2025年,本专栏的2篇文章《无替代,何谈取消》[1]和《非动物实验替代知多少》[2]从宏观层面梳理了动物实验替代的现状、方法和适用范围,系统、全面地介绍了动物实验替代的法规、技术等内容。本期,我们将探讨目前美国食品药品监督管理局(F...2025年,本专栏的2篇文章《无替代,何谈取消》[1]和《非动物实验替代知多少》[2]从宏观层面梳理了动物实验替代的现状、方法和适用范围,系统、全面地介绍了动物实验替代的法规、技术等内容。本期,我们将探讨目前美国食品药品监督管理局(Food and Drug Administration,FDA)的新政策在推动非人灵长类(non-human primate,NHP)实验动物替代方面存在的局限性,通过对比分析,指出需在保持科学严谨性的同时兼顾动物福利,在二者之间找到平衡点,而非“完全替代”,才是更可行的路径。展开更多
Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
目的:本研究旨在分析2022年1月—2024年7月间美国FDA在新药申请(new drug application,NDA)过程中真实世界证据(real-world evidence,RWE)的使用情况及其对监管决策的影响,为基于RWE的药品审评决策和申请人新药研发提供参考。方法:通过...目的:本研究旨在分析2022年1月—2024年7月间美国FDA在新药申请(new drug application,NDA)过程中真实世界证据(real-world evidence,RWE)的使用情况及其对监管决策的影响,为基于RWE的药品审评决策和申请人新药研发提供参考。方法:通过查阅美国FDA官网的公共资源,提取2022年1月1日—2024年7月1日期间所有美国药物评价与研究中心(Center for Drug Evaluation and Research,CDER)批准的新分子实体(new molecular entity,NME)NDA申请的公开文件,分析RWE在NDA中的使用占比、类型、数据来源及支持作用。并总结美国FDA对RWE研究的反馈,包括研究设计、数据质量、偏倚与混杂因素控制等方面的问题。结果:研究发现,在纳入审查的77项NDA申请中,36项(47%)包含RWE研究;其中仅支持安全性的有19项(53%),仅支持有效性的有6项(17%),支持安全性和有效性的有11项(30%);作为主要证据提交的有9项(25%),作为支持性证据提交的有27项(75%);36项批准中17项(47%)是罕见病药品。美国FDA对RWE研究的反馈主要集中在研究设计问题、数据质量问题、偏倚与混杂因素控制不足等方面。结论:RWE在NDA中的应用日益广泛,但美国FDA在审评过程中提出了诸多局限性反馈。为了使RWE更好地支持审评决策,申请人应注重研究设计的科学性和严谨性、数据来源的可靠性和相关性以及研究过程的透明度,采用高质量的数据和科学的研究设计,以提高RWE在NDA中的适用性和可靠性。展开更多
文摘2025年,本专栏的2篇文章《无替代,何谈取消》[1]和《非动物实验替代知多少》[2]从宏观层面梳理了动物实验替代的现状、方法和适用范围,系统、全面地介绍了动物实验替代的法规、技术等内容。本期,我们将探讨目前美国食品药品监督管理局(Food and Drug Administration,FDA)的新政策在推动非人灵长类(non-human primate,NHP)实验动物替代方面存在的局限性,通过对比分析,指出需在保持科学严谨性的同时兼顾动物福利,在二者之间找到平衡点,而非“完全替代”,才是更可行的路径。
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
文摘目的:本研究旨在分析2022年1月—2024年7月间美国FDA在新药申请(new drug application,NDA)过程中真实世界证据(real-world evidence,RWE)的使用情况及其对监管决策的影响,为基于RWE的药品审评决策和申请人新药研发提供参考。方法:通过查阅美国FDA官网的公共资源,提取2022年1月1日—2024年7月1日期间所有美国药物评价与研究中心(Center for Drug Evaluation and Research,CDER)批准的新分子实体(new molecular entity,NME)NDA申请的公开文件,分析RWE在NDA中的使用占比、类型、数据来源及支持作用。并总结美国FDA对RWE研究的反馈,包括研究设计、数据质量、偏倚与混杂因素控制等方面的问题。结果:研究发现,在纳入审查的77项NDA申请中,36项(47%)包含RWE研究;其中仅支持安全性的有19项(53%),仅支持有效性的有6项(17%),支持安全性和有效性的有11项(30%);作为主要证据提交的有9项(25%),作为支持性证据提交的有27项(75%);36项批准中17项(47%)是罕见病药品。美国FDA对RWE研究的反馈主要集中在研究设计问题、数据质量问题、偏倚与混杂因素控制不足等方面。结论:RWE在NDA中的应用日益广泛,但美国FDA在审评过程中提出了诸多局限性反馈。为了使RWE更好地支持审评决策,申请人应注重研究设计的科学性和严谨性、数据来源的可靠性和相关性以及研究过程的透明度,采用高质量的数据和科学的研究设计,以提高RWE在NDA中的适用性和可靠性。
