Bioequivalence and Bioavailability Forum

Hi all,

I wonder when and how you experts use pilot trials?
If you have a candidate formulation and you have no clue if you are anywhere close to a match versus the reference -for example when it is a non-trivial formulation- would you then do a pilot trial? And if yes, how would you use the info derived from it??
E.g. your pilot trial on N=12 says the GMR estimate is 92.6 with a CI from 78% to 110%. Would you assume GMR=95% or would you assume 92.6% or something even worse when planning the pivotal?

This paper was just published and discusses such use of pilot trials. As far as I have understood () the author, who is known to be a fellow of rather dubious qualities, argues that when there is genuine uncertainty about the match (which is to say the true GMR) then a pilot trial is perhaps not of much use. This is because using the GMR for the planning of a pivotal trial isn't necessarily a great idea according to the numbers. Pilots appear to be excellent when the uncertainty is on the variability, but then 2stage approaches may be smarter still.

Do you have any idea how to use a pilot trial to address a potential lack of match ?

Mucho complicado in my opinion and yet the question is so incredibly simple.