Liu Qiao-lan, Shen Zhuo-zhi, Li Xiao-song, Chen Feng, Yang Min
School of Public Health, Sichuan University, Chengdu 610041, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2010 Mar;31(3):333-9.
The main purpose of this paper is to explore the applicability of multivariate multilevel models for bioequivalence evaluation. Using an example of a 4 x 4 cross-over test design in evaluating bioequivalence of homemade and imported rosiglitazone maleate tablets, this paper illustrated the multivariate-model-based method for partitioning total variances of ln(AUC) and ln(C(max)) in the framework of multilevel models. It examined the feasibility of multivariate multilevel models in directly evaluating average bioequivalence (ABE), population bioequivalence (PBE) and individual bioequivalence (IBE). Taking into account the correlation between ln(AUC) and ln(C(max)) of rosiglitazone maleate tablets, the proposed models suggested no statistical difference between the two effect measures in their ABE bioequivalence via joint tests, whilst a contradictive conclusion was derived based on univariate multilevel models. Furthermore, the PBE and IBE for both ln(AUC) and ln(C(max)) of the two types of tablets were assessed with no statistical difference based on estimates of variance components from the proposed models. Multivariate multilevel models could be used to analyze bioequivalence of multiple effect measures simultaneously and they provided a new way of statistical analysis to evaluate bioequivalence.
本文的主要目的是探讨多变量多层次模型在生物等效性评价中的适用性。以4×4交叉试验设计为例，评估国产和进口马来酸罗格列酮片的生物等效性，本文阐述了在多层次模型框架下基于多变量模型的ln(AUC)和ln(C(max))总方差分解方法。研究了多变量多层次模型直接评估平均生物等效性(ABE)、群体生物等效性(PBE)和个体生物等效性(IBE)的可行性。考虑到马来酸罗格列酮片ln(AUC)和ln(C(max))之间的相关性，所提出的模型通过联合检验表明，两种效应指标在ABE生物等效性方面无统计学差异，而基于单变量多层次模型得出了矛盾的结论。此外，根据所提出模型的方差成分估计，评估了两种片剂ln(AUC)和ln(C(max))的PBE和IBE，无统计学差异。多变量多层次模型可用于同时分析多个效应指标的生物等效性，为生物等效性评价提供了一种新的统计分析方法。
