Bioequivalence and Bioavailability Forum

Dear all,

for higher order designs with more than one treatment the EMA guideline recommends us to use only the data relevant for the comparison under consideration.

My (seems too) naive attempt for obtaining the degrees of freedom (df) of the corresponding ANOVA (without a further decomposition of the subject effect into sequence and subject nested within sequence) for a 4x4 crossover was:

source  df
-------------
total   2N-1  (2*N values for a pair)
-------------
tmt      1    (2 treatments a pair)
period   3    (4 periods, no recoding)
subject N-1
-------------
MSerr   N-4
Looks correct?

But on the output of my SAS dragon for a 4x4 study with 12 subjects and the sequences (Williams design, A=T1, B=T2, C=T3, D=R)
CDBA
DACB
BCAD
ABDC
I see the following df for the pairs:
      A vs D
      C vs D  B vs D
tmt     1       1
period  3       2
Mserr   8       9


Any idea what's going on here?