title: The use of asymmetric distributions in average bioequivalence.
abstract: Generic drugs have been commercialized in numerous countries. Most of these countries approve the commercialization of a generic drug when there is evidence of bioequivalence between the generic drug and the reference drug. Generally, the pharmaceutical industry is responsible for the bioequivalence test under the supervision of a regulatory agency. This procedure is concluded after a statistical data analysis. Several agencies adopt a standard statistical analysis based on procedures that were previously established. In practice, we face situations in which this standard model does not fit to some sets of bioequivalence data. In this study, we propose an evaluation of bioequivalence using univariate and bivariate models based on an extended generalized gamma distribution and a skew-t distribution, under a Bayesian perspective. We introduce a study of the empirical power of hypothesis tests for univariate models, showing advantages in the use of an extended generalized gamma distribution. Three sets of bioequivalence data were analyzed under these new procedures and compared with the standard model proposed by the majority of regulatory agencies. In order to verify that the asymmetrical distributions are usually better fitted for the data, when compared with the standard model, model discrimination methods were used, such as the Deviance Information Criterion (DIC) and quantile-quantile plots. The research concluded that, in general, the use of the extended generalized gamma distribution may be more appropriate to model bioequivalence data in the original scale. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Department of Social Medicine, University of São Paulo, São Paulo, Brazil.|Department of Mathematics, Federal Technological University of Paraná, Cornélio Procópio, Brazil.
authors: Roberto Molina
authors: RM
authors: de Souza
authors: Department of Social Medicine, University of São Paulo, São Paulo, Brazil.
authors: Jorge Alberto
authors: JA
authors: Achcar
authors: Department of Social Medicine, University of São Paulo, São Paulo, Brazil.
authors: Edson Zangiacomi
authors: EZ
authors: Martinez
authors: Department of Statistics, State University of Maringá, Maringá, Brazil.
authors: Josmar
authors: J
authors: Mazucheli
mesh_terms: D001499:Bayes Theorem; D003627:Data Interpretation, Statistical; D016568:Drugs, Generic; D006801:Humans; D016008:Statistical Distributions; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic
keywords: Bayesian inference; average bioequivalence; copula functions; extended generalized gamma distribution; multivariate skew-t distribution