Bioequivalence and Bioavailability Forum

If the purpose of the study is to assess the bioequivalence between different dose formulations, wouldn't in that case a true cross-over design more appropriate instead of a single-sequence (not cross-over) design? I'm thinking of carry-over effects in this case. Imagine that one specific dose of the test formulation has pk properties you don't antecipate and all the subjects have pre-dose concentrations for the next dose. How would you handle that? Remove the entire cohort for that dose?

I believe the ANOVA model with subject as random effect as you proposed is ok. For this kind of design, I'm used to linear mixed models (random intercept & slope models). Nevertheless, I'm not sure if this is adequate for a bioequivalence study since you don't pretend to study a trend but to test for equivalence in each "period" or "dose level". Since it is a dose escalation study maybe you should present alpha-adjusted CI for bioequivalence between doses.