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Suppose one wishes to estimate the effect of a binary treatment on a binary endpoint conditional on a post-randomization quantity in a counterfactual world in which all subjects received treatment. It is generally difficult to identify this…

Methodology · Statistics 2019-11-12 Alex Luedtke , Jiacheng Wu

Case-control studies are designed towards studying associations between risk factors and a single, primary outcome. Information about additional, secondary outcomes is also collected, but association studies targeting such secondary…

Methodology · Statistics 2014-07-17 Tamar Sofer , Marilyn C. Cornelis , Peter Kraft , Eric J. Tchetgen Tchetgen

Randomized trials of infectious disease interventions, such as vaccines, often focus on groups of connected or potentially interacting individuals. When the pathogen of interest is transmissible between study subjects, interference may…

Applications · Statistics 2019-12-10 Daniel J. Eck , Olga Morozova , Forrest W. Crawford

Suppose one has data from one or more completed vaccine efficacy trials and wishes to estimate the efficacy in a new setting. Often logistical or ethical considerations make running another efficacy trial impossible. Fortunately, if there…

Methodology · Statistics 2017-01-25 Alexander R. Luedtke , Peter B. Gilbert

In oncology the efficacy of novel therapeutics often differs across patient subgroups, and these variations are difficult to predict during the initial phases of the drug development process. The relation between the power of randomized…

Methodology · Statistics 2025-06-05 Boyu Ren , Federico Ferrari , Sandra Fortini , Steffen Ventz , Lorenzo Trippa

Staggered treatment adoption arises in the evaluation of policy impact and implementation in many settings, including both randomized stepped-wedge trials and non-randomized quasi-experiments with panel data. In both settings, getting an…

Methodology · Statistics 2024-10-14 Lee Kennedy-Shaffer

Clinical trials or studies oftentimes require long-term and/or costly follow-up of participants to evaluate a novel treatment/drug/vaccine. There has been increasing interest in the past few decades in using short-term surrogate outcomes as…

Methodology · Statistics 2024-12-19 Xuan Wang , Tianxi Cai , Lu Tian , Layla Parast

In most medical research, the average treatment effect is used to evaluate a treatment's performance. However, precision medicine requires knowledge of individual treatment effects: What is the difference between a unit's measurement under…

Computation · Statistics 2022-08-30 Mingyang Cai , Stef van Buuren , Gerko Vink

We consider time to treatment initiation. This can commonly occur in preventive medicine, such as disease screening and vaccination; it can also occur with non-fatal health conditions such as HIV infection without the onset of AIDS. While…

Methodology · Statistics 2026-05-29 Zhichen Zhao , Andrew Ying , Ronghui Xu

Test-negative designs are widely used for post-market evaluation of vaccine effectiveness, particularly in cases when randomized trials are not feasible. Differing from classical test-negative designs where only healthcare-seekers with…

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

In many experimental and observational studies, the outcome of interest is often difficult or expensive to observe, reducing effective sample sizes for estimating average treatment effects (ATEs) even when identifiable. We study how…

Machine Learning · Statistics 2024-10-11 Nathan Kallus , Xiaojie Mao

Cross-sectional incidence estimation based on recency testing has become a widely used tool in HIV research. Recently, this method has gained prominence in HIV prevention trials to estimate the "placebo" incidence that participants might…

Methodology · Statistics 2024-12-18 Jianan Pan , Marlena Bannick , Fei Gao

Propensity scores are commonly used to reduce the confounding bias in non-randomized observational studies for estimating the average treatment effect. An important assumption underlying this approach is that all confounders that are…

Methodology · Statistics 2022-08-02 Youfei Yu , Jiacong Du , Min Zhang , Zhenke Wu , Andrew M. Ryan , Bhramar Mukherjee

During the COVID-19 pandemic, estimating the total deaths averted by vaccination has been of great public health interest. Instead of estimating total deaths averted by vaccination among both vaccinated and unvaccinated individuals, some…

Populations and Evolution · Quantitative Biology 2025-10-09 Katherine M. Jia , Christopher B. Boyer , Alyssa Bilinski , Marc Lipsitch

A full Bayesian approach to the estimation of Vaccine Efficacy is presented, which is an improvement over the currently used exact method conditional on the total number of cases. As an example, we reconsider the statistical sections of the…

Methodology · Statistics 2021-03-09 Mauro Gasparini

Hybrid controlled trials (HCTs), which augment randomized controlled trials (RCTs) with external controls (ECs), are increasingly receiving attention as a way to address limited power, slow accrual, and ethical concerns in clinical…

Methodology · Statistics 2025-05-02 Jiajun Liu , Ke Zhu , Shu Yang , Xiaofei Wang

The estimation of causal treatment effects from observational data is a fundamental problem in causal inference. To avoid bias, the effect estimator must control for all confounders. Hence practitioners often collect data for as many…

Machine Learning · Statistics 2020-11-05 Kristjan Greenewald , Dmitriy Katz-Rogozhnikov , Karthik Shanmugam

Predictive or treatment selection biomarkers are usually evaluated in a subgroup or regression analysis with focus on the treatment-by-marker interaction. Under a potential outcome framework (Huang, Gilbert and Janes [Biometrics 68 (2012)…

Applications · Statistics 2015-02-04 Zhiwei Zhang , Lei Nie , Guoxing Soon , Aiyi Liu

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