Degrees of freedom 3-period full replicate [RSABE / ABEL]

posted by d_labes  – Berlin, Germany, 2015-07-06 11:10 (2302 d 21:47 ago) – Posting: # 15042
Views: 24,717

Dear Zizou!

Did you check the output from your SAS code against your degrees of freedom tables?

Here an example:
Scott Patterson and Byron Jones
"Bioequivalence and Statistics in Clinical Pharmacology"
Chapman and Hall/CRC Press: Boca Raton, London and New York, 2005

/*EXAMPLE 4.2*/
74 subjects, 3 periods, sequences TRR/RTT, unfortunately unbalanced with 35/39 subjects
PK metric Cmax without missings

Your SAS code according to the EMA crippled model with Proc GLM gives:
                   degrees of freedom
source                type I  type III
subject                73       72
  -sequence             1        0
  -subject(sequence)   72       72
period                  1        1
error                  34       34
total                 108      108

The type III df=0 for sequence or the changing df for subjects effects illustrates the typical mess with the EMA model.

Some differences to yours w.r.t. subject and total :cool:.

Fortunately the df's for the intra-subject variability of the reference don't play a role in the EMA recommended method for scaling of the BE acceptance ranges.

BTW: Your df's are correct for sequence balanced designs, if you use only the data for subjects with replicates of the Reference or if you evaluate via intra-subject contrasts like in the FDA recommended evaluation according to the progesterone guidance.

Regards,

Detlew

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