Bioequivalence and Bioavailability Forum • Tricky…

Tricky… [RSABE / ABEL]

posted by Mikalai – Belarus, 2020-01-30 14:08 (1719 d 16:15 ago) – Posting: # 21102
Views: 22,401
(edited on 2020-01-30 15:08)

Dear Helmut,

❝ Tricky. In your original post you stated also a decision tree. Any of these decisions made can be wrong, which will inflate the TIE. Imagine you failed ABE not because the reference is highly variable but by lacking power. Then you would continue to #2. The observed CV_wR was >30% by chance and you expand the limits. However, the true CV_wR (in the patient population) is ≤30%, and the decision wrong – inflated TIE (see there). More in the answer to #4.

It is a bit confusing, but could you clarify a couple of points.

In the case of going by the ABE path (see the decision tree), I assume we do not use any population parameters and just compare concentrations from samples. There is no inflation TIE? Is it correct? And we do not use RR for the ref drug in our calculation. Is it correct?
But if the study fails, we then calculate RR and a new bioequivalence interval if CV is higher than 30%. That is when we use RR and where TIE can be inflated. Is it correct? But we do not recalculate our new CI we just use that from ABE to compare with a new or the old CI. In the latter case, we basically fail the study. Is it correct?

The identical decision tree was used in the BS of rasagiline (registration required) and was accepted by EMA. https://clinicaldata.ema.europa.eu/web/cdp/home
If I am correct, in my view it is a preferable solution to minimize the inflation TIE.
Best regards

Complete thread:

Statistical evaluation and BE hypotheses in full replicate design Elena777 2020-01-28 07:02 [RSABE / ABEL]
- 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
        
        Tricky… Mikalai 2020-01-30 16:02
        
        Deep shit Helmut 2020-01-30 16:59
        
        Deep shit Mikalai 2020-01-30 18:39
        
        Deep shit Mikalai 2020-01-30 19:31
        Deep shit Helmut 2020-01-30 20:07
        
        Deep shit Mikalai 2020-01-31 11:14
        
        Deep shit Helmut 2020-01-31 14:00
        
        Deep shit Mikalai 2020-01-31 16:07
        
        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
        
        The globe is flat! d_labes 2020-02-05 19:16
      - 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
  - 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
- 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