临床研究数据与安全监查国际发展现状与思考
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摘要
数据与安全监查委员会(Data and Safety Monitoring Board,DSMB)在国际范围内广泛应用于大规模、多中心临床试验及政府资助项目,它在全程保护受试者安全、提升临床研究质量与水平方面起着十分重要的作用。虽然DSMB在欧美发达国家运用经验较成熟,但在我国目前尚处于起步阶段。该文通过回顾DSMB的起源和工作流程,比较模式及国际现行各指导原则,分析其应用现状、发展趋势和存在的问题,提出根据各国国情及不同临床研究特点,除了对累积数据进行期中分析以动态评估干预措施的安全性有效性外,采取扩大监查范围、丰富监查模式、建立专业的技术队伍、制定符合各类临床研究特点的DSMB操作规程、重视并建立DSMB保险和赔偿机制等策略,不仅是在国际范围内推进和完善数据与安全监查工作的有效途径,也是提高我国临床研究技术与国际先进水平接轨亟待解决的问题。
The Data and Safety Monitoring Board(DSMB) is widely used worldwide in large scale,multicenter clinical trials and government-funded projects.It plays an important role in the protection of whole-course subject safety and improving the quality of clinical research.Although the developed countries have more experience in DSMB practice,it's still in its initial stage in China.By revision of the origin and workflow of DSMB and comparison of the models and the current guiding principles,the application status,development tendency and existing problems in different countries,along with making interim analysis on cumulative data to dynamically assess the efficacy and safety of the intervention,the authors propose that DSMB should expand the monitor scope,enrich monitor approaches,establish professional expert group,formulate operating instruction to satisfy the different clinical researches,and make a point of setting up DSMB insurance and indemnity mechanism according to different country's conditions and clinical research characteristics.This will not only enhance the data and safety monitor practice,but also improve the clinical research level in China to meet international standards.
The Data and Safety Monitoring Board(DSMB) is widely used worldwide in large scale,multicenter clinical trials and government-funded projects.It plays an important role in the protection of whole-course subject safety and improving the quality of clinical research.Although the developed countries have more experience in DSMB practice,it's still in its initial stage in China.By revision of the origin and workflow of DSMB and comparison of the models and the current guiding principles,the application status,development tendency and existing problems in different countries,along with making interim analysis on cumulative data to dynamically assess the efficacy and safety of the intervention,the authors propose that DSMB should expand the monitor scope,enrich monitor approaches,establish professional expert group,formulate operating instruction to satisfy the different clinical researches,and make a point of setting up DSMB insurance and indemnity mechanism according to different country's conditions and clinical research characteristics.This will not only enhance the data and safety monitor practice,but also improve the clinical research level in China to meet international standards.
引文
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[22]Zuckerman J,Vand S B,Cahill K.Developing training for data safety monitoring board members:A national institute of allergy and infectious diseases case study[J].Clin Trials,2015,12(6):688-691.
[23]Fleming T R,Demets D L,Roe MT,et al.Data monitoring committees:Promoting best practices to address emerging challenges[J].Clin Trials,2017,14(2):115-123.
[24]Calis K A,Archdeacon P,Bain R P,et al.Understanding the functions and operations of data monitoring committees:Survey and focus group findings[J].Clin Trials,2016,14(1):59-66.
[25]Czaja S J,Schulz R,Belle S H,et al.Data and safety monitoring in social behavioral intervention trials:The REACH II experience[J].Clin Trials,2006,3(2),107-118.
[26]Swedberg K,Borer J S,et al.Challenges to data monitoring committees when regulatory authorities intervene[J].New Engl J Med,2016,374(16):1580-1584.
[27]Steiner M.The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers[J].New Engl J Med,1994,330(15):1029-1035.
[28]David L,Curt D,Furberg L M.Data Monitoring Committees in Clinical Trials A case study approach[M].Friedman.2006.
[29]Department of Health and Human Services,Office of Inspector General.Data and safety monitoring boards in NIH clinical trials meeting guidance,but facing some issues.[EB/OL].(2013-06-28)[2018-09-13].https://www.oig.hhs.gov/oei/reports/oei-12-11-00070.pdf
[2]Baigent C,Harrell F E,Buyse M,et al.Ensuring trial validity by data quality assurance and diversification of monitoring methods[J].Clin Trials,2008,5(1):49-55.
[3]Hess C N,Roe M T,Gibson C M,et al.Independent data monitoring committees:preparing a path for the future[J].Am Heart J,2014,168(2):135-141.
