Dear NM-Users,
I'm a NONMEM beginner. The following are my control stream for a monoclonal
antibody which clears via target mediated disposition. However, when I ran
NONMEM, I didn't get minimization successful message (in fact, no message
at all), there are also no Table output and the xx.g77 file contains only
empty three output files. I will be appriciated if someone help
to find mistakes. Thanks.
Peggy
---------------------------------------------------------------------------------------------------------------------------------------
$PROBLEM **base model**
$DATA PKDATA.CSV IGNORE=C
$INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=2 NPAR=6
;COMP=(CENTRAL DEFOBSERVATION DEFDOSE)
;COMP=(PERIPH)
$PK
TVVMAX=THETA(1)
VMAX=TVVMAX*EXP(ETA(1))
KM=THETA(2)
TVV1=THETA(3)
V1=TVV1*EXP(ETA(2))
TVV2=THETA(4)
V2=TVV2*EXP(ETA(3))
Q=THETA(5)*EXP(ETA(4))
S1=V1
$DES
C1=A(1)/V1
C2=A(2)/V2
DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2)
DADT(2)=(Q*C1)-(Q*C2)
$ERROR
CALLFL=0
IPRED=LOG(F)
IRES=DV-IPRED
IWRES=IRES/IPRED
Y=IPRED+ERR(1)
$THETA
(0.1, 1.49, 5) ;VMAX (mg/hr)
(1, 50,300) ;KM (μg/mL)
(1.3, 2.72, 5) ;V1 (L)
(1.1, 2.43, 5) ;V2 (L)
(0.001, 0.095, 1) ;Q (L/hr)
$OMEGA .025 ;VMAX
$OMEGA .032 ;V1
$OMEGA .29 ;V2
$OMEGA .975 ;Q
$SIGMA
0.030 ;ERR(1)
$ESTIMATION METH=1 MAXEVAL=9999 PRINT=5 POSTHOC
$COVARIANCE
$TABLE ID TIME DV IPRED IWRES VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 BW AGE
NOPRINT ONEHEADER FILE=1.fit
$TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1
$TABLE ID VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 NOPRINT ONEHEADER FILE=patab1
$TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
----------------------------------------------------------------------------------------------------------------------------------
#IDTIMEAMT
NDV
LNDV
EVIDMDVCMTBWAGEDOSEA-P001081.3..11181.35081.3A-P0010.254.81.568616181.350
81.3A-P0011182.890372181.350
81.3
LNDV=Ln-transformed
con. (mcg/ml)
No message
Hi Peggy,
You need to define your compartments properly. You shouldn’t have a
semi-colon before them. You may try this;
$MODEL NCOMP=2 NPAR=6
COMP=(CENTRAL, DEFOBS, DEFDOSE)
COMP=(PERIPH)
Sincerely,
Ahmad Abuhelwa, PhD Candidate
Australian Center for Pharmacometrics |P1-09| Playford Building
School of Pharmacy and Medical Sciences
University of South Australia- City East Campus
Adelaide, South Australia
Australia
Email:
[email protected]<mailto:[email protected]>
Mobile: +61 413118743
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Chiaying Lin
Sent: Tuesday, 25 August 2015 10:46 AM
To: [email protected]
Subject: [NMusers] No message
Dear NM-Users,
I'm a NONMEM beginner. The following are my control stream for a monoclonal
antibody which clears via target mediated disposition. However, when I ran
NONMEM, I didn't get minimization successful message (in fact, no message at
all), there are also no Table output and the xx.g77 file contains only empty
three output files. I will be appriciated if someone help to find mistakes.
Thanks.
Peggy
---------------------------------------------------------------------------------------------------------------------------------------
$PROBLEM **base model**
$DATA PKDATA.CSV IGNORE=C
$INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=2 NPAR=6
;COMP=(CENTRAL DEFOBSERVATION DEFDOSE)
;COMP=(PERIPH)
$PK
TVVMAX=THETA(1)
VMAX=TVVMAX*EXP(ETA(1))
KM=THETA(2)
TVV1=THETA(3)
V1=TVV1*EXP(ETA(2))
TVV2=THETA(4)
V2=TVV2*EXP(ETA(3))
Q=THETA(5)*EXP(ETA(4))
S1=V1
$DES
C1=A(1)/V1
C2=A(2)/V2
DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2)
DADT(2)=(Q*C1)-(Q*C2)
$ERROR
CALLFL=0
IPRED=LOG(F)
IRES=DV-IPRED
IWRES=IRES/IPRED
Y=IPRED+ERR(1)
$THETA
(0.1, 1.49, 5) ;VMAX (mg/hr)
(1, 50,300) ;KM (μg/mL)
(1.3, 2.72, 5) ;V1 (L)
(1.1, 2.43, 5) ;V2 (L)
(0.001, 0.095, 1) ;Q (L/hr)
$OMEGA .025 ;VMAX
$OMEGA .032 ;V1
$OMEGA .29 ;V2
$OMEGA .975 ;Q
$SIGMA
0.030 ;ERR(1)
$ESTIMATION METH=1 MAXEVAL=9999 PRINT=5 POSTHOC
$COVARIANCE
$TABLE ID TIME DV IPRED IWRES VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 BW AGE
NOPRINT ONEHEADER FILE=1.fit
$TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1
$TABLE ID VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 NOPRINT ONEHEADER FILE=patab1
$TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
----------------------------------------------------------------------------------------------------------------------------------
#ID
TIME
AMT
NDV
LNDV
EVID
MDV
CMT
BW
AGE
DOSE
A-P001
0
81.3
.
