Bioequivalence testing by statistical shape analysis.
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.
Pereira
Luis Marcelo
LM
Pharmaceutical Sciences Department, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USA. luis.pereira@mcphs.edu
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
D016568:Drugs, Generic; D004364:Pharmaceutical Preparations; D002939:Ciprofloxacin