In clinical development,adequate and well-controlled randomised clinical trials are usually conducted to evaluate the safety and efficacy of test treatment under investigation.The purpose is to ensure that there is an...In clinical development,adequate and well-controlled randomised clinical trials are usually conducted to evaluate the safety and efficacy of test treatment under investigation.The purpose is to ensure that there is an accurate and reliable assessment of test treatment under study.In practice,however,some controversial issues inevitably appear despite the compliance of good clinical practice.These debatable issues include,but are not limited to,(1)appropriateness of hypotheses for clinical investigation,(2)feasibility of power calculation for sample size requirement,(3)integrity of randomisation/blinding,(4)strategy for clinical endpoint selection,(5)demonstrating effectiveness or ineffectiveness,(6)impact of protocol amendments and(7)independence of independent data monitoring committee.In this article,these controversial issues are discussed.The impact of these issues in evaluating the safety and efficacy of the test treatment under investigation is also assessed.Recommendations regarding possible resolutions to these issues are provided whenever possible.展开更多
对于具有较高受试者个体间差异的药物进行生物等效性(BE)和生物类似性评价时,使用通常的双单侧检验(TOST)法既十分困难,甚至也不可能;除非不考虑伦理规范,而进行大样本的人体试验。因此,美国食品药品管理局(FDA)和欧盟药品管理局(EMA)...对于具有较高受试者个体间差异的药物进行生物等效性(BE)和生物类似性评价时,使用通常的双单侧检验(TOST)法既十分困难,甚至也不可能;除非不考虑伦理规范,而进行大样本的人体试验。因此,美国食品药品管理局(FDA)和欧盟药品管理局(EMA)等监管机构对高个体差异药品的生物等效性评价分别颁布了替代方法。这2个监管机构的替代方法依据相同的原理,但是关键细节略有不同。FDA建议当受试者个体间差异超过30%时,使用"标化均值生物等效性"(scaled-average BE,SABE)评价;该方式使用已有计算机软件通过线性转换来计算等效性的95%上限;并要求采用第2级标准评价:两产品间相关参数的几何均值之比的点评估(point estimate)在0.80到1.25之间。而EMA则建议采用"带扩展限度的平均生物等效性"(average BE with expanding limits,ABEL)进行高个体差异药品的评价;该方式与SABE方式相关,但可以使用简单的双单侧检验方法进行评估;EMA也要求采用相同的第,2级标准评价,且要求这2个标准仅适用于受试者个体间差异不超过50%的情形。这2个机构采用了不同的监管常数(等效性评价指标)。FDA建议的计算指标会使生物等效限不连续,且所需样本量大,并且在CV=30%附近有很高的I型误差。而EMA的评价指标不会产生这种不连续性,I型误差也很低。总之,EMA的评价方法更好。展开更多
生物类似药是继原研生物制品之后进入市场,在安全性、纯度和效价上与原研生物制品具有高度相似性的新药物。欧洲药品管理局(EMA)在生物类似物制品注册审批政策的制定中发挥了引领作用,与此同时世界卫生组织(WHO)为促进全球的协调一致也...生物类似药是继原研生物制品之后进入市场,在安全性、纯度和效价上与原研生物制品具有高度相似性的新药物。欧洲药品管理局(EMA)在生物类似物制品注册审批政策的制定中发挥了引领作用,与此同时世界卫生组织(WHO)为促进全球的协调一致也发布了生物类似药审评指导原则。最近,美国食品药品管理局(FDA)依据美国国会2009年通过的"生物制品价格竞争与创新(Biologics Price Competition and Innovation,BPCI)法案"也被授权审批生物类似药。BPCI法案随后于2010年3月23日生效。为了听取民众对于生物类似药注册审批政策的意见,FDA于2010年11月2—3日举行了一场公众听证会。随后,FDA为了生物类似药的审批,成立了生物类似药审查委员会(BRC)专门负责生物类似药开发相关的科学问题,以及注册审批相关指南的制定。FDA于2012年2月9日颁布了3项生物类似药的指导原则草案(科学目的、关键质量指标、以及问题与解答),这些草案的颁布有2个目的:(1)首先,帮助开发商证明仿制生物类似药的生物相似性,并依据公共健康服务(PHS)法案第351(k)款提交上市申请;(2)其次,充分表达FDA在生物类似药开发与注册审批指导原则制定方面的立场。展开更多
Objective: To understand the current situation of network pharmacology, and to analyze external and internal characteristics of literature, is of great significance for the development of network pharmacology in the f...Objective: To understand the current situation of network pharmacology, and to analyze external and internal characteristics of literature, is of great significance for the development of network pharmacology in the future and its application in the modernization of Chinese medicine.Methods: Bibliometrics were adapted to perform visual analysis on the research status of network pharmacology with Citespace and SPSS for windows 22.0 version(IBM, Armonk, New York, USA).Knowledge map was used to analyze the knowledge system in the field, to identify the research hotspots and dynamic frontiers, and to elaborate the research status and development trend of domestic network pharmacology.Results: The research on network pharmacology in China is at the stage of the formation and construction of basic theories.At present, we focuses on the solution of actual disease problems and basic theoretical research, while the application in the research field of traditional Chinese medicine is a new hot spot and trend in the future development.Conclusions: It is important to pay attention to the connection and communication among the knowledge groups, so that a systematic knowledge system can be formed in the field of network pharmacology in domestic as soon as possible.展开更多
文摘In clinical development,adequate and well-controlled randomised clinical trials are usually conducted to evaluate the safety and efficacy of test treatment under investigation.The purpose is to ensure that there is an accurate and reliable assessment of test treatment under study.In practice,however,some controversial issues inevitably appear despite the compliance of good clinical practice.These debatable issues include,but are not limited to,(1)appropriateness of hypotheses for clinical investigation,(2)feasibility of power calculation for sample size requirement,(3)integrity of randomisation/blinding,(4)strategy for clinical endpoint selection,(5)demonstrating effectiveness or ineffectiveness,(6)impact of protocol amendments and(7)independence of independent data monitoring committee.In this article,these controversial issues are discussed.The impact of these issues in evaluating the safety and efficacy of the test treatment under investigation is also assessed.Recommendations regarding possible resolutions to these issues are provided whenever possible.
