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From: Julia Korell (Model Answers) <"Julia>

Date: Wed, 26 Aug 2015 11:42:42 +1000

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/>

=

__________________________________________________________________________=

______

This e-mail, together with any attachments, is confidential and intended =

for the named recipient(s) only. If you are not the intended recipient =

or have received this message in error, you are asked to immediately =

notify the sender and delete this message and any copies of this message =

from your computer system network and destroy any printed copies of this =

email. Any form of unauthorised disclosure, modification, distribution, =

publication or use of this e-mail message is prohibited.

*> On 25 Aug 2015, at 1:34 pm, luann <Luann.Phillips_at_cognigencorp.com> =
*

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 | =
*

luann.phillips_at_cognigencorp.com <mailto:luann.phillips_at_cognigencorp.com>

Received on Tue Aug 25 2015 - 21:42:42 EDT

Date: Wed, 26 Aug 2015 11:42:42 +1000

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/>

=

__________________________________________________________________________=

______

This e-mail, together with any attachments, is confidential and intended =

for the named recipient(s) only. If you are not the intended recipient =

or have received this message in error, you are asked to immediately =

notify the sender and delete this message and any copies of this message =

from your computer system network and destroy any printed copies of this =

email. Any form of unauthorised disclosure, modification, distribution, =

publication or use of this e-mail message is prohibited.

wrote:

etc. for each type of error model

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.

--------------------------------------------------------------------------=

-------------------------------------------------------------

AGE NOPRINT ONEHEADER FILE=1.fit

FILE=patab1

--------------------------------------------------------------------------=

--------------------------------------------------------

81.3 50 81.3

LNDV=Ln-transformed con. (mcg/ml)

Inc.

luann.phillips_at_cognigencorp.com <mailto:luann.phillips_at_cognigencorp.com>

Received on Tue Aug 25 2015 - 21:42:42 EDT