Bioequivalence and Bioavailability Forum • Alpha adjustment in higher order crossover

Alpha adjustment in higher order crossover [Power / Sample Size]

posted by d_labes – Berlin, Germany, 2018-02-01 15:01 (3057 d 12:55 ago) – Posting: # 18322
Views: 26,813

Dear Helmut,

❝ Be aware that simultaneous comparisons inflate the Type I Error (the patient’s risk). I guess that in your first design you will not compare the two test treatments but only T₁ vs. R₁, T₁ vs. R₂, T₂ vs. R₁, and T₂ vs. R₂. With these k=4 comparisons (each performed at the nominal α 0.05) the Familywise (Type I) Error Rate will be 1–(1–α)^k≤18.55%. Bonferroni’s adjusted α will be α/k or 0.0125 which translates into a 100(1–2α/k) or 97.5% two-sided confidence interval whilst keeping the FWER with 1–(1–α/k)^k≤4.91% below the nominal α 0.05. The lower α will substantially increase the sample size ...

Also you may be correct I must confess that I seldom or never had done this alpha-adjustment in case I used a higher order design. Reasons:

Never had problems with using un-adjusted alpha in more then 30 years.
Usually the comparisions evaluated stand for it's own, a global hypothesis is not defined.
An alpha-adjustment is only necessary if the single comparisions are combined to a global hypothesis via an OR. For combining them via an AND no alpha-adjustment is necessary.*
Using the EMA crippled but recommended method for evaluation there are only 2 treatment's involved, again no alpha-adjustment necessary.

Dieter Hauschke, Volker Steinijans, Iris Pigeot
Bioequivalence Studies in Drug Development
Chapter 7.4 Multiplicity

—
Regards,

Detlew

Complete thread:

Sample size for 4-period 4-sequence crossover BE study Bryony Simmons 2018-02-01 12:16
- function sampleN.TOST of package PowerTOST Helmut 2018-02-01 13:01
  - Alpha adjustment in higher order crossoverd_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