Vaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here ("PoDBAY," Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease ("PoD") curve. The PoDBAY framework is illustrated using clinical trial simulations and with data for influenza, zoster, and dengue virus vaccines. The simulations demonstrate that PoDBAY efficacy estimation (which integrates the PoD and biomarker data), can be accurate and more precise than the standard (case-count) estimation, contributing to more sensitive and specific decisions than threshold-based correlate of protection or case-count-based methods. For all three vaccine examples, the PoD fit indicates a substantial association between the biomarkers and protection, and efficacy estimated by PoDBAY from relatively little immunogenicity data is predictive of the standard estimate of efficacy, demonstrating how PoDBAY can provide early assessments of vaccine efficacy. Methods like PoDBAY can help accelerate and economize vaccine development using an immunological predictor of protection. For example, in the current effort against the COVID-19 pandemic it might provide information to help prioritize (rank) candidates both earlier in a trial and earlier in development.

1st Faculty of Medicine Charles University Prague Czech Republic

AH IT MSD Czech Republic Prague Czech Republic

Biostatistics and Research Decision Sciences Merck and Co Inc Kenilworth NJ USA

Department of Informatics and Predictive Sciences Celgene a BMS Company Boudry Switzerland

MRL IT Merck and Co Inc Kenilworth NJ USA

MRL IT MSD Czech Republic Prague Czech Republic

Quantitative Pharmacology and Pharmacometrics Merck and Co Inc Kenilworth NJ USA

Quantitative Pharmacology and Pharmacometrics MSD Czech Republic

Quantitative Sciences Janssen Research and Development San Diego CA USA

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Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models

Elucidating vaccine efficacy using a correlate of protection, demographics, and logistic regression