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Understanding vaccine effects on post-infection outcomes is critical for evaluating the full value proposition of a vaccine. However, defining appropriate causal effects on such outcomes is challenging because infection is affected by…

Studies of vaccine efficacy often record both the incidence of vaccine-targeted virus strains (primary outcome) and the incidence of non-targeted strains (secondary outcome). However, standard estimates of vaccine efficacy on targeted…

Applications · Statistics 2023-01-02 Lola Etievant , Joshua N. Sampson , Mitchell H. Gail

Probabilities of causation provide explanatory information on the observed occurrence (causal necessity) and non-occurrence (causal sufficiency) of events. Here, we adapt these probabilities (probability of necessity, probability of…

Quantitative Methods · Quantitative Biology 2025-04-28 Bronner P. Gonçalves

Randomized trials of infectious disease interventions, such as vaccines, often focus on groups of connected or potentially interacting individuals. When the pathogen of interest is transmissible between study subjects, interference may…

Applications · Statistics 2019-12-10 Daniel J. Eck , Olga Morozova , Forrest W. Crawford

Knowing the true effect size of clinical interventions in randomised clinical trials is key to informing the public health policies. Vaccine efficacy is defined in terms of the relative risk or the ratio of two disease risks. However, only…

Methodology · Statistics 2021-02-03 Yasin Memari

Suppose one has data from one or more completed vaccine efficacy trials and wishes to estimate the efficacy in a new setting. Often logistical or ethical considerations make running another efficacy trial impossible. Fortunately, if there…

Methodology · Statistics 2017-01-25 Alexander R. Luedtke , Peter B. Gilbert

Knowing whether vaccine protection wanes over time is important for health policy and drug development. However, quantifying waning effects is difficult. A simple contrast of vaccine efficacy at two different times compares different…

Methodology · Statistics 2025-10-15 Matias Janvin , Mats J. Stensrud

Determining whether vaccine efficacy wanes is important for individual and public decision making. Yet, quantification of waning is a subtle task. The classical approaches cannot be interpreted as measures of declining efficacy unless we…

Methodology · Statistics 2026-05-21 Gellért Perényi , Matias Janvin , Mats J. Stensrud

Consider the causal effect that one individual's treatment may have on another individual's outcome when the outcome is contagious, with specific application to the effect of vaccination on an infectious disease outcome. The effect of one…

Methodology · Statistics 2014-03-06 Elizabeth L. Ogburn , Tyler J. VanderWeele

The interpretation of vaccine efficacy estimands is subtle, even in randomized trials designed to quantify immunological effects of vaccination. In this article, we introduce terminology to distinguish between different vaccine efficacy…

Applications · Statistics 2023-11-15 Mats Stensrud , Daniel Nevo , Uri Obolski

Pathogens usually exist in heterogeneous variants, like subtypes and strains. Quantifying treatment effects on the different variants is important for guiding prevention policies and treatment development. Here we ground analyses of…

Applications · Statistics 2024-08-15 Gellert Perenyi , Mats J. Stensrud

Two observational methods are currently being used to monitor post-deployment vaccine effectiveness: the obvious crude method comparing rate testing positive per head of vaccinated population with that rate per head of unvaccinated…

Methodology · Statistics 2023-07-18 Roger F. Sewell

Observational data are often used to estimate real-world effectiveness and durability of vaccines. A sequence of trials can be emulated to draw inference from such data while minimizing selection bias, immortal time bias, and confounding.…

Methodology · Statistics 2025-09-03 Justin B. DeMonte , Bonnie E. Shook-Sa , Michael G. Hudgens

Principal stratification is a causal framework to analyze randomized experiments with a post-treatment variable between the treatment and endpoint variables. Because the principal strata defined by the potential outcomes of the…

Statistics Theory · Mathematics 2015-07-22 Zhichao Jiang , Peng Ding , Zhi Geng

In vaccine studies, investigators are often interested in studying effect modifiers of clinical treatment efficacy by biomarker-based principal strata, which is useful for selecting biomarker study endpoints for evaluating treatments in new…

Methodology · Statistics 2017-10-30 Yingying Zhuang , Ying Huang , Peter B. Gilbert

While the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, previous studies, biological theories, and the finding that immune response markers strongly correlated with infection in…

Applications · Statistics 2018-11-12 Peter B. Gilbert , Bryan S. Blette , Bryan E. Shepherd , Michael G. Hudgens

Randomized vaccine trials are used to assess vaccine efficacy and to characterize the durability of vaccine induced protection. If efficacy is demonstrated, the treatment of placebo volunteers becomes an issue. For COVID-19 vaccine trials,…

Applications · Statistics 2021-04-06 Jonathan Fintzi , Dean Follmann

We review vaccine efficacy (VE) estimands for susceptibility in individual randomized trials with natural (unmeasured) exposure, where individual responses are measured as time from vaccination until an event (e.g., disease from the…

Methodology · Statistics 2026-01-27 Michael P. Fay , Dean Follmann , Bruce J. Swihart , Lauren E. Dang

We develop semiparametric methods for estimating subgroup-specific relative vaccine efficacy against multiple viral strains in a partially vaccinated population. Focusing on observational case-only studies, we address informative…

Methodology · Statistics 2025-03-12 Lars van der Laan , Peter B. Gilbert

With the emergence and spread of infectious diseases with pandemic potential, such as COVID- 19, the urgency for vaccine development have led to unprecedented compressed and accelerated schedules that shortened the standard development…

Applications · Statistics 2025-04-22 Jiayue Wang , Ben Boukai
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