我国GCP与药物临床试验监管研究
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摘要
药物临床试验(Clinical Trial)是药品研发在临床方面的具体表现,是药品从研发到应用不可或缺的重要环节。作为一个高度专业化的领域,药物临床试验参与各方包括申办者、研究者、伦理委员会、合同研究组织(CRO)以及监管部门必须执行《药物临床试验质量管理规范》(GCP)及其他有关法律法规,所有活动均应该纳入到政府的监管范畴中。针对2002年以来的低水平重复申报、研发秩序混乱甚至试验数据造假的情形,始于2006年7月的全国药品注册核查行动,暴露出临床试验的监管尚存在很多问题,对临床试验的监管亟待加强。
本文运用法律法规梳理、文献研究、案例分析等非接触式研究方法,结合实地调研和专家访谈等接触式研究方法,对我国GCP与药物临床试验监管的历史、当前监管体系存在的主要问题、以及美国FDA的临床试验监管方式进行了深入研究。
全文首先总结了国内外药物临床试验监管的历史与概况,将世界药物临床试验管理的发展历程分为三个阶段,梳理了我国药物临床试验监管的历史,并将我国现行GCP与ICH GCP在细则上进行了对比,接着梳理了我国药物临床试验监管的框架及现状。然后全面分析了我国药物临床试验监管中存在的主要问题,包括:(1)监管体系不完善,主要涉及监管主体混乱,伦理委员会运作缺乏监管以及现场核查标准较低;(2)药物临床试验机构数量不足,并且发展不平衡;(3)临床试验备案制度执行不畅,试验实施过程监管缺失;(4)SOP的实施有待提高;(5)受试者的损害补偿机制不完善等。
最后,借鉴美国FDA的监管理念和方法,针对上述研究发现的问题,对我国未来临床试验的监管提出以下建议:(1)完善临床试验监管体系、明确监管部门的职能分工;(2)SFDA等相关部门定期评估与实时监督GCP的执行情况;(3)加强对伦理委员会的管理和监督;(4)指导临床试验机构建设、满足新药临床试验需求;(5)提高临床试验监管的公开和透明度等。
Clinical trial is a key procedure in the new drug research and development process. As a highly specialized area, the involved parties in clinical trials, including sponsors, investigators, ethics committees, contract research organizations (CRO) and regulatory agencies, need to implement "Good Clinical Practice" (GCP) and other relevant laws and regulations, and all of activities should be integrated into areas of government supervision. Several problems are revealed through the Special Registration Inspection Action by SFDA from July 2006 to December 2007, and the supervision for clinical trials should be strengthened.
In this paper, research methods including literature search, case studies and field research and interviews with experts have been used to study on China GCP, the regulatory history of clinical trials, major problems in the current regulatory system, as well as U.S. FDA regulation of clinical trials.
In this work, the domestic and international regulations of drug clinical trials are first summed up. Then China GCP and ICH GCP are compared in the details. By analyzing China's regulatory framework of clinical trials, major problems in the supervision for clinical trials are concluded, including: (1) imperfect regulatory system, such as the regulatory agencies confused, lack of regulating for ethics committees, as well as poor site-inspection standards; (2) lack of the drug clinical trials institutions (certificated hospitals); (3) lack of supervision for the conducting of clinical trials with poor filing system; (4) SOP implementation need to be improved; (5) lack of compensation mechanism to subjects who are damaged in the trials.
At last, through drawing on the regulatory experience of U.S. FDA, suggestions on supervision for clinical trials in China have been put forward as follows: (1) improve the regulatory system of clinical trials, and clearly allocate the functions of regulatory agencies; (2) real-time monitoring and regular evaluating of the implementation of GCP should be conducted by SFDA and other related agencies; (3) strengthen management and regulating of the ethics committee; (4) approve more clinical trials institutions, to meet the demand for clinical trials of new drugs; (5) improve the transparent of supervision for clinical trials.
