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Causal inference is the goal of randomized trials and many observational studies. The first step in a formal causal inference framework is to define the causal estimand, and in both types of study this can be intuitively defined as the…

Methodology · Statistics 2025-09-09 Margarita Moreno-Betancur , Rushani Wijesuriya , John B. Carlin

Observational studies provide the only evidence on the effectiveness of interventions when randomized controlled trials (RCTs) are impractical due to cost, ethical concerns, or time constraints. While many methodologies aim to draw causal…

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

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

Defining and identifying causal intervention effects for transmissible infectious disease outcomes is challenging because a treatment -- such as a vaccine -- given to one individual may affect the infection outcomes of others.…

Applications · Statistics 2019-12-11 Xiaoxuan Cai , Wen Wei Loh , Forrest W. Crawford

In causal inference, the correct formulation of the scientific question of interest is a crucial step. Here we apply the estimand framework to a comparison of the outcomes of patient-level clinical trials and observational data to help…

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

Inferring causal effects from an observational study is challenging because participants are not randomized to treatment. Observational studies in infectious disease research present the additional challenge that one participant's treatment…

Methodology · Statistics 2020-12-25 Brian G. Barkley , Michael G. Hudgens , John D. Clemens , Mohammad Ali , Michael E. Emch

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

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

Randomised controlled trials (RCTs) are regarded as the gold standard for estimating causal treatment effects on health outcomes. However, RCTs are not always feasible, because of time, budget or ethical constraints. Observational data such…

Methodology · Statistics 2024-02-20 Li Su , Roonak Rezvani , Shaun R. Seaman , Colin Starr , Isaac Gravestock

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

Early on during a pandemic, vaccine availability is limited, requiring prioritisation of different population groups. Evaluating vaccine allocation is therefore a crucial element of pandemics response. In the present work, we develop a…

Vaccination policies play a central role in public health interventions and models are often used to assess the effectiveness of these policies. Many vaccines are leaky, in which case the observed vaccine effectiveness depends on the force…

Populations and Evolution · Quantitative Biology 2025-04-21 Gray Manicom , Emily Harvey , Joshua Looker , David Wu , Oliver Maclaren , Dion O' Neale

We propose a restricted win probability estimand for comparing treatments in a randomized trial with a time-to-event outcome. We also propose Bayesian estimators for this summary measure as well as the unrestricted win probability. Bayesian…

Methodology · Statistics 2024-11-06 Michelle Leeberg , Xianghua Luo , Thomas A. Murray

We develop semiparametric methods for estimating subgroup-specific relative vaccine efficacy against multiple viral strains in a partially vaccinated population. Focusing on observational case-only studies, we address informative…

Methodology · Statistics 2025-03-12 Lars van der Laan , Peter B. Gilbert

The advent and subsequent widespread availability of preventive vaccines has altered the course of public health over the past century. Despite this success, effective vaccines to prevent many high-burden diseases, including HIV, have been…

Safe and effective preventive vaccines have the potential to help stem the HIV epidemic. The efficacy of such vaccines is typically measured in randomized, double-blind phase IIb/III trials and described as a reduction in newly acquired HIV…

Methodology · Statistics 2024-10-10 Yutong Jin , Alex Luedtke , Zoe Moodie , Holly Janes , David Benkeser

While conducting probabilistic surveys is the gold standard for assessing vaccine coverage, implementing these surveys poses challenges for global health. There is a need for more convenient option that is more affordable and practical.…

Applications · Statistics 2026-03-30 Nathaniel Dyrkton , Shomoita Alam , Susan Shepherd , Ibrahim Sana , Kevin Phelan , Jay JH Park

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