Bioequivalence and Bioavailability Forum

Dear ElMaestro, dear Helmut,

THX for sharing your opinion.

If I understand you right you suggest me to do the usual evaluation (ignoring the centers) and to wait for a deficiency letter?
And if it happens (low chance) then answer "Due to the identical protocol, due to the identical handling of blood samples, central assay of the blood samples, blah, blah ... no influence of the different centers was expected at all."? Eventually this could/should be included in the study report beforehand.

Helmut: Your suggestion of splitting the number of subjects not even between the centers sounds very reasonable. But we can not follow it. As I said, the multicenter design is used for speed reasons and therefore each center is asked to do its very best.

At the whole I agree with your (both of you) views. I think its the same story as with carry-over. We make our best to avoid any differences between centers and should therefore base our evaluation on that assumption that there are no such differences.
If we do it not that way, we ran into the same difficulties as with a test of carry-over. Test it with a test of low power and then decide on that test what to do next. Meanwhile its widely recognized (also between regulators) that this approach is flawed in the context of carry-over.

But especially the FDA citation and the discussions about 'group effect' here in the forum had let me to my questions, also the study is not intended for an FDA submission (at lest not yet).
To be prepared ...