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Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…

Methodology · Statistics 2022-01-10 Junwei Shen , Shirin Golchi , Erica E. M. Moodie , David Benrimoh

Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…

Methodology · Statistics 2011-05-18 Jay Bartroff , Tze Leung Lai

Background: When planning a cluster randomized trial, evaluators often have access to an enumerated cohort representing the target population of clusters. Practicalities of conducting the trial, such as the need to oversample clusters with…

Methodology · Statistics 2024-09-19 Sarah E. Robertson , Jon A. Steingrimsson , Issa J. Dahabreh

There are multiple cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at that time point. Identifying…

Methodology · Statistics 2023-07-20 Samuel I. Watson , Alan Girling , Karla Hemming

Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of, stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of…

Methodology · Statistics 2018-06-29 Michael Grayling , Adrian Mander , James Wason

Cluster-level dynamic treatment regimens can be used to guide sequential, intervention or treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level DTR, the…

Methodology · Statistics 2016-07-15 Timothy NeCamp , Amy Kilbourne , Daniel Almirall

Both cluster randomized trials and quasi-experimental designs are used to evaluate the impact of health and social policies and interventions. Stepped-wedge cluster randomized trials randomize a staggered adoption approach, while recent…

Methodology · Statistics 2026-04-15 Haidong Lu , Gregg S. Gonsalves , Fan Li , Guanyu Tong , Lee Kennedy-Shaffer

Typically, trials investigate the impact of either an individual-level intervention on participant outcomes, or the impact of a cluster-level intervention on participant outcomes. Factorial designs consider two (or more) treatments for each…

Methodology · Statistics 2026-05-04 Rhys Bowden , Rebecca Walwyn , Jessica Kasza , Andrew Copas , Fan Li , James Wason , Andrew Forbes

Recently, methodology was presented to facilitate the incorporation of interim analyses in stepped-wedge (SW) cluster randomised trials (CRTs). Here, we extend this previous discussion. We detail how the stopping boundaries, allocation…

Methodology · Statistics 2018-03-28 Michael Grayling , David Robertson , James Wason , Adrian Mander

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

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…

Longitudinal cluster randomized trials (L-CRTs) are increasingly used to evaluate the cost-effectiveness of healthcare interventions across multiple assessment periods, yet design methods for powering these trials remain underdeveloped.…

Methodology · Statistics 2026-03-20 Hao Wang , Jingxia Liu , Drew B. Cameron , Jiaqi Tong , Donna Spiegelman , Daniella Meeker , Fan Li

Complete randomization balances covariates on average, but covariate imbalance often exists in finite samples. Rerandomization can ensure covariate balance in the realized experiment by discarding the undesired treatment assignments. Many…

Methodology · Statistics 2022-07-07 Xin Lu , Tianle Liu , Hanzhong Liu , Peng Ding

For randomized clinical trials where a single, primary, binary endpoint would require unfeasibly large sample sizes, composite endpoints are widely chosen as the primary endpoint. Despite being commonly used, composite endpoints entail…

Methodology · Statistics 2022-09-27 Marta Bofill Roig , Guadalupe Gómez Melis , Martin Posch , Franz Koenig

The determination of the sample size required by a crossover trial typically depends on the specification of one or more variance components. Uncertainty about the value of these parameters at the design stage means that there is often a…

Methodology · Statistics 2018-03-28 Michael Grayling , Adrian Mander , James Wason

This paper studies inference in cluster randomized trials where treatment status is determined according to a "matched pairs" design. Here, by a cluster randomized experiment, we mean one in which treatment is assigned at the level of the…

Econometrics · Economics 2025-08-14 Yuehao Bai , Jizhou Liu , Azeem M. Shaikh , Max Tabord-Meehan

Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…

Methodology · Statistics 2022-10-21 Liwen Wu , Qing Li , Mengya Liu , Jianchang Lin

A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…

Statistics Theory · Mathematics 2011-05-25 Jay Bartroff , Tze Leung Lai

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…

Methodology · Statistics 2025-07-17 James M. McGree , Antony M. Overstall , Mark Jones , Robert K. Mahar

Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…

Applications · Statistics 2016-05-03 Kevin Kunzmann , Meinhard Kieser
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