Interpreting vaccine efficacy trial results for infection and transmission

Randomized controlled trials (RCTs) have shown high efficacy of multiple vaccines against SARS-CoV-2 disease (COVID-19), and recent studies have shown the vaccines are also effective against infection. Evidence for the effect of each of these vaccines on ability to transmit the virus is also beginning to emerge. We describe an approach to estimate these vaccines' effects on viral positivity, a prevalence mea-sure which under the reasonable assumption that vaccinated individuals who become infected are no more infectious than unvaccinated individuals forms a lower bound on efficacy against transmission. Specifically, we recommend separate analysis of positive tests triggered by symptoms (usually the pri-mary RCT outcome) and cross-sectional prevalence of positive tests obtained regardless of symptoms. The odds ratio of carriage for vaccine vs. placebo provides an unbiased estimate of vaccine effectiveness against viral positivity, under certain assumptions, and we show through simulations that likely depar -tures from these assumptions will only modestly bias this estimate. Applying this approach to published data from the RCT of the Moderna vaccine, we estimate that one dose of vaccine reduces the potential for transmission by at least 61%, possibly considerably more. We describe how these approaches can be translated into observational studies of vaccine effectiveness. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Randomized controlled trials have demonstrated the efficacy of various vaccines against COVID-19, with recent studies also showing effectiveness against infection and transmission. By estimating viral positivity, a measure of prevalence, vaccine effectiveness against transmission can be assessed, providing a lower bound. These methods can be translated into observational studies to further evaluate vaccine effectiveness.