A method for the evaluation of individual bioequivalence.

ABSTRACT

A method is presented for the evaluation of individual bioequivalence. The approach is simple and effective. It considers two drugs to be inequivalent in individuals if their contrast shows larger variation than that observed within formulations, which are repeatedly administered to the subjects. The necessary information can be obtained in 3- or 4-period crossover trials, in which individuals receive not only both drug products but also the replicate application of at least one of them. In the implementation of the procedure, it is suggested that two drug products could be considered to show individual bioequivalence if the upper, one-sided confidence limit for the ratio of intraindividual variances estimated between and within formulations does not exceed a preset critical value, Fcr. For initial considerations, a confidence level of 90% and Fcr = 4.0 are recommended. The intraindividual variances between and within formulations can be estimated either by simple, direct calculations or by an analysis of variance (ANOVA). The structure of the latter is different from that of the ANOVA applied for the assessment of average bioequivalence. Another approach assessing individual bioequivalence from an estimated variance component is less favoured. Graphical, exploratory analysis of the multiperiod crossover trials is recommended and illustrated. The suggested procedures are demonstrated on an example evaluating the individual (and average) bioequivalence of olsalazine tablets and capsules.