高变异药物生物等效性评价中多组试验的设计与统计研究

Design and Statistical Study of Multiple Groups of Experiments in Bioequivalence Evaluation of Highly Variable Drugs

目的探讨高变异药物生物等效性评价中多组试验设计及其统计情况。方法选取2018年1—6月本试验中心接待的受试者60例作为研究对象,随机为A、B两组,每组30例受试者,两组受试者采取相同的参比制剂、受试制剂处理,A组双交叉试验结束1周后,再开始B组双交叉试验,试验结束后一并完成样品分析与统计。通过总结高变异药物生物等效性评价试验特点,然后结合实例进行多组试验设计,计算90%置信区间与个体内变异系数等。结果通过试验设计与统计分析,显示多组试验AUC生物等效性评价结果中,90%置信区间在84.74%～104.32%之间,把握度为82.41%。结论多组试验设计可增加把握度,可促进试验管理,设计的统计模型在阶段设计、多中心设计等生物等效性评价中均可应用。

Objective To explore the design and statistics of multiple trials in the bioequivalence evaluation of highly variable drugs.Methods Sixty subjects enrolled in the trial center from January to June 2018 were selected as subjects.They were randomly assigned to groups A and B.Each group of 30 subjects received the same reference preparation.After the test preparation was treated,the group B double crossover test was started one week after the end of the double crossover test in group A,and the sample analysis and statistics were completed after the end of the experiment.By summarizing the characteristics of the bioequivalence evaluation test of highvariation drugs,and then combining multiple examples of experimental design,the 90%confidence interval and the intra-individual coefficient of variation were calculated.Results Through experimental design and statistical analysis,the results showed that the 90%confidence interval was between 84.74%and 104.32%and the power was 82.41%.Conclusion Multiple sets of test designs can increase the power of the test,which can promote the test management.The statistical model of the design can be applied in the bioequivalence evaluation such as stage design and multi-center design.