Incorporating efficacy data from initial trials into subsequent evaluations: Application to vaccines against respiratory syncytial virus

Abstract

Background. When a randomized controlled trial fails to demonstrate statistical efficacy against the primary endpoint, a costly new trial would need to be conducted to receive a license. Partially incorporating data from previous trials might allow for the conduct of a more efficient follow-up trial to demonstrate efficacy, speeding the availability of effective vaccines. Methods Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. The data were analyzed either ignoring data from the previous trial (minimally informative priors) or using priors that partially incorporate the historical data into the analysis. We evaluated scenarios where the efficacy in the new trial was the same, greater than, or less than the efficacy in the original trial. For each scenario, we evaluated the frequentist power and Type I error following interim analyses. Results If a stringent threshold is used to control Type I error, the analyses that incorporated historical data had a small advantage over trials that did not. If control of Type I error is less important (e.g., in a post-licensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency. Conclusions. Due to the need to control Type I error in a trial used to license a vaccine, the incorporation of historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure.