Bioequivalence and Bioavailability Forum

Dear BEman!

❝ […] we want to do it in an 'extreme' way, which is not explicitly forbidden in the Guideline.

Right.

❝ What do you think about such an approach ?

Personally I’m not happy with it – see also ElMaestro’s comments.

❝ Do you have any experience with authority concerning this issue?

According to hearsay (!) similar approaches were accepted in the past – but I have never seen an actual example.

❝ Does the penalty assignment to the stages keeps the 'overall' type 1 error of the study under control?

As ElMaestro said: Without (exhaustive!) simulations we simply don’t ‘know’. For an overview of α-inflations see the references given the section IIa of Schwartz & Denne (2003).*

❝ Do you know literature about an alpha-spending function, which i can use to calculate such extreme alpha spending described above?

No. A major pitfall is the way the Null-hypothesis is formulated in BE (H₀ bioinequivalence, H_a bioequivalence). The abundance of literature on sequential / adaptive designs deals with the much more common superiority test (H₀ no difference, H_a difference) – which is the other way ’round. I would be very wary to simply apply any of these methods in an other context.
The only papers I’m aware of are Gould (1995), Potvin et al. (2008) and Montague et al. (2011). For the references search the forum.

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• Schwartz TA and JS Denne
  Common threads between sample size recalculation and group sequential procedures
  Pharmaceut Statist 2, 263–71 (2003)
  DOI: 10.1002/pst.68