Bioequivalence and Bioavailability Forum

Dear Andrew!

❝ Thank you very much for such a comprehensive reply.

Oh, I'm always at little bit epic.

❝ You will recall that my statistical knowledge amounts to less than a pimple on the backside of most users of this forum […]

1. I love that phrase.
   
2. I wouldn't bet one the statistical knowledge of most users of this forum.

❝ […] I had assumed that the regulators would be illogical and that, or a two-stage design, they would expect us to pre-specify the size of ]both[/i] first and second groups.

In the drafted quideline they didn't mention a specific method. Health Canada is planning to implement Potvin's method in their guideline (see here; but nothing published yet).

❝ […] The idea would be to adjust the confidence intervals according the method of Gould 1995 […]

I like Gould's paper and tried it a couple of times (three times in Germany, once in France). Regulators did not accept the proposals. I gave up in 2002.

❝ In your view, is Gould's approach unlikely to be acceptable to the regulators?

No. Not only from said experiences, but also two members of the PK-drafting group telling me "Gould's method is ridiculous" without giving further explanations.
For interested readers:

LA Gould
Group Sequential Extension of a Standard Bioequivalence Testing Procedure
J Pharmacokinet Biopharm 23(1), 57-86 (1995)
online abstract