.
1
1
1
81.3
50
81.3
A-P001
0.25
4.8
1.568616
1
81.3
50
81.3
A-P001
1
18
2.890372
1
81.3
50
81.3
LNDV=Ln-transformed con. (mcg/ml)
Please see my comments inserted below about the values of IPRED,W, etc. for each type of error model
I hope the modeling goes well.
Luann
Quoted reply history
On 8/24/2015 9:16 PM, Chiaying Lin wrote:
> Dear NM-Users,
>
> I'm a NONMEM beginner. The following are my control stream for a monoclonal antibody which clears via target mediated disposition. However, when I ran NONMEM, I didn't get minimization successful message (in fact, no message at all), there are also no Table output and the xx.g77 file contains only empty three output files. I will be appriciated if someone help to find mistakes. Thanks.
>
> Peggy
>
> ---------------------------------------------------------------------------------------------------------------------------------------
> $PROBLEM **base model**
>
> $DATA PKDATA.CSV IGNORE=C
>
> $INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE
>
> $SUBROUTINE ADVAN6 TRANS1 TOL=3
>
> $MODEL NCOMP=2 NPAR=6
> ;COMP=(CENTRAL DEFOBSERVATION DEFDOSE)
> ;COMP=(PERIPH)
>
> $PK
> TVVMAX=THETA(1)
> VMAX=TVVMAX*EXP(ETA(1))
> KM=THETA(2)
> TVV1=THETA(3)
> V1=TVV1*EXP(ETA(2))
> TVV2=THETA(4)
> V2=TVV2*EXP(ETA(3))
> Q=THETA(5)*EXP(ETA(4))
> S1=V1
>
> $DES
> C1=A(1)/V1
> C2=A(2)/V2
> DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2)
> DADT(2)=(Q*C1)-(Q*C2)
>
> $ERROR
> CALLFL=0
> IPRED=LOG(F)
> IRES=DV-IPRED
> IWRES=IRES/IPRED
For CCV error model
IPRED=F
W=IPRED
Y=IPRED+W*ERR(1)
For LOG error model
IPRED=LOG(F)
W=1
Y=IPRED+W*ERR(1)
For additive error model
IPRED=F
W=1
Y=IPRED+W*ERR(1)
For additive + CCV error model
IPRED=F
W=SQRT(IPRED**2*SIGMA(1,1) + SIGMA(2,2))
Y=F + F*EPS(1)+EPS(2)
The following is true for all of the above models
IRES=DV-IPRED
IWRES=IRES/W
> Y=IPRED+ERR(1)
>
> $THETA
> (0.1, 1.49, 5) ;VMAX (mg/hr)
> (1, 50,300) ;KM (μg/mL)
> (1.3, 2.72, 5) ;V1 (L)
> (1.1, 2.43, 5) ;V2 (L)
> (0.001, 0.095, 1) ;Q (L/hr)
>
> $OMEGA .025 ;VMAX
> $OMEGA .032 ;V1
> $OMEGA .29 ;V2
> $OMEGA .975 ;Q
>
> $SIGMA
> 0.030 ;ERR(1)
>
> $ESTIMATION METH=1 MAXEVAL=9999 PRINT=5 POSTHOC
>
> $COVARIANCE
>
> $TABLE ID TIME DV IPRED IWRES VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 BW AGE NOPRINT ONEHEADER FILE=1.fit
>
> $TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1
>
> $TABLE ID VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 NOPRINT ONEHEADER FILE=patab1
>
> $TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
> ----------------------------------------------------------------------------------------------------------------------------------
> #ID TIME AMT
>
> NDV
>
> LNDV
>
> EVID MDV CMT BW AGE DOSE
> A-P001 0 81.3 . . 1 1 1 81.3 50
> 81.3
> A-P001 0.25
> 4.8 1.568616
>
> 1 81.3 50 81.3
> A-P001 1
> 18 2.890372
>
> 1 81.3 50
>
> 81.3
>
> LNDV=Ln-transformed con. (mcg/ml)
--
*Luann Phillips*| Director, Pharmacometrics
Cognigen Corporation, a wholly owned subsidiary of Simulations Plus, Inc.
1780 Wehrle Drive, Suite 110 | Buffalo, NY 14221-7000
Phone: 716.633.3463 x236 | Fax: 716.633.7404 | [email protected] < mailto: [email protected] >
Hi Peggy
When modelling log-transformed data, it’s useful to add a safeguard for IPRED
to prevent taking a log of 0, e.g.:
IPRED = -5
IF (F.GT.0) IPRED = LOG(F)
Similarly, when using a proportional (CCV) error model, use the following to
prevent division by 0:
W = IPRED
IF (W.LE.0) W = 0.0001
IRES = DV-IPRED
IWRES = IRES/W
But as Luann pointed out, for log-transformed data the additive error model (on
log scale) is generally used (W=1), which translates to a proportional error on
normal scale.
