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Broadening eligibility criteria in cancer trials has been advocated to represent the true patient population more accurately. While the advantages are clear in terms of generalizability and recruitment, novel dose-finding designs are needed…

Applications · Statistics 2023-01-12 Rebecca B. Silva , Bin Cheng , Richard D. Carvajal , Shing M. Lee

Targeted therapies on the basis of genomic aberrations analysis of the tumor have shown promising results in cancer prognosis and treatment. Regardless of tumor type, trials that match patients to targeted therapies for their particular…

Applications · Statistics 2018-04-18 Yanxun Xu , Peter Mueller , Apostolia M Tsimberidou , Donald Berry

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

An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of…

Methodology · Statistics 2021-01-08 Xu Gao , Weining Shen , Jing Ning , Ziding Feng , Jianhua Hu

We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such sub-populations could be defined by a biomarker or risk factor measured at…

Methodology · Statistics 2016-11-26 Michael Rosenblum , Han Liu , and En-Hsu Yen

As a future trend of healthcare, personalized medicine tailors medical treatments to individual patients. It requires to identify a subset of patients with the best response to treatment. The subset can be defined by a biomarker (e.g.…

Methodology · Statistics 2021-08-16 Yitao Lu , Julie Zhou , Li Xing , Xuekui Zhang

Hierarchical random effect models are used for different purposes in clinical research and other areas. In general, the main focus is on population parameters related to the expected treatment effects or group differences among all units of…

Applications · Statistics 2021-04-07 Maryna Prus , Norbert Benda , Rainer Schwabe

Biomarker subpopulations have become increasingly important for drug development in targeted therapies. The use of biomarkers has the potential to facilitate more effective outcomes by guiding patient selection appropriately, thus enhancing…

Methodology · Statistics 2020-08-07 Ting-Yu Chen , Jing Zhao , Linda Sun , Keaven Anderson

Recent works have proposed optimal subsampling algorithms to improve computational efficiency in large datasets and to design validation studies in the presence of measurement error. Existing approaches generally fall into two categories:…

Methodology · Statistics 2025-12-25 Jasper B. Yang , Thomas Lumley , Bryan E. Shepherd , Pamela A. Shaw

We consider the problem of selecting the optimal subgroup to treat when data on covariates is available from a randomized trial or observational study. We distinguish between four different settings including (i) treatment selection when…

Methodology · Statistics 2018-02-28 Tyler J. VanderWeele , Alex R. Luedtke , Mark J. van der Laan , Ronald C. Kessler

Clinical trials are notorious for their high failure rates and steep costs, leading to wasted time and resources spend, prolonged development timelines, and delayed patient access to new therapies. A key contributor to these failures is…

Quantum Physics · Physics 2026-01-19 Laia Domingo , Christine Johnson

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

Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining…

Quantitative Methods · Quantitative Biology 2025-02-18 Simon F. Martina-Perez , Samuel W. S. Johnson , Rebecca M. Crossley , Jennifer C. Kasemeier , Paul M. Kulesa , Ruth E. Baker

Therapeutic advancements in oncology have shifted towards targeted therapy based on genomic aberrations. This necessitates innovative statistical approaches in clinical trials, particularly in master protocol studies. Basket trials, a type…

Applications · Statistics 2025-02-12 Antonios Daletzakis , Rutger van den Bor , Vincent van der Noort , Kit CB Roes

In biomedical research, to obtain more accurate prediction results from a target study, leveraging information from multiple similar source studies is proved to be useful. However, in many biomedical applications based on real-world data,…

Methodology · Statistics 2025-12-29 Xiaokang Liu , Jie Hu , Naimin Jing , Yang Ning , Cheng Yong Tang , Runze Li , Yong Chen

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…

Methodology · Statistics 2020-02-17 José L. Jiménez , Sungjin Kim , Mourad Tighiouart

Performing optimal Bayesian design for discriminating between competing models is computationally intensive as it involves estimating posterior model probabilities for thousands of simulated datasets. This issue is compounded further when…

Methodology · Statistics 2022-04-07 Markus Hainy , David J. Price , Olivier Restif , Christopher Drovandi

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

Significant evidence has become available that emphasizes the importance of personalization in medicine. In fact, it has become a common belief that personalized medicine is the future of medicine. The core of personalized medicine is the…

Methodology · Statistics 2020-04-30 Qiong Zhang , Amin Khademi , Yongjia Song
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