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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

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is…

Applications · Statistics 2020-01-01 Tianjian Zhou , Wentian Guo , Yuan Ji

The effectiveness of personalized oncology treatments ultimately depends on whether outcomes can be causally attributed to the treatment. Advances in precision oncology have improved molecular profiling of individuals, and tailored…

Applications · Statistics 2025-09-29 Lydia Jang , Stefan Konigorski

The purpose of a phase I dose-finding clinical trial is to investigate the toxicity profiles of various doses for a new drug and identify the maximum tolerated dose. Over the past three decades, various dose-finding designs have been…

Methodology · Statistics 2021-11-25 Yunshan Duan , Shijie Yuan , Yuan Ji , Peter Mueller

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent…

Methodology · Statistics 2014-05-07 Joseph S. Koopmeiners , Andrew Wey

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

This study investigates the applicability of 3D dose predictions from a model trained on one modality to a cross-modality automated planning workflow. Additionally, we explore the impact of integrating a multi-criteria optimizer on adapting…

Medical Physics · Physics 2024-02-26 Gregory Szalkowski , Xuanang Xu , Shiva Das , Pew-Thian Yap , Jun Lian

Inter-observer variation is a significant problem in clinical target volume(CTV) segmentation in postoperative settings, where there is no gross tumor present. In this scenario, the CTV is not an anatomically established structure, but one…

An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

Objective: The objective of this study is to develop a machine learning (ML)-based framework for early risk stratification of clinical trials (CTs) according to their likelihood of exhibiting a high rate of dosing errors, using information…

Machine Learning · Computer Science 2026-02-27 Félicien Hêche , Sohrab Ferdowsi , Anthony Yazdani , Sara Sansaloni-Pastor , Douglas Teodoro

A multicompartment mathematical model is presented with the goal of studying the role of dose-dense protocols in the context of combination cancer chemotherapy. Dose-dense protocols aim at reducing the period between courses of chemotherapy…

Populations and Evolution · Quantitative Biology 2019-09-04 Álvaro G. López , Kelly C. Iarosz , Antonio M. Batista , Jesús M. Seoane , Ricardo L. Viana , Miguel A. F. Sanjuán

In many clinical trials, individuals in different subgroups have experience differential treatment effects. This leads to individualized differences in treatment benefit. In this article, we introduce the general concept of predictive…

Methodology · Statistics 2018-07-11 Debashis Ghosh , Youngjoo Cho

Individualized treatment rules (ITRs) for treatment recommendation is an important topic for precision medicine as not all beneficial treatments work well for all individuals. Interpretability is a desirable property of ITRs, as it helps…

Methodology · Statistics 2023-11-06 Jacob M. Maronge , Jared D. Huling , Guanhua Chen

There has been an increasing use of master protocols in oncology clinical trials because of its efficiency and flexibility to accelerate cancer drug development. Depending on the study objective and design, a master protocol trial can be a…

Applications · Statistics 2023-11-13 Jie Chen , Xiaoyun , Li , Chengxing , Lu , Sammy Yuan , Godwin Yung , Jingjing Ye , Hong Tian , Jianchang Lin

We apply the superiorization methodology to the intensity-modulated radiation therapy (IMRT) treatment planning problem. In superiorization, linear voxel dose inequality constraints are the fundamental modeling tool within which a…

Medical Physics · Physics 2022-07-28 Florian Barkmann , Yair Censor , Niklas Wahl

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

The primary objective of phase I oncology studies is to establish the safety profile of a new treatment and determine the maximum tolerated dose (MTD). This is motivated by the development of cytotoxic agents based on the underlying…

Applications · Statistics 2023-02-10 Yiding Zhang , Zhixing Xu , Hui Quan , Ji Lin

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

Radiotherapy treatment planning often relies on time-consuming, trial-and-error adjustments that heavily depend on the expertise of specialists, while existing deep learning methods face limitations in generalization, prediction accuracy,…

Computer Vision and Pattern Recognition · Computer Science 2026-01-06 Hui Xie , Haiqin Hu , Lijuan Ding , Qing Li , Yue Sun , Tao Tan

Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock
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