Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ yesterday EMA’s PK working party published Rev. 7 of the Q&A document. According to the new #14:

1. The expected analysis for the combined data in a two-stage design is ANOVA with terms for stage, sequence, sequence × stage, subject(sequence × stage), period(stage), formulation.
   

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2. This model can be fitted provided that in each stage, there is at least one subject randomised to each sequence. This does not supersede the requirement for at least 12 subjects overall.
   

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3. A term for a formulation × stage interaction should not be fitted.

If you have a Two-Stage study underway, amend your SAP.

Thanks for posting this.
Given that they request those sequence-related fixed factors it sounds to me like they implicitly are assuming that all two-stage studies are crossovers. While it is of course true that Potvin & Montague so far only studied those cases I can't believe the intention is to eliminate an option for parallel 2-stage studies. But what do I know?!?