[4]Friedman L.The NHLBI model:a 25 year history[J].Stat Med,2010,12(5-6):425-431.
[5]Listed N.Organization,review,and administration of cooperative studies(Greenberg Report):a report from the Heart Special Project Committee to the National Advisory Heart Council,May 1967.[J].Contr Clin Trials,1988,9(2):137-148.
[6]Guideline for the format and content of the clinical and statistical sections of new drug applications[S].1988.
[7]Marshall E.Review boards:A system'in jeopardy'?[J].Science,1998,280(5371):1830-1831.
[8]National Institutes of Health.NIH policy for data and safety monitoring[EB/OL].(1988-06-10)[2018-09-13].http://grants.nih.gov/grants/guide/notice-files/not98-084.html
[9]Whalen E R.Clinical trials driven by investigatorsponsors:GCP compliance with or without previous industry sponsorship[D].Southern California.Faculty of the USC School of Pharmacy University,2013.
[10]高灵灵,阎小妍,姚晨.临床试验数据监查委员会的操作规范和实践[J].中国新药杂志,2013(14):1667-1672.
[11]Everitt B.Data monitoring committees in clinical trials:Apractical perspective[J].Stat Meth Med Res,2004(2):173.
[12]Wittes J.On independent data monitoring committees in oncology clinical trials[J].Chin Clin Oncol,2014,3(3):40.
[13]U.S.Food and Drug Administration.The establishment and operation of clinical trial data monitoring committees for clinical trial sponsors[EB/OL].(2016-01-15)[2018-01-15].https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm127073.pdf
[14]Guideline on data monitoring committees[S].2005.
[15]UNICEF,UNDP,Bank W.Operational guidelines for the establishment and functioning of data and safety monitoring boards[J].Int J Pharm Med,2006,20(1):25-36.
[16]Zarin D A,Tse T,Williams R J,et al.The ClinicalTrials gov results database--update and key issues[J].New Engl J Med,2011,364(22):852-60.
[17]国家食品药品监督管理总局药品审评中心.儿科人群药物临床试验技术指导原则[EB/OL].(2016-03-01)[2018-09-13].http://www.cde.org.cn/zdyz.do?method=largePage&id=264
[18]国家食品药品监督管理总局药品审评中心.药物临床试验的生物统计学指导原则[EB/OL].(2016-06-03)[2018-09-13].http://www.cde.org.cn/zdyz.do?method=largePage&id=272
[19]国家食品药品监督管理总局药品审评中心.临床试验数据管理工作技术指南[EB/OL].(2016-01-29[2018-09-13].http://www.cde.org.cn/news.do?method=largeInfo&id=313520
[20]中国政府法制信息网.国家市场监督管理总局关于公开征求?药物临床试验质量管理规范(修订草案征求意见稿)?意见的通知[EB/OL].(2018-07-17)[2018-09-13].http://www.chinalaw.gov.cn/art/2018/7/17/art_33_208770.html
[21]王蕾,刘骏,党海霞,等.丹红注射液Ⅳ期临床试验的数据与安全监查[J].中国药学杂志,2015,50(04):375-378.
[22]Zuckerman J,Vand S B,Cahill K.Developing training for data safety monitoring board members:A national institute of allergy and infectious diseases case study[J].Clin Trials,2015,12(6):688-691.
[23]Fleming T R,Demets D L,Roe MT,et al.Data monitoring committees:Promoting best practices to address emerging challenges[J].Clin Trials,2017,14(2):115-123.
[24]Calis K A,Archdeacon P,Bain R P,et al.Understanding the functions and operations of data monitoring committees:Survey and focus group findings[J].Clin Trials,2016,14(1):59-66.
[25]Czaja S J,Schulz R,Belle S H,et al.Data and safety monitoring in social behavioral intervention trials:The REACH II experience[J].Clin Trials,2006,3(2),107-118.
[26]Swedberg K,Borer J S,et al.Challenges to data monitoring committees when regulatory authorities intervene[J].New Engl J Med,2016,374(16):1580-1584.
[27]Steiner M.The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers[J].New Engl J Med,1994,330(15):1029-1035.
[28]David L,Curt D,Furberg L M.Data Monitoring Committees in Clinical Trials A case study approach[M].Friedman.2006.
[29]Department of Health and Human Services,Office of Inspector General.Data and safety monitoring boards in NIH clinical trials meeting guidance,but facing some issues.[EB/OL].(2013-06-28)[2018-09-13].https://www.oig.hhs.gov/oei/reports/oei-12-11-00070.pdf