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RegisterTricky… [RSABE / ABEL]
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.
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.
Complete thread:
- Statistical evaluation and BE hypotheses in full replicate design Elena777 2020-01-28 07:02 [RSABE / ABEL]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Inflation of the TIE as well Helmut 2020-01-29 15:38
- Inflation of the TIE as well Elena777 2020-01-29 20:01
- Tricky… Helmut 2020-01-30 12:07
- Tricky… Mikalai 2020-01-30 13:08
- Terrible… Helmut 2020-01-30 15:09
- Flawed evaluation accepted Helmut 2020-01-31 12:19
- Flawed evaluation accepted Mikalai 2020-01-31 12:40
- Flawed evaluation accepted Helmut 2020-01-31 14:17
- Flawed evaluation accepted Mikalai 2020-01-31 16:41
- Flawed approach even if accepted ? Helmut 2020-01-31 20:28
- Flawed approach even if accepted ? Mikalai 2020-02-01 16:18
- misunderstanding mittyri 2020-02-01 21:34
- misunderstanding Mikalai 2020-02-06 13:41
- misunderstanding mittyri 2020-02-06 16:23
- misunderstanding Mikalai 2020-02-06 13:41
- The globe is flat! d_labes 2020-02-05 19:16
- misunderstanding mittyri 2020-02-01 21:34
- Flawed approach even if accepted ? Mikalai 2020-02-01 16:18
- Flawed approach even if accepted ? Helmut 2020-01-31 20:28
- Flawed evaluation accepted Mikalai 2020-01-31 16:41
- Flawed evaluation accepted Helmut 2020-01-31 14:17
- Flawed evaluation accepted Mikalai 2020-01-31 12:40
- Tricky… wienui 2020-01-30 18:53
- Tricky… Helmut 2020-01-30 19:18
- Tricky… wienui 2020-02-03 07:10
- ABE vs. ABEL Helmut 2020-02-03 12:25
- zigzag d_labes 2020-02-05 18:53
- zigzag Helmut 2020-02-05 19:46
- zigzag Mikalai 2020-02-06 11:38
- helter-skelter Helmut 2020-02-06 20:12
- helter-skelter Mikalai 2020-02-10 16:10
- helter-skelter Helmut 2020-02-06 20:12
- zigzag Mikalai 2020-02-06 11:38
- zigzag Helmut 2020-02-05 19:46
- zigzag d_labes 2020-02-05 18:53
- ABE vs. ABEL Helmut 2020-02-03 12:25
- Tricky… wienui 2020-02-03 07:10
- Tricky… Helmut 2020-01-30 19:18
- Tricky… Mikalai 2020-01-30 13:08
- Tricky… Helmut 2020-01-30 12:07
- Inflation of the TIE as well zizou 2020-02-01 17:00
- Inflation of the TIE as well nobody 2020-02-01 23:30
- Inflation of the TIE as well Elena777 2020-03-10 19:28
- Fishing in the dark Helmut 2020-03-10 21:06
- Inflation of the TIE as well Elena777 2020-01-29 20:01
- Statistical evaluation and BE hypotheses in full replicate design nobody 2020-02-03 15:07
- TIE, repeat once more please... Astea 2020-04-02 12:41
- Inflation of the TIE as well Helmut 2020-01-29 15:38
Ing. Helmut Schütz