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Dual agent dose-finding trials study the effect of a combination of more than one agent, where the objective is to find the Maximum Tolerated Dose Combination (MTC), the combination of doses of the two agents that is associated with a…

Applications · Statistics 2025-02-10 Helen Barnett , Oliver Boix , Dimitris Kontos , Thomas Jaki

When facing many options, we narrow down our focus to very few of them. Although behaviors like this can be a sign of heuristics, they can actually be optimal under limited cognitive resources. Here we study the problem of how to optimally…

Neurons and Cognition · Quantitative Biology 2021-02-03 Jorge Ramírez-Ruiz , Rubén Moreno-Bote

For simulation-based systems, finding a set of test cases with the least cost by exploring multiple goals is a complex task. Domain-specific optimization goals (e.g. maximize output variance) are useful for guiding the rapid selection of…

Software Engineering · Computer Science 2023-05-08 Xiao Ling , Tim Menzies

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…

An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…

Methodology · Statistics 2021-05-17 Hongtao Zhang , Alan Y Chiang , Jixian Wang

Phase I clinical trials are designed to test the safety (non-toxicity) of drugs and find the maximum tolerated dose (MTD). This task becomes significantly more challenging when multiple-drug dose-combinations (DC) are involved, due to the…

Machine Learning · Computer Science 2021-01-27 Hyun-Suk Lee , Cong Shen , William Zame , Jang-Won Lee , Mihaela van der Schaar

We consider the procedure proposed by Bhandari et al. (2009) in the context of two-treatment clinical trials, with the objective of minimizing the applications of the less effective drug to the least number of patients. Our focus is on an…

Statistics Theory · Mathematics 2025-06-30 Sampurna Kundu , Jayant Jha , Subir Kumar Bhandari

In this paper, a Bayesian approach is developed for simultaneously comparing multiple experimental treatments with a common control treatment in an exploratory clinical trial. The sample size is set to ensure that, at the end of the study,…

Statistics Theory · Mathematics 2019-11-14 John Whitehead , Faye Cleary , Amanda Turner

Molecular optimization is a fundamental goal in the chemical sciences and is of central interest to drug and material design. In recent years, significant progress has been made in solving challenging problems across various aspects of…

Computational Engineering, Finance, and Science · Computer Science 2022-10-11 Wenhao Gao , Tianfan Fu , Jimeng Sun , Connor W. Coley

The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerable dose (MTD) to determining the optimal…

Methodology · Statistics 2025-09-16 Kai Chen , Yixuan Zhao , Kentaro Takeda , Ying Yuan

This paper studies a two-stage model of experimentation, where the researcher first samples representative units from an eligible pool, then assigns each sampled unit to treatment or control. To implement balanced sampling and assignment,…

Econometrics · Economics 2023-08-22 Max Cytrynbaum

In this paper we focus on comparative diagnostic trials which are frequently employed to compare two markers with continuous or ordinal results. We derive explicit expressions for the optimal sampling ratio based on a common variance…

Applications · Statistics 2012-06-19 Ting Dong , Liansheng Larry Tang , William F. Rosenberger

Modern clinical trials and cohort studies gather low-cost data on all participants but may have limited resources to assess expensive exposures such as biomarkers or genomic data. When interest lies in associations involving expensive…

Robust optimization typically follows a worst-case perspective, where a single scenario may determine the objective value of a given solution. Accordingly, it is a challenging task to reduce the size of an uncertainty set without changing…

Optimization and Control · Mathematics 2022-09-02 Marc Goerigk , Mohammad Khosravi

The dose delivered to the planning target volume by proton beams is highly conformal, sparing organs at risk and normal tissues. New treatment planning systems adapted to spot scanning techniques have been recently proposed to…

Medical Physics · Physics 2022-05-18 François Smekens , Nicolas Freud , Bruno Sixou , Guillaume Beslon , Jean M Létang

While sample efficiency is the main motive for use of Bayesian optimisation when black-box functions are expensive to evaluate, the standard approach based on type II maximum likelihood (ML-II) may fail and result in disappointing…

Machine Learning · Computer Science 2022-08-31 Yuji Saikai

We propose a data-dependent early completion of dose finding trials for drug-combination. The early completion is determined when a beta-binomial probability for dose retainment with the trial data and the number of remaining patients is…

Methodology · Statistics 2022-02-10 Masahiro Kojima

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

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

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