Bioequivalence and Bioavailability Forum • EMA: ANOVA and replicate studies

EMA: ANOVA and replicate studies [RSABE / ABEL]

posted by d_labes – Berlin, Germany, 2010-03-05 11:51 (5164 d 06:45 ago) – Posting: # 4864
Views: 26,965

Dear all,

after reading the tons of answers to the comments regarding the DRAFT of the new EMA Guidance I am more and more confused.

As Helmut has already noted they insists on using ANOVA, ANOVA, ANOVA ... and nothing else in the statistical evaluation of bioequivalence (in SAS speak Proc GLM or for Rusers function lm()). And more over all effects in the ANOVA as fixed!

Beside their joke "It is out of the scope of the guideline to give details on how to analyse the data of a replicate design, since it is standard statistical analysis " in the comments I would ask the community:

How do we formulate an ANOVA for replicate designs (or partial replicate)? Some code highly appreciated, SAS or not SAS is not the question!
How do we get the right ("appropriate") tests for the effects in the ANOVA with all effects fixed? In fixed effects models the denominator is always the MS(error) term as far as I know.
From where do we get the intra-individual variabilities within Test or Reference? One of the ANOVA assumptions is equal variabilities within groups I think.
Can we have an evaluation that is not only EMA accepted? FDA suggests mixed models in their statistical guidance.

I had used the FDA code for replicate designs up to now. But it relies definitely on mixed model (i.e. assuming subject as a random effect, factor) and thus on more elaborate and sophistic statistical method, but lacking anything that looks like ANOVA table. But this now obsolete in the light of the new EMA guidance! :crying:

So how to react? How to proceed with replicate studies practically, technically ... to be EMA conform?

—
Regards,

Detlew

Complete thread:

EMA: ANOVA and replicate studiesd_labes 2010-03-05 10:51 [RSABE / ABEL]
- EMA: ANOVA and replicate studies Helmut 2010-03-05 14:17
  - Orouboros mixed up d_labes 2010-03-09 09:33
    - Orouboros mixed up Helmut 2010-03-09 14:55
      - Liu ANOVA PtC d_labes 2010-03-11 11:07
      - A walk on the wild side - the Bear way d_labes 2010-03-26 14:01
        
        New adventures from the Bear way d_labes 2010-03-29 16:17
        
        New adventures from the Bear way ElMaestro 2010-03-29 17:26
        
        Posology Helmut 2010-03-29 18:41
        
        Lost on the Bear way d_labes 2010-03-30 09:20
        
        Lost on the Bear way ElMaestro 2010-03-30 16:01
        
        Nice looking three-headed hydra mutant d_labes 2010-04-01 15:20
- EMA: ANOVA and replicate studies ElMaestro 2010-03-05 23:02
  - Prayers quest d_labes 2010-03-09 09:02
    - Go for the referral ElMaestro 2010-03-09 19:02
- EMA: ANOVA and replicate studies yjlee168 2010-03-08 03:23
  - R: aov(), lm() and what does it mean? d_labes 2010-03-09 08:52