In Reply We thank Drs Mathew and Feldmann for their comments on the results of ACTIV-1. We agree that mortality is a very important clinical outcome, but designing a trial such as ACTIV-1 to have sufficient power to detect an effect on mortality was challenging in June 2020, when data on clinical outcomes of severe COVID-19 were in flux. Indeed, the design of ACTIV-1 was heavily influenced by the results of ACTT-1, the initial placebo-controlled trial of remdesivir, which showed evidence of improved time to recovery but not improved mortality.
