国外创新药Ⅰ期临床试验剂量探索设计方法及其对我国的启示  

Dose exploration design of phase I clinical trial of new drugs in foreign countries and its enlightenment to China

作　　者：刘晋 杨嘉莹 朱文博 邵凤[1] 周辰[1] 王璐[1] 李天萍[1] 汪秀琴[1] 梁宁霞[1] LIU Jin;YANG Jia-ying;ZHU Wen-bo;SHAO Feng;ZHOU Chen;WANG Lu;LI Tian-ping;WANG Xiu-qin;LIANG Ning-xia(The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;School of Public Health of South East University,Nanjing 210029,China;GCP Office,Jiangsu Cancer Hospital,Nanjing 210009,China)

机构地区：[1]南京医科大学第一附属医院,南京210029 [2]东南大学公共卫生学院,南京210009 [3]江苏省肿瘤医院机构办公室,南京210009

出　　处：《中国新药杂志》2020年第15期1746-1751,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金青年基金(81602938);GCP平台创新药物临床评价的同位素示踪技术平台建设(2017ZX09304032)。

摘　　要：Ⅰ期临床试验剂量探索设计方法已成为国外新药研发的热点问题之一,及时引进国外新方法对提升我国Ⅰ期临床试验水平具有实际意义。本文从基于规则、基于模型和基于模型辅助的设计方法 3 个方面较系统介绍了目前国际主流Ⅰ期临床试验剂量探索方法。从有效性、安全性、可靠性 3 个层面介绍了国外新方法的评价指标和评价结果。结果显示,以 BOIN、键盘、mTPI-2 为代表的基于模型辅助的设计方法和以 CRM 为代表的基于模型的设计方法明显优于我国目前惯用的 3 + 3 设计。模型辅助设计方法和基于模型设计的方法具有相似的准确性但简单易用。在分析国外Ⅰ期临床试验剂量探索方法发展经验的基础上,探讨了引进国外新方法对提升我国创新药Ⅰ期临床试验剂量探索设计水平的四点启示。Dose exploration design of phase I clinical trial has become one of the hottest topics in the development of new drugs in foreign countries.Introduction of new methods has practical significance to improve the level of phase I clinical trials in China.This paper systematically introduces the dose exploration methods of current international mainstream phase I clinical trials from three aspects:rule-based,model-based and model-assisted design methods.The evaluation criteria and outcome of new methods are introduced from three aspects of effectiveness,safety and reliability.The results show that the model-assisted design method represented by BOIN,keyboard and mTPI-2,and the model-based design method represented by CRM are obviously superior to the 3+3 design widely used in China currently.The model-assisted design and the model-based design have similar accuracy but is simpler and easier to utilize.Based on the analysis of the development experience of dose exploration methods in phase I clinical trials abroad,this paper discusses four points of inspiration of introducing new methods to improve the dose exploration design level of phase I clinical trials in China.

关 键 词：Ⅰ期临床试验 剂量探索 设计方法 

分 类 号：R95[医药卫生—药学]