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Stepped-wedge cluster randomized trials (SW-CRTs) evaluate interventions rolled out across clusters over time. Standard analyses typically use immediate-treatment (IT) models, which assume effects begin at crossover and remain constant…

Methodology · Statistics 2026-04-21 Yongdong Ouyang , Monica Taljaard , James P. Hughes , Fan Li

Statistical power is often a concern for clustered RCTs due to variance inflation from design effects and the high cost of adding study clusters (such as hospitals, schools, or communities). While covariate pre-specification is the…

Methodology · Statistics 2020-05-07 Peter Z. Schochet

Background: In settings where proof-of-principle trials have succeeded but the effectiveness of different forms of implementation remains uncertain, trials that not only generate information about intervention effects but also provide…

Quantitative Methods · Quantitative Biology 2017-05-16 Guy Harling , Rui Wang , Jukka-Pekka Onnela , Victor De Gruttola

Sample size determination for cluster randomised trials (CRTs) is challenging as it requires robust estimation of the intra-cluster correlation coefficient (ICC). Typically, the sample size is chosen to provide a certain level of power to…

Applications · Statistics 2023-08-23 S. Faye Williamson , Svetlana V. Tishkovskaya , Kevin J. Wilson

The Stepped Wedge Design (SWD) is a form of cluster randomized trial, usually comparing two treatments, which is divided into time periods and sequences, with clusters allocated to sequences. Typically all sequences start with the standard…

Methodology · Statistics 2020-11-06 John N. S. Matthews

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

Sequential Multiple Assignment Randomized Trials (SMARTs) are considered the gold standard for estimation and evaluation of treatment regimes. SMARTs are typically sized to ensure sufficient power for a simple comparison, e.g., the…

Stepped wedge cluster randomized trials (SW-CRTs) are a form of randomized trial whereby clusters are progressively transitioned from control to intervention, with the timing of transition randomized for each cluster. An important task at…

Methodology · Statistics 2025-06-27 Mary Ryan Baumann , Denise Esserman , Monica Taljaard , Fan Li

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

Linear Predictive Clustering (LPC) partitions samples based on shared linear relationships between feature and target variables, with numerous applications including marketing, medicine, and education. Greedy optimization methods, commonly…

Machine Learning · Computer Science 2026-04-08 Jiazhou Liang , Hassan Khurram , Scott Sanner

Evaluating heterogeneity of treatment effects (HTE) across subgroups is common in both randomized trials and observational studies. Although several statistical challenges of HTE analyses including low statistical power and multiple…

Methodology · Statistics 2024-07-10 Noorie Hyun , Abisola E. Idu , Andrea J. Cook , Jennifer F. Bobb

Mixed outcome endpoints that combine multiple continuous and discrete components to form co-primary, multiple primary or composite endpoints are often employed as primary outcome measures in clinical trials. There are many advantages to…

Methodology · Statistics 2019-12-12 Martina McMenamin , Jessica K. Barrett , Anna Berglind , James M. S. Wason

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

In stepped wedge cluster randomized trials (SW-CRTs), observations collected under the control condition are, on average, from an earlier time than observations collected under the intervention condition. In a cohort design, participants…

Methodology · Statistics 2023-02-23 Jale Basten , Katja Ickstadt , Nina Timmesfeld

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…

Methodology · Statistics 2023-08-31 Peng Yang , Daniel Li , Ruitao Lin , Bo Huang , Ying Yuan

Meta-analyses frequently include trials that report multiple effect sizes based on a common set of study participants. These effect sizes will generally be correlated. Cluster-robust variance-covariance estimators are a fruitful approach…

Methodology · Statistics 2022-03-07 Thilo Welz , Wolfgang Viechtbauer , Markus Pauly

Stepped wedge designs (SWDs) are increasingly used to evaluate longitudinal cluster-level interventions but pose substantial challenges for valid inference. Because crossover times are randomized, intervention effects are intrinsically…

Methodology · Statistics 2026-05-12 Fan Xia , K. C. Gary Chan , Emily Voldal , Avi Kenny , Patrick J. Heagerty , James P. Hughes

Background. Designing trials to reduce treatment duration is important in several therapeutic areas, including TB and antibiotics. We recently proposed a new randomised trial design to overcome some of the limitations of standard two-arm…

This article investigates the model-robustness of fixed-effects models for analyzing a broad class of longitudinal cluster trials (CTs) such as stepped-wedge, parallel-with-baseline and crossover designs, encompassing both randomized (CRTs)…

Methodology · Statistics 2026-04-10 Kenneth M. Lee , Fan Li

Group sequential designs (GSDs) are well established and the most commonly used adaptive design in confirmatory clinical trials with interim analyses. However, they remain underutilised, and their implementation involves unique theoretical…

Methodology · Statistics 2025-09-09 Zhangyi He , Suzie Cro , Laurent Billot