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The primary goal of randomized trials is to compare the effects of different interventions on some outcome of interest. In addition to the treatment assignment and outcome, data on baseline covariates, such as demographic characteristics or…

Applications · Statistics 2014-01-09 Alisa J. Stephens , Eric J. Tchetgen Tchetgen , Victor De Gruttola

For time-to-event data with finitely many competing risks, the proportional hazards model has been a popular tool for relating the cause-specific outcomes to covariates [Prentice et al. Biometrics 34 (1978) 541--554]. This article studies…

Statistics Theory · Mathematics 2009-03-04 Yanqing Sun , Peter B. Gilbert , Ian W. McKeague

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

Matched case-control studies are commonly employed in epidemiological research for their convenience and efficiency. Analysis of secondary outcomes can yield valuable insights into biological pathways and help identify genetic variants of…

Methodology · Statistics 2026-02-24 Shanshan Liu , Guoqing Diao

Comparative effectiveness evidence from randomized trials may not be directly generalizable to a target population of substantive interest when, as in most cases, trial participants are not randomly sampled from the target population.…

Methodology · Statistics 2022-04-12 Fan Li , Ashley L. Buchanan , Stephen R. Cole

Misclassification in binary outcomes is not uncommon and statistical methods to investigate its impact on policy-driving study results are lacking. While misclassifying binary outcomes is a statistically ubiquitous phenomena, we focus on…

Clinical trials often collect data on multiple outcomes, such as overall survival (OS), progression-free survival (PFS), and response to treatment (RT). In most cases, however, study designs only use primary outcome data for interim and…

Applications · Statistics 2026-04-28 Massimiliano Russo , Steffen Ventz , Lorenzo Trippa

Randomized trials are considered the gold standard for making informed decisions in medicine, yet they often lack generalizability to the patient populations in clinical practice. Observational studies, on the other hand, cover a broader…

Methodology · Statistics 2026-04-14 Piersilvio De Bartolomeis , Javier Abad , Konstantin Donhauser , Fanny Yang

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

COVID-19 vaccines are highly efficacious at preventing symptomatic infection, severe disease, and death. Most of the evidence that COVID-19 vaccines also reduce transmission of SARS-CoV-2 is based on retrospective, observational studies.…

Applications · Statistics 2022-06-16 Marlena S. Bannick , Fei Gao , Elizabeth R. Brown , Holly E. Janes

When assessing the causal effect of a binary exposure using observational data, confounder imbalance across exposure arms must be addressed. Matching methods, including propensity score-based matching, can be used to deconfound the causal…

Methodology · Statistics 2024-10-01 Ernesto Ulloa-Pérez , Marco Carone , Alex Luedtke

Knowledge of the protection afforded by vaccines might, in some circumstances, modify a vaccinated individual's behaviour, potentially increasing exposure to pathogens and hindering effectiveness. Although vaccine studies typically do not…

Randomized controlled trials are the gold standard for evaluating the efficacy of an intervention. However, there is often a trade-off between selecting the most scientifically relevant primary endpoint versus a less relevant, but more…

Methodology · Statistics 2026-01-12 Jack M. Wolf , Joseph S. Koopmeiners , David M. Vock

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

The aim of clinical effectiveness research using repositories of electronic health records is to identify what health interventions 'work best' in real-world settings. Since there are several reasons why the net benefit of intervention may…

Methodology · Statistics 2020-06-19 Jie Zhu , Blanca Gallego

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

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

Causal inference with interference is a rapidly growing area. The literature has begun to relax the "no-interference" assumption that the treatment received by one individual does not affect the outcomes of other individuals. In this paper…

Methodology · Statistics 2015-03-06 Tyler J. VanderWeele , Eric J. Tchetgen Tchetgen , M. Elizabeth Halloran

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

Outcome Reporting Bias (ORB) poses significant threats to the validity of meta-analytic findings. It occurs when researchers selectively report outcomes based on the significance or direction of results, potentially leading to distorted…

Methodology · Statistics 2025-07-17 Alessandra Gaia Saracini , Leonhard Held