Multivariate Extensions of Population Bioequivalence: Comparison of Measures

• Activity Number: 468
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Bassam A. Dahman*+ and Viswanathan Ramakrishnan
• Companies: Virginia Commonwealth University and Virginia Commonwealth University
• Keywords: population bioequivalence ; bioequivalence ; generic ; multivariate bioequivalence ; AUC ; Cmax

Abstract

Population bioequivalence (PBE) is of special interest in generic drug testing because it simultaneously includes the means and the variances in the comparisons. For univariate measures the FDA recommended a criterion and a method to test PBE. Two viable Multivariate extensions of the method have been proposed. The first is based on the Kullback-Leibler divergence, scaled by variance covariance matrix of both formulations, while the FDA recommends scaling only by the reference variance. The second is an extension of the univariate measure using trace of the variance covariance matrix. Trace does not adequately accounts for correlations. A method that extends FDA criterion appropriately to the multivariate case is presented. Comparisons using parametric bootstrap method is used to determine the distributions of these three criteria is presented.