Bioequivalence and Bioavailability Forum • TIE: questions

TIE: questions [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2015-02-03 14:24 (3752 d 22:09 ago) – Posting: # 14364
Views: 22,611

Dear Mittyri,

❝ 1. Could you explain:

❝ ❝ At 30% the chance for such a wrong decision is 50%. Therefore, we can expect the highest inflation of the TIE at 30%.

❝ But:

❝ ❝ Maximum inflation of the TIE 0.0684 (at CV 30.1%).

❝ (in your post below)

❝ Why the maximum inflation is not observed exactly at 30%?

For the EMA scaling starts at CV >30% and for the FDA at ≥30%. Therefore, I explored 30% and the slightly larger value 30.1%. No big deal. Actually the maximum inflation for the EMA is expected at 30% + ε, where ε is infinitely small.

❝ 2. Where did you get the image with inflation of the TIE?

My own simulations.

❝ (is it possible to find it in high resolution?)

I can send you the originals. Take FDA’s results with a grain of salt. I have to rethink what Detlew posted.

❝ As I understand the TIE in this image can be changed to CI for adjusted α. (So the black line is the line of 90% CI)

Yes and no. You can find an adjusted α and calculate the CI accordingly. The black lines enclose the area of significant inflation of the TIE (for 10⁶ simulations that’s 0.05036).

❝ 3. I read this thread one more time, but didn't catch one thing

❝ For example before the study (TRT|RTR) I have estimated number of subjects 42 proceeded from expected CV (40%), required power (80%), TIE (5%) and expected Ratio (90% for HVD).

❝ OK, I'm on a lucky side, the CV and GMR were as expected.

❝ After that I should adjust the TIE (and wide the CI). And new CI could be outside the limits!

Yes, that’s possible. If you plan the study for α 0.05 and adjust afterwards you might loose up to ~10% power.

❝ Could I expect it and plan the study in accordance with coming procedure of TIE adjusting?

Yes, that is what I would do. Find an adjusted α based on a “best guess” CV and estimate the sample size accordingly. It seems that 0.025 for fully replicated designs and 0.0304 for the partial replicate will be conservative (i.e., cover the inflation at 30%).

❝ Yes, it is not possible to counteract the inflation by a prespecified adjusted α, but as well as for power is it possible to use some "critical limits"?

Not sure what you mean by that. Run some sim’s. For really high CVs (say >40%) this entire story is not important anyway.

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Complete thread:

EMA oracle Helmut 2015-01-27 16:27
- EMA oracle nobody 2015-01-27 17:07
- Personal opinion ElMaestro 2015-01-27 17:56
- EMA oracle d_labes 2015-01-27 19:44
  - EMA oracle nobody 2015-01-28 09:04
    - EMA oracle ElMaestro 2015-01-28 13:11
- Response from Alfredo García-Arieta Helmut 2015-01-30 10:55
  - Response from Alfredo García-Arieta nobody 2015-01-30 14:55
    - Wonnemann’s Figure 4 on steroids Helmut 2015-02-01 01:35
      - Wonnemann’s Figure 4 on steroids nobody 2015-02-01 11:18
        
        Wonnemann’s Figure 4 on steroids Helmut 2015-02-01 14:49
      - General remarks ElMaestro 2015-02-01 18:43
        
        General remarks nobody 2015-02-01 22:04
        General remarks Helmut 2015-02-02 00:48
        
        General remarks nobody 2015-02-02 08:09
        
        General remarks Helmut 2015-02-02 14:06
        
        TIE: questions mittyri 2015-02-03 12:44
        
        TIE: questionsHelmut 2015-02-03 13:24
        
        FDA RSABE & alpha inflation d_labes 2015-02-03 12:02
        
        FDA RSABE & alpha inflation Helmut 2015-02-03 12:22
        
        FDA RSABE & alpha inflation d_labes 2015-02-03 13:07
        
        FDA RSABE & alpha inflation Helmut 2015-02-03 13:41
- New Zealand nobody 2015-01-31 11:25
  - New Zealand Helmut 2015-02-01 16:08
    - New Zealand nobody 2015-02-01 22:08
      - New Zealand Helmut 2015-02-01 23:54
        
        New Zealand nobody 2015-02-02 08:07