The effect of pandemic prevalence on the reported efficacy of SARS-CoV-2 vaccines

The efficacy of SARS-CoV-2 vaccines reported in Phase 3 trials varies from ~45% to ~95%. This study tests the hypothesis that the observed variation in efficacy of SARS-CoV-2 vaccine candidates can be explained by the prevalence of the COVID-19 pandemic at trial sites. To test the proposed hypothesis, we conducted a systematic search following PRISMA guidelines. Our search resulted in 8 vaccine candidates that had reported efficacy data from a total of 20 Phase 3 trials, representing a total of 221,968 subjects, 453 infections across the vaccinated groups and 1,554 infections across the placebo groups. We use meta-regression models to analyse the potential associations between prevalence of COVID-19 pandemic at trial sites and efficacy of the reported SARS-CoV2 vaccines. The overall estimate of the risk-ratio is 0.24 (95% CI, 0.17–0.34, p ≤ 0.01), with a high degree of heterogeneity (τ(2) = 0.50, I(2) = 88.73%). Our meta-regression analysis with pandemic prevalence as the predictor explains almost half the variance in risk ratios across trials (R(2) = 49.06%, p ≤ 0.01). This study finds that efficacy of SARS-CoV-2 vaccines reported in Phase 3 trial declines as pandemic prevalence at trial sites increases. Trials conducted in locations with low pandemic prevalence reported higher efficacies as compared to trials conducted in high pandemic prevalence locations.