACTICE GUIDELINES

There was an unprecedented response from the scientific community to the COVID-19 pandemic with many randomised therapeutic trials registered within a short time. However, many trials were too small or poorly conducted and thus did not contribute to evidence generation. We aim to quantify the overall policy impact of COVID-19 related clinical research by assessing the proportion and characteristics of randomised controlled trials (RCTs) used as evidence for developing the WHO COVID-19 treatment guideline (WHO guideline). All RCTs that enrolled SARS-CoV-2 positive patients and evaluated therapeutic agents listed in the WHO guideline (version 13, Jan 2023) were eligible for inclusion. Registration information for these RCTs was obtained from the Infectious Diseases Data Observatory's living systematic review of COVID-19 clinical trial registries. Pre-print and peer-reviewed publications were obtained through a systematic search of the Europe PMC database. Each trial registration was linked with a resulting publication through its registry ID. Between Jan 2020 and Nov 2023, 332 registered and/or published RCTs were considered eligible for use as evidence in the WHO guideline. Of the 332 RCTs, 3 (0.9%) were published but never registered, 172 (51.8%) were registered and published, and 157 (47.3%) were registered but not yet published. Only 63 out of 332 RCTs (19.0%) were used as evidence in the WHO guideline. The sample size of RCTs that were incorporated as evidence into the guidelines was larger (median: 432, interquartile range (IQR): 145-2,330) than RCTs that were not used (median: 145, , IQR 82-382). Of the 269 studies not used in the WHO guideline, 40 (15%) were registered after the first recommendation for the drug the study was evaluating had already been made. For published studies, the median time to publication was 14 months (95% confidence interval: 12-17). These findings demonstrate that a large proportion of RCTs had no impact on clinical guidelines. The pandemic response was marked by a delay in initiating trials and their subsequent publication, which hindered their prompt utilisation as evidence in clinical guidelines.