文摘对于具有较高受试者个体间差异的药物进行生物等效性(BE)和生物类似性评价时,使用通常的双单侧检验(TOST)法既十分困难,甚至也不可能;除非不考虑伦理规范,而进行大样本的人体试验。因此,美国食品药品管理局(FDA)和欧盟药品管理局(EMA)等监管机构对高个体差异药品的生物等效性评价分别颁布了替代方法。这2个监管机构的替代方法依据相同的原理,但是关键细节略有不同。FDA建议当受试者个体间差异超过30%时,使用"标化均值生物等效性"(scaled-average BE,SABE)评价;该方式使用已有计算机软件通过线性转换来计算等效性的95%上限;并要求采用第2级标准评价:两产品间相关参数的几何均值之比的点评估(point estimate)在0.80到1.25之间。而EMA则建议采用"带扩展限度的平均生物等效性"(average BE with expanding limits,ABEL)进行高个体差异药品的评价;该方式与SABE方式相关,但可以使用简单的双单侧检验方法进行评估;EMA也要求采用相同的第,2级标准评价,且要求这2个标准仅适用于受试者个体间差异不超过50%的情形。这2个机构采用了不同的监管常数(等效性评价指标)。FDA建议的计算指标会使生物等效限不连续,且所需样本量大,并且在CV=30%附近有很高的I型误差。而EMA的评价指标不会产生这种不连续性,I型误差也很低。总之,EMA的评价方法更好。
文摘生物类似药是继原研生物制品之后进入市场,在安全性、纯度和效价上与原研生物制品具有高度相似性的新药物。欧洲药品管理局(EMA)在生物类似物制品注册审批政策的制定中发挥了引领作用,与此同时世界卫生组织(WHO)为促进全球的协调一致也发布了生物类似药审评指导原则。最近,美国食品药品管理局(FDA)依据美国国会2009年通过的"生物制品价格竞争与创新(Biologics Price Competition and Innovation,BPCI)法案"也被授权审批生物类似药。BPCI法案随后于2010年3月23日生效。为了听取民众对于生物类似药注册审批政策的意见,FDA于2010年11月2—3日举行了一场公众听证会。随后,FDA为了生物类似药的审批,成立了生物类似药审查委员会(BRC)专门负责生物类似药开发相关的科学问题,以及注册审批相关指南的制定。FDA于2012年2月9日颁布了3项生物类似药的指导原则草案(科学目的、关键质量指标、以及问题与解答),这些草案的颁布有2个目的:(1)首先,帮助开发商证明仿制生物类似药的生物相似性,并依据公共健康服务(PHS)法案第351(k)款提交上市申请;(2)其次,充分表达FDA在生物类似药开发与注册审批指导原则制定方面的立场。
基金National Natural Science Foundation of Liaoning(No.20170540850)Basic Research Project of Liaoning Provincial Department of Education(NO.2017 LFW02)
文摘Objective: To understand the current situation of network pharmacology, and to analyze external and internal characteristics of literature, is of great significance for the development of network pharmacology in the future and its application in the modernization of Chinese medicine.Methods: Bibliometrics were adapted to perform visual analysis on the research status of network pharmacology with Citespace and SPSS for windows 22.0 version(IBM, Armonk, New York, USA).Knowledge map was used to analyze the knowledge system in the field, to identify the research hotspots and dynamic frontiers, and to elaborate the research status and development trend of domestic network pharmacology.Results: The research on network pharmacology in China is at the stage of the formation and construction of basic theories.At present, we focuses on the solution of actual disease problems and basic theoretical research, while the application in the research field of traditional Chinese medicine is a new hot spot and trend in the future development.Conclusions: It is important to pay attention to the connection and communication among the knowledge groups, so that a systematic knowledge system can be formed in the field of network pharmacology in domestic as soon as possible.
