Public Health Impacts of Vaccines for COVID-19 and Beyond: Opportunities to Overcome Technical and Regulatory Barriers for Randomized Trials.

The COVID-19 pandemic has revealed the importance of the population-scale effects of both diseases and interventions. Vaccines have had an enormous impact, greatly reducing the suffering caused by COVID-19. Clinical trials have focused on individual-level clinical benefits, however, so the broader effects of the vaccines on preventing infection and transmission, and their overall effect at the community level, remain unclear. These questions can be addressed through alternative designs for vaccine trials, including assessing different endpoints and randomizing at the cluster instead of individual level. Although these designs exist, various factors have limited their use as preauthorization pivotal trials. They face statistical, epidemiological, and logistical limitations as well as regulatory barriers and uncertainty. Addressing these hindrances through research, communication, and policy can improve the evidence base of vaccines, their strategic deployment, and population health, both in the COVID-19 pandemic and in future infectious disease outbreaks. (. 2023;113(7):778-785. https://doi.org/10.2105/AJPH.2023.307302).