Characterization of the likelihood continual reassessment method

• 成果类型: Article
• 署名作者: Jia, Xiaoyu; Lee, Shing M.; Cheung, Ying Kuen
• 署名单位: Boehringer Ingelheim; Columbia University
• 刊物名称: BIOMETRIKA
• ISSN/ISSBN: 0006-3444
• DOI: 10.1093/biomet/asu012
• 发表日期: 2014
• 页码: 599612
• 关键词: clinical-trials; phase-i; MODEL; DESIGN

摘要

This paper deals with the design of the likelihood continual reassessment method, which is an increasingly widely used model-based method for dose-finding studies. It is common to implement the method in a two-stage approach, whereby the model-based stage is activated after an initial sequence of patients has been treated. While this two-stage approach is practically appealing, it lacks a theoretical framework, and it is often unclear how the design components should be specified. This paper develops a general framework based on the coherence principle, from which we derive a design calibration process. A real clinical-trial example is used to demonstrate that the proposed process can be implemented in a timely and reproducible manner, while offering competitive operating characteristics. We explore the operating characteristics of different models within this framework and show the performance to be insensitive to the choice of dose-toxicity model.