Bioequivalence and Bioavailability Forum • alpha... where is omega?

alpha... where is omega? [Power / Sample Size]

posted by Astea – Russia, 2018-02-02 22:45 (2634 d 13:25 ago) – Posting: # 18335
Views: 21,995

Dear Smart People!

I am suffering trying to understand the problems and perspectives of alpha-adjustment.
Wherever I look I see TIE inflation...
For HVD:

EMA SABE seemed to have problems with TIE for CV in 25-45%
FDA RSABE seemed to have problems for CV around 30%

For well-known adaptive designs (Potvin, Xu...) TIE also behaves badly...
TIE may be also inflated by evaluating different methods for PK metrics (when one of them turns to be overpowered - as in the case of adaptive design or different CI for two Cmax and AUC).
I suspect TIE will be also inflated in studies of NTDs also (by using FDA approach or by using different confidence limits for two metrics).
Now you talk about higher-order design and dose-proportional studies...

So... Are there any ways to deal with it excepting the bright idea of iteratively adjusted alpha? While looking through the literature I've found only some suggestions of modificating ABE (with new procedures or nonlinear CI limits) or alternatives for ABE (like GSD or Two-stage designs)...

Knahl SIE, Lang B, Fleischer F, Kieser M., A comparison of group sequential and fixed sample size designs for bioequivalence trials with highly variable drugs, J Clin Pharmacol, 2018, doi:10.1007/s00228-018-2415-7.
Molins E., Cobo E., Ocaña J. Two-stage designs versus European scaled average designs in bioequivalence studies for highly variable drugs: Which to choose? Statistics in Medicine, V. 36, I. 30, pp 4777–4788, 2017 doi:10.1002/sim.7452.

—
"Being in minority, even a minority of one, did not make you mad"

Complete thread:

Sample size for 4-period 4-sequence crossover BE study Bryony Simmons 2018-02-01 12:16 [Power / Sample Size]
- function sampleN.TOST of package PowerTOST Helmut 2018-02-01 13:01
  - Alpha adjustment in higher order crossover d_labes 2018-02-01 14:01
    - Deficiencies Helmut 2018-02-01 15:48
      - Deficiencies nobody 2018-02-01 17:10
      - Deficiencies d_labes 2018-02-01 18:57
        
        Deficiencies Relaxation 2018-02-02 11:12
        
        Deficiencies nobody 2018-02-02 12:49
        Deficiencies Helmut 2018-02-02 16:14
        
        Deficiencies Relaxation 2018-02-02 19:41
        
        alpha... where is omega?Astea 2018-02-02 21:45
        
        α and no ω Helmut 2018-02-02 23:39
        
        TIE for NTIDs d_labes 2018-02-04 12:40
        
        TIE for NTIDs Astea 2018-02-04 20:04
        
        TIE for NTIDs Helmut 2018-02-05 01:01
        
        TIE for NTIDs d_labes 2018-02-05 16:40
        
        TIE for NTIDs Helmut 2018-02-05 17:49
        
        TIE for NTIDs d_labes 2018-02-05 22:17
        
        TIE for NTIDs Helmut 2018-02-06 12:34
        
        TIE for NTIDs d_labes 2018-02-05 16:35
        
        bow TIE for NTIDs Astea 2018-02-05 17:52
        
        bow TIE for NTIDs Helmut 2018-02-05 18:10
        
        111.11 for NTIDs Astea 2018-02-05 19:27
        
        111.11 for NTIDs Helmut 2018-02-06 00:12
        
        bow TIE for NTIDs d_labes 2018-02-05 22:33