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Related papers: Estimating Waning of Vaccine Effectiveness: a Simu…

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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

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

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

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

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

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

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-…

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

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

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

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

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

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

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

Understanding how the causal effect of a treatment evolves over time, including the potential for waning, is important for informed decisions on treatment discontinuation or repetition. For example, waning vaccine protection influences…

Methodology · Statistics 2025-11-25 Eni Musta , Joris Mooij

The potential waning of the vaccination immunity to COVID-19 could pose threats to public health, as it is tenable that the timing of such waning would synchronize with the near-complete restoration of normalcy. Should also testing be…

Populations and Evolution · Quantitative Biology 2022-01-28 Agnieszka Truszkowska , Lorenzo Zino , Sachit Butail , Emanuele Caroppo , Zhong-Ping Jiang , Alessandro Rizzo , Maurizio Porfiri

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

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

Combating the SARS-CoV2 pandemic will require the fast development of effective preventive vaccines. Regulatory agencies may open accelerated approval pathways for vaccines if an immunological marker can be established as a mediator of a…

Methodology · Statistics 2021-03-05 David Benkeser , Iván Díaz , Jialu Ran

In Cox regression it is sometimes of interest to study time-varying effects (TVE) of exposures and to test the proportional hazards assumption. TVEs can be investigated with log hazard ratios modelled as a function of time. Missing data on…

Methodology · Statistics 2021-12-07 Ruth H. Keogh , Tim P. Morris
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