Alpha adjustment in higher order crossover [Power / Sample Size]
❝ 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 [Power / Sample Size]
- 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 22:17
- TIE for NTIDs Helmut 2018-02-05 17:49
- TIE for NTIDs d_labes 2018-02-05 16:40
- 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
- 111.11 for NTIDs Astea 2018-02-05 19:27
- bow TIE for NTIDs d_labes 2018-02-05 22:33
- bow TIE for NTIDs Helmut 2018-02-05 18:10
- bow TIE for NTIDs Astea 2018-02-05 17:52
- TIE for NTIDs Helmut 2018-02-05 01:01
- TIE for NTIDs Astea 2018-02-04 20:04
- TIE for NTIDs d_labes 2018-02-04 12:40
- α and no ω Helmut 2018-02-02 23:39
- alpha... where is omega? Astea 2018-02-02 21:45
- Deficiencies Relaxation 2018-02-02 19:41
- Deficiencies Relaxation 2018-02-02 11:12
- Deficiencies Helmut 2018-02-01 15:48
- Alpha adjustment in higher order crossoverd_labes 2018-02-01 14:01
- function sampleN.TOST of package PowerTOST Helmut 2018-02-01 13:01