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Understanding the interplay between high-dimensional data from different views is essential in biomedical research, particularly in fields such as genomics, neuroimaging and biobank-scale studies involving high-dimensional features.…

Methodology · Statistics 2026-03-31 Ruyi Pan , Yinqiu He , Jun Young Park

In recent years, real-world external controls have grown in popularity as a tool to empower randomized placebo-controlled trials, particularly in rare diseases or cases where balanced randomization is unethical or impractical. However, as…

Methodology · Statistics 2024-11-14 Chenyin Gao , Shu Yang , Mingyang Shan , Wenyu Ye , Ilya Lipkovich , Douglas Faries

Randomized Controlled Trials (RCTs) may suffer from limited scope. In particular, samples may be unrepresentative: some RCTs over- or under- sample individuals with certain characteristics compared to the target population, for which one…

Methodology · Statistics 2024-03-15 Bénédicte Colnet , Julie Josse , Gaël Varoquaux , Erwan Scornet

Randomized controlled trials (RCTs) often suffer from limited sample sizes due to high costs and lengthy recruitment periods, compromising precision in treatment effect estimation. External real-world control data offer a valuable…

Applications · Statistics 2026-05-05 Peng Wu , Jile Chaoge , Shu Yang

Randomized Controlled Trials (RCT)s are relied upon to assess new treatments, but suffer from limited power to guide personalized treatment decisions. On the other hand, observational (i.e., non-experimental) studies have large and diverse…

Methodology · Statistics 2023-03-07 Zeshan Hussain , Ming-Chieh Shih , Michael Oberst , Ilker Demirel , David Sontag

Use of historical control data to augment a small internal control arm in a randomized control trial (RCT) can lead to significant improvement of the efficiency of the trial. It introduces the risk of potential bias, since the historical…

Methodology · Statistics 2022-10-05 Jixian Wang , Hongtao Zhang , Ram Tiwari

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

This paper investigates the theoretical foundation and develops analytical formulas for sample size and power calculations for causal inference with observational data. By analyzing the variance of an inverse probability weighting estimator…

Methodology · Statistics 2026-05-19 Bo Liu , Chengxin Yang , Fan Li

Background: Subgroup analyses are frequently conducted in randomized clinical trials to assess evidence of heterogeneous treatment effect across patient subpopulations. Although randomization balances covariates within subgroups in…

Methodology · Statistics 2021-05-27 Siyun Yang , Fan Li , Laine E. Thomas , Fan Li

Power analyses are an important aspect of experimental design, because they help determine how experiments are implemented in practice. It is common to specify a desired level of power and compute the sample size necessary to obtain that…

Methodology · Statistics 2022-12-09 Zach Branson , Xinran Li , Peng Ding

In a randomized control trial, the precision of an average treatment effect estimator can be improved either by collecting data on additional individuals, or by collecting additional covariates that predict the outcome variable. We propose…

Methodology · Statistics 2017-09-27 Pedro Carneiro , Sokbae Lee , Daniel Wilhelm

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

We present a general framework for using existing data to estimate the efficiency gain from using a covariate-adjusted estimator of a marginal treatment effect in a future randomized trial. We describe conditions under which it is possible…

Methodology · Statistics 2021-05-03 Xiudi Li , Sijia Li , Alex Luedtke

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

We argue that randomized controlled trials (RCTs) are special even among settings where average treatment effects are identified by a nonparametric unconfoundedness assumption. This claim follows from two results of Robins and Ritov (1997):…

Methodology · Statistics 2021-09-28 P. M. Aronow , James M. Robins , Theo Saarinen , Fredrik Sävje , Jasjeet Sekhon

Leveraging external or historical data to improve the efficiency of randomized clinical trials without introducing bias or inflating the Type I error rate remains challenging. Recent work on externally trained prognostic scores, such as…

Methodology · Statistics 2026-05-28 Junyi Zhou , Qing Liu , May Mo , Amy Xia

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

Adapting the final sample size of a trial to the evidence accruing during the trial is a natural way to address planning uncertainty. Designs with adaptive sample size need to account for their optional stopping to guarantee strict type-I…

Estimating causal effects from randomized experiments is central to clinical research. Reducing the statistical uncertainty in these analyses is an important objective for statisticians. Registries, prior trials, and health records…

Machine Learning · Statistics 2021-12-06 Alejandro Schuler , David Walsh , Diana Hall , Jon Walsh , Charles Fisher

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