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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

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

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

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

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

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

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

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

The test-negative design (TND) has become a standard approach to evaluate vaccine effectiveness against the risk of acquiring infectious diseases in real-world settings, such as Influenza, Rotavirus, Dengue fever, and more recently…

Methodology · Statistics 2023-03-09 Kendrick Qijun Li , Xu Shi , Wang Miao , Eric Tchetgen Tchetgen

The test-negative design (TND) is widely used to evaluate vaccine effectiveness in real-world settings. In a TND study, individuals with similar symptoms who seek care are tested, and effectiveness is estimated by comparing vaccination…

Methodology · Statistics 2025-09-19 Christopher B. Boyer , Kendrick Qijun Li , Xu Shi , Eric J. Tchetgen Tchetgen

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

Randomization inference is a powerful tool in early phase vaccine trials when estimating the causal effect of a regimen against a placebo or another regimen. Randomization-based inference often focuses on testing either Fisher's sharp null…

Methodology · Statistics 2024-02-27 Zhe Chen , Xinran Li , Bo Zhang

The test-negative design has become popular for evaluating the effectiveness of post-licensure vaccines using observational data. In addition to its logistical convenience on data collection, the design is also believed to control for the…

Methodology · Statistics 2026-05-15 Soumyabrata Kundu , Peng Ding , Jingshu Wang , Xinran Li

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

In order to meet regulatory approval, pharmaceutical companies often must demonstrate that new vaccines reduce the total risk of a post-infection outcome like transmission, symptomatic disease, severe illness, or death in randomized,…

Methodology · Statistics 2024-09-23 Rob Trangucci , Yang Chen , Jon Zelner

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

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

Understanding waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness…

Populations and Evolution · Quantitative Biology 2023-08-02 Ariel Nikas , Hasan Ahmed , Veronika I. Zarnitsyna

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

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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