陈霞;
CHEN Xia;Clinical Trial Center of China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University;

• 1:首都医科大学附属北京天坛医院国家神经系统疾病临床医学研究中心-临床试验中心

摘要(Abstract)：

2016年1月,在法国进行的BIA 10-2474Ⅰ期临床试验中,1名健康受试者在给药后发生脑死亡。为了探寻事件原因,尽可能从系统上降低类似悲剧重现的风险,本文根据BIA 10-2474专家调查组的报告,从药物作用机制、临床前研究发现、临床研究设计和实施等方面梳理了这个悲剧性事件的前因后果,并获得以下启示:第一,应在药物进入临床研发前根据已获得的研究数据和同类药物的相关信息审慎决策,以便提高研发成功率,规避不必要的风险;第二,研究设计既要考虑药物的临床前安全性特征,还要考虑药效特征,在兼顾受试者安全的前提下达成试验的科学目的;第三,高风险新药早期临床研究应始终保持高度警惕性,不放过任何可能提示药物风险的信号,遇到问题全面分析,保守处理。
In January 2016,a healthy subject in the Phase Ⅰ clinical trial of BIA 10-2474 in France experienced brain death after administration of the studied medicine. In order to explore the cause of this event and systematically mitigate the risk of early-phase clinical trials,this article sorted out the potential reasons in terms of the mechanism of drug effect,preclinical findings,design and execution of the clinical study based on the report written by the Temporary Specialist Scientific Committee involved in the survey of the BIA 10-2474 study.The lessons learnt from this tragedy may include:( 1) the decision on clinical development should be made carefully according to available research data and relevant information obtained from similar drugs,so as to improve the rate of success and avoid unnecessary risks;( 2) the trial design should consider safety findings and pharmacody-namic properties of the drug in pre-clinical studies,as well as the scientific objectives of the study;( 3) in early-stage clinical trials of novel drugs,investigators should be fully aware of the potential risks,even small signals should be noted. Whenever there is an emerging event,it is recommended to perform a comprehensive analysis on the event and then treat it conservatively.

关键词(KeyWords)： 药物临床研发;首次人体研究;风险控制
clinical drug development;first-in-human study;risk mitigation

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(81671369);; “十三五”重大专项基金(2017ZX09304018)

作者(Authors): 陈霞;
CHEN Xia;Clinical Trial Center of China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University;

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