Dear all,
I am trying to fit a model for tumor growth (like in Simeoni et al, Cancer
Res., 64, February 1, 2004). So far, I only tried to fit the unperturbed
growth model. I have the tumor area as DV from time= 480 h and would like
to estimate the area at time = 0. However, there seems to be an error in
the control stream as when running the model the gradient for this
parameter stays at zero. From my understanding this area at time= 0 would
represent the 'tumor dose' (AMT), however, I did not know how I could
implement it in the dataset as the 'dose' is not known. That's why I
incorporated it in the differential equations. Can anybody help me with
the coding?
Thanks and best regards
Nele
Data:
#ID TIME DOSE DV CMT AMT RATE MDV DAY FLAG
DVID EVID
3 0 0 0.0 1 0 0 1 1 5
2 2
3 0 0 0.0 1 0 0 1 1 5
2 0
3 20 0 0.0 1 0 0 1 1 5
2 0
3 40 0 0.0 1 0 0 1 2 5
2 0
3 60 0 0.0 1 0 0 1 3 5
2 0
3 100 0 0.0 1 0 0 1 5 5
2 0
3 150 0 0.0 1 0 0 1 7 5
2 0
3 200 0 0.0 1 0 0 1 9 5
2 0
3 280 0 0.0 1 0 0 1 12 5
2 0
3 380 0 0.0 1 0 0 1 17 5
2 0
3 480 0 30.0 1 0 0 0 21 5
2 0
3 648 0 41.3 1 0 0 0 28 5
2 0
3 864 0 51.3 1 0 0 0 37 5
2 0
3 984 0 67.5 1 0 0 0 42 5
2 0
3 1152 0 83.7 1 0 0 0 49 5
2 0
3 1320 0 99.4 1 0 0 0 56 5
2 0
3 1488 0 104.1 1 0 0 0 63 5
2 0
Model:
$PROBLEM XYZ
$INPUT ID TIME DOSE DV CMT AMT RATE MDV DAY FLAG DVID EVID
$DATA ../PD_data.NMdat IGNORE=#
$SUBROUTINES ADVAN6 TOL=3
$MODEL
COMP=(PD)
$PK
;
TVL0=THETA(1)
L0=TVL0*EXP(ETA(1))
;
TVL1=THETA(2)
L1=TVL1
TVW0=THETA(3)
W0=0.01
IF (EVID.EQ.2) W0=TVW0
S1=1
PSI=20
;
$ERROR
IPRED=F
DEL=0
IF (IPRED.EQ.0) DEL=0.0001
W=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=F+SQRT(THETA(5)*THETA(5)+THETA(4)*THETA(4)*F**2)*EPS(1)
;
$DES
DADT(1)= W0+L0*A(1)/(1+(L0/L1*A(1))**PSI)**(1/PSI)
$THETA
(0,0.25) ;L0
(0,1) ;L1
(0,0.02) ;W0
(0,0.1) ; prop. error
(0,0.1) ; add. error
;
$OMEGA
0 FIX ;IIV_L0
;
$SIGMA
1 FIX ;prop.error
;
$EST METHOD=1 INTERACTION MAXEVAL=9999 PRINT=5 NOABORT MSFO=msf001
$COV
$TABLE ID TIME IPRED IWRES TAD NOPRINT ONEHEADER FILE=sdtab1
$TABLE ID ETA1 CMT FLAG NOPRINT ONEHEADER FILE=patab1
$TABLE ID TIME TVL0 TVL1 TVW0 NOPRINT ONEHEADER FILE=mytab1
$TABLE ID TIME L0 L1 W0 NOPRINT ONEHEADER FILE=notab1
_________________________
Dr. Nele Plock
Bayer Schering Pharma AG
GPD/Pharmacokinetics
Metabolism & Bioanalysis
D- 13342 Berlin
Phone : +49-30-468 15146
Fax: +49-30-468 95146
[EMAIL PROTECTED]
http://www.bayerscheringpharma.de
Vorstand: Arthur J. Higgins, Vorsitzender | Werner Baumann, Andreas Busch,
Ulrich Köstlin, Kemal Malik, Gunnar Riemann
Vorsitzender des Aufsichtsrats: Werner Wenning
Sitz der Gesellschaft: Berlin | Eintragung: Amtsgericht Charlottenburg 93
HRB 283
tumor growth model
In Nonmem V (and VI as well), you can put a unit dose to compartment 1, and then estimate "bioavailability" F1
F1=THETA(...)*EXP(ETA(...))
In Nonmem VI, you can directly supply initial conditions to the compartmental amounts via parameter A_0(1), e.g.,
A_0(1)=THETA(...)*EXP(ETA(...))
