Concordance between the results of randomized and non-randomized interventional clinical trials assessing the efficacy of drugs for COVID-19: a cross-sectional study.

ABSTRACT

OBJECTIVES: To assess whether results of observational studies of potential anti-COVID-19 drugs were reproduced in subsequent randomized controlled trials (RCTs). METHODS: This was a retrospective cross-sectional study, including studies published online between 1 January and 27 October 2020 that evaluated potential COVID-19 treatments and reported all-cause mortality. RESULTS: Of 133 comparisons included in 117 studies, most were non-randomized (104/133, 78%). Hydroxychloroquine was the most common drug type, combined with azithromycin (n = 27, 20%) or alone (n = 22, 16%), followed by IL-6 inhibitors (n = 36, 27%) and corticosteroids (n = 26, 20%). Seventy-one percent (74/104) of non-randomized studies reported adjusted survival results and only 8% (8/104) adjusted for immortal time bias. Only two RCTs (2/29, 7%) reported significant survival benefit, both reporting treatment with corticosteroids, while 32/104 (31%) non-randomized studies showed statistically significant survival benefit associated with the intervention arm. The results of the majority (28/32, 88%) of non-randomized studies reporting survival benefit were not replicated by large-scale RCTs. CONCLUSIONS: The results of most non-randomized studies reporting survival benefit of potential anti-COVID-19 drugs were not replicated by large RCTs. Regulators and healthcare professionals should exercise caution and resist the pressure to approve and prescribe drugs of unproven efficacy and potential toxicity to optimize patient care and maintain public trust in medical science.