Bioequivalence and Bioavailability Forum

Hi Detlew,

❝ If you aimed for an EMA submission you have to do some sort of that.

❝ To cite the EMA guideline again (we had this already occasionally discussed here, also by yourself!):

❝ "In studies with more than two treatment arms (e.g. a three period study including two references, one from EU and another from USA, or a four period study including test and reference in fed and fasted states), the analysis for each comparison should be conducted excluding the data from the treatments that are not relevant for the comparison in question."

Sorry I was going to mention that in my post but I got carried away

But you get my point correct? There is no alteration of the study data or the method of analysis. I can present the study data into two sets of results by removing each of the test formulation data from the dataset (yes keeping the period and sequence as a 3-way study) and run stats on each. The point is to show that one formulation actually fails because of the pool variance effect attributed to the high CV from the other formulation and removing the "bad" formulation data results in passing BE.

Of course I have multiple parameters (Cmax and AUCs) to deal with... What if one parameter passes and one (or two) fails after doing the split data analysis...

We actually spoke with FDA about the pool variance effect (at a conference) and they didn't seem to care. Our question was "Would you raise a question about the results of a 3-way '2 formulation vs 1 reference' study because of the pool variance effect?". I wasn't there but if I was then I would have asked "What if the study fails marginally due to pool variance? Can I re-evaluate the data by removing each formulation and run stats to show that one formulation actually passes BE?"

John