Re: [NMusers] Problem of STS in NONMEM

From: Jeroen Elassaiss-Schaap (PD-value B.V.) <"Jeroen>
Date: Tue, 22 Dec 2015 10:26:15 +0100

Dear Anyue,

It has been a long time since I used this method. Nowadays NONMEM has
much added functionality, such as the non-parameteric step and the
possibility to repeat problems over individuals in your dataset. My
advise would actually be to use those. The latter especially gives you a
much cleaner implementation of extended least squares if that is what
you are looking for.

Anyway, your code seems fine. Your entries into $THETA and $SIGMA
however do matter. I would suggest to run this once, and than take the
median of parameters and input that into $THETA. Also take the variance
of residuals and put that number into $SIGMA. Now run it again, and the
result should be unbiased. I do not have a reference for this recipe,
please use this at your own discretion.

Hope this helps,
Jeroen

http://pd-value.com
jeroen_at_pd-value.com
_at_PD_value
+31 6 23118438
-- More value out of your data!



On 12/22/2015 07:36 AM, Anyue Yin wrote:
> Dear all,
>
> I got a problem when using NONMEM with STS method. My aim is to get
> individual parameter estimates. I would like to let NONMEM estimate
> individual parameter one subject by one subject. My control stream is
> partially listed below, which is edited according to this thread
> http://www.cognigencorp.com/nonmem/nmo/topic035.html
>
> /$SUBROUTINES ADVAN1 TRANS2/
> /
> /
> /$PK/
> /CL = THETA(1) * EXP(ETA(1))/
> /V = THETA(2) * EXP(ETA(2))/
> /S1 = V/
> /
> /
> /$ERROR/
> /IPRED = F/
> / W = F/
> / Y = IPRED*(1+EXP(ETA(3))*EPS(1))/
> / IRES = DV-IPRED/
> /IWRES = IRES/W/
> /
> /
> /$THETA/
> /(10,20,30) ; CL/
> /(10,80,100) ; V/
> /
> /
> /$OMEGA/
> /100 ; IIV CL/
> /100 ; IIV V/
> /100 ; IIV SIGMA/
> /
> /
> /$SIGMA/
> /1 FIXED ; PRO/
> /$EST METHOD=1 INTER MAXEVAL=0 NOABORT SIG=3 PRINT=1 POSTHOC/
> /$COV/
> /$TABLE ID TIME AMT CMT DV PRED IPRED IWRES CL V ETA(1) ETA(2) ETA(3)
> ONEHEADER NOPRINT FILE=sdtab101.tab/
>
> The model can run successfully, and I got individual parameter
> estimates from output file. I found that for each subject the
> individual parameter estimate changed if I change the initial value
> of THETA. It seems that NONMEM regarded the initial value fixed (just
> like a fixed typical value). But I expected NONMEM to estimate
> individual parameters based on individual data rather than the initial
> value. Is there anything wrong with the code? Thanks in advance.
>
> Anyue


Received on Tue Dec 22 2015 - 04:26:15 EST

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