Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ Phantastic! Should be put in the same drawer like “TOST is not valid in Nanjing – use the I Ching instead.”

❝ See also this thread and ElMaestro’s wonderful P_t.

The post is about method B or C. However, here the thing is bit different. What I forgot to mention is that after sending out synopsis based on method C one of the comments I got, apart from "not valid in Europe ", is that "power does not count in order to make a decision. The decision can not depend on the results of the power."

I don't know how many ways we can interpret this phrase. Since Potvin's methods are all somehow based on power evaluation in its flowchart so may be this is the reason they say "not valid ..."? Anyway, this is the reason we changed synopsis to use another method without power evaluation as I mentioned.

❝ BTW, you are not alone (see this post).

Don't know if that's comforting or frustrating.

❝ Seems that some regulators believe sic in B, but then they should be happy with the even more strict method D as well. Or are they really thinking that α 0.0294 is a universal constant?

If they don't like power evaluation in the flowchart, B and D should also be unacceptable to them.

❝ Great. This is not even Method B (abandoning the power estimation step).

Nope. We knew that and did it deliberately to avoid power evaluation.

❝ If the agency accepted your method without an intermediate power estimation they should ask themselves which risk to patients they are actually accepting.

Don't know if there's some kind of pact here (this is a BE for certain SUPAC and I'm not the one contact the agency). We were warned that the agency accept this study only in this specific country. It implied that the design might not be valid in other EU countries. It's a little bit complicate so I don't want to go to details.

❝ • For example, using 94.12% confidence intervals for both the analysis of stage 1 and the combined data from stage 1 and stage 2 would be acceptable, …

❝ That’s Method B!

My understanding is different. B involve power evaluation as well (After BE failed in stage 1, there's a step of evaluation power to determine if it should be stopped (Pt>= 80%) or continue (Pt<80%). What I understood from the guideline is that no power evaluation is involved in this example.

❝ ❝ Hi Helmut, it was nice talking to you in Budapest last month by the way.

❝ Same with me. Enjoyed especially the talks outside in the smoker’s Ghetto.

It's a surprise that we actually talked about BE until 2 or 3 AM .

❝ Your memory is correct; see this post. The BfArM (not in Europe according to the BSWP?) had no problems with Method C. Maybe it’s worthwhile noticing that two of the studies were submitted to Berlin’s IECs. Member was Prof. Joachim Röhmel (1990–2004 head of the biostatistical department of the BfArM and an expert in adaptive designs).

That's good to know. I didn't find this post before. Thanks.

Shuanghe