Bioequivalence and Bioavailability Forum

Dear Detlew,

❝ ❝ Bonus question: Is interim power acceptable for “type 1” TSDs?

❝

❝ If not, use power.2stage.fC() with arguments (powerstep = FALSE, method="B", fClower=0, ...) and simsalabim interim power has vanished !

That’s what I’ve done.

One interpretation of the MEB’s statement would be that interim power is not accept­able for “type 2” TSDs (aka variants of Method C) but still for “type 1”. Since interim power is the root of the decision tree in “type 2” TSDs it cannot be dropped – bad luck.
Beheaded Justitia standing firm.

❝ BTW: This n2=2 at minimum is totally incomprehensible to me.

I don’t get it as well.*

❝ One of the arguments was if not used alpha will be inflated.

I’m not sure. The Q&A stated only:

From the perspective of type I error control it is considered that there is no minimal number of subjects to be included in the second stage of a two-stage design, so long as it can be demonstrated that the type I error of the study is controlled [sic].

I would rather say, the BSWP had the sequence × stage term in mind (to perform a test for pool­ability or what?):

However, the analysis model for analysing the combined data also needs to be considered.
To fit this model it is necessary to have in each stage at least one patient in each sequence – so a minimum of two patients in each stage of the study, but more if both happen to be ran­do­mised to the same sequence.

❝ Seems you have shown that the opposite is true.

Since Alfedo García suggested to ask questions concerning TSDs directly to the BSWP I’m currently preparing an open letter. I will clearly state that I will make the answer public. I’m sick of lacking trans­pa­rency (<span lang="de"> “Im stillen Kämmerlein.” </span> = on the Q.T.)…

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• Edit: I compared a more detailed matrix (n₁: 12, 14, 16, 18, 20, 22, 24, 30, 36, 42, 48, 54, 60, 70 and CV: 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.25, 0.3, 0.35, 0.4, 0.5, 0.6, 0.7, 0.8) without and with this “minimum n₂ = 2” requirement for both “types”. Empiric TIE and power were identical to the fifth decimal… What a waste of time.