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Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…

Seamless phase II/III trials have become a cornerstone of modern drug development, offering a means to accelerate evaluation while maintaining statistical rigor. However, most existing inference procedures are model-based, designed…

Methodology · Statistics 2025-12-17 Kun Yi , Lucy Xia

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

The primary goal of randomized trials is to compare the effects of different interventions on some outcome of interest. In addition to the treatment assignment and outcome, data on baseline covariates, such as demographic characteristics or…

Applications · Statistics 2014-01-09 Alisa J. Stephens , Eric J. Tchetgen Tchetgen , Victor De Gruttola

Randomized trials are considered the gold standard for estimating causal effects. Trial findings are often used to inform policy and programming efforts, yet their results may not generalize well to a relevant target population due to…

External controls (ECs) from historical trials or real-world data have gained increasing attention as a way to augment hybrid and single-arm trials, especially when balanced randomization is infeasible. While most existing work has focused…

Methodology · Statistics 2025-12-15 Yujing Gao , Xiang Zhang , Shu Yang

The target trial framework enables causal inference from longitudinal observational data by emulating randomized trials initiated at multiple time points. Precision is often improved by pooling information across trials, with standard…

Methodology · Statistics 2026-01-08 Edoardo Efrem Gervasoni , Liesbet De Bus , Stijn Vansteelandt , Oliver Dukes

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials. Both industry and…

Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

Multistate models offer a powerful framework for studying disease processes and can be used to formulate intensity-based and more descriptive marginal regression models. They also represent a natural foundation for the construction of joint…

The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

Detection of interactions between treatment effects and patient descriptors in clinical trials is critical for optimizing the drug development process. The increasing volume of data accumulated in clinical trials provides a unique…

Applications · Statistics 2017-12-25 Baptiste Goujaud , Eric W. Tramel , Pierre Courtiol , Mikhail Zaslavskiy , Gilles Wainrib

We propose a novel regression adjustment method designed for estimating distributional treatment effect parameters in randomized experiments. Randomized experiments have been extensively used to estimate treatment effects in various…

Econometrics · Economics 2024-07-24 Undral Byambadalai , Tatsushi Oka , Shota Yasui

We consider methods for causal inference in randomized trials nested within cohorts of trial-eligible individuals, including those who are not randomized. We show how baseline covariate data from the entire cohort, and treatment and outcome…

Analysis of longitudinal randomised controlled trials is frequently complicated because patients deviate from the protocol. Where such deviations are relevant for the estimand, we are typically required to make an untestable assumption…

Methodology · Statistics 2018-05-16 Suzie Cro , James R Carpenter , Michael G Kenward

As the frontiers of applied statistics progress through increasingly complex experiments we must exploit increasingly sophisticated inferential models to analyze the observations we make. In order to avoid misleading or outright erroneous…

Methodology · Statistics 2018-03-23 Michael Betancourt

A basic feature of many field experiments is that investigators are only able to randomize clusters of individuals--such as households, communities, firms, medical practices, schools or classrooms--even when the individual is the unit of…

Methodology · Statistics 2009-10-21 Kosuke Imai , Gary King , Clayton Nall

Comparison and contrast are the basic means to unveil causation and learn which treatments work. To build good comparison groups, randomized experimentation is key, yet often infeasible. In such non-experimental settings, we illustrate and…

Methodology · Statistics 2024-01-30 Ambarish Chattopadhyay , Jose R. Zubizarreta

Pragmatic trials increasingly define outcomes using real-world data such as electronic health records, where assessments are collected during routine care rather than at fixed timepoints. Consequently, these uncontrolled assessments may be…

Pragmatic trials evaluating health care interventions often adopt cluster randomization due to scientific or logistical considerations. Previous reviews have shown that co-primary endpoints are common in pragmatic trials but infrequently…

Methodology · Statistics 2022-05-03 Siyun Yang , Mirjam Moerbeek , Monica Taljaard , Fan Li