Assessment of bioequivalence using a multiplicative model.
In many bioavailability/bioequivalence studies, the distributions of responses such as AUC and Cmax are often positively skewed and exhibit a lack of homogeneity of variances. In this situation, a logarithmic transformation is usually considered for reduction of skewness and achievement of an additive model with relatively homogeneous variance. In this paper, consideration is given to a multiplicative model based on empirical evidence. A method is proposed using individual subject ratios for assessing the bioequivalence of two different formulations. This method is then subsequently extended to several commonly used crossover experiments.
Chow
S C
SC
Biostatistics Department, Bristol-Myers Squibb Company, Plainsboro, New Jersey 08536.
Peace
K E
KE
Shao
J
J
D001682:Biological Availability; D004358:Drug Therapy / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D012107:Research Design; D013810:Therapeutic Equivalency