Bioequivalence and Bioavailability Forum

Hi GM,

❝ ❝ Which agency’s guidance?

❝

❝ FDA Guidance only.

Sorry that I didn’t ask for the specific guidance. I guess you are referring to this one stating in Section VII.A.:

If a crossover study is carried out in two or more groups of subjects (e.g., if for logistical reasons only a limited number of subjects can be studied at one time), the statistical model should be modified to reflect the multigroup nature of the study. In particular, the model should reflect the fact that the periods for the first group are different from the periods for the second group. This applies to all of the approaches (average, population, and individual BE) described in this guidance.

Since studies for PBE and IBE are also performed in replicate designs, one can conclude that the same is applicable to RSABE.

❝ ❝ What do you mean by “checked”? Have group – together with some nested terms – as part of the model (only report the MSEs, p-values) or do you additionally want to base any decision on it? That’s not a good idea, since power might be compromised and the Type I Error inflated (see this presentation).

❝

❝ Sorry for poor english.

No worries. Mine is hardly better. But please answer my question.

❝ For RSABE approch, only sequence effect will be sufficient in the model? or any group terms need to be include here.

Here you lost me. You will have a lot of effects… Honestly, I have no clue how to modify the models given in the progesterone-guidance.