Bioequivalence and Bioavailability Forum

Group effect: the endless story [General Sta­tis­tics]

posted by Helmut  – Vienna, Austria, 2019-12-22 11:30 (1817 d 03:41 ago) – Posting: # 21015
Views: 9,201

Hi Nastia,

❝ Recently I've known that Belorussian experts referring to EAEC rules require to recalculate the results of large studies using FDA's Model II, that is: Group, Sequence, Treatment, Period(Group), Group×Sequence as fixed and Subject(Group×Sequence) as Random though it was not stated in protocol beforehand.

Regulators are always right.

❝ I don't think it is a good idea. Moreover it could be contagious! What do you think about it?

Recalculating a study is never a good idea. Entire α already spent, right?

❝ Critical points: as standard model requires Sequence, Treatment, Period and Subject(Sequence) as fixed terms, the results of the random effect model obviously will be different.

Possible but only to a (very) small degree.

❝ What if they will change the overall result of BE?

You mean that the fixed model passes and the mixed model fails? Cannot imagine to happen (see below).

❝ What if the Group×Sequence effect would be significant by chance?

Not even the FDA asks for testing Group×Sequence in Model II.

❝ How to deal with excluded subjects? For example, if we have a subject with only one period the fixed-effect model would automatically neglect it while the random-effect model would use it.

Yep. On the other hand, the residual variance in the mixed model should not be larger than the one of fixed model. I had a few cases in the past where European regulators asked for recalculation according to the new GL (the mixed model was my standard before). The CI was sometimes narrower but differed only in the second decimal place…

❝ As I understand currently it is impossible to calculate it via R, isn't it?

I agree with PharmCat. Doable in R.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• Group by sequence interaction Mutasim 2019-08-07 13:16 [General Sta­tis­tics] 
  • Group by sequence interaction, an urban myth? Helmut 2019-08-07 14:35
    • pristine, genuine, holy, magnificent, inexplicable beautiful variation ElMaestro 2019-08-08 10:06
      • I love your subject line! Helmut 2019-08-08 10:31
        • Group effect, did you miss it? Astea 2019-12-21 14:12
          • Group effect, did you miss it? PharmCat 2019-12-22 01:37
          • Group effect: the endless storyHelmut 2019-12-22 10:30
            • Group effect: the endless river Astea 2019-12-22 21:23
              • Group effect: the endless river PharmCat 2019-12-22 22:52
              • replicateBE solution with interactions mittyri 2019-12-23 14:30
                • replicateBE solution with interactions Astea 2019-12-23 17:26
                  • datasets issues mittyri 2019-12-24 10:53
                  • datasets Helmut 2019-12-24 11:03
                    • datasets Astea 2019-12-24 19:18
                      • lmer / lme Helmut 2019-12-25 19:12
          • What do you mean exactly? Beholder 2019-12-27 13:44
            • What do you mean exactly? Astea 2019-12-29 21:59
              • ANOVA acc. to GL Helmut 2019-12-30 12:32