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To improve precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes, researchers and regulatory agencies recommend using g-computation as a reliable…

Methodology · Statistics 2023-03-29 Ting Ye , Marlena Bannick , Yanyao Yi , Jun Shao

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

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…

Binary endpoints are common in clinical trials and conditional odds ratios have traditionally been used to assess treatment effects. However, the interpretation of odds ratios is difficult, they are non-collapsible and rely on strong…

Methodology · Statistics 2026-05-20 Martin Schnuerch , Alex Ocampo , Klaus Kähler Holst , Christian Stock

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

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

In randomized clinical trials, adjustments for baseline covariates at both design and analysis stages are highly encouraged by regulatory agencies. A recent trend is to use a model-assisted approach for covariate adjustment to gain…

Methodology · Statistics 2021-07-14 Ting Ye , Jun Shao , Yanyao Yi , Qingyuan Zhao

There has been a growing interest in covariate adjustment in the analysis of randomized controlled trials in past years. For instance, the U.S. Food and Drug Administration recently issued guidance that emphasizes the importance of…

Methodology · Statistics 2023-06-12 Kelly Van Lancker , Frank Bretz , Oliver Dukes

Randomized trials balance all covariates on average and provide the gold standard for estimating treatment effects. Chance imbalances nevertheless exist more or less in realized treatment allocations and intrigue an important question: what…

Methodology · Statistics 2023-07-18 Anqi Zhao , Peng Ding

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

Background: It has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced…

Methodology · Statistics 2021-12-09 Tim P. Morris , A. Sarah Walker , Elizabeth J. Williamson , Ian R. White

Analyses of randomised trials are often based on regression models which adjust for baseline covariates, in addition to randomised group. Based on such models, one can obtain estimates of the marginal mean outcome for the population under…

Methodology · Statistics 2017-07-17 Jonathan W. Bartlett

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

It is common to conduct causal inference in matched observational studies by proceeding as though treatment assignments within matched sets are assigned uniformly at random and using this distribution as the basis for inference. This…

Methodology · Statistics 2023-11-14 Samuel D. Pimentel , Yaxuan Huang

Weighting procedures are used in observational causal inference to adjust for covariate imbalance within the sample. Common practice for inference is to estimate robust standard errors from a weighted regression of outcome on treatment.…

Methodology · Statistics 2025-07-29 Erin Hartman , Chad Hazlett , Arisa Sadeghpour

Complete randomization allows for consistent estimation of the average treatment effect based on the difference in means of the outcomes without strong modeling assumptions on the outcome-generating process. Appropriate use of the…

Methodology · Statistics 2021-08-03 Anqi Zhao , Peng Ding

Covariate adjustment aims to improve the statistical efficiency of randomized trials by incorporating information from baseline covariates. Popular methods for covariate adjustment include analysis of covariance for continuous endpoints and…

Methodology · Statistics 2025-05-09 Zhiwei Zhang , Ya Wang , Dong Xi

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

Two commonly used methods for improving precision and power in clinical trials are stratified randomization and covariate adjustment. However, many trials do not fully capitalize on the combined precision gains from these two methods, which…

Generalized linear models are a popular tool in applied statistics, with their maximum likelihood estimators enjoying asymptotic Gaussianity and efficiency. As all models are wrong, it is desirable to understand these estimators' behaviours…

Methodology · Statistics 2024-12-10 Elliot H. Young , Rajen D. Shah
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