NONMEM Users Network Archive

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Re: Simulation with uncertainty + estimation

From: Gastonguay, Marc <marcg>
Date: Thu, 8 Apr 2010 08:43:52 -0400

Matts,
You should be cautious about implementing this example as you've =
parameterized the model. There is an inconsistency between your model =
parameterization and the multivariate-normal assumption made when you =
use the var-cov matrix of the estimates to incorporate parameter =
uncertainty. See earlier discussions on this topic:
http://www.cognigencorp.com/nonmem/current/2009-July/1816.html

Marc


On Apr 8, 2010, at 4:20 AM, Kågedal, Matts wrote:

>
> Hi all,
> A model for simulation with uncertainty was previously posted by Mats =
Karlsson in this forum.
> After a few bug fixes (with help from Mats) it now actually works. See =
below:
> Matts Kågedal
> AstraZeneca
>
> $PROB
> $DATA data1.csv IGNORE=
> $INPUT ID DV TIME XVCL XVV AMT
>
> ;data1=
> ; 1 0 0 0 0 100
> ; 1 0 1 0 0 0
> ; 1 0 21 0 0 0
> ; 2 0 0 0 0 100
> ; etc
> $SIM (20090726 NEW) SUBPROBLEMS=30 ;
> $THETA ; estimates of THETA and OMEGA from previous run
> (0,1) ; POP_CL theta1
> (0,10) ; POP_V theta2
> $OMEGA
> 0.01 ; PPV_CL eta1
> 0.01 ; PPV_V eta2
> ;variance-covariance matrix of the THETA estimates from previous run
> $OMEGA BLOCK(2)
> 0.02 ; UNC_POP_CL eta3
> 0.0001 0.2 FIX; UNC_POP_V eta 4
>
> $SIGMA .001
> $SUB ADVAN1
> $PK
> CL=THETA(1)*EXP(ETA(1)) ;
> V=THETA(2)*EXP(ETA(2)) ;
> ;S1=V
> TCLE=THETA(1); estimated typical value
> TVE=THETA(2); estimated typical value
>
> IF (ICALL.EQ.4.AND.NEWIND.EQ.0) THEN ; do this just once per =
subproblem
> DO WHILE (ETA(3).LT.-.99.OR.ETA(4).LT.-9.9) CALL SIMETA(ETA) =
;resample if "bad" values
> END DO
> TVCL=THETA(1)+ETA(3)
> TVV =THETA(2)+ETA(4)
>
> WRITE (53,*) TVCL, TVV ; Output simulated THETAs to file
> ENDIF
>
> IF (ICALL.EQ.4) THEN ; do this for all simulated values
> CL=TVCL*EXP(ETA(1)) ; with uncertainty for CL
> V =TVV*EXP(ETA(2)) ; with uncertainty for V
> ENDIF
>
> S1=V
> K=CL/V
>
> $ERROR
> Y =F*EXP(EPS(1))
> $INFN
> IF (NEWIND.EQ.0) THEN
> WRITE (52,*) THETA ; Output estimated THETAs to file
> ENDIF
> $EST MAX=9999 METH=1 INTER
>
>
>
>
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Received on Thu Apr 08 2010 - 08:43:52 EDT

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