Evidence for the Efficacy of COVID-19 Convalescent Plasma.

During the global health emergency caused by the coronavirus disease 2019 (COVID-19), evidence relating to the efficacy of convalescent plasma therapy-evidence critically needed for both public policy and clinical practice-came from multiple levels of the epistemic hierarchy. The challenges of conducting clinical research during a pandemic, combined with the biological complexities of convalescent plasma treatment, required the use of observational data to fully assess the impact of convalescent plasma therapy on COVID symptomatology, hospitalization rates, and mortality rates. Observational studies showing the mortality benefits of convalescent plasma emerged early during the COVID-19 pandemic from multiple continents and were substantiated by real-time pragmatic meta-analyses. Although many randomized clinical trials (RCTs) were initiated at the onset of the pandemic and were designed to provide high-quality evidence, the relative inflexibility in the design of clinical trials meant that findings generally lagged behind other forms of emerging information and ultimately provided inconsistent results on the efficacy of COVID-19 convalescent plasma. In the pandemic framework, it is necessary to emphasize more flexible analytic strategies in clinical trials, including secondary, subgroup, and exploratory analyses. We conclude that in totality, observational studies and clinical trials taken together provide strong evidence of a mortality benefit conferred by COVID-19 convalescent plasma, while acknowledging that some randomized clinical trials examined suboptimal uses of convalescent plasma.