2015—2020年美国加速审批与欧洲附条件批准的上市所附条件特点  

Post-marketing requirements of the US accelerated approval and European conditional marketing authorization during 2015—2020

作　　者：张晓方 白雪[2] 孙婉[2] 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 First Hospital,Beijing 100034,China;Clinical Research Institute,Institute of Advanced Clinical Medicine,Peking University,Beijing 100191,China;Peking University Health Science-China National Biotech Group Clinical and Regulatory Sciences Joint Laboratory,Beijing 100191,China)

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

出　　处：《中国新药杂志》2024年第8期737-744,共8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,美国加速审批与欧洲附条件批准的上市所附条件。方法:通过美国和欧洲公开数据库,确定研究期间美国加速审批与欧洲附条件批准的所有药品的上市所附条件及上市后确证性临床研究。结果:2015—2020年,美国和欧洲分别有122和35个获批事项通过加速审批/附条件批准上市。美国FDA对每个获批事项平均提出了1.2个上市所附条件,欧洲EMA平均提出了2.3个,明显高于美国FDA(P<0.001)。美国上市所附条件的目的大部分是进一步确定产品有效性(61.5%),而欧洲大部分是既要确定产品的有效性也要确定安全性(85.7%)。美国和欧洲分别对54.9%和61.8%的上市后确证性临床研究要求使用替代终点作为主要终点指标,对95.1%和88.2%的上市后确证性临床研究要求使用干预,77.9%和61.8%的使用随机,63.1%和67.7%的使用对照。美国上市后确证性临床研究报告提交时限平均为46.8个月,≥5年的占31.6%。欧洲的平均时限为37.5个月,≥5年的占21.9%。结论:在上市所附条件方面,欧洲比美国更加谨慎和保守。对于上市后确证性临床研究,美国和欧洲的要求均以随机对照试验为主,但过多地应用了替代终点。而对于上市后确证性临床研究的报告时限,美国和欧洲大部分均在5年以内。我国可充分借鉴美国和欧洲的经验教训,进一步完善我国的附条件批准政策。Objectives:To describe and compare the characteristics of the specific post-marketing requirements of the US accelerated approval(AA)and European conditional marketing authorization(CMA)from January 1,2015 to December 31,2020.Methods:The characteristics of all the drugs approved through AA and CMA pathway and their specific post-marketing requirements during the study phase were collected and analyzed.Results:From 2015 to 2020,the US FDA approved 122 and EMA approved 35 drugs and their indications(DAIs)through the AA/CMA pathway.For each DAI on average,the US FDA required 1.2 specific post-marketing requirements,and EMA required 2.3 specific post-marketing requirements(P<0.001).Most of the aims of US FDA's specific post-marketing requirements were to confirm the efficacy of the DAI(61.5%),while EMA's were to confirm both the efficacy and safety(85.7%).Surrogate endpoints were asked to be the primary endpoint for the post-approval confirmatory studies in most DAIs(AA,54.9%;CMA,61.8%).Intervention was required by 95.1% and 88.2%,randomization was required by 77.9% and 61.8%,and control was required by 63.1% and 67.7% for the post-approval confirmatory studies on the DAIs.The average time slot for submission of post-approval confirmatory studies was 46.8 months for AA and 37.5 months for CMA,with 31.6% and 21.9% DAIs had a time slot more than five years.Conclusion:EMA is more cautious and conservative than the US FDA on the specific post-marketing requirement.For the post-approval confirmatory studies,both US FDA and EMA required randomized controlled trials for most of the DAIs,however there were an overuse of surrogate endpoints.The average time slot for submission of post-approval confirmatory studies was within five years.Experience and lessons from US FDA and EMA could be learned to improve the conditional approval policy in China.

关 键 词：加速审批 附条件批准 上市所附条件 

分 类 号：R95[医药卫生—药学]