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Response-adaptive clinical trial designs allow targeting a given objective by skewing the allocation of participants to treatments based on observed outcomes. Response-adaptive designs face greater regulatory scrutiny due to potential type…

Methodology · Statistics 2025-03-19 Stef Baas , Peter Jacko , Sofía S. Villar

Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer…

Methodology · Statistics 2024-05-13 Abigail Burdon , Thomas Jaki , Xijin Chen , Pavel Mozgunov , Haiyan Zheng , Richard Baird

Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…

Applications · Statistics 2022-06-28 Guanhong Miao , Jason J. Z. Liao , Jing Yang , Keaven Anderson

It is recognised that treatment-related clustering should be allowed for in the sample size and analyses of individually-randomised parallel-group trials that evaluate therapist-delivered interventions such as psychotherapy. Here,…

Methodology · Statistics 2026-02-03 Rebecca EA Walwyn , Rosemary A Bailey , Arpan Singh , Neil Corrigan , Steven G Gilmour

We consider the design and analysis of multi-factor experiments using fractional factorial and incomplete designs within the potential outcome framework. These designs are particularly useful when limited resources make running a full…

Methodology · Statistics 2022-01-31 Nicole E. Pashley , Marie-Abele C. Bind

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

Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock

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

In small sample studies with binary outcome data, use of a normal approximation for hypothesis testing can lead to substantial inflation of the type-I error-rate. Consequently, exact statistical methods are necessitated, and accordingly,…

Methodology · Statistics 2017-11-29 Michael Grayling , Adrian Mander , James Wason

Existing multi-outcome designs focus almost entirely on evaluating whether all outcomes show evidence of efficacy or whether at least one outcome shows evidence of efficacy. While a small number of authors have provided multi-outcome…

Methodology · Statistics 2020-12-21 Martin Law , Michael J. Grayling , Adrian P. Mander

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

This PhD thesis covers breakthroughs in several areas of adaptive experiment design: (i) (Chapter 2) Novel clinical trial designs and statistical methods in the era of precision medicine. (ii) (Chapter 3) Multi-armed bandit theory, with…

Methodology · Statistics 2022-05-20 Michael Sklar

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

Multi-armed bandit problems (MABPs) are a special type of optimal control problem well suited to model resource allocation under uncertainty in a wide variety of contexts. Since the first publication of the optimal solution of the classic…

Methodology · Statistics 2015-07-30 Sofía S. Villar , Jack Bowden , James Wason

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

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

Major Depressive Disorder (MDD) is one of the most common causes of disability worldwide. Unfortunately, about one-third of patients do not benefit sufficiently from available treatments and not many new drugs have been developed in this…

The graph based approach to multiple testing is an intuitive method that enables a study team to represent clearly, through a directed graph, its priorities for hierarchical testing of multiple hypotheses, and for propagating the available…

Methodology · Statistics 2025-01-07 Cyrus Mehta , Ajoy Mukhopadhyay , Martin Posch

Adaptive interventions, aka dynamic treatment regimens, are sequences of pre-specified decision rules that guide the provision of treatment for an individual given information about their baseline and evolving needs, including in response…

Methodology · Statistics 2024-05-02 Wenchu Pan , Daniel Almirall , Amy M. Kilbourne , Andrew Quanbeck , Lu Wang

Due to ethical and economical reasons, sequential single-arm trial designs are used for assessing the therapeutic efficacy of new treatments in phase II trials. Simon's 2-stage design and Lan-DeMets' $\alpha$-spending function method with…

Methodology · Statistics 2023-03-31 Tasuku Inao , Isao Yokota