A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against novel coronavirus disease-2019 (COVID-19). Most Phase 3 tri- als have adopted virologically confirmed symptomatic COVID-19 disease as the primary efficacy endpoint, although laboratory-confirmed SARS-CoV-2 is also of interest. In addi- tion, it is important to evaluate the effect of vaccination on disease severity. To provide a full picture of vaccine efficacy and make efficient use of available data, we propose using SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19 as dual or triple pri- mary endpoints. We demonstrate the advantages of this strategy through realistic simulation studies. Finally, we show how this approach can provide rigorous interim monitoring of the trials and efficient assessment of the durability of vaccine efficacy.
Keywords: Phase 3 trials; SARS-CoV-2; multiple primary endpoints; severe COVID-19; totality of evidence.
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