title: Bioequivalence testing by statistical shape analysis.
abstract: Bioequivalence testing has been traditionally centered in summary variables such as AUC, C (max) and t (max) which filter out the intrinsic information conveyed by discrete sequential concentration-time observations. Comparing entire concentration-time profiles between test and reference formulations for bioequivalence purposes provides stronger evidence about either their similarity or their discrepancy. The Kullback-Leibler information criterion (KLIC) may be computed for each concentration-time across all subjects between formulations of the same drug, with a standard crossover study design. It has been shown that if properly scaled it follow a chi-squared distribution and dependent p-values may be computed in order to construct a bioequivalence criterion. Extensive simulations and real data were used to compare it with the current standard procedures. This statistical shape analysis method may provide important clinical and regulatory advantages.
authors.affiliation: Pharmaceutical Sciences Department, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USA. luis.pereira@mcphs.edu
authors.forename: Luis Marcelo
authors.initials: LM
authors.lastname: Pereira
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D001682:Biological Availability; D002939:Ciprofloxacin / Q000493:pharmacokinetics; D003198:Computer Simulation; D016001:Confidence Intervals; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000097:blood; D010599:Pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic; D004364:Pharmaceutical Preparations; D002939:Ciprofloxacin