本文运用法律法规梳理、文献研究、案例分析等非接触式研究方法,结合实地调研和专家访谈等接触式研究方法,对我国GCP与药物临床试验监管的历史、当前监管体系存在的主要问题、以及美国FDA的临床试验监管方式进行了深入研究。
全文首先总结了国内外药物临床试验监管的历史与概况,将世界药物临床试验管理的发展历程分为三个阶段,梳理了我国药物临床试验监管的历史,并将我国现行GCP与ICH GCP在细则上进行了对比,接着梳理了我国药物临床试验监管的框架及现状。然后全面分析了我国药物临床试验监管中存在的主要问题,包括:(1)监管体系不完善,主要涉及监管主体混乱,伦理委员会运作缺乏监管以及现场核查标准较低;(2)药物临床试验机构数量不足,并且发展不平衡;(3)临床试验备案制度执行不畅,试验实施过程监管缺失;(4)SOP的实施有待提高;(5)受试者的损害补偿机制不完善等。
最后,借鉴美国FDA的监管理念和方法,针对上述研究发现的问题,对我国未来临床试验的监管提出以下建议:(1)完善临床试验监管体系、明确监管部门的职能分工;(2)SFDA等相关部门定期评估与实时监督GCP的执行情况;(3)加强对伦理委员会的管理和监督;(4)指导临床试验机构建设、满足新药临床试验需求;(5)提高临床试验监管的公开和透明度等。
Clinical trial is a key procedure in the new drug research and development process. As a highly specialized area, the involved parties in clinical trials, including sponsors, investigators, ethics committees, contract research organizations (CRO) and regulatory agencies, need to implement "Good Clinical Practice" (GCP) and other relevant laws and regulations, and all of activities should be integrated into areas of government supervision. Several problems are revealed through the Special Registration Inspection Action by SFDA from July 2006 to December 2007, and the supervision for clinical trials should be strengthened.
In this paper, research methods including literature search, case studies and field research and interviews with experts have been used to study on China GCP, the regulatory history of clinical trials, major problems in the current regulatory system, as well as U.S. FDA regulation of clinical trials.
In this work, the domestic and international regulations of drug clinical trials are first summed up. Then China GCP and ICH GCP are compared in the details. By analyzing China's regulatory framework of clinical trials, major problems in the supervision for clinical trials are concluded, including: (1) imperfect regulatory system, such as the regulatory agencies confused, lack of regulating for ethics committees, as well as poor site-inspection standards; (2) lack of the drug clinical trials institutions (certificated hospitals); (3) lack of supervision for the conducting of clinical trials with poor filing system; (4) SOP implementation need to be improved; (5) lack of compensation mechanism to subjects who are damaged in the trials.
At last, through drawing on the regulatory experience of U.S. FDA, suggestions on supervision for clinical trials in China have been put forward as follows: (1) improve the regulatory system of clinical trials, and clearly allocate the functions of regulatory agencies; (2) real-time monitoring and regular evaluating of the implementation of GCP should be conducted by SFDA and other related agencies; (3) strengthen management and regulating of the ethics committee; (4) approve more clinical trials institutions, to meet the demand for clinical trials of new drugs; (5) improve the transparent of supervision for clinical trials.
