Bioequivalence and Bioavailability Forum

Dear Helmut,

If I get the point correctly, your idea is to reproduce the same ANOVA model as what you would have in a conventional 2x2 study, is that right ? I mean, to introduce in the ANOVA the sequence effect (normally TR or RT) which you wouldn't have in your study as you only have RR ?

If I look at slide 63 of your lecture, sequence effect can be due to either a real sequence effect (you wouldn't have one with a single RR sequence), a failure of randomisation (not with no randomisation), a true carryover effect (you know enough about BE trials to plan your trial properly, at least if the sponsor listens to you ), or a formulation by period interaction (which I'm not sure you would be able to detect with your artifical R₁R₂ / R₂R₁ randomisation). Adding a "randomisation" in your trial and in your model would indeed introduce a "sequence" effect in your ANOVA, and therefore reduce the MSE somehow (and then reduce the intra-CV), but wouldn't it just be an artefact ? Couldn't you then be under-estimating your intra-CV ?

I'm just thinking aloud, you know much more about these things than I do.

Best regards
Ohlbe