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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)…

统计方法学 · 统计学 2025-08-18 Andrea Nizzardo , Luca Genetti , Marco Pergher

In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…

应用统计 · 统计学 2023-02-23 Lukas A. Widmer , Andrew Bean , David Ohlssen , Sebastian Weber

Model-assisted designs have garnered significant attention in recent years due to their high accuracy in identifying the maximum tolerated dose (MTD) and their operational simplicity. To identify the MTD, they employ estimated dose limiting…

应用统计 · 统计学 2025-08-19 Rentaro Wakayama , Tomotaka Momozaki , Shuji Ando

Traditionally, the major objective in phase I trials is to identify a working-dose for subsequent studies, whereas the major endpoint in phase II and III trials is treatment efficacy. The dose sought is typically referred to as the maximum…

统计方法学 · 统计学 2016-08-14 Mourad Tighiouart , André Rogatko

This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…

统计方法学 · 统计学 2018-07-17 Pavel Mozgunov , Thomas Jaki

The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However,…

统计方法学 · 统计学 2024-09-02 Yunlong Yang , Ying Yuan

Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…

Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…

统计方法学 · 统计学 2022-09-13 Christian Röver , Moreno Ursino , Tim Friede , Sarah Zohar

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…

机器学习 · 统计学 2025-04-15 Keiichiro Seno , Kota Matsui , Shogo Iwazaki , Yu Inatsu , Shion Takeno , Shigeyuki Matsui

In the development of new cancer treatment, an essential step is to determine the maximum tolerated dose (MTD) via phase I clinical trials. Generally speaking, phase I trial designs can be classified as either model-based or algorithm-based…

应用统计 · 统计学 2022-03-02 Huaqing Jin , Wenbin Du , Guosheng Yin

We propose an adaptive design for early phase drug combination cancer trials with the goal of estimating the maximum tolerated dose (MTD). A nonparametric Bayesian model, using beta priors truncated to the set of partially ordered dose…

应用统计 · 统计学 2019-10-22 Zahra S. Razaee , Galen Wien-Cook , Mourad Tighiouart

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…

组织与器官 · 定量生物学 2013-06-21 Sebastien Benzekry , Philip Hahnfeldt

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…

统计方法学 · 统计学 2025-03-21 Jiapeng Xu , Dehua Bi , Shenghua Kelly Fan , Bee Leng Lee , Ying Lu

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…

This paper describes a method for a model-based analysis of clinical safety data called multivariate Bayesian logistic regression (MBLR). Parallel logistic regression models are fit to a set of medically related issues, or response…

统计方法学 · 统计学 2012-10-02 William DuMouchel

An important objective in environmental risk assessment is estimation of minimum exposure levels, called Benchmark Doses (BMDs) that induce a pre-specified Benchmark Response (BMR) in a target population. Established inferential approaches…

统计方法学 · 统计学 2014-06-12 Qijun Fang , Walter W. Piegorsch , Katherine Y. Barnes

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…

统计方法学 · 统计学 2014-05-07 Joseph S. Koopmeiners , Andrew Wey

Novel dose-finding designs, using estimation to assign the best estimated maximum- tolerated-dose (MTD) at each point in the experiment, most commonly via Bayesian techniques, have recently entered large-scale implementation in Phase I…

统计方法学 · 统计学 2017-01-24 Assaf P. Oron , Peter D. Hoff

Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase…

统计方法学 · 统计学 2020-12-08 Moreno Ursino , Lucie Biard , Sylvie Chevret

Dynamic treatment regimes (DTRs) are sequences of decision rules designed to tailor treatment based on patients' treatment history and evolving disease status. Ordinal outcomes frequently serve as primary endpoints in clinical trials and…

统计方法学 · 统计学 2025-03-11 Xinru Wang , Tanujit Chakraborty , Bibhas Chakraborty
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