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

From: <R.terHeine_at_radboudumc.nl>
Date: Tue, 12 Apr 2016 09:07:07 +0000

Dear Navin Goyal,

Thanks for helping us out. It worked! We performed some clinical trial simulations for probability of target attainment and parameter uncertainty certainly made a difference.

Sincerely,

Rob

Van: Heine, Rob ter
Verzonden: maandag 11 april 2016 19:48
Aan: Navin Goyal
Onderwerp: Re: [NMusers] Some help with simulation with uncertainty using $PRIOR TNPRI

Dear Navin! Thank you a lot! We will try tomorrow and will keep you informed.

Sincerely,
Rob

Van: Navin Goyal <navingoyal_at_gmail.com<mailto:navingoyal_at_gmail.com>>
Datum: Monday, April 11, 2016 at 6:32 PM
Aan: Rob ter Heine <R.terHeine_at_radboudumc.nl<mailto:R.terHeine_at_radboudumc.nl>>
CC: nmusers <nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>>
Onderwerp: Re: [NMusers] Some help with simulation with uncertainty using $PRIOR TNPRI

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<mailto: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’s, eta’s 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 Register of the Chamber of Commerce under file number 41055629.



--
Navin Goyal

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 Register of the Chamber of Commerce under file number 41055629.

Received on Tue Apr 12 2016 - 05:07:07 EDT

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