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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

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

Understanding how vaccine effectiveness (VE) changes over time can provide evidence-based guidance for public health decision making. While commonly reported by practitioners, time-varying VE estimates obtained using Cox regression are vul-…

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

Vaccine effectiveness (VE) is typically defined as incidence rate ratio, cumulative-risk ratio, or odds ratio. The VE based on incidence rate ratio is known to be time-invariant over the study period for leaky action vaccines and, the VE…

Applications · Statistics 2022-02-15 Anirudh Tomer , Jorne Biccler

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

Statistical methods are developed for analysis of clinical and virus genetics data from phase 3 randomized, placebo-controlled trials of vaccines against novel coronavirus COVID-19. Vaccine efficacy (VE) of a vaccine to prevent COVID-19…

Methodology · Statistics 2022-01-25 Fei Heng , Yanqing Sun , Peter B. Gilbert

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

Vaccine randomized trials are typically designed to be blinded, ensuring that the estimated vaccine efficacy (VE) reflects the immunological effect of the vaccine. When blinding is broken, however, the estimated VE reflects not only the…

Methodology · Statistics 2026-03-12 Rachel Axelrod , Uri Obolski , Daniel Nevo

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

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

In survival analysis, Cox model is widely used for most clinical trial data. Alternatives include the additive hazard model, the accelerated failure time (AFT) model and a more general transformation model. All these models assume that the…

Methodology · Statistics 2016-03-24 Cheng Zheng , Ying Qing Chen

Assessing immune responses to study vaccines as surrogates of protection plays a central role in vaccine clinical trials. Motivated by three ongoing or pending HIV vaccine efficacy trials, we consider such surrogate endpoint assessment in a…

Applications · Statistics 2008-12-18 Li Qin , Peter B. Gilbert , Dean Follmann , Dongfeng Li

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

Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power…

Populations and Evolution · Quantitative Biology 2021-05-21 Rob Johnson , Chris Jackson , Anne Presanis , Sofia S. Villar , Daniela De Angelis

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

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

In this article, we propose a theory to explain the reduction in vaccine effectiveness (VE) against the Delta SARS-CoV-2 variant and decreasing VE over time reported in recent studies. Using a model illustration, we show that in-host viral…

Populations and Evolution · Quantitative Biology 2021-12-09 Wan Yang , Jeffrey Shaman

In two harmonized efficacy studies to prevent HIV infection through multiple infusions of the monoclonal antibody VRC01, a key objective is to evaluate whether the serum concentration of VRC01, which changes cyclically over time along with…

Methodology · Statistics 2018-01-26 Yunda Huang , Yuanyuan Zhang , Zong Zhang , Peter B. Gilbert

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
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