Analysis of a Bioequivalence Trial Using Mixed Effects Modeling

Abstract

The evaluation of individual bioequivalence (ie, switchability) and population (distribution) bioequivalence both require the explicit recognition and estimation of intraindividual and interindividual variability, as can be accomplished with a mixed effects model (MEM). Using this method, the components of individual and population bioequivalence, as well as of standard average bioequivalence, of three generic formulations of furosemide to the brand name product were assessed. (Only bioequivalence of extent absorbed is reported here.) The average bioequivalence to reference was met for all products with regard to extent absorbed. Because the correlation of individual (long-term average) bioavailability between each test-reference pair was reasonably good, and the confidence intervals of the ratios of intraindividual variability (test/reference) include one, individual bioequivalence of each test product, for extent absorbed, cannot be excluded. With respect to the ratios of interindividual variability (te...