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

doi:10.12092/j.issn.1009-2501.2019.01.009

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (1): 49-56.doi: 10.12092/j.issn.1009-2501.2019.01.009

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

张慧敏¹，刘霭明²，朱文烽³，余灵芝⁴，陈方亮¹

¹恩泽医疗中心（集团）恩泽医院药剂科，台州 318000，浙江； ²南方医科大学顺德医院药学部临床药学科，顺德 528300，广东； ³浙江华海药业股份有限公司，临海 317000，浙江； ⁴浙江省台州医院药剂科，临海 317000，浙江

收稿日期:2018-07-22 修回日期:2018-10-12 出版日期:2019-01-26 发布日期:2019-01-25
通讯作者: 陈方亮，男，本科，主任药师，研究方向：临床药学。 E-mail:chenfl5068@enzemed.com
作者简介:张慧敏，女，硕士，主管药师，研究方向：临床药学。 Tel: 0576-89218614 E-mail: fwz0805@163.com
基金资助:
浙江省药学会资助课题基金(2017ZJYY29); 台州市路桥区科技局基金（2018A23001）

Scientific decision process and regulation requirements based on the current guidelines of data extrapolation from adult to pediatric population

ZHANG Huimin¹, LIU Aiming², ZHU Wenfeng³, YU Lingzhi⁴,CHEN Fangliang¹

¹ Enze Hospital of Enze Medical Center (Group), Taizhou 317000, Zhejiang, China; ²Shunde Hospital of Southern Medical University, Shunde 528300, Guangdong, China; ³ Zhejiang Huahai Pharmaceutical Co., Ltd, Linhai 317000, Zhejiang, China; ⁴Taizhou Hospital of Zhejiang Province, Taizhou 317000, Zhejiang, China

Received:2018-07-22 Revised:2018-10-12 Online:2019-01-26 Published:2019-01-25

摘要/Abstract

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。

关键词: 数据外推, 超说明书, 儿科用药, 建模与模拟

Abstract:

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.

Key words: data extrapolation, off-label, pediatric drug, modeling and simulation

中图分类号:

张慧敏，刘霭明，朱文烽，余灵芝，陈方亮. 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[J]. 中国临床药理学与治疗学, 2019, 24(1): 49-56.

ZHANG Huimin, LIU Aiming, ZHU Wenfeng, YU Lingzhi, CHEN Fangliang. Scientific decision process and regulation requirements based on the current guidelines of data extrapolation from adult to pediatric population[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 49-56.

参考文献

［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&timeFrame=&dateBrowse=&govAuthBrowse=&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/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/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/DevelopmentApprovalProcess/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/GuidanceComplianceRegulatoryInformation/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-montreal-canada-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］Langerová P, 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.

[1]	张进华, 刘茂柏, 蔡铭智, 郑英丽, 劳海燕, 向倩, 都丽萍, 朱珠, 董婧, 左笑丛, 李新刚, 尚德为, 陈冰, 叶岩荣, 王玉珠, 高建军, 张健, 陈万生, 谢海棠, 焦正. 模型引导的华法林精准用药：中国专家共识（2022版）[J]. 中国临床药理学与治疗学, 2022, 27(11): 1201-1212.
[2]	张宁远, 郑锡军, 许羚, 刘红霞, 郑青山. 阿尔兹海默病的疾病进展模型与研究进展[J]. 中国临床药理学与治疗学, 2021, 26(6): 687-694.
[3]	焦正, 李新刚, 尚德为, 董婧, 左笑丛, 陈冰, 刘剑敏, 潘雁, 周田彦, 张菁, 刘东阳, 李禄金, 方翼, 马广立, 丁俊杰, 赵维, 陈锐, 相小强, 王玉珠, 高建军, 谢海棠, 胡蓓, 郑青山. 模型引导的精准用药：中国专家共识（2021版）[J]. 中国临床药理学与治疗学, 2021, 26(11): 1215-1228.
[4]	沈斌，蒋利亚，王晓凌，徐龙生，陆晓蕾，何家杨，孙佩玉，周月红，张小平. 中药注射剂超说明书用药研究与合理性评价[J]. 中国临床药理学与治疗学, 2019, 24(2): 223-227.
[5]	尹芳，王玉珠，郑青山. 茚达特罗上市剂量选择的论战：美国FDA定量药理学审评的故事[J]. 中国临床药理学与治疗学, 2018, 23(9): 1031-1039.
[6]	沈斌，张斌，徐亮，杨艳英. 风湿免疫科门诊超说明书用药调查与分析[J]. 中国临床药理学与治疗学, 2017, 22(3): 337-341.
[7]	唐洪梅, 涂星, 柴玉娜. 阿米洛利超说明书治疗原发性醛固酮增多症合理性的实验研究[J]. 中国临床药理学与治疗学, 2014, 19(10): 1116-1120.
[8]	黄继汉, 黄晓晖, 李禄金, 王钦, 王鲲, 郑青山. 新药临床试验的计算机模拟[J]. 中国临床药理学与治疗学, 2010, 15(6): 691-699.
[9]	黄晓晖, 谢海棠, 史军, 宋建国, 郑青山. 现代定量药理学的研究进展及展望[J]. 中国临床药理学与治疗学, 2009, 14(6): 601-612.
[10]	黄晓晖, 史军, 李俊, 宋国强, 谢海棠, 郑青山, 孙瑞元. 药代动力学和药效动力学中数学建模与模拟的基本原理(2)[J]. 中国临床药理学与治疗学, 2007, 12(3): 334-341.

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

Scientific decision process and regulation requirements based on the current guidelines of data extrapolation from adult to pediatric population

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价