肿瘤学中使用带协变量逻辑回归的贝叶斯病例研究：I期联合剂量探索。

A Bayesian case study in oncology Phase I combination dose-finding using logistic regression with covariates.

作者信息

Bailey Stuart, Neuenschwander Beat, Laird Glen, Branson Michael

机构信息

Novartis Pharma AG, Basel, Switzerland.

出版信息

J Biopharm Stat. 2009;19(3):469-84. doi: 10.1080/10543400902802409.

DOI:10.1080/10543400902802409

PMID:19384689

Abstract

A Bayesian approach to finding the maximum tolerated dose (MTD) is presented. The approach is flexible, allowing inclusion of covariates, and enables transparent dose recommendations based on comprehensive inferential summaries on the probability of dose-limiting toxicities (DLT). A case study is presented for a Phase I combination of two oncology drugs, nilotinib and imatinib. Data obtained and decisions made during the study are described. Final determination of the MTD pair is outlined, along with discussion regarding the use and interpretability of within- and end-of-study data.

摘要

本文提出了一种用于寻找最大耐受剂量（MTD）的贝叶斯方法。该方法具有灵活性，允许纳入协变量，并能基于对剂量限制毒性（DLT）概率的全面推断总结给出透明的剂量建议。文中给出了一个关于两种肿瘤药物尼洛替尼和伊马替尼联合使用的I期试验案例研究。描述了该研究过程中获取的数据和做出的决策。概述了MTD组合的最终确定方法，以及关于研究期间和研究结束时数据的使用和可解释性的讨论。