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Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies

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In recent years, precision treatment strategy have gained significant attention in medical research, particularly for patient care. We propose a novel framework for estimating conditional average treatment effects (CATE) in time-to-event…

Methodology · Statistics 2024-07-29 Runjia Li , Victor B. Talisa , Chung-Chou H. Chang

Given the prominence of targeted therapy and immunotherapy in cancer treatment, it becomes imperative to consider heterogeneity in patients' responses to treatments, which contributes greatly to the widely used proportional hazard…

Methodology · Statistics 2024-09-01 Powei Chen , Siying Hu , Haojin Zhou

This work introduces the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement of the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. The BLRM determines the maximum tolerated dose (MTD)…

Methodology · Statistics 2025-08-18 Andrea Nizzardo , Luca Genetti , Marco Pergher

Although optimal control theory has been used for the theoretical study of anti-cancerous drugs scheduling optimization, with the aim of reducing the primary tumor volume, the effect on metastases is often ignored. Here, we use a previously…

Tissues and Organs · Quantitative Biology 2013-06-21 Sebastien Benzekry , Philip Hahnfeldt

Toxicity monitoring is essential in Phase II clinical trials to ensure participant safety. While monitoring rules are well-established for single-arm trials, two-cohort trials present unique challenges because toxicities are expected to be…

Methodology · Statistics 2026-03-31 Yu Wang , Aniko Szabo

Agent-based simulation with a synthetic population can help us compare different treatment conditions while keeping everything else constant within the same population (i.e., as digital twins). Such population-scale simulations require…

Methodology · Statistics 2024-03-26 Abdulrahman A. Ahmed , M. Amin Rahimian , Mark S. Roberts

Randomized controlled trials are the gold standard for evaluating the efficacy of an intervention. However, there is often a trade-off between selecting the most scientifically relevant primary endpoint versus a less relevant, but more…

Methodology · Statistics 2026-01-12 Jack M. Wolf , Joseph S. Koopmeiners , David M. Vock

One common approach for dose optimization is a two-stage design, which initially conducts dose escalation to identify the maximum tolerated dose (MTD), followed by a randomization stage where patients are assigned to two or more doses to…

Methodology · Statistics 2024-11-11 Yixuan Zhao , Rachael Liu , Jianchang Lin , Ying Yuan

Phase I oncology trials aim to identify a safe dose - often the maximum tolerated dose (MTD) - for subsequent studies. Conventional designs focus on population-level toxicity modeling, with recent attention on leveraging pharmacokinetic…

Applications · Statistics 2026-01-13 Kyong Ju Lee , Yuan Ji

While the use of combination therapy is increasing in prevalence for cancer treatment, it is often difficult to predict the exact interactions between different treatment forms, and their synergistic/antagonistic effects on patient health…

Optimization and Control · Mathematics 2021-01-29 Jayanth Pratap

Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs…

Applications · Statistics 2024-04-18 Arnab Kumar Maity , Satrajit Roy Chowdhury , Ray Li , Lada Markovtsova , Roberto Bugarini

Large Language Models (LLMs) demonstrate strong generalization and reasoning abilities, making them well-suited for complex decision-making tasks such as medical consultation (MC). However, existing LLM-based methods often fail to capture…

Computation and Language · Computer Science 2025-10-13 Zhihao Jia , Mingyi Jia , Junwen Duan , Jianxin Wang

The FDA's Project Optimus initiative emphasizes patient-centered dose selection in oncology that balances efficacy and safety. We develop a framework for randomized dose optimization studies that uses clinically interpretable utility scores…

Applications · Statistics 2026-03-24 Xuemin Gu , Cong Xu , Lei Xu , Ying Yu

The primary analysis of clinical trials in diabetes therapeutic area often involves a mixed-model repeated measure (MMRM) approach to estimate the average treatment effect for longitudinal continuous outcome, and a generalized linear mixed…

Applications · Statistics 2022-08-03 Lingjing Jiang , Michael Rosenblum , Yu Du

We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose…

Applications · Statistics 2024-04-03 Jiaxin Liu , Shijie Yuan , B. Nebiyou Bekele , Yuan Ji

Project Optimus, an initiative by the FDA's Oncology Center of Excellence, seeks to reform the dose-optimization and dose-selection paradigm in oncology. We propose a dose-optimization design that considers plateau efficacy profiles,…

Applications · Statistics 2025-04-22 Rebecca B. Silva , Bin Cheng , Shing M. Lee

Decision-making in personalized medicine such as cancer therapy or critical care must often make choices for dosage combinations, i.e., multiple continuous treatments. Existing work for this task has modeled the effect of multiple…

Machine Learning · Computer Science 2023-10-30 Jonas Schweisthal , Dennis Frauen , Valentyn Melnychuk , Stefan Feuerriegel

While many novel therapies have been approved in recent years for treating patients with multiple myeloma, there is still no established curative regimen, especially for patients with high risk disease. In this work, we use a mathematical…

Optimization and Control · Mathematics 2022-11-18 Mahya Aghaee , Urszula Ledzewicz , Michael Robbins , Natalie Bezman , Hearn Jay Cho , Helen Moore

Therapy recommendation for chronic patients with multimorbidity is challenging due to risks of treatment conflicts. Existing decision support systems face scalability limitations. Inspired by the way in which general practitioners (GP)…

Artificial Intelligence · Computer Science 2025-07-16 Yicong Wu , Ting Chen , Irit Hochberg , Zhoujian Sun , Ruth Edry , Zhengxing Huang , Mor Peleg

We consider the problem of estimating the effects of a binary treatment on a continuous outcome of interest from observational data in the absence of confounding by unmeasured factors. We provide a new estimator of the population average…

Methodology · Statistics 2020-08-04 James Robins , Mariela Sued , Quanhong Lei-Gomez , Andrea Rotnitzky
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