## Group effects obsolete? [Two-Stage / GS Designs]

Dear Helmut!

» I have seen some FDA code a good while ago:
» PROC GLM DATA = DATASET;
»   CLASS SUB TRT PER SEQ GRP;
»   MODEL Y = GRP SEQ SEQ*GRP SUBJ(SEQ*GRP) PER(GRP) TRT TRT*GRP /SS3;
»   RANDOM SUBJ(SEQ*GRP);
»   TEST H = SEQ GRP E = SUBJ(SEQ*GRP)/HTYPE=3 ETYPE=3;
»   ESTIMATE 'T VS R' TRT 1 -1;
»   LSMEANS TRT/STDERR PDIFF CL ALPHA=.1;
» RUN;

Yep. Implementation of what is written in the letter.
But IMHO the RANDOM statement is superfluous since it doesn't do anything other than printing a symbolic representation of expected mean squares. If one is really interested in having a random effect for subj(seq*group) Proc MIXED should be used.

» Followed by:
» ...
Same wording in the letter I have.

But the most interesting part of my letter:
"If all of the following criteria are met, it may not be necessary to test for group effects in the model:
• the clinical study takes place at one site;
• all study subjects have been recruited from the same enrollment pool;
• all of the subjects have similar demographics; and
• all enrolled subjects are randomly assigned to treatment groups at study outset
In this latter case, the appropriate statistical model would include only the factors Sequence, Period, Treatment and Subject(nested within sequence."

Can't imagine BE studies where this is not true, except multi-center studies, but these are rare for BE evaluation.
So what? Group effects are a Chimera?

» » BTW: Helmut, how had you planned the evaluation of the second stage, if it would be necessary?
»
» Probably too naïvely:
» fixed:  sequence, treatment, stage, period, group,
»         group × treatment, stage × treatment
» random: subject(sequence × stage)

Too naïvely may be true .

Regards,

Detlew