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G-computation has become a widely used robust method for estimating unconditional (marginal) treatment effects with covariate adjustment in the analysis of randomized clinical trials. Statistical inference in this context typically relies…

Methodology · Statistics 2025-03-18 Xin Zhang , Haitao Chu , Lin Liu , Satrajit Roychoudhury

Difference in proportions is frequently used to measure treatment effect for binary outcomes in randomized clinical trials. The estimation of difference in proportions can be assisted by adjusting for prognostic baseline covariates to…

Methodology · Statistics 2023-08-31 Jialuo Liu , Dong Xi

G-computation is a powerful method for estimating unconditional treatment effects with covariate adjustment in randomized clinical trials. It typically relies on fitting canonical generalized linear models. However, this could be…

Methodology · Statistics 2025-09-10 Xin Zhang , Lin Liu , Haitao Chu

Cluster-randomized experiments are increasingly used to evaluate interventions in routine practice conditions, and researchers often adopt model-based methods with covariate adjustment in the statistical analyses. However, the validity of…

Methodology · Statistics 2023-12-08 Bingkai Wang , Chan Park , Dylan S. Small , Fan Li

There is growing interest in a hybrid control design for treatment evaluation, where a randomized controlled trial is augmented with external control data from a previous trial or a real world data source. The hybrid control design has the…

Methodology · Statistics 2026-05-06 Zhiwei Zhang , Peisong Han , Wei Zhang

Covariate adjustment is a general method for improving precision when estimating treatment effects in randomized trials and is recommended by the FDA in its 2023 guidance when baseline variables are prognostic for the primary outcome. We…

G-computation is a useful estimation method that can be adapted to address various biases in epidemiology. However, these adaptations may not be obvious for some complex causal structures. This challenge is an example of the much wider…

Methodology · Statistics 2025-08-01 Paul N Zivich , Haidong Lu

In a clinical trial, the random allocation aims to balance prognostic factors between arms, preventing true confounders. However, residual differences due to chance may introduce near-confounders. Adjusting on prognostic factors is…

Methodology · Statistics 2024-11-18 Joe de Keizer , Rémi Lenain , Raphaël Porcher , Sarah Zoha , Arthur Chatton , Yohann Foucher

Researchers are often interested in using longitudinal data to estimate the causal effects of hypothetical time-varying treatment interventions on the mean or risk of a future outcome. Standard regression/conditioning methods for…

In clinical trials, there is potential to improve precision and reduce the required sample size by appropriately adjusting for baseline variables in the statistical analysis. This is called covariate adjustment. Despite recommendations by…

Methodology · Statistics 2022-06-20 Kelly Van Lancker , Joshua Betz , Michael Rosenblum

To maximize clinical benefit, clinicians routinely tailor treatment to the individual characteristics of each patient, where individualized treatment rules are needed and are of significant research interest to statisticians. In the…

Methodology · Statistics 2021-11-23 Trinetri Ghosh , Yanyuan Ma , Rui Song , Pingshou Zhong

Linear regression is arguably the most fundamental statistical model; however, the validity of its use in randomized clinical trials, despite being common practice, has never been crystal clear, particularly when stratified or…

Methodology · Statistics 2023-02-14 Wei Ma , Fuyi Tu , Hanzhong Liu

Randomized controlled trials (RCTs) with binary primary endpoints introduce novel challenges for inferring the causal effects of treatments. The most significant challenge is non-collapsibility, in which the conditional odds ratio estimand…

Methodology · Statistics 2024-03-01 Yunfan Li , Arman Sabbaghi , Jonathan R. Walsh , Charles K. Fisher

When analyzing data from randomized clinical trials, covariate adjustment can be used to account for chance imbalance in baseline covariates and to increase precision of the treatment effect estimate. A practical barrier to covariate…

Methodology · Statistics 2023-07-04 Chia-Rui Chang , Yue Song , Fan Li , Rui Wang

In randomized experiments, covariates are often used to reduce variance and improve the precision of treatment effect estimates. However, in many real-world settings, interference between units, where one unit's treatment affects another's…

Methodology · Statistics 2026-04-10 Xinyi Wang , Shuangning Li

Adjusting for covariates is a well established method to estimate the total causal effect of an exposure variable on an outcome of interest. Depending on the causal structure of the mechanism under study there may be different adjustment…

Statistics Theory · Mathematics 2021-04-27 Jack Kuipers , Giusi Moffa

We often seek to estimate the causal effect of an exposure on a particular outcome in both randomized and observational settings. One such estimation method is the covariate-adjusted residuals estimator, which was designed for individually…

Methodology · Statistics 2019-10-28 Stephen A. Lauer , Nicholas G. Reich , Laura B. Balzer

Participant noncompliance, in which participants do not follow their assigned treatment protocol, often obscures the causal relationship between treatment and treatment effect in randomized trials. In the longitudinal setting, the…

Methodology · Statistics 2023-02-09 Ross L Peterson , David M Vock , Joseph S Koopmeiners

Many clinical questions involve estimating the effects of multiple treatments using observational data. When using longitudinal data, the interest is often in the effect of treatment strategies that involve sustaining treatment over time.…

Methodology · Statistics 2024-05-03 Emily Granger , Gwyneth Davies , Ruth H. Keogh

We consider a longitudinal data structure consisting of baseline covariates, time-varying treatment variables, intermediate time-dependent covariates, and a possibly time dependent outcome. Previous studies have shown that estimating the…

Statistics Theory · Mathematics 2018-10-09 Linh Tran , Maya Petersen , Joshua Schwab , Mark J van der Laan
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