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Purpose: We propose a general framework for quantifying predictive uncertainties of dose-related quantities and leveraging this information in a dose mimicking problem in the context of automated radiation therapy treatment planning.…

Medical Physics · Physics 2021-09-08 Tianfang Zhang , Rasmus Bokrantz , Jimmy Olsson

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…

Accurate prediction of Drug-Target Affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet…

Biomolecules · Quantitative Biology 2023-10-18 Qizhi Pei , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Haiguang Liu , Tie-Yan Liu , Rui Yan

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

Determining the optimal initial dose for warfarin is a critically important task. Several factors have an impact on the therapeutic dose for individual patients, such as patients' physical attributes (Age, Height, etc.), medication profile,…

Machine Learning · Computer Science 2019-03-25 Ashkan Sharabiani , Adam Bress , William Galanter , Rezvan Nazempour , Houshang Darabi

We study the problem of learning individualized dose intervals using observational data. There are very few previous works for policy learning with continuous treatment, and all of them focused on recommending an optimal dose rather than an…

Methodology · Statistics 2022-02-25 Guanhua Chen , Xiaomao Li , Menggang Yu

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

In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…

Systems and Control · Electrical Eng. & Systems 2022-05-17 Mazen Alamir

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models…

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

Background: Phase I dose-finding trials increasingly encounter delayed-onset toxicities, especially with immunotherapies and targeted agents. The time-to-event continual reassessment method (TITE-CRM) handles incomplete follow-up using…

Methodology · Statistics 2026-02-24 Robert Amevor , Emmanuel Kubuafor , Dennis Baidoo

Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed,…

Methodology · Statistics 2025-08-19 Ayon Mukherjee , Jonathan L. Moscovici , Zheng Liu

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…

Methodology · Statistics 2024-11-14 Hao Sun , Hsin-Yu Lin , Jieqi Tu , Revathi Ananthakrishnan , Eunhee Kim

The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…

Methodology · Statistics 2025-01-16 Hao Sun , Jerry Li

Early-phase clinical trials face the challenge of selecting optimal drug doses that balance safety and efficacy due to uncertain dose-response relationships and varied participant characteristics. Traditional randomized dose allocation…

Methodology · Statistics 2026-02-13 Rohit Kanrar , Chunlin Li , Zara Ghodsi , Margaret Gamalo

We consider clinical trials in which an experimental treatment is compared with a control in pre-specified patient subpopulations. In such settings, adaptive enrichment designs allow the enrolled population to be modified at an interim…

Methodology · Statistics 2026-03-17 Enyu Li , Nigel Stallard , Ekkehard Glimm , Dominic Magirr , Peter K. Kimani

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms,…

Active learning has shown to reduce the number of experiments needed to obtain high-confidence drug-target predictions. However, in order to actually save experiments using active learning, it is crucial to have a method to evaluate the…

Quantitative Methods · Quantitative Biology 2015-04-10 Maja Temerinac-Ott , Armaghan W. Naik , Robert F. Murphy

Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is…

Methodology · Statistics 2022-12-13 José L. Jiménez , Mourad Tighiouart

Bandit algorithms sequentially accumulate data using adaptive sampling policies, offering flexibility for real-world applications. However, excessive sampling can be costly, motivating the devolopment of early stopping methods and reliable…

Statistics Theory · Mathematics 2025-02-06 Zihan Cui
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