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Re: [NMusers] Problem of STS in NONMEM

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Tue, 22 Dec 2015 08:40:02 -0500

You may try to remove eta3. As you set it now, you allow very large residual=
 error, and nonmem returns initial estimates as final
Leonid



> On Dec 22, 2015, at 5:32 AM, Anyue Yin <anyueyin929_at_gmail.com> wrote:
>
> Dear all,
>
> Thanks for replying me.
>
> I am trying to carry out the first stage of Standard Two Stage estimation m=
ethod in NONMEM (i.e. estimate individual parameter by ID). For the sake of a=
rgument, 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 i=
ndividual data, so I will be able to get 10 individual parameter estimates. B=
ut I found that these 10 individual parameter estimates were all around the i=
nitial value what I assigned to the THETA. For example, if I assign 20 to th=
e initial value of THETA, then these 10 parameter estimates are all around 2=
0. If I assign 30, then all around 30... It looks like NONMEM uses initial v=
alue of THETA as prior to estimate individual parameters. What I expect is t=
o estimate individual parameters by ID, as if these 10 subjects are separate=
d into 10 data file and estimate 10 times to get each result. So the key poi=
nt of my question is individual parameter estimation by the first stage of S=
TS 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 y=
ou change THETA. For CL and V to be the same, ETA need to change when THETA c=
hange. It may be that you are at local minima for EBEs. You may want to add M=
CETA=1000 on the $EST line in order to test more initial estimates. I woul=
d use MAXEVAL=0, not MAXEVAL=9999. Possibly I would use MAXEVAL=9999 a=
fter 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] O=
n 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
>>
>> <image001.jpg>
>>
>>
>>
>> ICON plc made the following annotations.
>>
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>> From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] O=
n 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 indiv=
idual parameter estimates. I would like to let NONMEM estimate individual pa=
rameter one subject by one subject. My control stream is partially listed be=
low, which is edited according to this thread http://www.cognigencorp.com/no=
nmem/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) ONEH=
EADER NOPRINT FILE=sdtab101.tab
>>
>>
>>
>> The model can run successfully, and I got individual parameter estimates f=
rom output file. I found that for each subject the individual parameter esti=
mate changed if I change the initial value of THETA. It seems that NONMEM r=
egarded the initial value fixed (just like a fixed typical value). But I exp=
ected NONMEM to estimate individual parameters based on individual data rath=
er than the initial value. Is there anything wrong with the code? Thanks in a=
dvance.
>>
>>
>>
>> Anyue
>>
>>
>>
>
>

Received on Tue Dec 22 2015 - 08:40:02 EST

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