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Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by…

Applications · Statistics 2021-02-08 Sebastian Weber , Andrew Gelman , Daniel Lee , Michael Betancourt , Aki Vehtari , Amy Racine

Adaptive approaches, allowing for more flexible trial design, have been proposed for individually randomized trials to save time or reduce sample size. However, adaptive designs for cluster-randomized trials in which groups of participants…

Methodology · Statistics 2022-01-10 Junwei Shen , Shirin Golchi , Erica E. M. Moodie , David Benrimoh

Bayesian experimental design is a technique that allows to efficiently select measurements to characterize a physical system by maximizing the expected information gain. Recent developments in deep neural networks and normalizing flows…

Quantum Physics · Physics 2023-06-27 Leopoldo Sarra , Florian Marquardt

An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

Randomized controlled trials (RCTs) are the gold standard for assessing drug safety and efficacy. However, RCTs have some drawbacks which have led to the use of single-arm studies to make certain internal drug development and regulatory…

Major advances have been made regarding the utilization of artificial intelligence in health care. In particular, deep learning approaches have been successfully applied for automated and assisted disease diagnosis and prognosis based on…

Methodology · Statistics 2020-03-24 Max Westphal , Antonia Zapf , Werner Brannath

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

External controls from historical trials or observational data can augment randomized controlled trials when large-scale randomization is impractical or unethical, such as in drug evaluation for rare diseases. However, non-randomized…

Methodology · Statistics 2025-05-08 Ke Zhu , Shu Yang , Xiaofei Wang

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

In pre- and non-clinical toxicology, the reduction of animal use is highly desireable. Although approaches for possible sample size reduction in the concurrent control group were suggested previously under the virtual control groups…

Randomized clinical trials (RCTs) are widely considered the gold standard for evaluating the effectiveness of new treatments or interventions in drug development. Still, they may not be feasible in certain cases, such as with rare diseases…

Methodology · Statistics 2025-08-05 Di Ran , Fanni Zhang , Sima Shahsavari , Kristine Broglio , Alasdair Henderson , Binbing Yu

In many scientific and engineering domains, physical experiments are often costly, non-replicable, or time-consuming. The Kennedy and O'Hagan (KOH) model framework has become a widely used approach for combining simulator runs with limited…

Computation · Statistics 2026-03-18 Hao Zhu , Markus Hainy

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

Basket trials are increasingly used for the simultaneous evaluation of a new treatment in various patient subgroups under one overarching protocol. We propose a Bayesian approach to sample size determination in basket trials that permit…

Methodology · Statistics 2022-09-02 Haiyan Zheng , Michael J. Grayling , Pavel Mozgunov , Thomas Jaki , James M. S. Wason

The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…

Methodology · Statistics 2021-11-25 Yunshan Duan , Shijie Yuan , Yuan Ji , Peter Mueller

Machine learning models, and deep neural networks in particular, are increasingly deployed in risk-sensitive domains such as healthcare, environmental forecasting, and finance, where reliable quantification of predictive uncertainty is…

Machine Learning · Computer Science 2026-04-07 Asena Karolin Özdemir , Lars H. Heyen , Arvid Weyrauch , Achim Streit , Markus Götz , Charlotte Debus

There is currently a focus on statistical methods which can use external trial information to help accelerate the discovery, development and delivery of medicine. Bayesian methods facilitate borrowing which is "dynamic" in the sense that…

Methodology · Statistics 2024-08-09 Sophia Axillus , Alex Lewin , Darren Scott

Psychological interventions, especially those leveraging mobile and wireless technologies, often include multiple components that are delivered and adapted on multiple timescales (e.g., coaching sessions adapted monthly based on clinical…

Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…

Methodology · Statistics 2024-04-18 James Willard , Shirin Golchi , Erica EM Moodie

Bayesian dynamic borrowing methods incorporate historical control data into current clinical trial analyses while allowing the degree of borrowing to depend on the compatibility between historical and current data. Although many methods…

Methodology · Statistics 2026-05-27 Tomohiro Ohigashi , Wataru Murasaki , Masahiko Gosho