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Re: [NMusers] Some help with simulation with uncertainty using $PRIOR TNPRI

From: Navin Goyal <navingoyal_at_gmail.com>
Date: Mon, 11 Apr 2016 12:32:19 -0400

Hi Rob,

This may help. I have used the Theophylline example that comes with the NM
installation - CONTROL5 model.

*Step 1* - You execute that model with only one minor change - addition of
MSFO at the EST step (which generates and stores the information in the
MSFI file you will need during simulation - step2)
$EST MAXEVAL=450 PRINT=5 MSFO=MSFICONTROL5

*Step 2*- The simulation control stream is very similar to the control
stream used for estimation. It has two $PROB sections and few extra
statements, I have italicized the extra statements needed in the simulation
step.
PS. Use the exact same initial estimates as you had in the estimation
control stream in Step 1 (just leave them as they were in the original
control stream). If you change the initial estimates, the simulation step
will not work.

$PROB THEOPHYLLINE POPULATION DATA
$INPUT ID DOSE=AMT TIME CP=DV WT
$DATA THEOPP
*$PRIOR TNPRI (PROBLEM 2) PLEV=.999 IVAR=1*
$SUBROUTINES ADVAN2
*$MSFI MSFICONTROL5 ONLYREAD ;; uses the msfi file generated during model
fitting*
$PK
   CALLFL=1
   KA=THETA(1)+ETA(1)
   K=THETA(2)+ETA(2)
   CL=THETA(3)*WT+ETA(3)
   SC=CL/K/WT
ISIM =IREP

$ERROR
   Y=F+EPS(1)


*$PROBLEM Sim part *
*$INPUT ID DOSE=AMT TIME CP=DV WT *
*$DATA THEOPP REWIND*

$THETA (.1,3,5) (.008,.08,.5) (.004,.04,.9)
$OMEGA BLOCK(3) 6 .005 .0002 .3 .006 .4
$SIGMA .4

*$SIM (12345) ONLY NSUB=5 TRUE=PRIOR*
;$EST MAXEVAL=450 PRINT=5 MSFO=MSFICONTROL5 ;; commented out =
in
step 2
;$COV ;; commented out in step 2
$TABLE ISIM ID DOSE WT TIME FILE=sdtab5_uncertainty


As far as I can remember, control streams from Step 1 and 2 need to be run
within same NM version. You cannot fit a model in version 7.1 and then
simulate using ver 7.2 or 7.3 to use the $TNPRI option.


Good luck!
--
Navin Goyal

On Mon, Apr 11, 2016 at 9:38 AM, <R.terHeine_at_radboudumc.nl> wrote:

> Dear all,
>
> I would like to perform a simulation (based on a finished model),
> incorporating parameter uncertainty (for all theta‚Äôs, eta‚Ä=
ôs and epsilons)
> with the $PRIOR TNPRI option in Nonmem V7.3, using the results of the
> covariance step as an input. I am still struggling how to implement this.
> Does anybody have an example control stream I could look at?
>
> Sincerely,
>
> Rob ter Heine
>
> Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het
> handelsregister onder nummer 41055629.
> The Radboud university medical center is listed in the Commercial Registe=
r
> of the Chamber of Commerce under file number 41055629.
>



--
Navin Goyal

Received on Mon Apr 11 2016 - 12:32:19 EDT

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