# Re: [NMusers] Problem of STS in NONMEM

From: Anyue Yin <anyueyin929_at_gmail.com>
Date: Tue, 22 Dec 2015 18:32:10 +0800

Dear all,

I am trying to carry out the first stage of Standard Two Stage estimation
method in NONMEM (i.e. estimate individual parameter by ID). For the sake
of argument, let's assume that I have a data file which includes 10
subjects (ID from 1 to 10). Now I wish to estimate individual parameter by
fitting each individual data, so I will be able to get 10 individual
parameter estimates. But I found that these 10 individual parameter
estimates were all around the initial value what I assigned to the THETA.
For example, if I assign 20 to the initial value of THETA, then these 10
parameter estimates are all around 20. If I assign 30, then all around
30... It looks like NONMEM uses initial value of THETA as prior to estimate
individual parameters. What I expect is to estimate individual parameters
by ID, as if these 10 subjects are separated into 10 data file and estimate
10 times to get each result. So the key point of my question is individual
parameter estimation by the first stage of STS in NONMEM. Thank you very
much.

Sincerely,
Anyue

On Tue, Dec 22, 2015 at 5:33 PM, Mats Karlsson <Mats.Karlsson_at_farmbio.uu.se=
>
wrote:

> Dear Anyue,
>
>
>
> I don’t know what you mean by “the individual parameter e=
stimate 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 wa=
nt
> to add MCETA=1000 on the \$EST line in order to test more initial estima=
tes.
> 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/
>
>
>
> *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*
>
> [image: http://emailsignature/stationary/Icon_Development_Solutions.gif]
>
>
>
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> *From:* owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com
> <owner-nmusers_at_globomaxnm.com>] *On Behalf Of *Anyue Yin
> *Sent:* 22 December 2015 06:36
> *To:* 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
>
>
>
>
>
>
> *\$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)
>
>
>
> 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 individu=
al
> data rather than the initial value. Is there anything wrong with the code=
?