Tricky… [RSABE / ABEL]

posted by Mikalai  – Belarus, 2020-01-30 16:02  – Posting: # 21106
Views: 8,174

Dear Helmut,
I would like to apologize because I confused you in my previous post. I should have used ABE instead of ABEL as an abbreviation because I meant the average bioequivalence. I corrected it recently.
Thus, we do not use RR for the ref drug in our calculations and should not control TIE if we initially go by the ABE approach and reach bioequivalence within 125-80% interval (alpha at 0.05).

Also, it seems the only reason that we should calculate RR for the ref drug first is to calculate and control TIE latter if the CV is higher than 30%. If it turns out that it is lower than 30% then we simply use the ABE and no control TIE. However, if we do not plan to do this (control TIE), then it is not important to calculate the RR ref first. As you mentioned there Post and there post no regulatory agency issued a formal guideline on TIE in replicate studies, and FDA and EMA do not require and accept replicate studies without controlling TIE. In this case (no control TIE), we can calculate the RR only when we fail in Cmax. We do not recalculate our new CI we just use that from ABE to compare with a new or the standard CI if CV less than 30. In the latter case, we basically fail the study.

I would not like to discuss whether we should or not control TIE in replicate studies in this branch. In my view, probably we should not, and it is also probably that leading agencies won't do anything with this issue unless a safety signal occurs.

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