AUC <5% of TEST geometric mean AUC [Outliers]

posted by ElMaestro  – Denmark, 2019-02-13 12:09 (798 d 03:36 ago) – Posting: # 19906
Views: 1,884

Hi vezz,

» Could you please expand a little bit on your suggestion related to Cmax? I think you are referring to the following recommendation included in section 4.1.7 (Bioanalytical methodology) of the EMA guideline: "The lower limit of quantitation should be 1/20 of Cmax or lower, as pre-dose concentrations should be detectable at 5% of Cmax or lower". However, it is not completely clear to me how to justify the exclusion of the period based on this statement.

When it comes to justifying exclusions, nothing is clear :-)
I think I will abstain from trying to give a recipe that always works. If I could, I most definitely would. I think you need to review the protocol, the bioanalytical plan+report, and the SAP. It is all about wording. Perhaps something is stated somewhere about qualifying subject profiles?

Note also: In BE we usually only evaluate for stats those subjects who contribute at least one Test measurement and one Ref measurement. So in a 222BE trial, if one subject's period is lost, the entire subject is dropped from stats.

I have rather frequently discussed the matter with regulators. There seems to be no widely agreed consensus on the implementation of the guideline (just like the stereoselective bioanalysis :lol2:).

Pass or fail!

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