All Times EDT
Keywords: COVID-19, vaccines, clinical trials
Coronavirus Disease 2019 (COVID-19) was declared by the WHO as a global pandemic in March of 2020. Since then, over 100 candidate vaccines around the world have been under clinical evaluation (WHO), with statisticians playing a pivotal role in clinical studies to assess safety and effectiveness. In the United States, two FDA guidances were published to advise sponsors on the development and licensure of COVID-19 vaccines (June, 2020) and data to support Emergency Use Authorization (EUA; March, 2022). In addition, several Vaccines and Related Biological Products Advisory Committee (VRBPAC) Meetings have been convened to discuss the general development of COVID-19 vaccines, considerations for vaccine booster doses, process for vaccine strain selection to address current and emerging COVID-19 variants, and product-specific data. While several vaccines have been authorized under EUA and/or licensed in the United States, waning immunity, combined with emerging variants, necessitate evaluation of booster doses and strain modifications to ensure continued protection from COVID-19 complications. However, development of both new and authorized/licensed vaccines have become operationally and ethically challenging amid an ever-evolving epidemiology. We consider various statistical challenges in the design of vaccine trials and the evaluation of long-term vaccine effectiveness after authorization, where data are critical to inform the need and timing of booster doses. Furthermore, we explore challenges in assessing the effectiveness of modified vaccines and new vaccines, both as a primary series and as a heterologous booster, when efficacy trials become increasingly difficult to conduct.