成人用药数据外推至儿科人群的科学决策过程和法规依据研究进展分析
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摘要
目的:通过分析现行基于成人用药数据外推至儿科人群的科学决策过程和法规依据,及数据外推的优势和局限性,为儿科药物开发提供一些思路和指导。方法:检索美国药品食品管理局(USFDA)、欧洲医药管理局(EMA)、国家药品食品监督管理局(CFDA)、人用药品注册技术要求国际协调会(ICH)相关网站,以及万方、CNKI、Pubmed等相关数据库,比较不同国家的成人用药数据外推至儿科人群的相关法规指南。结果:现行USFDA、EMA、CFDA以及ICH儿科数据外推指南基本上一致,但各自又有所区别,需对现行指南进行完善;现行数据外推指南对某些关键性概念及算法描述不清。结论:采用数据外推,可以加快儿科用药研发,增加儿科临床用药数量,即将推出的ICH E11(R1)儿科临床研究补充指南,将提供统一的数据外推指南,更好地指导儿科药品的开发。
AIM:To provide a general overview of the regulatory guidelines on the extrapolation from adult and other data to pediatric population,and to provide some practical advices for following these guidelines.METHODS:Literatures about the topic of " data extrapolation/and pediatric " from website of CFDA,EMA,USFDA,ICH and databases such as Wanfang,CNKI and Pubmed were searched,then the current guidelines on this topic were analyzed and compared,and the strategy for this topic was discussed.RESULTS:The current guidelines of EMA,U.S.FDA and ICH maintained consistent in critical principles.But the difference still required further improvement.The current data extrapolation guidelines laced maneuverability,and the description for some critical concepts and algorithm was not clear.CONCLUSION:Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals drug for pediatric use,and the ICH E11(R1) that may replace the current guidelines will provide a better way for the pharmaceutical manufacturers to develop drug for pediatric use.
AIM:To provide a general overview of the regulatory guidelines on the extrapolation from adult and other data to pediatric population,and to provide some practical advices for following these guidelines.METHODS:Literatures about the topic of " data extrapolation/and pediatric " from website of CFDA,EMA,USFDA,ICH and databases such as Wanfang,CNKI and Pubmed were searched,then the current guidelines on this topic were analyzed and compared,and the strategy for this topic was discussed.RESULTS:The current guidelines of EMA,U.S.FDA and ICH maintained consistent in critical principles.But the difference still required further improvement.The current data extrapolation guidelines laced maneuverability,and the description for some critical concepts and algorithm was not clear.CONCLUSION:Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals drug for pediatric use,and the ICH E11(R1) that may replace the current guidelines will provide a better way for the pharmaceutical manufacturers to develop drug for pediatric use.
引文
[1]国家食品药品监督管理局.成人用药数据外推至儿科人群的技术指导原则[EB/OL].(2017-08-15)http://www.sda.gov.cn/WS01/CL0087/172743.html.
[2]United States Government Publishing Office.Specific requirements on content and format of labeling for human prescription drugs:Proposed revision of"pediatric use"subsection in the labeling.Federal Register/Vol.57,No 201[EB/OL].(1992-10-16)https://www.gpo.gov/fdsys/search/search.action?sr=22&originalSearch=57+FR&st=57+FR&ps=10&na=&se=&sb=re&time Frame=&date Browse=&gov Auth Browse=&collection=&historical=false.
[3]United States Government Publishing Office.Specific requirements on content and format of labeling for human prescription drugs:revision of"pediatric use"subsection in the labeling:final rule.Federal Register/Vol.59,No 238[EB/OL].(1994-12-13)https://www.gpo.gov/fdsys/pkg/FR-1994-12-13/html/94-30555.htm.
[4]Food and Drug Administration.Food and Drug Administration modernization act of 1997[EB/OL].(1997-11-21)https://www.fda.gov/Regulatory Information/Laws Enforcedby FDA/Significant Amendmentstothe FDCAct/FDAMA/default.htm.
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[7]Food and Drug Administration.Breakdown of requested studies report[EB/OL].(2007)www.fda.gov/Drugs/Development Approval Process/DevelopmentResources/ucm 050001.htm.
[8]Food and Drug Administration.Guidance for industry:Exposure-response relationships:Study design,data analysis,and regulatory applications[EB/OL].(2003-04)www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM072109.pdf.
[9]European Medicines Agency.Concept paper on extrapolation of efficacy and safety in medicine development[EB/OL].(2013-3-19)http://101.96.10.63/www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/04/WC500142358.pdf.
[10]European Medicines Agency.Reflection paper on extrapolation of efficacy and safety in paediatric medicine development[EB/OL].(2017-10-09)https://www.ema.europa.eu/documents/scientific-guideline/reflection-paper-use-extrapolation-development-medicines-paediatrics_en.pdf.
[11]International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.E11(R1)addendum:Clinical investigation of medicinal products in the pediatric population[EB/OL].(2017-7-20)http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E11/E11-R1EWG_Step4_Addendum_2017_0818.pdf.
[12]International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.The association begins new work on medicines for children and better clinical trials and China Food and Drug Administration joins ICH[EB/OL].(2017-5-27)http://www.ich.org/ichnews/press-releases/view/article/ich-assembly-montrealcanada-mayjune-2017.html.
[13]Conroy S,Choonara I,Impicciatore P,et al.Survey of unlicensed and off label drug use in paediatric wards in European countries[J].BMJ,2000,8,320(7227):79-82.
[14]Stafford RS.Regulating off-label drug use-rethinking the role of the FDA[J].N Engl J Med,2008,358(14):1427-1429.
[15]LangerováP,Vrtal J,Urbánek K.Incidence of unlicensed and off-label prescription in children[J].Ital J Pediatr,2014,40:12.
