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
王庚莉 1杨进涛 2冯斐斐 3张巧 3单晓蕾 4张素才1
作者信息
- 1. 郑州大学公共卫生学院,郑州 450066;北京昭衍新药研究中心股份有限公司,北京 100176
- 2. 北京昭衍新药研究中心股份有限公司,北京 100176
- 3. 郑州大学公共卫生学院,郑州 450066
- 4. 国家药品监督管理局药品审评中心,北京 100022
- 折叠
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 Statistics 27.0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12 mg·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40mg·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.
Abstract
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·kg1 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Key words
safety pharmacology study/one-way analysis of variance/repeated measures analysis of variance/repeated data/statistical analysis引用本文复制引用
基金项目
国家重点研发计划(021YFC2302505)
出版年
2024
NETL
NSTL
万方数据