Misunderstanding? [Regulatives / Guidelines]

posted by ElMaestro  – Denmark, 2021-08-28 10:00 (152 d 00:45 ago) – Posting: # 22554
Views: 1,447

Hi Hötzi,

» » However, since FDA now threw the mixed model out for semi-replicate designs, …
» What on earth gives you this impression? I’m talking about ABE (Stats guidance Appendix E, Progesterone guidance page 8, ANDA guidance page 29):

Wow, that is actually right.
Page 27: "PROC GLM should be used for partially replicate (3-way) BE studies"
Page 29: "For PK parameters with a sWR < 0.294, use the unscaled average BE approach." (which implies PROC MIXED in their code)

So, we must start to work out sWR using the equations. Once we got it, we know whether we need a mixed model or not for the evaluation of BE. We may need the mixed model for one metric, like AUCt and AUCinf, and the equations (ref scaled ABE) for another, like Cmax.
I guess this is also the gist of the decision tree you gave. I wonder if this is truly their intention. The mixed model therefore seems to have been saved by the bell. This really emphasizes the need for a CI solution that allows V estimated without the existence of Z and R separately.

I am curious now - we should make a little study on the type I error in case of missing ref values.

Pass or fail!

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