Bioequivalence and Bioavailability Forum

Hi All,

I have a rather 'stupid' question...

We all know that in planning a BE study and estimating/calculating sample sizes, we should never assume a GMR of 1.00, but always plan more conservatively by taking a GMR of 0.95 or less (or 1.0526 or more), especially when no pilot has been performed (apart from not treating a CV reported earlier in a pilot or literature as 'carved in stone').

I have been struggling a bit with a CRO, who quite reluctantly keep on planning with a GMR of 1.00 (and a CV carved in stone). I have stated that no product would ever give a GMR of exactly 1.00 (or a CV would be reproducible) and that they are always underestimating sample sizes (but then they compensate it by including a few additional subjects in their calculations to "protect the study's power" stating that they in the end come to the same sample size, which is the world upside-down, and makes me laugh and cry at the same time ). As a standard, I would like them to perform the calculations with a GMR of 0.95 (if no other information on the in vivo performance is available and dissolution shows no apparent difference).

In the end I am the sponsor so they will do as I tell them to, but it would help to put an end to this misery and to convince them if anyone would have a reference (to an article or guideline, preferably EMA) or a solid justification on especially the GMR to take into account when planning a BE study... I am running out of justifications, rationales, creativity, energy and persuasive power with these guys

Many thanks in advance.