重复测量方差分析在安全药理学研究中的应用探讨  

Application of Repeated Measures Analysis of Variance in Safety Pharmacology Study

作　　者：王庚莉 杨进涛 冯斐斐[1] 张巧[1] 单晓蕾 张素才 Wang Gengli;Yang Jintao;Feng Feifei;Zhang Qiao;Shan Xiaolei;Zhang Sucai(School of Public Health,Zhengzhou University,Zhengzhou 450066,China;Beijing Zhaoyan New Drug Research Center Co.,Ltd.,Beijing 100176,China;Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]郑州大学公共卫生学院,郑州450066 [2]北京昭衍新药研究中心股份有限公司,北京100176 [3]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国药事》2024年第8期891-898,共8页Chinese Pharmaceutical Affairs

基　　金：国家重点研发计划资助项目(编号021YFC2302505)。

摘　　要：目的:以新药ZY711安全药理学试验中测量的雄性QTc指标为案例,探讨重复测量方差分析在安全药理学研究中的必要性,为临床研究和应用提供更为可靠的依据。方法:采用IBM SPSS Statistics27.0进行统计分析,QTc间期采用均数±标准差(ms,Mean±SD)进行统计学描述,比较单因素方差分析和重复测量方差分析统计方法对试验结果的影响。结果:单因素方差分析结果在4 mg·kg^(-1)和12mg·kg^(-1)剂量组药后1 h QTc间期的延长有统计学意义,在40 mg·kg^(-1)剂量组药后0.5 h、1 h、2 h、4 h QTc间期的延长有统计学意义;而重复测量方差分析结果在4 mg·kg^(-1)和12 mg·kg^(-1)剂量组药后1 h、2 h QTc间期的延长有统计学意义,在40 mg·kg^(-1)剂量组药后0.5 h、1 h、2 h、4 h和6 h QTc间期的延长有统计学意义。结论:重复测量方差分析可用于非临床安全药理学试验结果的评估,其可以清楚了解药物的起效与持续时间,并且可以对药物不同剂量之间的显著性检验进行全面判断。Objective:To explore the necessity of repeated measures analysis of variance in safety pharmacology study by using male QTc index measured in safety pharmacology test of new drug ZY711 as a case,and to provide a more reliable basis for clinical study and application.Methods:Statistical analysis was performed by using IBM SPSS Statistics 27.0.QTc interval was statistically described by using mean±standard deviation(ms,Mean±SD).The effects of one-way analysis of variance and repeated measures analysis of variance statistical methods on the test results were compared.Results:For the results of one-way analysis of variance,the prolongation of QTc interval at 1 h after administration was statistically significant in 4 and 12 mg·kg^(-1)dose groups,and the prolongation of QTc interval at 0.5 h,1 h,2 h and 4 h after administration was statistically significant in 40 mg·kg^(-1)dose group;while for the results of repeated measures analysis of variance,the prolongation of QTc interval at 1 h and 2 h after administration was statistically significant in 4 and 12 mg·kg^(-1)dose groups,and the prolongation of QTc interval at 0.5 h,1 h,2 h,4 h and 6 h after administration was statistically significant in 40 mg·kg^(-1) dose group.Conclusion:Repeated measures analysis of variance can be used to assess the results of nonclinical safety pharmacology trials,which could clearly understand the onset and duration of action of drugs,and comprehensively judge the significance test between different doses of drugs.

关 键 词：安全药理学研究 单因素方差分析 重复测量方差分析 重复资料 统计分析 

分 类 号：R96[医药卫生—药理学]