Ethical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine

Type Journal Article Author Rafael Dal-Ré Author Arthur L. Caplan Author Christian Gluud Author Raphaël Porcher URL https://www.acpjournals.org/doi/10.7326/M20-7357 Publication Annals of Internal Medicine ISSN 0003-4819 Date 20/11/2020 Extra Publisher: American College of Physicians Journal Abbr Ann Intern Med DOI 10.7326/M20-7357 Accessed 2020-11-27 14:39:59 Library Catalog acpjournals.org (Atypon) Abstract The current pandemic demands early licensing and deployment of a vaccine against coronavirus disease 2019 (COVID-19) that provides “worthwhile” efficacy (1). However, accomplishing this goal could compromise 2 ethical principles that guide clinical research—scientific validity, which is based on the tradeoff between risk and benefit, and social value, which depends on the short-term and long-term prevention of COVID-19. Five Western companies are conducting placebo-controlled, phase 3, randomized clinical trials (RCTs) whose primary outcome is the prevention of clinical disease (Table). Each trial will last for up to 2 years and have at least 1 interim analysis. As soon as one of these RCTs establishes vaccine efficacy and provides 2 months of safety data (2), the U.S. Food and Drug Administration (FDA) could within a few days or weeks license the vaccine or provide Emergency Use Authorization (EUA). Deployment could begin immediately after either decision. Early approval is possible because each of these trials has recruited tens of thousands of participants, and the World Health Organization and the FDA (3) require that vaccines show only at least 50% efficacy. These conditions mean that the primary efficacy outcome could be established by some 50 cases in vaccine recipients and 100 cases in placebo recipients (1). Among secondary outcomes are seroconversion rate and geometric mean titers of neutralizing antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).