Bioequivalence and Bioavailability Forum

Hi all,

I was about to make a new post when I saw this, so ElMaestro, I just borrow your place to make some comments and ask a few questions.

I had some unofficial feedback regarding sequential design just a few days ago. We send a protocol synopsis with statistical analysis details with Method C from Potvin's article and were told that "Potvin's method is not valid in Europe". I have no idea if that means all method ABCD (well, A is not recommended so I could probably take it off) or just method C since that is the one we used in a synopsis. Long story short, after some discussion back and forth we end up with one of the examples mentioned in EMA's BE guideline and got OK from agency. Basically, we do stage 1 BE, analysis with alpha=0.0294, if BE, stop, if not, calculate sample size for stage 2 and analyse all data with alpha=0.0294 again.

I got the opinion of "not valid in Europe" unofficially from certain agency who in turn got it from BSWP (which we assume is BioStatistics Working Party). I'm not sure it will be reflected somewhere in an official document (e.g QA) or not.

so my first question is: You guys have any insight with this regard?

and Hi Helmut, it was nice talking to you in Budapest last month by the way. For those of you didn't know, Helmut has so many fans, esp. from India, who want to have a picture with him I couldn't remember how many times I was asked to help with taking pictures.

Anyway, I remember that you had several protocols accepted by certain agency using adaptive sequential design. I thought they were based on method C? Now since I have this feedback, I started to doubt my memory. maybe I mixed up what I read and what I heard. Is it OK if I ask for your confirmation? you don't have to go in detail about study design in case of confidential issue. maybe just a rough idea?

Thanks,

Shuanghe