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When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Methodology · Statistics 2020-08-03 Johannes Krisam , Dorothea Weber , Richard F. Schlenk , Meinhard Kieser

Background: We aimed to design a Bayesian adaption trial through extensive simulations to determine values for key design parameters, demonstrate error rates, and establish the expected sample size. The complexity of the proposed outcome…

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 most common objective for response adaptive clinical trials is to seek to ensure that patients within a trial have a high chance of receiving the best treatment available by altering the chance of allocation on the basis of accumulating…

Methodology · Statistics 2020-11-09 Helen Yvette Barnett , Sofia S Villar , Helena Geys , Thomas Jaki

In recent years, real-world external controls have grown in popularity as a tool to empower randomized placebo-controlled trials, particularly in rare diseases or cases where balanced randomization is unethical or impractical. However, as…

Methodology · Statistics 2024-11-14 Chenyin Gao , Shu Yang , Mingyang Shan , Wenyu Ye , Ilya Lipkovich , Douglas Faries

In conventional randomized controlled trials, adjustment for baseline values of covariates known to be at least moderately associated with the outcome increases the power of the trial. Recent work has shown particular benefit for more…

Methodology · Statistics 2023-11-27 James Willard , Shirin Golchi , Erica EM Moodie

Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical and efficient. These benefits are achieved while preserving the integrity and validity of the…

Randomized controlled trials (RCTs) with binary primary endpoints introduce novel challenges for inferring the causal effects of treatments. The most significant challenge is non-collapsibility, in which the conditional odds ratio estimand…

Methodology · Statistics 2024-03-01 Yunfan Li , Arman Sabbaghi , Jonathan R. Walsh , Charles K. Fisher

Clinical trials with a hybrid control arm (a control arm constructed from a combination of randomized patients and real-world data on patients receiving usual care in standard clinical practice) have the potential to decrease the cost of…

Methodology · Statistics 2021-08-20 Joanna Harton , Brian Segal , Ronac Mamtani , Nandita Mitra , Rebecca Hubbard

Designing clinical trials requires evaluating multiple operating characteristics (OCs), such as the likelihood of an early stopping decision, the probability of detecting a treatment effect, and the Type I error rate. In most cases, these…

Methodology · Statistics 2026-03-23 Susanna Gentile , Daniel E. Schwartz , Riddhiman Saha , Lorenzo Trippa

Clinical trials are complex and usually involve multiple objectives such as controlling type I error rate, increasing power to detect treatment difference, assigning more patients to better treatment, and more. In literature, both…

Statistics Theory · Mathematics 2010-10-20 Hongjian Zhu , Feifang Hu

Traditional hypothesis tests for differences between binomial proportions are at risk of being too liberal (Wald test) or overly conservative (Fisher's exact test). This problem is exacerbated in small samples. Regulators favour exact…

Methodology · Statistics 2025-07-31 Stef Baas , Yaron Racah , Elad Berkman , Sofia S. Villar

Given n experiment subjects with potentially heterogeneous covariates and two possible treatments, namely active treatment and control, this paper addresses the fundamental question of determining the optimal accuracy in estimating the…

Machine Learning · Statistics 2024-11-13 Jiachun Li , David Simchi-Levi , Yunxiao Zhao

This paper considers real-time control and learning problems for finite-dimensional linear systems under binary-valued and randomly disturbed output observations. This has long been regarded as an open problem because the exact values of…

Systems and Control · Electrical Eng. & Systems 2024-11-12 Lantian Zhang , Lei Guo

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

Response-adaptive randomization allows the probabilities of allocating patients to treatments in a clinical trial to change based on the previously observed response data, in order to achieve different experimental goals. One concern over…

Methodology · Statistics 2022-04-13 Ekkehard Glimm , David Robertson

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

Practical employment of Bayesian trial designs is still rare. Even if accepted in principle, the regulators have commonly required that such designs be calibrated according to an upper bound for the frequentist type I error rate. This…

Methodology · Statistics 2026-03-25 Elja Arjas , Dario Gasbarra

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

Our paper discovers a new trade-off of using regression adjustments (RAs) in causal inference under covariate-adaptive randomizations (CARs). On one hand, RAs can improve the efficiency of causal estimators by incorporating information from…

Econometrics · Economics 2025-02-19 Liang Jiang , Liyao Li , Ke Miao , Yichong Zhang