The Burden of Selecting a Primary Efficacy Endpoint: Consideration of a COVID-19 Burden of Disease Endpoint

• Activity Number: 150 - COVID-19 Vaccine Statistics: A Reflection on a Year at Warp Speed
• Type: Invited
• Date/Time: Tuesday, August 10, 2021 : 10:00 AM to 11:50 AM
• Sponsor: Biometrics Section
• Author(s): Jonathan V Hartzel* and Devan V Mehrotra
• Companies: Merck & Co., Inc. and Merck & Co., Inc.
• Keywords: Burden of disease; COVID-19; Vaccine Efficacy

Abstract

Per regulatory guidance, the recommended primary efficacy endpoint for development of a COVID-19 vaccine is virologically confirmed symptomatic SARS-CoV-2 infection. However, the importance of assessing vaccine efficacy against severe COVID-19 is also recognized, especially considering that a vaccine may be more effective in preventing severe versus mild disease. Since the expected incidence of severe disease in a clinical trial would likely be very low, powering a trial solely on a severe disease endpoint would lead to much larger trials. Alternatively, in this talk we will consider the use of a “burden of disease” composite endpoint that quantitatively differentiates severe and non-severe COVID-19. We will focus on the derivation of the endpoint and corresponding test statistic, the interpretation of the endpoint, and how it can be incorporated as a primary and/or co-primary endpoint in assessing the efficacy of a COVID-19 vaccine.