Bioequivalence and Bioavailability Forum

Hi ElMaestro
Honestly, I am no friend of pilot studies and of two stage designs either. IMHO a pilot study makes sense if you
1. use a complete different formulation (the situation you described = proof-of-concept)
2. have an alternative (three period design) or know how to reformulate (IVIVC)
3. can not find any PK data in literature.

❝ 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?

No risk, no fun. Do you have an alternative? IMHO a pilot study with only one test formulation does not make any sense and I agree that using the GMR for the planning of a pivotal trial isn't necessarily a great idea. I disagree with your opinion that pilots appear to be excellent when the uncertainty is on the variability, but then 2stage approaches may be smarter still. So if you do not know if variability is 35 or 45% does it matter if you use a replicate design? You can not use replicate in a two-stage.
Kind regards
Dr_Dan