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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

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

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 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

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

Counterfactual prediction is a fundamental task in decision-making. G-computation is a method for estimating expected counterfactual outcomes under dynamic time-varying treatment strategies. Existing G-computation implementations have…

Machine Learning · Computer Science 2020-03-25 Rui Li , Zach Shahn , Jun Li , Mingyu Lu , Prithwish Chakraborty , Daby Sow , Mohamed Ghalwash , Li-wei H. Lehman

Covariate adjustment is widely recommended to improve statistical efficiency in randomized clinical trials (RCTs), yet empirical evidence comparing available strategies remains limited. This lack of real-world evaluation leaves unresolved…

Applications · Statistics 2026-02-03 Yulin Shao , Liangbo Lyu , Menggang Yu , Bingkai Wang

The question of how individual patient data from cohort studies or historical clinical trials can be leveraged for designing more powerful, or smaller yet equally powerful, clinical trials becomes increasingly important in the era of…

Methodology · Statistics 2022-09-01 Sandra Siegfried , Stephen Senn , Torsten Hothorn

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

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

Randomization is a common technique used in clinical trials to eliminate potential bias and confounders in a patient population. Equal allocation to treatment groups is the standard due to its optimal efficiency in many cases. However, in…

Applications · Statistics 2020-04-09 Thevaa Chandereng , Xiaodan Wei , Rick Chappell

Population adjustment methods such as matching-adjusted indirect comparison (MAIC) are increasingly used to compare marginal treatment effects when there are cross-trial differences in effect modifiers and limited patient-level data. MAIC…

Methodology · Statistics 2022-12-06 Antonio Remiro-Azócar , Anna Heath , Gianluca Baio

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

Performing causal inference in observational studies requires we assume confounding variables are correctly adjusted for. G-computation methods are often used in these scenarios, with several recent proposals using Bayesian versions of…

Methodology · Statistics 2021-10-25 Daniel Daly-Grafstein , Paul Gustafson

Although randomized controlled trials (RCTs) are a cornerstone of comparative effectiveness, they typically have much smaller sample size than observational studies because of financial and ethical considerations. Therefore there is…

Methodology · Statistics 2023-11-16 Lauren D. Liao , Emilie Højbjerre-Frandsen , Alan E. Hubbard , Alejandro Schuler

Modern randomization methods in clinical trials are invariably adaptive, meaning that the assignment of the next subject to a treatment group uses the accumulated information in the trial. Some of the recent adaptive randomization methods…

Methodology · Statistics 2024-02-12 Alan R. Vazquez , Weng Kee Wong

In 2023, the U.S. Food and Drug Administration issued guidance for adjustment of covariates in randomized clinical trials, emphasizing its role in enhancing precision and power through prognostic baseline variables. Despite its potential,…

Methodology · Statistics 2026-05-28 Kelly Van Lancker , Iván Díaz , Stijn Vansteelandt

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

Randomized Controlled Trials (RCTs) are the gold standard for comparing the effectiveness of a new treatment to the current one (the control). Most RCTs allocate the patients to the treatment group and the control group by uniform…

Machine Learning · Statistics 2018-10-22 Onur Atan , William R. Zame , Mihaela van der Schaar

Clinical machine learning applications are often plagued with confounders that are clinically irrelevant, but can still artificially boost the predictive performance of the algorithms. Confounding is especially problematic in mobile health…

Applications · Statistics 2018-11-29 Elias Chaibub Neto
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