引文
[1]王建英,美国药品申报与法规管理,北京:中国医药科技出版社,2005,69~70
[2]国家食品药品监督管理局网站,http://www.sda.gov.cn/WS01/CL0053/24473.html,《药物临床试验质量管理规范》(局令第3号)
[3]邵颖,我国药物临床试验的科学发展史与期望,中国临床药理学杂志,2008, 24(2):180~186
[4]袁方,我国开展国际多中心临床试验的现状及改进措施,医药导报,2007, 26(1):100~102
[5]薛迪,周萍,唐智柳等,上海市医院伦理委员会功能与管理状况研究概述,中国卫生资源,2008,11(4):158~159
[6]稚子归,药物临床试验之开篇:姿态和选择,中国处方药,2007,62:20~22
[7]于丽,美国:渐进完善,中国处方药杂志,2007,62:26~28
[8]曹立亚,郭林,美国药品安全监管历程与监测体系,北京:中国医药科技出版社,2006,28~38
[9]同[8],47~55
[10] ICH指导委员会,药品注册的国际技术要求(中英文对照),2007临床部分,周海钧主译,北京:人民卫生出版社,2007,1~4
[11]同[10],7~10
[12]徐荣周,卫生部有关药政管理的若干规定,医药导报,1993,12(6):302~303
[13]田少雷,宫岩华,我国GCP的实施与药品临床研究基地的发展,中国临床药理学杂志,2000,16(4):315~318
[14]中国处方药编辑部,一个资深专家的调研样本,中国处方药杂志,2007,63:24~25
[15]毛冬蕾,临床试验在中国:审评质量与时间的博弈,中国处方药,2008,80:28~31
[16]栾雪梅,临床试验:向新兴国家进发,中国处方药,2007,62:23~25
[17]国家食品药品监督管理局网站,http://www.sda.gov.cn/WS01/CL0010/
[18]赵帼英,江滨,史录文等,我国药物临床试验伦理委员会运作模式及监管机制探讨,中国药事,2007,21(1):25~28
[19]国新办就全国药品专项整治等方面情况举行新闻发布会,http://www.china.com.cn/zhibo/2007-12/03/content_9325031.htm
[20]国家食品药品监督管理局网站,2007年度统计年报,http://www.sda.gov.cn/WS01/CL0108/32801.html
[21]国家食品药品监督管理局药品审评中心网站,与浙江省医药行业协会技术交流视频会议纪要,http://www.cde.org.cn/newspic.do?method=view&id=310912
[22]唐智柳,周萍,薛迪等,上海市医院伦理委员会伦理审核工作现状分析,中国卫生资源,2008,11(6):263~264
[23]王彤,毛佩佩,周萍等,上海市医院伦理委员会机构建设与功能定位的现状分析,中国卫生资源,2008,11(5):214~215
[24]国家食品药品监督管理局网站,《关于印发药品注册现场核查管理规定的通知》(国食药监注[2008]255号),http://www.sda.gov.cn/WS01/CL0055/30285.html
[25] 2008中国卫生统计提要,http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjty/200805/35671.htm
[26]姚晨,杉野敬一,大桥靖雄等,外国制药企业在中国开展临床试验现况分析,中国新药杂志,2008,17(21):1901~1904
[27]袁方,我国开展国际多中心临床试验的现状及改进措施,医药导报,2007, 26(1):100~102
[28]王停,董润生,一起中药临床试验严重不良事件带给我们的思考,中国新药杂志,2008,17(14):1185~1187
[29] Karen E. Woodin, John C. Schneider, The CRA’s guide to monitoring clinical research, Thomson Place ? Boston, 2004, 206~211
[30] FDA网站,http://www.fda.gov/oc/gcp/hsp_bimo.html
[31]同[1],69~70
[32]左根勇,以ICH-GCP为基础的国际GCP规制及对我国的启示,中国处方药杂志,2007,66:41~42
[33]田少雷,GCP对药物临床试验的质量保证同,中国新药杂志,2002,11(11):825~829
[34]郭英调,杨志新,何桡通,改善多中心临床试验伦理审查的方法,2006第四届中国肿瘤学术大会论文集:1111
[35]罗彩琴,张志坚,程小燕等,浅谈接受药物临床试验机构现场资格认定检查的启示与思考,中国现代药物应用,2008,2(20):118~120