[16]张伶俐,李幼平,黄亮,等.四川大学华西第二医院儿科门诊处方超药品说明书用药情况调查[J].中国循证医学杂志,2011,11(10):1120-1124.
[17]张伶俐,李幼平,胡蝶,等.四川大学华西第二医院2010年儿科住院患儿超说明书用药情况调查[J].中国循证医学杂志,2012,12(2):267-273.
[18]Dunne J,Rodriguez WJ,Murphy MD,et al.Extrapolation of adult data and other data in pediatric drug-development programs[J].Pediatrics,2011,128(5):e1242.
[19]Sun H,Temeck JW,Chambers W,et al.Extrapolation of efficacy in pediatric drug development and evidence-based medicine:Progress and lessons learned[J].Ther Innov Regul Sci,2017:216847901772555.
[20]Parrott N,Davies B,Hoffmann G,et al.Development of a physiologically based model for oseltamivir and simulation of pharmacokinetics in neonates and infants[J].Clin Pharmacokinet,2011,50(9):613-623.
[21]Willmann S,Becker C,Burghaus R,et al.Development of a pediatric population-based model of the pharmacokinetics of rivaroxaban[J].Clin Pharmacokinet,2014,53(10):89-102.
[2]United States Government Publishing Office.Specific requirements on content and format of labeling for human prescription drugs:Proposed revision of"pediatric use"subsection in the labeling.Federal Register/Vol.57,No 201[EB/OL].(1992-10-16)https://www.gpo.gov/fdsys/search/search.action?sr=22&originalSearch=57+FR&st=57+FR&ps=10&na=&se=&sb=re&time Frame=&date Browse=&gov Auth Browse=&collection=&historical=false.
[3]United States Government Publishing Office.Specific requirements on content and format of labeling for human prescription drugs:revision of"pediatric use"subsection in the labeling:final rule.Federal Register/Vol.59,No 238[EB/OL].(1994-12-13)https://www.gpo.gov/fdsys/pkg/FR-1994-12-13/html/94-30555.htm.
[4]Food and Drug Administration.Food and Drug Administration modernization act of 1997[EB/OL].(1997-11-21)https://www.fda.gov/Regulatory Information/Laws Enforcedby FDA/Significant Amendmentstothe FDCAct/FDAMA/default.htm.
[5]Food and Drug Administration.Guidance for industrial:Providing clinical evidence of effectiveness for human drug and biological products[EB/OL].(1998-5)https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072008.pdf.
[6]Food and Drug Administration.General clinical pharmacology considerations for pediatric studies for drugs and biological products[EB/OL].(2014-12)https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm425885.pdf.
[7]Food and Drug Administration.Breakdown of requested studies report[EB/OL].(2007)www.fda.gov/Drugs/Development Approval Process/DevelopmentResources/ucm 050001.htm.
[8]Food and Drug Administration.Guidance for industry:Exposure-response relationships:Study design,data analysis,and regulatory applications[EB/OL].(2003-04)www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM072109.pdf.
[9]European Medicines Agency.Concept paper on extrapolation of efficacy and safety in medicine development[EB/OL].(2013-3-19)http://101.96.10.63/www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/04/WC500142358.pdf.
[10]European Medicines Agency.Reflection paper on extrapolation of efficacy and safety in paediatric medicine development[EB/OL].(2017-10-09)https://www.ema.europa.eu/documents/scientific-guideline/reflection-paper-use-extrapolation-development-medicines-paediatrics_en.pdf.
[11]International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.E11(R1)addendum:Clinical investigation of medicinal products in the pediatric population[EB/OL].(2017-7-20)http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E11/E11-R1EWG_Step4_Addendum_2017_0818.pdf.
[12]International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.The association begins new work on medicines for children and better clinical trials and China Food and Drug Administration joins ICH[EB/OL].(2017-5-27)http://www.ich.org/ichnews/press-releases/view/article/ich-assembly-montrealcanada-mayjune-2017.html.
[13]Conroy S,Choonara I,Impicciatore P,et al.Survey of unlicensed and off label drug use in paediatric wards in European countries[J].BMJ,2000,8,320(7227):79-82.
[14]Stafford RS.Regulating off-label drug use-rethinking the role of the FDA[J].N Engl J Med,2008,358(14):1427-1429.
[15]LangerováP,Vrtal J,Urbánek K.Incidence of unlicensed and off-label prescription in children[J].Ital J Pediatr,2014,40:12.
[16]张伶俐,李幼平,黄亮,等.四川大学华西第二医院儿科门诊处方超药品说明书用药情况调查[J].中国循证医学杂志,2011,11(10):1120-1124.
[17]张伶俐,李幼平,胡蝶,等.四川大学华西第二医院2010年儿科住院患儿超说明书用药情况调查[J].中国循证医学杂志,2012,12(2):267-273.
[18]Dunne J,Rodriguez WJ,Murphy MD,et al.Extrapolation of adult data and other data in pediatric drug-development programs[J].Pediatrics,2011,128(5):e1242.
[19]Sun H,Temeck JW,Chambers W,et al.Extrapolation of efficacy in pediatric drug development and evidence-based medicine:Progress and lessons learned[J].Ther Innov Regul Sci,2017:216847901772555.
[20]Parrott N,Davies B,Hoffmann G,et al.Development of a physiologically based model for oseltamivir and simulation of pharmacokinetics in neonates and infants[J].Clin Pharmacokinet,2011,50(9):613-623.
[21]Willmann S,Becker C,Burghaus R,et al.Development of a pediatric population-based model of the pharmacokinetics of rivaroxaban[J].Clin Pharmacokinet,2014,53(10):89-102.