NONMEM Unexpected result with the $LEVEL statement

3 messages 2 people Latest: Aug 22, 2019

NONMEM Unexpected result with the $LEVEL statement

From: Thomas Dumortier Date: August 13, 2019 technical
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 [email protected]<mailto:[email protected]>

Re: NONMEM Unexpected result with the $LEVEL statement

From: Leonid Gibiansky Date: August 13, 2019 technical
You need to use FNLETA=0 option. Thanks Leonid
Quoted reply history
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 > > [email protected] <mailto:[email protected]>__

RE: NONMEM Unexpected result with the $LEVEL statement

From: Thomas Dumortier Date: August 22, 2019 technical
Hello Leonid, Your solution (FNLETA=0 in the $EST statement) works very well: The EBEs for the random study effects (ETA9) make now sense: all IDs of the same study has the same estimated ETA9 value. Many thanks for your help Best regards, Thomas Dumortier Director Pharmacometrics Novartis Pharma AG Postfach CH-4002 Basel SWITZERLAND Phone +41 61 3240946 Fax +41 61 3241246 [email protected]
Quoted reply history
-----Original Message----- From: Leonid Gibiansky <[email protected]> Sent: Tuesday, August 13, 2019 10:56 PM To: Dumortier, Thomas <[email protected]>; [email protected] Subject: Re: [NMusers] NONMEM Unexpected result with the $LEVEL statement 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 > > [email protected] <mailto:[email protected]>__ >