Bioequivalence and Bioavailability Forum

Hi Louis,

❝ Two pilot studies (2x2) passed for AUC and Cmax, a pivotal study (4x2) failed for both AUC and Cmax (AUC and Cmax ~130%, U95%CI ~1.40). Another large scale study passed. Would like to invalidate the failed pivotal study which had significant period effects (AUC and Cmax); a significant product*period*sequence effect; significant product differences were seen in periods 1 & 3, not in 2 & 4; within sequence product differences were significant within period 1 but not in sequence 2; CV ~ 35% for both AUC and Cmax in failed study; ~ 25% in past studies. I would like to use the second large study as pivotal. How can I do this - do I need to invalidate the pivotol study.

This is all a bit confusing, and some of it makes little sense to me.
Is there anything you don't like about the first pivotal, other than its result? Period effects happen occasionally and do not invalidate results. You mention significant product*period*sequence, how did that find its way into your analysis? I have no idea what to do with such info. Out of curiosity: Did you test that against the residual or against the between-subject MS?
Do you think you just had too low sample size for the observed CV in your failed trial? Let us hear the whole story.
You might wish to audit your trials, to find out if one trial is more credible than the other. But be fair about it; it might be that the first trial turns out to be the more credible. 35% CV in one trial and 25% in the next is perhaps an OK trigger, especially if the trials were conducted under the same conditions. More details please