抗癌药Ⅰ期临床试验连续重评估方法解析及应用

An Introduction of Continual Reassessment Method and Its Application in Phase Ⅰ Trial for Anti-cancer Drug

本文回顾性剖析了抗癌药Ⅰ期临床试验的相关概念实质,阐明传统"3+3"剂量爬坡设计的局限及连续重评估方法(Continual reassessment method,CRM)的优势,对Ⅰ期临床试验中基于单参数功效模型的CRM、贝叶斯模型平均CRM、数据增强CRM、时间-事件CRM、分数CRM及其应用分别进行了详细解析,最后就CRM的试验设计流程进行了系统性概括,旨在为我国抗癌药Ⅰ期临床试验设计的方法学提供参考。

This article briefly introduced the aim and concept of phaseⅠclinical trial for anti-cancer drugs.We analyzed and pointed out the disadvantages of traditional“3+3”design and the advantages of continual reassessment method(CRM)for dose-escalation trial.Then we introduced in detail the concept and application of CRM,including the CRM based on single skeleton,Bayesian model averaging CRM,data augmentation CRM,time-to-event CRM and fractional CRM for phaseⅠtrial.In the end,we described the trial design process using the CRM.The information in this article we provide is aimed at clinicians and sponsors for their methodological references of phaseⅠtrial design of anti-cancer drugs in China.