Estimating Vaccine Efficacy Over Time After a Randomized Study is Unblinded

DOI10.48550/ARXIV.2102.13103MaRDI QIDQ106191zbMATH OpenFDO

Authors Anastasios A. Tsiatis, Marie Davidian, Anastasios A. Tsiatis, Marie Davidian

Publication date 24 February 2021

Published in Biometrics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2102.13103

zbMATH Keywords

crossoverinverse probability weightingpotential outcomesrandomized phase 3 vaccine trialwaning vaccine efficacy

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10)

Abstract: The COVID-19 pandemic due to the novel coronavirus SARS CoV-2 has inspired remarkable breakthroughs in development of vaccines against the virus and the launch of several phase 3 vaccine trials in Summer 2020 to evaluate vaccine efficacy (VE). Trials of vaccine candidates using mRNA delivery systems developed by Pfizer-BioNTech and Moderna have shown substantial VEs of 94-95%, leading the US Food and Drug Administration to issue Emergency Use Authorizations and subsequent widespread administration of the vaccines. As the trials continue, a key issue is the possibility that VE may wane over time. Ethical considerations dictate that all trial participants be unblinded and those randomized to placebo be offered vaccine, leading to trial protocol amendments specifying unblinding strategies. Crossover of placebo subjects to vaccine complicates inference on waning of VE. We focus on the particular features of the Moderna trial and propose a statistical framework based on a potential outcomes formulation within which we develop methods for inference on whether or not VE wanes over time and estimation of VE at any post-vaccination time. The framework clarifies assumptions made regarding individual- and population-level phenomena and acknowledges the possibility that subjects who are more or less likely to become infected may be crossed over to vaccine differentially over time. The principles of the framework can be adapted straightforwardly to other trials.

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Cites work

• scientific article; zbMATH DE number 2237384 (Why is no real title available?)
• A Frailty Mixture Model for Estimating Vaccine Efficacy
• Bias Reduction Using Mahalanobis-Metric Matching
• Modeling survival distribution as a function of time to treatment discontinuation: a dynamic treatment regime approach

Cited in

(5)

• Estimating correlations between vaccine clinical trial outcomes
• Methods for the estimation of direct and indirect vaccination effects by combining data from individual- and cluster-randomized trials
• VEwaning
• Discussion on “Estimating vaccine efficacy over time after a randomized study is unblinded” by Anastasios A. Tsiatis and Marie Davidian
• scientific article; zbMATH DE number 1741804 (Why is no real title available?)

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