2015—2020年美国加速审批与欧洲附条件批准的上市前有效性科学证据特点  

Characteristics of pre⁃approval efficacy evidence for US accelerated approval and European conditional marketing authorization during 2015—2020

作　　者：张晓方[1,2] 白雪 孙婉[1] 王凤至 陈思宇 武阳丰 ZHANG Xiao-fang;BAI Xue;SUN Wan;WANG Feng-zhi;CHEN Si-yu;WU Yang-feng(Peking University Clinical Research Institute,Beijing 100191,China;Peking University Health Science-China National Biotech Group Clinical and Regulatory Sciences Joint Laboratory,Beijing 100191,China;Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学临床研究所,北京100191 [2]北大医学-中国生物临床与监管科学联合实验室,北京100191 [3]北京大学第一医院,北京100034

出　　处：《中国新药杂志》2024年第1期1-9,共9页Chinese Journal of New Drugs

摘　　要：目的:描述和比较2015年1月1日—2020年12月31日期间,美国加速审批和欧洲附条件批准的上市前有效性证据特征。方法:通过美国、欧洲公开数据库,确定研究期间美国加速审批和欧洲附条件批准的所有药品及其上市前研究,收集并分析支持药品上市的有效性证据特点。结果:2015—2020年,美国、欧洲分别有122和35个获批事项通过加速审批/附条件批准上市。美国、欧洲上市前有效性证据主要基于替代终点(美国:93.3%;欧洲:91.4%)产生。提供上市前有效性证据的总样本量分别为88和124,美国显著低于欧洲(P=0.015)。美国、欧洲支持上市的效应值大部分为有效率(美国:77.3%;欧洲:60.0%),其中有效率低于30.0%的美国占21.7%,欧洲占4.7%,差异显著(P=0.005)。美国和欧洲上市前关键研究大多是Ⅱ期临床试验(美国:65.6%;欧洲:60.0%)、单臂临床试验(美国:79.8%;欧洲:65.7%)。结论:美国加速审批和欧洲附条件批准大多数依据Ⅱ期单臂临床试验在替代终点上显示的有效率上市,但是美国上市前有效性证据的强度低于欧洲,其差别主要来源于政策要求的不同。Objectives:To describe and compare the characteristics of the pre⁃approval efficacy evidence for the US accelerated approval(AA)and European conditional marketing authorization(CMA)from January 1,2015 to December 31,2020.Methods:All the drugs approved through AA and CMA pathway and their pre⁃approval studies were collected and analyzed based on the characteristics of their pre⁃approval efficacy evidence from public databases of US and Europe.Results:From 2015 to 2020,US FDA approved 122 and EMA approved 35 drugs and its indications(DAIs)through the AA/CMA pathway.The pre⁃approval efficacy evidence was mainly based on the surrogate endpoint(AA,93.3%;CMA,91.4%).The median of the sample size which provided the pre⁃approval efficacy evidence for AA and CMA were 88 and 124,with the size in AA was smaller than that in CMA(P=0.015).Most of the pre⁃approval evaluations were based on the response rate(AA,77.3%;CMA,60.0%)in single⁃arm study.There were 21.7%DAIs in AA and 4.7%in CMA had a response rate lower than 30.0%(P=0.005).Most of the pre⁃approval pivotal efficacy studies were PhII(AA,65.6%;CMA,60.0%)single⁃arm(AA,79.8%;CMA,65.7%)study.Conclusion:Most of the AA and CMA DAIs were granted based on the response rate of surrogate endpoint from phase II single⁃arm studies.The AA's strength of the pre⁃approval efficacy evidence is lower than CMA's.The difference came from the different policies of AA and CMA.

关 键 词：加速审批 附条件批准 获批事项 有效性证据 

分 类 号：R95[医药卫生—药学]