Best regards
Julia
________________________________________________________________________________
Julia Korell, PhD
Pharmacometrician
Model Answers Pty Ltd
Tel: +61 (0) 7 3221 1315
www.model-a.com.au http://www.model-a.com.au/
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Quoted reply history
> On 25 Aug 2015, at 1:34 pm, luann <[email protected]> wrote:
>
> Please see my comments inserted below about the values of IPRED,W, etc. for
> each type of error model
>
> I hope the modeling goes well.
>
> Luann
>
> On 8/24/2015 9:16 PM, Chiaying Lin wrote:
>> Dear NM-Users,
>> I'm a NONMEM beginner. The following are my control stream for a monoclonal
>> antibody which clears via target mediated disposition. However, when I ran
>> NONMEM, I didn't get minimization successful message (in fact, no message at
>> all), there are also no Table output and the xx.g77 file contains only empty
>> three output files. I will be appriciated if someone help to find mistakes.
>> Thanks.
>>
>> Peggy
>>
>> ---------------------------------------------------------------------------------------------------------------------------------------
>> $PROBLEM **base model**
>> $DATA PKDATA.CSV IGNORE=C
>>
>> $INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE
>>
>> $SUBROUTINE ADVAN6 TRANS1 TOL=3
>>
>> $MODEL NCOMP=2 NPAR=6
>> ;COMP=(CENTRAL DEFOBSERVATION DEFDOSE)
>> ;COMP=(PERIPH)
>>
>> $PK
>> TVVMAX=THETA(1)
>> VMAX=TVVMAX*EXP(ETA(1))
>> KM=THETA(2)
>> TVV1=THETA(3)
>> V1=TVV1*EXP(ETA(2))
>> TVV2=THETA(4)
>> V2=TVV2*EXP(ETA(3))
>> Q=THETA(5)*EXP(ETA(4))
>> S1=V1
>>
>> $DES
>> C1=A(1)/V1
>> C2=A(2)/V2
>> DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2)
>> DADT(2)=(Q*C1)-(Q*C2)
>>
>> $ERROR
>> CALLFL=0
>> IPRED=LOG(F)
>> IRES=DV-IPRED
>> IWRES=IRES/IPRED
>
>
> For CCV error model
> IPRED=F
> W=IPRED
> Y=IPRED+W*ERR(1)
>
> For LOG error model
> IPRED=LOG(F)
> W=1
> Y=IPRED+W*ERR(1)
>
> For additive error model
> IPRED=F
> W=1
> Y=IPRED+W*ERR(1)
>
> For additive + CCV error model
> IPRED=F
> W=SQRT(IPRED**2*SIGMA(1,1) + SIGMA(2,2))
> Y=F + F*EPS(1)+EPS(2)
>
> The following is true for all of the above models
> IRES=DV-IPRED
> IWRES=IRES/W
>
>
>> Y=IPRED+ERR(1)
>>
>> $THETA
>> (0.1, 1.49, 5) ;VMAX (mg/hr)
>> (1, 50,300) ;KM (μg/mL)
>> (1.3, 2.72, 5) ;V1 (L)
>> (1.1, 2.43, 5) ;V2 (L)
>> (0.001, 0.095, 1) ;Q (L/hr)
>>
>> $OMEGA .025 ;VMAX
>> $OMEGA .032 ;V1
>> $OMEGA .29 ;V2
>> $OMEGA .975 ;Q
>>
>> $SIGMA
>> 0.030 ;ERR(1)
>>
>> $ESTIMATION METH=1 MAXEVAL=9999 PRINT=5 POSTHOC
>>
>> $COVARIANCE
>>
>> $TABLE ID TIME DV IPRED IWRES VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 BW AGE
>> NOPRINT ONEHEADER FILE=1.fit
>> $TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1
>> $TABLE ID VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 NOPRINT ONEHEADER FILE=patab1
>> $TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
>> ----------------------------------------------------------------------------------------------------------------------------------
>> #ID TIME AMT
>>
>>
>> NDV
>>
>>
>>
>>
>> LNDV
>>
>>
>>
>> EVID MDV CMT BW AGE DOSE
>> A-P001 0 81.3 . . 1 1 1 81.3
>> 50 81.3
>> A-P001 0.25
>> 4.8 1.568616
>>
>> 1 81.3 50 81.3
>> A-P001 1
>> 18 2.890372
>>
>> 1 81.3 50
>> 81.3
>>
>>
>> LNDV=Ln-transformed con. (mcg/ml)
>
> --
> Luann Phillips | Director, Pharmacometrics
> Cognigen Corporation, a wholly owned subsidiary of Simulations Plus, Inc.
> 1780 Wehrle Drive, Suite 110 | Buffalo, NY 14221-7000
> Phone: 716.633.3463 x236 | Fax: 716.633.7404 |
> [email protected] <mailto:[email protected]>