[2]国家食品药品监督管理局网站,http://www.sda.gov.cn/WS01/CL0053/24473.html,《药物临床试验质量管理规范》(局令第3号)
[3]邵颖,我国药物临床试验的科学发展史与期望,中国临床药理学杂志,2008, 24(2):180~186
[4]袁方,我国开展国际多中心临床试验的现状及改进措施,医药导报,2007, 26(1):100~102
[5]薛迪,周萍,唐智柳等,上海市医院伦理委员会功能与管理状况研究概述,中国卫生资源,2008,11(4):158~159
[6]稚子归,药物临床试验之开篇:姿态和选择,中国处方药,2007,62:20~22
[7]于丽,美国:渐进完善,中国处方药杂志,2007,62:26~28
[8]曹立亚,郭林,美国药品安全监管历程与监测体系,北京:中国医药科技出版社,2006,28~38
[9]同[8],47~55
[10] ICH指导委员会,药品注册的国际技术要求(中英文对照),2007临床部分,周海钧主译,北京:人民卫生出版社,2007,1~4
[11]同[10],7~10
[12]徐荣周,卫生部有关药政管理的若干规定,医药导报,1993,12(6):302~303
[13]田少雷,宫岩华,我国GCP的实施与药品临床研究基地的发展,中国临床药理学杂志,2000,16(4):315~318
[14]中国处方药编辑部,一个资深专家的调研样本,中国处方药杂志,2007,63:24~25
[15]毛冬蕾,临床试验在中国:审评质量与时间的博弈,中国处方药,2008,80:28~31
[16]栾雪梅,临床试验:向新兴国家进发,中国处方药,2007,62:23~25
[17]国家食品药品监督管理局网站,http://www.sda.gov.cn/WS01/CL0010/
[18]赵帼英,江滨,史录文等,我国药物临床试验伦理委员会运作模式及监管机制探讨,中国药事,2007,21(1):25~28
[19]国新办就全国药品专项整治等方面情况举行新闻发布会,http://www.china.com.cn/zhibo/2007-12/03/content_9325031.htm
[20]国家食品药品监督管理局网站,2007年度统计年报,http://www.sda.gov.cn/WS01/CL0108/32801.html
[21]国家食品药品监督管理局药品审评中心网站,与浙江省医药行业协会技术交流视频会议纪要,http://www.cde.org.cn/newspic.do?method=view&id=310912
[22]唐智柳,周萍,薛迪等,上海市医院伦理委员会伦理审核工作现状分析,中国卫生资源,2008,11(6):263~264
[23]王彤,毛佩佩,周萍等,上海市医院伦理委员会机构建设与功能定位的现状分析,中国卫生资源,2008,11(5):214~215
[24]国家食品药品监督管理局网站,《关于印发药品注册现场核查管理规定的通知》(国食药监注[2008]255号),http://www.sda.gov.cn/WS01/CL0055/30285.html
[25] 2008中国卫生统计提要,http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/ptjty/200805/35671.htm
[26]姚晨,杉野敬一,大桥靖雄等,外国制药企业在中国开展临床试验现况分析,中国新药杂志,2008,17(21):1901~1904
[27]袁方,我国开展国际多中心临床试验的现状及改进措施,医药导报,2007, 26(1):100~102
[28]王停,董润生,一起中药临床试验严重不良事件带给我们的思考,中国新药杂志,2008,17(14):1185~1187
[29] Karen E. Woodin, John C. Schneider, The CRA’s guide to monitoring clinical research, Thomson Place ? Boston, 2004, 206~211
[30] FDA网站,http://www.fda.gov/oc/gcp/hsp_bimo.html
[31]同[1],69~70
[32]左根勇,以ICH-GCP为基础的国际GCP规制及对我国的启示,中国处方药杂志,2007,66:41~42
[33]田少雷,GCP对药物临床试验的质量保证同,中国新药杂志,2002,11(11):825~829
[34]郭英调,杨志新,何桡通,改善多中心临床试验伦理审查的方法,2006第四届中国肿瘤学术大会论文集:1111
[35]罗彩琴,张志坚,程小燕等,浅谈接受药物临床试验机构现场资格认定检查的启示与思考,中国现代药物应用,2008,2(20):118~120