Bioequivalence and Bioavailability Forum • Multiplicity: Mixed feelings

Multiplicity: Mixed feelings [Design Issues]

posted by ElMaestro – Denmark, 2012-11-30 16:24 (4950 d 19:26 ago) – Posting: # 9646
Views: 25,007

Hi Helmut,

❝ Out of curiosity: Did FDA want you to adjust α to deal with multiplicity (>90% CIs: Bonferroni, Holmes, Hochberg, :blahblah: )?

Some personal observations from the bag of EU/US/other memories:

Agency statisticians seem to very much like the the idea of multiplicity adjustment. So if you ask if they want you to do it, the answer is often a clear Yes (Bonferroni) in autopilot mode referencing this book.
When the assessment report comes and the poor assessor -who isn't the statistician- realises that there are no 90% CI's in the dossier, there will be a deficiency letter and 90% CI's must be submitted.
I see companies trying to adjust alphas even when they do one test and two refs (as in Ref₁ EU sourced and Ref₂ US sourced). It results in funny and endless discussions around e.g. the EU guideline stating that BE must be shown on data reflecting the products of interest, pt. 1 above, and the fact that sponsors are hoping for BE to be shown against both Refs.

So while I think the underlying idea of multiplicity adjustment is appealing in theory I find the whole matter slightly pseudo-scientific in practice. Am eager to hear your views or any other user's views.

—
Pass or fail!
ElMaestro

Complete thread:

Two Tests with Same Reference Noha Abdeljawad 2012-11-27 08:18
- Crossover designs with more than 2 treatments d_labes 2012-11-27 09:51
  - Crossover designs with more than 2 treatments Noha Abdeljawad 2012-11-29 07:43
- Sounds wrong to me ElMaestro 2012-11-27 12:10
  - Sounds wrong to me Dr_Dan 2012-11-27 14:32
  - Sounds wrong to me Noha Abdeljawad 2012-11-29 07:52
- Two Tests with Same Reference jag009 2012-11-28 21:26
  - FDA & multiplicity Helmut 2012-11-30 14:04
    - FDA & multiplicity jag009 2012-11-30 15:16
      - FDA & multiplicity Helmut 2012-11-30 16:12
        
        FDA & multiplicity jag009 2012-11-30 22:47
        
        FDA & multiplicity Helmut 2012-12-01 02:00
        
        FDA & multiplicity jag009 2012-12-03 21:53
    - Multiplicity: Mixed feelingsElMaestro 2012-11-30 15:24
      - Multiplicity: Mixed feelings Helmut 2012-11-30 15:52
        
        Multiplicity: Mixed feelings martin 2012-12-03 09:24
      - Multiplicity: Mixed feelings kumarnaidu 2013-12-12 11:03
        
        More infos, please Helmut 2013-12-12 15:27
  - Two Tests with Same Reference Noha Abdeljawad 2012-12-03 08:29
    - Two Tests with Same Reference jag009 2012-12-03 15:35
      - X-way d_labes 2012-12-04 09:25
        
        design kvgreddy06 2013-12-19 15:32
        
        design kvgreddy06 2013-12-30 16:48
        
        design intuitivepharma 2013-12-31 06:44
        
        design kumarnaidu 2013-12-31 08:24
        
        Problematic design Helmut 2013-12-31 15:02
        
        Problematic design kvgreddy06 2014-01-03 14:46
        Problematic design kumarnaidu 2014-12-24 12:56
        
        Problematic design Helmut 2014-12-24 16:10
        
        Problematic design kumarnaidu 2014-12-26 05:38
        
        Two fully replicated designs? Helmut 2014-12-27 15:52