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In the setting of multi-armed trials, adaptive designs are a popular way to increase estimation efficiency, identify optimal treatments, or maximize rewards to individuals. Recent work has considered the case of estimating the effects of K…

Methodology · Statistics 2026-02-10 Evan T. R. Rosenman , Kristen B. Hunter

Understanding causality should be a core requirement of any attempt to build real impact through AI. Due to the inherent unobservability of counterfactuals, large randomised trials (RCTs) are the standard for causal inference. But large…

Concerns have been expressed over the validity of statistical inference under covariate-adaptive randomization despite the extensive use in clinical trials. In the literature, the inferential properties under covariate-adaptive…

Methodology · Statistics 2022-07-05 Li Yang , Wei Ma , Yichen Qin , Feifang Hu

In confirmatory clinical trials with small sample sizes, hypothesis tests based on asymptotic distributions are often not valid and exact non-parametric procedures are applied instead. However, the latter are based on discrete test…

Methodology · Statistics 2018-02-22 Robin Ristl , Dong Xi , Ekkehard Glimm , Martin Posch

Cluster-randomized experiments are widely used due to their logistical convenience and policy relevance. To analyze them properly, we must address the fact that the treatment is assigned at the cluster level instead of the individual level.…

Methodology · Statistics 2021-08-06 Fangzhou Su , Peng Ding

Response-Adaptive Randomization (RAR) is part of a wider class of data-dependent sampling algorithms, for which clinical trials are typically used as a motivating application. In that context, patient allocation to treatments is determined…

Methodology · Statistics 2022-06-09 David S. Robertson , Kim May Lee , Boryana C. Lopez-Kolkovska , Sofia S. Villar

External controls from historical trials or observational data can augment randomized controlled trials when large-scale randomization is impractical or unethical, such as in drug evaluation for rare diseases. However, non-randomized…

Methodology · Statistics 2025-05-08 Ke Zhu , Shu Yang , Xiaofei Wang

Individualized treatment effect lies at the heart of precision medicine. Interpretable individualized treatment rules (ITRs) are desirable for clinicians or policymakers due to their intuitive appeal and transparency. The gold-standard…

Methodology · Statistics 2021-08-20 Lili Wu , Shu Yang

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

Hierarchical composite endpoints, such as those analyzed using the Finkelstein-Schoenfeld (FS) statistic, are increasingly used in clinical trials for their ability to incorporate clinically prioritized outcomes. However, adaptive design…

Methodology · Statistics 2025-04-22 Krishna Padmanabhan , Cyrus Mehta

We consider clinical trials in which an experimental treatment is compared with a control in pre-specified patient subpopulations. In such settings, adaptive enrichment designs allow the enrolled population to be modified at an interim…

Methodology · Statistics 2026-03-17 Enyu Li , Nigel Stallard , Ekkehard Glimm , Dominic Magirr , Peter K. Kimani

Loss of power and clear description of treatment differences are key issues in designing and analyzing a clinical trial where non-proportional hazard is a possibility. A log-rank test may be very inefficient and interpretation of the hazard…

Applications · Statistics 2021-01-13 Satrajit Roychoudhury , Keaven M Anderson , Jiabu Ye , Pralay Mukhopadhyay

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

Effective decision making from randomised controlled clinical trials relies on robust interpretation of the numerical results. However, the language we use to describe clinical trials can cause confusion both in trial design and in…

In randomized clinical trials, adjusting for baseline covariates can improve credibility and efficiency for demonstrating and quantifying treatment effects. This article studies the augmented inverse propensity weighted (AIPW) estimator,…

Methodology · Statistics 2024-03-27 Marlena S. Bannick , Jun Shao , Jingyi Liu , Yu Du , Yanyao Yi , Ting Ye

The majority of response-adaptive randomisation (RAR) designs in the literature rely on efficacy data to guide dynamic patient allocation. However, their applicability becomes limited in settings where efficacy outcomes, such as survival,…

Methodology · Statistics 2026-02-23 Maria Vittoria Chiaruttini , Lukas Pin , Sofia S. Villar

We consider the design of a two-arm superiority cluster randomised controlled trial (RCT) with a continuous outcome. We detail Bayesian inference for the analysis of the trial using a linear mixed-effects model. The treatment is compared to…

Methodology · Statistics 2022-08-29 Kevin J Wilson

We consider the problem of estimating and inferring treatment effects in randomized experiments. In practice, stratified randomization, or more generally, covariate-adaptive randomization, is routinely used in the design stage to balance…

Methodology · Statistics 2022-09-27 Hanzhong Liu , Fuyi Tu , Wei Ma

Plausible identification of conditional average treatment effects (CATEs) may rely on controlling for a large number of variables to account for confounding factors. In these high-dimensional settings, estimation of the CATE requires…

Econometrics · Economics 2023-01-18 Adam Baybutt , Manu Navjeevan

In clinical trials, response-adaptive randomization (RAR) has the appealing ability to assign more subjects to better-performing treatments based on interim results. The traditional RAR strategy alters the randomization ratio on a…

Methodology · Statistics 2021-10-01 David Merrell , Thevaa Chandereng , Yeonhee Park
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