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Related papers: Nonparametric bounds for vaccine effects in random…

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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

Outcome-dependent sampling designs are common in many different scientific fields including epidemiology, ecology, and economics. As with all observational studies, such designs often suffer from unmeasured confounding, which generally…

Methodology · Statistics 2020-10-13 Erin E. Gabriel , Michael C. Sachs , Arvid Sjölander

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…

Applications · Statistics 2021-03-01 Anastasios A. Tsiatis , Marie Davidian

Nonignorable missingness and noncompliance can occur even in well-designed randomized experiments making the intervention effect that the experiment was designed to estimate nonidentifiable. Nonparametric causal bounds provide a way to…

Statistics Theory · Mathematics 2020-10-13 Erin E. Gabriel , Arvid Sjölander , Michael C. Sachs

Incorporating vaccination into mathematical models appears deceptively simple: models integrate vaccine-derived protections, such as reduced susceptibility to infection, using parameters informed by empirical estimates of vaccine efficacy…

Populations and Evolution · Quantitative Biology 2026-05-19 Casey E. Middleton , Oliver Eales , James M. McCaw , Freya M. Shearer

Traditional measures of vaccine efficacy (VE) are inherently asymmetric, constrained above by $1$ but unbounded below. As a result, VE estimates and corresponding confidence intervals can extend far below zero, making interpretation…

Methodology · Statistics 2025-12-09 Lucy D'Agostino McGowan , Sarah C. Lotspeich , Michael G. Hudgens

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

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…

Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning…

Quantitative Methods · Quantitative Biology 2022-05-26 Ariel Nikas , Hasan Ahmed , Veronika I. Zarnitsyna

Evaluating the value of new clinical treatment rules based on patient characteristics is important but often complicated by hidden confounding factors in observational studies. Standard methods for estimating the average patient outcome if…

Methodology · Statistics 2025-08-21 Johannes Hruza , Erin Gabriel , Arvid Sjölander , Samir Bhatt , Michael Sachs

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

Studies of HPV vaccine efficacy usually record infections with vaccine targeted and nontargeted strains. Contrary to blinded randomized controlled trials, confounding bias can be a threat and risk compensation may occur in observational…

Methodology · Statistics 2026-05-13 Lola Etievant

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

During the COVID-19 pandemic, estimating the total deaths averted by vaccination has been of great public health interest. Instead of estimating total deaths averted by vaccination among both vaccinated and unvaccinated individuals, some…

Populations and Evolution · Quantitative Biology 2025-10-09 Katherine M. Jia , Christopher B. Boyer , Alyssa Bilinski , Marc Lipsitch

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

Cluster-randomized trials are often conducted to assess vaccine effects. Defining estimands of interest before conducting a trial is integral to the alignment between a study's objectives and the data to be collected and analyzed. This…

Methodology · Statistics 2019-10-10 Kayla W. Kilpatrick , Michael G. Hudgens , M. Elizabeth Halloran

Background: The Cox model and its extensions assuming proportional hazards is widely used to estimate vaccine efficacy (VE). In the typical situation that VE wanes over time, the VE estimates are not only sensitive to study duration and…

Applications · Statistics 2025-09-10 Ziwei Zhao , Xiangmei Ma , Paul Milligan , Yin Bun Cheung

Real-world vaccine effectiveness has increasingly been studied using matching-based approaches, particularly in observational cohort studies following the target trial emulation framework. Although matching is appealing in its simplicity,…

Methodology · Statistics 2026-04-07 Emily Wu , Elizabeth Rogawski McQuade , Mats Stensrud , Razieh Nabi , David Benkeser

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

We review standard mediation assumptions as they apply to identifying antibody effects in a randomized vaccine trial and propose new study designs to allow identification of an estimand that was previously unidentifiable. For these…

Methodology · Statistics 2024-06-11 Michael P. Fay , Dean A. Follmann
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