Bioequivalence and Bioavailability Forum

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

posted by d_labes  – Berlin, Germany, 2015-07-06 13:10 (3478 d 16:35 ago) – Posting: # 15042
Views: 30,075

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 .

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.

Complete thread:

• 3 period full repli­cate Dr_Dan 2015-06-24 13:55 [RSABE / ABEL] 
  • 3 period full replicate ElMaestro 2015-06-24 14:11
  • 3 period full replicate Helmut 2015-06-24 14:29
  • 3 period full replicate d_labes 2015-06-24 14:38
    • 3 period full replicate Dr_Dan 2015-06-24 16:43
      • 3 period full replicate Helmut 2015-06-24 18:00
        • 3 period full replicate ElMaestro 2015-06-24 18:11
          • 3 period full replicate Helmut 2015-06-24 18:25
            • 3 period full replicate d_labes 2015-06-25 08:52
              • 3 period full replicate ElMaestro 2015-06-25 10:37
                • OT d_labes 2015-06-25 11:20
                  • OT ElMaestro 2015-06-25 11:54
                    • OT d_labes 2015-06-25 13:51
      • CVs (borderline OT) Helmut 2015-06-26 13:51
        • CVs (R, T) from pooled CV d_labes 2015-07-02 09:09
          • Answering an un­asked ques­tion Helmut 2015-07-02 13:03
            • Answer to an un­asked answer d_labes 2015-07-02 14:21
              • Bloody typo! Helmut 2015-07-02 14:33
        • CVs (borderline OT) zizou 2015-07-05 19:20
          • Degrees of freedom 3-period full replicated_labes 2015-07-06 11:10
            • Degrees of freedom 3-period full replicate ElMaestro 2015-07-06 11:59
              • Degrees of freedom 3-period full replicate d_labes 2015-07-06 13:53
            • Degrees of freedom 3-period full replicate zizou 2015-07-06 17:25
  • The almighty oracle has spoken! Helmut 2015-07-23 23:54
    • Almighty oracle's mysterious saying d_labes 2015-07-24 08:23