Abstract
We develop population-averaged and subject-specific continuation ratio logit models for assessing bioequivalence of two formulations with respect to TMAX under a 2 x 2 crossover design. We propose generalized estimating equations and mixed-effects estimators for obtaining confidence intervals for odds ratios representing population-averaged and subject-specific formulation effects. We show analytically that the population-averaged approach leads to asymptotic intervals that are narrower than the subject-specific intervals when the intrasubject correlation is positive. Hence, asymptotically, it is easier to show bioequivalence with respect to TMAX under the pop-ulation-averaged approach than under the subject-specific approach. We illustrate these results with an analysis of a multiple-dose bio-equivalence study.
Original language | English (US) |
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Pages (from-to) | 185-199 |
Number of pages | 15 |
Journal | Journal of Biopharmaceutical Statistics |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Jan 1 1995 |
All Science Journal Classification (ASJC) codes
- Statistics and Probability
- Pharmacology
- Pharmacology (medical)