Chinchilli V M, Elswick R K
Center for Biostatistics and Epidemiology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
J Biopharm Stat. 1997 Mar;7(1):113-23. doi: 10.1080/10543409708835173.
We propose an approach for comparing directly the reference and test blood concentration x time profiles of subjects in a bioequivalence trial under a crossover design. We compare the test and reference profiles via the construction of two regions, namely, an acceptable region based on the reference profile and another region based on reflecting the test profile about the reference profile. Also, we describe how to construct these regions if the assay for measuring the concentration has a lower limit of detection and how to adjust the reference and test concentrations of the n subjects participating in a bioequivalence trial. If the test and reference formulations are bioequivalent, then the area displaced by the latter region should be less than the area displaced by the acceptable region. Therefore, we construct a ratio of these areas for each subject. Then we calculate upper confidence limits for quantiles, either under theassumption of lognormality or based on a bootstrapping algorithm, to investigate population and/or individual bioequivalence.
我们提出了一种方法，用于在交叉设计的生物等效性试验中直接比较受试者的参比血药浓度-时间曲线和受试血药浓度-时间曲线。我们通过构建两个区域来比较受试曲线和参比曲线，即基于参比曲线的可接受区域和另一个基于受试曲线相对于参比曲线的反射曲线的区域。此外，我们还描述了在测量浓度的分析方法有检测下限的情况下如何构建这些区域，以及如何调整参与生物等效性试验的n名受试者的参比浓度和受试浓度。如果受试制剂和参比制剂具有生物等效性，则后一个区域所覆盖的面积应小于可接受区域所覆盖的面积。因此，我们为每个受试者构建这些面积的比值。然后，我们在对数正态分布假设下或基于自抽样算法计算分位数的上置信限，以研究总体和/或个体生物等效性。
