Bioequivalence and Bioavailability Forum • EMA: ANOVA and replicate studies

EMA: ANOVA and replicate studies [RSABE / ABEL]

posted by ElMaestro – Denmark, 2010-03-06 00:02 (5550 d 10:26 ago) – Posting: # 4869
Views: 27,028

Dear d_labes,

❝ • How do we formulate an ANOVA for replicate designs (or partial

❝ replicate)? Some code highly appreciated, SAS or not SAS is not the

❝ question!

Go to church, pray, and hope for a miracle. Or go to the EMA at their upcoming event for people interested in this guideline and ask 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.

Disagree. You still can get the effects right (in particular we talk sequence, right?) by considering all effects fixed. but you will have to do some manual brain-work still. By the way, there is even in this case a non-trivial issue with that effect. One can rightfully claim it must be null for a type III SS, because type III SS for Seq reflects a model with Per Trt and Subj, and since Subj is nested in Seq, one does not achieve anything by this single term deletion. Compare R's "drop1" with Proc GLM and see the difference.

❝ • 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.

Mixed models or nothing. Church or EMA.
I am not competent to tell if there is a potential gain in the Method of Moments, but I have not seen it working in bioequivalence.

❝ • Can we have an evaluation that is not only EMA accepted? FDA suggests

❝ mixed models in their statistical guidance.

FDA got it right. It's standard. ;-)

❝ 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?

Church or EMA.

When you figure out the answers, please inform us all. I completely agree with your disorientation and I think this is a lapse in the guidance that merits a correction (better sooner than later).
EM.

Complete thread:

EMA: ANOVA and replicate studies d_labes 2010-03-05 10:51
- 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 studiesElMaestro 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