SAS Proc Mixed coding, replicate design [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2008-03-11 10:43 (5751 d 18:50 ago) – Posting: # 1678
Views: 14,161

Dear Matz,

❝ One doubt ...

the deeper the thoughts, the numerously the questions ;-) .

❝ How can I include a SUB(SEQ) term in the above SAS code?.

SUB(SEQ) is the random subject term in the syntax of PROC GLM in case of a 2x2 cross over.
It is included in the PROC MIXED code but by different syntax.
If you need comparable code you can go with:
PROC MIXED data=yours;
  class treatment period sequence subject;
  model lnPKParam=treatment period sequence / DDFM=KR;
  random subject(sequence) subject*treatment;

But with that you loose the disparate variance terms (between and within) for the formulations under study.

❝ Why the covariance structure FA0(2) is used in this code?.Why not the other covariance structures?

The FA0(2) structure is chosen to ensure a positive definite covariance matrix, what ever this means to us as run-of-the-mill statisticians (in german: Feld-Wald-und-Wiesen-) ;-) .
Roughly spoken it ensures variance terms in the model that are >0, a very reasonable assumption for such terms I think :-D .
Type=CSH (heterogenous compound symmetry) is mentioned in the FDA guidance also.
Both parameterizations should be theoretically the same.
Even type UN (unstructured) may be used, but suffer from sometimes negative estimates of variance components and is therefore not recommended in the FDA guidance.

❝ Is there any method to choose the covariance structure?

This is too wide a subject and goes beyond the themes discussed here. Keywords are 'likelihood ratio test' and 'information criteria'. Ask the great mahatma Goooooogle.

❝ Why DDFM=satterth ? Why not DDFM=kenwardroger?.

Seems the personal view of the author(s?) of the FDA guidance.
The book

B Jones and MG Kenward
Design and Analysis of Cross-over Trials
Chapman & Hall/CRC, Boca Raton (2nd ed. 2003)

uses DDFM=KR (abbreviations, abbreviations, abbreviations ...) most time. Not so astonishing in looking at the second author :yes: .

So if you need deeper insight, I recommend this book and once again (see above) the papers by
Patterson and Jones
GSK BDS Technical Report 2002 – 01 (part I)
GSK BDS Technical Report 2002 – 05 (part II)

Edit: Updated URLs. [Helmut]



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