You need to use FNLETA=0 option.
Thanks
Leonid

On 8/13/2019 4:39 PM, Dumortier, Thomas wrote:
Hello

I would like to model inter-study variability on the of the inter-subject variability  with NONMEM 74

A subject belongs to a study, therefore those two random effects are nested

Following the instruction, I code  as below, where ETA8 is at the subject level and ETA9 is at the study (STUD) level.

$INPUT      ID STUD TIME TIM2 TAD NT CMT EVID MDV BLOQ AMT DOSE RATE LIDV=DV LNDV WT0 TRT1S TRT2S PAS0

...

$PK

...

     TVF1 = THETA(8) + ETA(8) + ETA(9)

     F1  = (EXP(TVF1)/(1+EXP(TVF1)))

...

$LEVEL STUD=(9[8])

The fit with NONMEM 743 (fortran compliler) seems correct and the estimates for the variance (OMEGA) of ETA8 and for ETA9 are provided.

But when looking at the ETA9 values (the empirical bayes estimates), I notice that

(1)Different subjects of the same study have different ETA9 values, while I would expect that all subjects of a study have same ETA9 value

(2)The ETA9 value is proportional to the ETA8 value (ie, plotting ETA8 versus ETA9 from all subjects of all studiers results in all points on the same diagonal line)

Am I coding incorrectly ?

Any help would be more than welcome

Many thanks

Thomas Dumortier

*Thomas Dumortier*

Director Pharmacometrics

Novartis Pharma AG

Postfach

CH-4002 Basel

SWITZERLAND

Phone   +41 61 3240946

Fax         +41 61 3241246

thomas.dumort...@novartis.com <mailto:thomas.dumort...@novartis.com>__


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