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Pilot feasibility studies play a pivotal role in the development of clinical trials for rare diseases, where small populations and slow recruitment often threaten trial viability. While such studies are commonly used to assess operational…

Applications · Statistics 2025-07-15 Lara Maleyeff , Valérie Leclair , Shirin Golchi , Marie Hudson

Adaptive enrichment trials aim to identify and recruit participants most likely to benefit from treatment based on evolving biomarker evidence, with the goal of informing individualized treatment recommendations. Bayesian methods are well…

Methodology · Statistics 2026-03-11 Lara Maleyeff , Shirin Golchi , Erica E. M. Moodie

Bayesian adaptive designs enable flexible clinical trials by adapting features based on accumulating data. Among these, Bayesian Response-Adaptive Randomization (BRAR) skews patient allocation towards more promising treatments based on…

Methodology · Statistics 2025-12-05 Daniel Kaddaj , Stef Baas , Edwin Y. N. Tang , David S. Robertson , Lukas Pin , Sofía S. Villar

Benkeser et al. demonstrate how adjustment for baseline covariates in randomized trials can meaningfully improve precision for a variety of outcome types. Their findings build on a long history, starting in 1932 with R.A. Fisher and…

Methodology · Statistics 2026-03-03 Laura B. Balzer , Erica Cai , Lucas Godoy Garraza , Pracheta Amaranath

This paper proposes Bayesian Adaptive Trials (BAT) as both an efficient method to conduct trials and a unifying framework for evaluation social policy interventions, addressing limitations inherent in traditional methods such as Randomized…

The current work is motivated by the need for robust statistical methods for precision medicine; as such, we address the need for statistical methods that provide actionable inference for a single unit at any point in time. We aim to learn…

Statistics Theory · Mathematics 2021-07-02 Ivana Malenica , Aurelien Bibaut , Mark J. van der Laan

Efforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. Six antibodies acting on programmed death ligand 1 or programmed death 1 pathways were approved in 75 cancer indications between 2015 and…

Methodology · Statistics 2022-10-07 Emily C. Zabor , Alexander M. Kaizer , Nathan A. Pennell , Brian P. Hobbs

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

We consider estimation of an optimal individualized treatment rule from observational and randomized studies when a high-dimensional vector of baseline variables is available. Our optimality criterion is with respect to delaying expected…

Methodology · Statistics 2017-11-09 Iván Díaz , Oleksandr Savenkov , Karla Ballman

Primarily motivated by the drug development process, several publications have now presented methodology for the design of multi-arm multi-stage experiments with normally distributed outcome variables of known variance. Here, we extend…

Methodology · Statistics 2017-12-04 Michael Grayling , James Wason , Adrian Mander

When an experimenter has the option of running an adaptive trial, is it admissible to ignore this option and run a non-adaptive trial instead? We provide a negative answer to this question in the best-arm identification problem, where the…

Machine Learning · Statistics 2025-06-06 Guido Imbens , Chao Qin , Stefan Wager

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

Experimental design is an approach for selecting samples among a given set so as to obtain the best estimator for a given criterion. In the context of linear regression, several optimal designs have been derived, each associated with a…

Statistics Theory · Mathematics 2021-01-01 Geovani Rizk , Igor Colin , Albert Thomas , Moez Draief

Interval designs are a class of phase I trial designs for which the decision of dose assignment is determined by comparing the observed toxicity rate at the current dose with a prespecified (toxicity tolerance) interval. If the observed…

Methodology · Statistics 2013-09-20 Suyu Liu , Ying Yuan

The use of historical controls offers a valuable alternative when traditional randomized controlled trials are not feasible. However, such approaches may introduce bias due to temporal changes in patient populations, diagnostic criteria,…

Methodology · Statistics 2025-12-24 Marco Ratta , Pavel Mozgunov , Sandrine Boulet , Moreno Ursino

We propose to use Bayesian optimization (BO) to improve the efficiency of the design selection process in clinical trials. BO is a method to optimize expensive black-box functions, by using a regression as a surrogate to guide the search.…

Methodology · Statistics 2021-05-20 Jakob Richter , Tim Friede , Jörg Rahnenführer

Systems with both quantitative and qualitative responses are widely encountered in many applications. Design of experiment methods are needed when experiments are conducted to study such systems. Classic experimental design methods are…

Methodology · Statistics 2023-04-24 Lulu Kang , Xinwei Deng , Ran Jin

Modern randomization methods in clinical trials are invariably adaptive, meaning that the assignment of the next subject to a treatment group uses the accumulated information in the trial. Some of the recent adaptive randomization methods…

Methodology · Statistics 2024-02-12 Alan R. Vazquez , Weng Kee Wong

Tie-breaker designs trade off a statistical design objective with short-term gain from preferentially assigning a binary treatment to those with high values of a running variable $x$. The design objective is any continuous function of the…

Methodology · Statistics 2022-10-20 Harrison H. Li , Art B. Owen

Multi-arm bandit experimental designs are increasingly being adopted over standard randomized trials due to their potential to improve outcomes for study participants, enable faster identification of the best-performing options, and/or…

Methodology · Statistics 2025-06-04 Brian M Cho , Aurélien Bibaut , Nathan Kallus
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