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RE: [NMusers] Problem of STS in NONMEM

From: Mats Karlsson <Mats.Karlsson_at_farmbio.uu.se>
Date: Tue, 22 Dec 2015 09:33:40 +0000

Dear Anyue,

I don’t know what you mean by “the individual parameter estimate changed if I change the initial value of THETA”

If you mean that individual ETA estimates change, that is expected when you change THETA. For CL and V to be the same, ETA need to change when THETA change. It may be that you are at local minima for EBEs. You may want to add MCETA=1000 on the $EST line in order to test more initial estimates. I would use MAXEVAL=0, not MAXEVAL=9999. Possibly I would use MAXEVAL=9999 after having fixed $OMEGA parameters to the high values you use now.

Best regards,
Mats


Mats Karlsson, PhD
Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala

Phone: +46 18 4714105
Fax + 46 18 4714003
www.farmbio.uu.se/research/researchgroups/pharmacometrics/<http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/>

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Mills, Richard
Sent: Tuesday, December 22, 2015 8:54 AM
To: Anyue Yin; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Problem of STS in NONMEM

Hi Anyue,

You need to amend MAXEVAL=0 in $EST (I suggest MAXEVAL=9999) in order to allow estimation.

Kind regards,
Richard
Richard Mills PhD
Senior Scientist, PKPDM&S
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From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Anyue Yin
Sent: 22 December 2015 06:36
To: nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>
Subject: [NMusers] Problem of STS in NONMEM

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




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Received on Tue Dec 22 2015 - 04:33:40 EST

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