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Covariate adjustment is desired by both practitioners and regulators of randomized clinical trials because it improves precision for estimating treatment effects. However, covariate adjustment presents a particular challenge in…

Methodology · Statistics 2023-07-20 Yunfan Li , Jessica L. Ross , Aaron M. Smith , David P. Miller

Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary…

Methodology · Statistics 2021-08-20 J Hoogland , J IntHout , M Belias , MM Rovers , RD Riley , FE Harrell , KGM Moons , TPA Debray , JB Reitsma

Previous work on causal inference has primarily focused on averages and conditional averages of treatment effects, with significantly less attention on variability and uncertainty in individual treatment responses. In this paper, we…

Machine Learning · Computer Science 2026-02-10 Liyuan Xu , Bijan Mazaheri

AI models are often evaluated based on their ability to predict the outcome of interest. However, in many AI for social impact applications, the presence of an intervention that affects the outcome can bias the evaluation. Randomized…

Machine Learning · Computer Science 2025-11-18 Winston Chen , Michael W. Sjoding , Jenna Wiens

Common causal estimands include the average treatment effect (ATE), the average treatment effect of the treated (ATT), and the average treatment effect on the controls (ATC). Using augmented inverse probability weighting methods, parametric…

Methodology · Statistics 2022-09-23 Roland A. Matsouaka , Yi Liu , Yunji Zhou

Real-World Data (RWD), with its large sample sizes and rich clinical detail, offers a compelling alternative to randomized controlled trials (RCTs) for studying treatment effects in diverse and complex patient populations. However, its…

Applications · Statistics 2026-05-26 Yifei Xu , Hwiyoung Lee , Zhenyao Ye , Yezhi Pan , Jingsong Zhou , Yun Yang , Chixiang Chen , Shuo Chen

We extend Fisher's randomization test (FRT) to test conditional independence between observed outcomes and treatments given covariates in both randomized experiments and observational studies, with no restriction on the variable type of…

Methodology · Statistics 2025-06-12 Zhen Zhong

Cluster-randomized trials (CRTs) involve randomizing entire groups of participants -- called clusters -- to treatment arms but are often comprised of a limited or fixed number of available clusters. While covariate adjustment can account…

Methodology · Statistics 2022-11-29 Angela Y. Zhu , Nandita Mitra , Karla Hemming , Michael O. Harhay , Fan Li

We develop new semiparametric methods for estimating treatment effects. We focus on settings where the outcome distributions may be thick tailed, where treatment effects may be small, where sample sizes are large and where assignment is…

Methodology · Statistics 2023-08-24 Susan Athey , Peter J. Bickel , Aiyou Chen , Guido W. Imbens , Michael Pollmann

For robust statistical inference it is crucial to obtain a good estimator of the variance of the proposed estimator of the statistical estimand. A commonly used estimator of the variance for an asymptotically linear estimator is the sample…

Methodology · Statistics 2025-05-19 Yunwen Ji , Mark van der Laan , Alan Hubbard

Covariate adjustment and methods of incorporating historical data in randomized clinical trials (RCTs) each provide opportunities to increase trial power. We unite these approaches for the analysis of RCTs with binary outcomes based on the…

Methodology · Statistics 2022-12-21 Alyssa M. Vanderbeek , Jessica L. Ross , David P. Miller , Alejandro Schuler

Causal inference is vital for informed decision-making across fields such as biomedical research and social sciences. Randomized controlled trials (RCTs) are considered the gold standard for internal validity of inferences, whereas…

Methodology · Statistics 2025-12-02 Ruoqi Yu , Bikram Karmakar , Jessica Vandeleest , Eleanor Bimla Schwarz

What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has…

Methodology · Statistics 2023-04-18 José L. Jiménez , Isobel Barrott , Francesca Gasperoni , Dominic Magirr

Randomized experiments (a.k.a. A/B tests) are a powerful tool for estimating treatment effects, to inform decisions making in business, healthcare and other applications. In many problems, the treatment has a lasting effect that evolves…

Machine Learning · Computer Science 2022-10-17 Ziyang Tang , Yiheng Duan , Stephanie Zhang , Lihong Li

Augmenting randomized controlled trials (RCTs) with external real-world data (RWD) has the potential to improve the finite sample efficiency of treatment effect estimators. We describe using adaptive targeted maximum likelihood estimation…

Methodology · Statistics 2025-01-30 Sky Qiu , Jens Tarp , Andrew Mertens , Mark van der Laan

Randomized Controlled Trials (RCTs) often adjust for baseline covariates in order to increase power. This technical note provides a short derivation of a simple rule of thumb for approximating the ratio of the power of an adjusted analysis…

Methodology · Statistics 2023-08-16 Charles K. Fisher

The regression discontinuity (RD) design is a quasi-experimental design that estimates the causal effects of a treatment by exploiting naturally occurring treatment rules. It can be applied in any context where a particular treatment or…

When estimating treatment effects, the golden standard is to conduct a randomized experiment and then contrast outcomes associated with the treatment group and the control group. However, in many cases, randomized experiments are either…

Methodology · Statistics 2023-06-08 Kevin Han

Interference occurs when the treatment (or exposure) of one individual affects the outcomes of others. In some settings it may be reasonable to assume individuals can be partitioned into clusters such that there is no interference between…

Methodology · Statistics 2018-06-21 Lan Liu , Michael G. Hudgens , Bradley Saul , John D. Clemens , Mohammad Ali , Michael E. Emch

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