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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

An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002, Biostatistics 3(1), 51-56) that provides an upper bound on the performance of a design under a given scenario. The…

Statistics Theory · Mathematics 2018-03-06 Pavel Mozgunov , Thomas Jaki , Xavier Paoletti

The commonplace description of phase 1 clinical trials in oncology as "primarily concerned with safety" is belied by their near universal adoption of dose-escalation practices which are inherently unsafe. In contrast with dose titration,…

Methodology · Statistics 2020-04-28 David C. Norris

We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…

Applications · Statistics 2023-03-29 Shijie Yuan , Tianjian Zhou , Yawen Lin , Yuan Ji

In medical treatment and elsewhere, it has become standard to base treatment intensity (dosage) on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has…

Econometrics · Economics 2023-05-30 Charles F. Manski

Cancer evolves continuously over time through a complex interplay of genetic, epigenetic, microenvironmental, and phenotypic changes. This dynamic behavior drives uncontrolled cell growth, metastasis, immune evasion, and therapy resistance,…

Quantitative Methods · Quantitative Biology 2025-07-08 Luoting Zhuang , Stephen H. Park , Steven J. Skates , Ashley E. Prosper , Denise R. Aberle , William Hsu

An individualized dose rule recommends a dose level within a continuous safe dose range based on patient level information such as physical conditions, genetic factors and medication histories. Traditionally, personalized dose finding…

Methodology · Statistics 2020-07-21 Liangyu Zhu , Wenbin Lu , Michael R. Kosorok , Rui Song

With the advancement of precision medicine there is an increasing need for design and analysis methods in clinical trials with the objective of investigating effect heterogeneity and estimating subgroup effects. As this requires precise…

Methodology · Statistics 2026-03-12 Shirin Golchi , Satoshi Morita

Precision medicine stands as a transformative approach in healthcare, offering tailored treatments that can enhance patient outcomes and reduce healthcare costs. As understanding of complex disease improves, clinical trials are being…

Methodology · Statistics 2024-05-15 Lara Maleyeff , Shirin Golchi , Erica E. M. Moodie , Marie Hudson

The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies…

Methodology · Statistics 2017-11-16 Kirsten Schorning , Maria Konstantinou

We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…

Applications · Statistics 2024-09-05 Jiaxin Liu , Shijie Yuan , Qiqi Deng , Yuan Ji

Personalized cancer treatment requires a thorough understanding of complex interactions between drugs and cancer cell lines in varying genetic and molecular contexts. To address this, high-throughput screening has been used to generate…

Machine Learning · Computer Science 2023-07-03 Vishal Dey , Xia Ning

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

Personalizing combination therapies in oncology requires navigating an immense space of possible drug and dose combinations, a task that remains largely infeasible through exhaustive experimentation. Recent developments in patient-derived…

Machine Learning · Computer Science 2025-09-10 Antoine de Mathelin , Christopher Tosh , Wesley Tansey

Dose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches have…

Methodology · Statistics 2025-09-15 Xijin Chen , Pavel Mozgunov , Richard D. Baird , Thomas Jaki

Gene selection plays a pivotal role in oncology research for improving outcome prediction accuracy and facilitating cost-effective genomic profiling for cancer patients. This paper introduces two gene selection strategies for deep…

Genomics · Quantitative Biology 2024-03-05 Akhila Krishna , Ravi Kant Gupta , Pranav Jeevan , Amit Sethi

Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…

Methodology · Statistics 2025-05-07 Fanni Zhang , Kristine Broglio , Michael Sweeting , Gina D'Angelo

Background Clinical trials are essential to advancing cancer treatments, yet fewer than 10% of adults with cancer enroll in trials, and many studies fail to meet accrual targets. Artificial intelligence (AI) could improve identification of…

Assessing the quality of cancer care administered by US health providers poses numerous challenges due to meaningful heterogeneity in patient populations. Patients undergoing oncology treatment exhibit substantial variation in disease…

Applications · Statistics 2025-02-17 Yige Li , Nancy L. Keating , Mary Beth Landrum , Jose R. Zubizarreta

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
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