Extension to the use of tolerance intervals for the assessment of individual bioequivalence

For the determination of bioequivalence, researchers have recently shifted their emphasis from average bioequivalence alone to average and individual bioequivalence Existing methods for assessing average bioequivalence were first developed for the standard 2 x 2 crossover design, but these methods are easily generalized to the two-treatment, p-period crossover designs (e.g., TRR, RTT, and TTRR, RRTT, TRRT, RTTR). With respect to individual bioequi-valence, Westlake (1, 2) implemented the use of parametric anddis-tribution-free tolerance intervals for assessing individual bioequivalence. Andersonand Hauck (3) described what they call the testof individual equivalence ratios (TIER)for the same purpose. Note that these methods have been applied and/or developed only for the standard 2 X 2 crossover design. The present work extends the method of using parametric tolerance intervals for assessing individual bioequivalence.