기저치를 가진 생물학적 동등성 평가의 통계적 고찰: 내인성 제제사례연구

Abstract

Objectives: To assess bioequivalence between two endogenous drugs in 2×2 crossover trial with baseline measurements. Methods: Two statistical methods are applied to assess bioequivalence between two endogenous drugs in 2×2 crossover trials. The first method is based on the current regula tory guideline published by Ministry of Food and Drug Safety (MFDS), which is based on the difference between baseline measurements and responses. The second method is more general approach, so-called general linear model method, which is defined the baseline measurements as covariates. Results: The first method based on current guideline shows that two drugs are not bioequivalent; however, the second method by general linear model shows that two drugs are bioequivalent. When the baselines of the subjects are expected to be highly variable, general linear model approach is more suitable to assess the bioequivalence by adjusting high subjects’ variations. Conclusions: General linear model with covariates should be considered in assessing bioequivalence of endogenous substances when highly subject variations of baseline measurements are expected.

Objectives: To assess bioequivalence between two endogenous drugs in 2×2 crossover trial with baseline measurements. Methods: Two statistical methods are applied to assess bioequivalence between two endogenous drugs in 2×2 crossover trials. The first method is based on the current regula tory guideline published by Ministry of Food and Drug Safety (MFDS), which is based on the difference between baseline measurements and responses. The second method is more general approach, so-called general linear model method, which is defined the baseline measurements as covariates. Results: The first method based on current guideline shows that two drugs are not bioequivalent; however, the second method by general linear model shows that two drugs are bioequivalent. When the baselines of the subjects are expected to be highly variable, general linear model approach is more suitable to assess the bioequivalence by adjusting high subjects’ variations. Conclusions: General linear model with covariates should be considered in assessing bioequivalence of endogenous substances when highly subject variations of baseline measurements are expected.