Group effect in replicate study

Phoenix Certara Forums Phoenix WNL basics
1

We conducted a replicate study which is RRT, RTR and TRR. We completed 90%CI with default setting, such as attachments. However, the study was completed with 5 groups, so that I want to know how group effect is analyzed. I have searched BABE forum for couple of days. but still can not get the answer. Would anyone please guide me how to do it in the WLN? thank you.

I have seen a paper use: Group+Sequence+Period+Treatment+Random errors where Random errors is Random within and between subject errors. However, what about Formulation*Group such in the 2x2 crossover study? I am not so sure it is correct.

Charlie

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Dear All:

Due to cannot find out the answer for group effet in the replicated study, we are considering to use following SAS code to analysis the 2x3x3 replicated study with 5 groups

proc mixed data=mydata;
class Seq Subject Period Drug batch;
model ln_AUC0_t= Group Sequence Period(Group) Subject(SequenceGroup) Formulation FormulationGroup/ ddfm=satterth;
random Drug/type=FA0(2) sub=Subject G;
repeated/grp=Drug sub=Subject;
estimate ‘test-ref’ Drug -1 1/ CL alpha=0.10;
title ‘lnAUC0-t’ ;
ods output Estimates=out1;
run;

We have modified the default setting of Phoenix WinNonlin and put “Group Sequence Period(Group) Formulation FormulationGroup" as fixed effects, however, we can not figure out how to deal with "Subject(SequenceGroup)” effect. In default setting, a random terms for FormulationSubject is already existing, therefore, we added another random effect for Subject(SequenceGroup), but result shows same as before the effect was added. Does it mean that the effect we do not condider in the model?

3

Dear Tsang,

it is very strange that you didn’t find the model in BEBAC.

Citing the Guru:

  • Group model I:
  • fixed: Group+Sequence+Sequence(Group)+Period(Group)+Treatment+Treatment×Group
    random: Subject(Sequence×Group)
    If the Treatment-by-Group term is not significant (p ≥0.1) this term can be dropped from the model, proceeding to Group Model II.
    If the Treatment-by-Group term is significant (p <0.1), FDA’s Division of Bioequivalence requests that equiva ­lence be demonstrated in one of the groups, provided that the group meets minimum requirements for a com ­plete BE study (i.e., 12).
  • Group model II:
    fixed: Group+Sequence+Sequence(Group)+Period(Group)+Treatment
    random: Subject(Sequence×Group)