Randomized controlled trials in patients with COVID-19: a systematic review and critical appraisal

OBJECTIVES: This study aimed to describe the prevalence of risks of bias in randomized trials of therapeutic interventions for COVID-19. METHODS: Systematic review and risk of bias assessment performed by two independent reviewers of a random sample of 40 randomized trials of therapeutic interventions for moderate-severe COVID-19. We used the RoB 2.0 tool to assess the risk of bias, which evaluates bias under five domains as well as an overall assessment of each trial as high or low risk of bias. RESULTS: Of the 40 included trials, 19 (47%) were at high risk of bias, and this was particularly frequent in trials from low-middle income countries (11/14, 79%). Potential deviations to intended interventions (i.e., control participants accessing experimental treatments) were considered a potential source of bias in some studies (14, 35%), as was the risk due to selective reporting of results (6, 15%). The randomization process was considered at low risk of bias in most studies (34, 95%), as were missing data (36, 90%) and measurement of the outcome (35, 87%). CONCLUSION: Many randomized trials evaluating COVID-19 interventions are at risk of bias, particularly those conducted in low-middle income countries. Biases are mostly due to deviations from intended interventions and partly due to the selection of reported results. The use of placebo control and publicly available protocol can mitigate many of these risks.