Group effect: the endless story [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2019-12-22 10:30  – Posting: # 21015
Views: 2,221

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. :-D

» 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.

Cheers,
Helmut Schütz
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