Jun,

In addition to Elodie's clear explanation of the basic process of using $SIM and $EST in the same control stream you may wish to know that you don't have to use the same parameters for simulation as those used for estimation. The ICALL variable has a value of 4 when NONMEM is simulating so you can do this:

$THETA
1 FIX ; sim_CL
10 ; est_CL

$PK

IF (ICALL.EQ.4) THEN ; for simulation
CL=THETA(1)
ELSE ; for estimation
CL=THETA(2)
ENDIF

Nick


Elodie Plan wrote:

Dear Jun,

When $SIM and $EST on the same model file, the simulation will be run first, based on initial values, and then, afterwards, the estimation of the simulated data will be done, that’s it, no further re-simulation based on the estimated parameters will follow.

So what you should do is first to analyze your observed data in an estimation model file, and then report your estimated parameters as initial values to run your simulation-estimation study; this allows you to compare estimates of real data to estimates of simulated data, so to check simulation properties of your model.

I hope this helps,

Elodie

/ Elodie Plan, PharmD, MSc, ///

/ PhDstudent// ///

/*****************************************///

/Div. of Pharmacokinetics and Drug Therapy,
Department of Pharmaceutical Biosciences,
Faculty of Pharmacy, //Uppsala University/

/ PO - Box 591 - 751 24 //Uppsala - SWEDEN/

/Office +46 18 4714385 - Fax +46 18 4714003
------------------------------------------------------------///

*From:* [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] *On Behalf Of *Jun Shen
*Sent:* Wednesday, October 15, 2008 1:01 AM
*To:* nmusers@globomaxnm.com
*Subject:* [NMusers] How $simulation work with $estimation

Dear NMusers,

I wonder how does $Simulation work with $Estimation in NONMEM exactly?
The manual says, NONMEM will simulate DVs and replace the original DVs
based on the parameter initial values. But the initial values are not final
estimates. Does the simulation based on initial values make sense? Do
$Estimation and $Simulation run alternatively? The $Simulation generates a
set of data based on which the parameters are estimated? And then the
predictions are made on the estimated parameters? A little confused.

Appreciate any comment.

Jun


--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)923-6730 fax:+64(9)373-7090
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

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