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.