Bioequivalence and Bioavailability Forum

Dear All,

according to the new EMA-Guideline we want to perform a study in 2-Stage Design. But we want to do it in an 'extreme' way, which is not explicitly forbidden in the Guideline.

Stage 1:
12 Subject, 'nearly full penalty for the interims analysis' ⇒ 99.9% CI

positive stopping criteria: BE passed (never happens)
positive stopping criteria: calculated sample size for stage 2 is more than 60 subjects (due to ethical reasons).

Stage 2:
amount of subjects to reached 85 % Power based on the results of stage 1, maximum 60 subjects, 'nearly no penalty' ⇒ 90.1% CI

Questions:
What do you think about such an approach?
Do you have any experience with authority concerning this issue?
Does the penalty assignment to the stages keeps the 'overall' type 1 error of the study under control?
Do you know literature about an alpha-spending function, which i can use to calculate such extreme alpha spending described above?

Thanks

BEman

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Edit: Category changed. [Helmut]