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RE: [NMusers] Problem of STS in NONMEM

From: Standing Joseph (GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUS <joseph.standing_at_nhs.net>
Date: Tue, 22 Dec 2015 12:05:02 +0000

Dear Anyue,

I think you are trying to make a short-cut to getting individual parameter =
estimates in one go. It maybe possible for someone more intelligent than m=
e, but can I suggest just doing it the long way round by fitting the model =
to each individual in turn. Something like this should work if you use R:

two.st.par <- NULL
for(i in c(1:10)){
  all.data <- read.csv("ALLDATA.csv",h=T)
  one.data <- all.data[all.data$ID==i,]
  write.csv(one.data,"i.data.csv",row.names=F,quote=F) # set $DATA i.da=
ta.csv in your control stream
  # Summons NONMEM - I think in windows you might use shell rather than sys=
tem?
  system("nmfe73 run1.mod run1.lst",wait=TRUE) # Set $OMEGA 0 FIX in your=
 model file, estimate residual with e.g. $SIGMA 0.1
  param.out <- read.table("run1.ext",skip=1,h=T)
  param.out <- param.out[param.out$ITERATION==-1000000000,]
  param.out <- c(param.out$THETA1,param.out$THETA2)
  two.st.par <- rbind(two.st.par,param.out)
}


then two.st.par contains individual parameter ests for each individual.

Best wishes,

Joe


Joseph F Standing
MRC Fellow, UCL Institute of Child Health
Antimicrobial Pharmacist, Great Ormond Street Hospital
Tel: +44(0)207 905 2370
Mobile: +44(0)7970 572435
________________________________________
From: owner-nmusers_at_globomaxnm.com [owner-nmusers_at_globomaxnm.com] On Behalf=
 Of Anyue Yin [anyueyin929_at_gmail.com]
Sent: 22 December 2015 10:32
To: Mats Karlsson; Mills, Richard; Jeroen Elassaiss-Schaap (PD-value B.V.);=
 R.terHeine_at_radboudumc.nl
Cc: nmusers_at_globomaxnm.com
Subject: Re: [NMusers] Problem of STS in NONMEM

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=
 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 e=
ach individual data, so I will be able to get 10 individual parameter estim=
ates. But I found that these 10 individual parameter estimates were all aro=
und the initial value what I assigned to the THETA. For example, if I assig=
n 20 to the initial value of THETA, then these 10 parameter estimates are a=
ll around 20. If I assign 30, then all around 30... It looks like NONMEM us=
es initial value of THETA as prior to estimate individual parameters. What =
I expect is to estimate individual parameters by ID, as if these 10 subject=
s 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=
<mailto:Mats.Karlsson_at_farmbio.uu.se>> wrote:
Dear Anyue,

I don’t know what you mean by “the individual parameter estimate change=
d 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 c=
hange. 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 w=
ould use MAXEVAL=0, not MAXEVAL=9999. Possibly I would use MAXEVAL=99=
99 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<tel:%2B46%2018%204714105>
Fax + 46 18 4714003<tel:%2B%2046%2018%204714003>
www.farmbio.uu.se/research/researchgroups/pharmacometrics/<http://www.farmb=
io.uu.se/research/researchgroups/pharmacometrics/>

From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [ma=
ilto: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<mailto: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 t=
o allow estimation.

Kind regards,
Richard
Richard Mills PhD
Senior Scientist, PKPDM&S
 [cid:image001.jpg_at_01D13CA4.38DCE9C0]

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From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [ma=
ilto: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 individ=
ual parameter estimates. I would like to let NONMEM estimate individual par=
ameter one subject by one subject. My control stream is partially listed be=
low, which is edited according to this thread http://www.cognigencorp.com/n=
onmem/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) ONEHEA=
DER NOPRINT FILE=sdtab101.tab

The model can run successfully, and I got individual parameter estimates fr=
om 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 =
regarded the initial value fixed (just like a fixed typical value). But I e=
xpected NONMEM to estimate individual parameters based on individual data r=
ather 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 - 07:05:02 EST

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