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Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…

Methodology · Statistics 2021-08-31 Elja Arjas , Dario Gasbarra

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

In the design of clinical trials, it is essential to assess the design operating characteristics (e.g., power and the type I error rate). Common practice for the evaluation of operating characteristics in Bayesian clinical trials relies on…

Methodology · Statistics 2026-03-17 Luke Hagar , Shirin Golchi

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

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…

Methodology · Statistics 2025-11-27 Luke Hagar , Shirin Golchi , Marina B. Klein

Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review…

Methodology · Statistics 2023-03-13 Tianjian Zhou , Yuan Ji

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

Most Bayesian response-adaptive designs unbalance randomization rates towards the most promising arms with the goal of increasing the number of positive treatment outcomes during the study, even though the primary aim of the trial is…

Applications · Statistics 2018-07-02 Steffen Ventz , Matteo Cellamare , Sergio Bacallado , Lorenzo Trippa

We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding…

Applications · Statistics 2011-08-09 Ying Yuan , Guosheng Yin

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

In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the…

Applications · Statistics 2019-09-19 Xiao Wu , Yi Xu , Bradley P. Carlin

Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID-19 pandemic, the need to establish evidence for the effectiveness of vaccines,…

Methodology · Statistics 2022-03-08 Shirin Golchi

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

Platform trials evaluate multiple experimental treatments against a common control group (and/or against each other), which often reduces the trial duration and sample size. Bayesian platform designs offer several practical advantages,…

Methodology · Statistics 2025-07-18 Luke Hagar , Lara Maleyeff , Shirin Golchi , Dick Menzies

It is crucial to design Phase II cancer clinical trials that balance the efficiency of treatment selection with clinical practicality. Sargent and Goldberg proposed a frequentist design that allow decision-making even when the primary…

Methodology · Statistics 2025-05-15 Moka Komaki , Satoru Shinoda , Haiyan Zheng , Kouji Yamamoto

Bayesian response adaptive clinical trials are currently evaluating experimental therapies for several diseases. Adaptive decisions, such as pre-planned variations of the randomization probabilities, attempt to accelerate the development of…

Methodology · Statistics 2021-05-25 Marta Bonsaglio , Sandra Fortini , Steffen Ventz , Lorenzo Trippa

It is generally appreciated that a frequentist analysis of a group sequential trial must in order to avoid inflating type I error account for the fact that one or more interim analyses were performed. It is also to a lesser extent realised…

Methodology · Statistics 2025-12-12 Simon Bang Kristensen , Erik Thorlund Parner
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