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In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…

Methodology · Statistics 2025-05-21 José L. Jiménez , Mourad Tighiouart

The question of how individual patient data from cohort studies or historical clinical trials can be leveraged for designing more powerful, or smaller yet equally powerful, clinical trials becomes increasingly important in the era of…

Methodology · Statistics 2022-09-01 Sandra Siegfried , Stephen Senn , Torsten Hothorn

Navigating the vast chemical space of druggable compounds is a formidable challenge in drug discovery, where generative models are increasingly employed to identify viable candidates. Conditional 3D structure-based drug design (3D-SBDD)…

Machine Learning · Computer Science 2025-02-04 Kiwoong Yoo , Owen Oertell , Junhyun Lee , Sanghoon Lee , Jaewoo Kang

The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose…

Methodology · Statistics 2025-03-21 Jiapeng Xu , Dehua Bi , Shenghua Kelly Fan , Bee Leng Lee , Ying Lu

Basket trials test a single therapeutic treatment on several patient populations under one master protocol. A desirable adaptive design feature in these studies may be the incorporation of new baskets to an ongoing study. Limited basket…

Methodology · Statistics 2024-07-09 Libby Daniells , Pavel Mozgunov , Helen Barnett , Alun Bedding , Thomas Jaki

We define a Bayesian semi-parametric model to effectively conduct inference with unaligned longitudinal binary data. The proposed strategy is motivated by data from the Human Epilepsy Project (HEP), which collects seizure occurrence data…

Methodology · Statistics 2025-05-13 Beatrice Cantoni , Giovanni Poli , Elizabeth Juarez-Colunga , Peter Müller

We consider the optimal design problem for identifying effective dose combinations within drug combination studies where the effect of the combination of two drugs is investigated. Drug combination studies are becoming increasingly…

In clinical care, obtaining a correct diagnosis is the first step towards successful treatment and, ultimately, recovery. Depending on the complexity of the case, the diagnostic phase can be lengthy and ridden with errors and delays. Such…

Information Retrieval · Computer Science 2019-08-26 Carsten Eickhoff , Floran Gmehlin , Anu V. Patel , Jocelyn Boullier , Hamish Fraser

We study the problem of designing optimal learning and decision-making formulations when only historical data is available. Prior work typically commits to a particular class of data-driven formulation and subsequently tries to establish…

Machine Learning · Statistics 2024-03-13 Amine Bennouna , Bart P. G. Van Parys

Optimal design of a Phase I cancer trial can be formulated as a stochastic optimization problem. By making use of recent advances in approximate dynamic programming to tackle the problem, we develop an approximation of the Bayesian optimal…

Methodology · Statistics 2010-12-01 Jay Bartroff , Tze Leung Lai

The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set…

Machine Learning · Statistics 2025-04-15 Keiichiro Seno , Kota Matsui , Shogo Iwazaki , Yu Inatsu , Shion Takeno , Shigeyuki Matsui

In the era of diminishing returns from Moores Law, heterogeneous computing systems have emerged as a vital approach to enhance computational efficiency. This paper introduces a novel MLIR-based dialect, named hyper, designed to optimize…

Cryptography and Security · Computer Science 2025-06-05 Zhiyuan Tan , Liutong Han , Mingjie Xing , Yanjun Wu

An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment…

Applications · Statistics 2021-05-03 Helen Barnett , Oliver Boix , Dimintris Kontos , Thomas Jaki

Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…

Methodology · Statistics 2025-06-04 Nan Miles Xi , Man Mandy Jin , Lin Wang , Xin Huang

Purpose: Various dose calculation algorithms are available for radiation therapy for cancer patients. However, these algorithms are faced with the tradeoff between efficiency and accuracy. The fast algorithms are generally less accurate,…

Medical Physics · Physics 2020-07-01 Yixun Xing , Dan Nguyen , Weiguo Lu , Ming Yang , Steve Jiang

It is increasingly common for therapies in oncology to be given in combination. In some cases, patients can benefit from the interaction between two drugs, although often at the risk of higher toxicity. A large number of designs to conduct…

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with…

Biomolecules · Quantitative Biology 2025-03-07 Xiangxin Zhou , Yi Xiao , Haowei Lin , Xinheng He , Jiaqi Guan , Yang Wang , Qiang Liu , Feng Zhou , Liang Wang , Jianzhu Ma

Algorithms and technologies are essential tools that pervade all aspects of our daily lives. In the last decades, health care research benefited from new computer-based recruiting methods, the use of federated architectures for data…

Computers and Society · Computer Science 2023-01-26 Chiara Criscuolo , Tommaso Dolci , Mattia Salnitri

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…

Methodology · Statistics 2023-08-31 Peng Yang , Daniel Li , Ruitao Lin , Bo Huang , Ying Yuan

Electronic health records represent a holistic overview of patients' trajectories. Their increasing availability has fueled new hopes to leverage them and develop accurate risk prediction models for a wide range of diseases. Given the…