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In this paper we consider two-stage adaptive dose-response study designs, where the study design is changed at an interim analysis based on the information collected so far. In a simulation study, two approaches will be compared for these…

Methodology · Statistics 2016-02-08 Emma McCallum , Björn Bornkamp

In oncology, phase II studies are crucial for clinical development plans as such studies identify potent agents with sufficient activity to continue development in the subsequent phase III trials. Traditionally, phase II studies are…

Methodology · Statistics 2023-08-08 Takuya Yoshimoto , Satoru Shinoda , Kouji Yamamoto , Kouji Tahata

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II…

Methodology · Statistics 2014-02-12 Jay Bartroff , Tze Leung Lai , Balasubramanian Narasimhan

The treatment assignment mechanism in a randomized clinical trial can be optimized for statistical efficiency within a specified class of randomization mechanisms. Optimal designs of this type have been characterized in terms of the…

Methodology · Statistics 2025-09-03 Wei Zhang , Zhiwei Zhang , Aiyi Liu

We consider a Bayesian persuasion or information design problem where the sender tries to persuade the receiver to take a particular action via a sequence of signals. This we model by considering multi-phase trials with different…

Theoretical Economics · Economics 2021-11-24 Shih-Tang Su , Vijay G. Subramanian , Grant Schoenebeck

Leveraging preclinical animal data for a phase I first-in-man trial is appealing yet challenging. A prior based on animal data may place large probability mass on values of the dose-toxicity model parameter(s), which appear infeasible in…

Applications · Statistics 2020-04-15 Haiyan Zheng , Lisa V. Hampson

Recent FDA guidance on adaptive clinical trial designs defines bias as "a systematic tendency for the estimate of treatment effect to deviate from its true value", and states that it is desirable to obtain and report estimates of treatment…

Bayesian statistics plays a pivotal role in advancing medical science by enabling healthcare companies, regulators, and stakeholders to assess the safety and efficacy of new treatments, interventions, and medical procedures. The Bayesian…

Applications · Statistics 2023-12-04 Se Yoon Lee

Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer time to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more…

Methodology · Statistics 2018-10-02 Ruitao Lin , Robert L Coleman , Ying Yuan

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

This study examines the application of Bayesian approach in the context of clinical trials, emphasizing their increasing importance in contemporary biomedical research. While conventional frequentist approach provides a foundational basis…

Methodology · Statistics 2026-01-16 Paramahansa Pramanik , Arnab Kumar Maity , Anjan Mandal , Haley Kate Robinson

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

The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…

Methodology · Statistics 2023-09-13 Ying Yuan , Heng Zhou , Suyu Liu

Adaptive designs have been proposed for clinical trials in which the nuisance parameters or alternative of interest are unknown or likely to be misspecified before the trial. Whereas most previous works on adaptive designs and mid-course…

Methodology · Statistics 2011-05-18 Jay Bartroff , Tze Leung Lai

Phase I dose-escalation trials constitute the first step in investigating the safety of potentially promising drugs in humans. Conventional methods for phase I dose-escalation trials are based on a single treatment schedule only. More…

Applications · Statistics 2021-03-04 Burak Kürsad Günhan , Sebastian Weber , Abdelkader Seroutou , Tim Friede

Phase I oncology trials aim to identify a safe dose - often the maximum tolerated dose (MTD) - for subsequent studies. Conventional designs focus on population-level toxicity modeling, with recent attention on leveraging pharmacokinetic…

Applications · Statistics 2026-01-13 Kyong Ju Lee , Yuan Ji

Clinical trials are an indispensable part of the drug development process, bridging the gap between basic research and clinical application. During the development of new drugs, clinical trials are used not only to evaluate the safety and…

Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions.…

Methodology · Statistics 2021-02-19 William Hua , Hongyuan Mei , Sarah Zohar , Magali Giral , Yanxun Xu

The design of an experiment can be always be considered at least implicitly Bayesian, with prior knowledge used informally to aid decisions such as the variables to be studied and the choice of a plausible relationship between the…

Methodology · Statistics 2017-01-03 David C. Woods , Antony M. Overstall , Maria Adamou , Timothy W. Waite

Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…

Applications · Statistics 2025-04-22 Rebecca B. Silva , Bin Cheng , Shing M. Lee