(see help for COMPARTMENT INITIALIZATION BLOCK).
Leonid
[EMAIL PROTECTED] wrote:
> Dear all,
>
> I am trying to fit a model for tumor growth (like in Simeoni et al, Cancer Res., 64, February 1, 2004). So far, I only tried to fit the unperturbed growth model. I have the tumor area as DV from time= 480 h and would like to estimate the area at time = 0. However, there seems to be an error in the control stream as when running the model the gradient for this parameter stays at zero. From my understanding this area at time= 0 would represent the 'tumor dose' (AMT), however, I did not know how I could implement it in the dataset as the 'dose' is not known. That's why I incorporated it in the differential equations. Can anybody help me with the coding?
>
> Thanks and best regards
> Nele
>
> Data:
>
> #ID TIME DOSE DV CMT AMT RATE MDV DAY FLAG DVID EVID 3 0 0 0.0 1 0 0 1 1 5 2 2 3 0 0 0.0 1 0 0 1 1 5 2 0 3 20 0 0.0 1 0 0 1 1 5 2 0 3 40 0 0.0 1 0 0 1 2 5 2 0 3 60 0 0.0 1 0 0 1 3 5 2 0 3 100 0 0.0 1 0 0 1 5 5 2 0 3 150 0 0.0 1 0 0 1 7 5 2 0 3 200 0 0.0 1 0 0 1 9 5 2 0 3 280 0 0.0 1 0 0 1 12 5 2 0 3 380 0 0.0 1 0 0 1 17 5 2 0 3 480 0 30.0 1 0 0 0 21 5 2 0 3 648 0 41.3 1 0 0 0 28 5 2 0 3 864 0 51.3 1 0 0 0 37 5 2 0 3 984 0 67.5 1 0 0 0 42 5 2 0 3 1152 0 83.7 1 0 0 0 49 5 2 0 3 1320 0 99.4 1 0 0 0 56 5 2 0 3 1488 0 104.1 1 0 0 0 63 5 2 0
>
> Model:
> $PROBLEM XYZ
>
> $INPUT ID TIME DOSE DV CMT AMT RATE MDV DAY FLAG DVID EVID
> $DATA ../PD_data.NMdat IGNORE=#
> $SUBROUTINES ADVAN6 TOL=3
> $MODEL
> COMP=(PD)
>
> $PK
> ;
> TVL0=THETA(1)
> L0=TVL0*EXP(ETA(1))
> ;
> TVL1=THETA(2)
> L1=TVL1
>
> TVW0=THETA(3)
> W0=0.01
> IF (EVID.EQ.2) W0=TVW0
>
> S1=1
> PSI=20
> ;
> $ERROR
> IPRED=F
> DEL=0
> IF (IPRED.EQ.0) DEL=0.0001
> W=F
> IRES=DV-IPRED
> IWRES=IRES/(W+DEL)
> Y=F+SQRT(THETA(5)*THETA(5)+THETA(4)*THETA(4)*F**2)*EPS(1)
> ;
> $DES
> DADT(1)= W0+L0*A(1)/(1+(L0/L1*A(1))**PSI)**(1/PSI)
>
> $THETA
> (0,0.25) ;L0
> (0,1) ;L1
> (0,0.02) ;W0
> (0,0.1) ; prop. error
> (0,0.1) ; add. error
> ;
> $OMEGA
> 0 FIX ;IIV_L0
> ;
> $SIGMA
> 1 FIX ;prop.error
> ;
> $EST METHOD=1 INTERACTION MAXEVAL=9999 PRINT=5 NOABORT MSFO=msf001
> $COV
> $TABLE ID TIME IPRED IWRES TAD NOPRINT ONEHEADER FILE=sdtab1
> $TABLE ID ETA1 CMT FLAG NOPRINT ONEHEADER FILE=patab1
> $TABLE ID TIME TVL0 TVL1 TVW0 NOPRINT ONEHEADER FILE=mytab1
> $TABLE ID TIME L0 L1 W0 NOPRINT ONEHEADER FILE=notab1
>
> _________________________
> Dr. Nele Plock
> Bayer Schering Pharma AG
> GPD/Pharmacokinetics
> Metabolism & Bioanalysis
> D- 13342 Berlin
>
> Phone : +49-30-468 15146
> Fax: +49-30-468 95146
> [EMAIL PROTECTED]
> http://www.bayerscheringpharma.de
>
> Vorstand: Arthur J. Higgins, Vorsitzender | Werner Baumann, Andreas Busch, Ulrich Köstlin, Kemal Malik, Gunnar Riemann
>
> Vorsitzender des Aufsichtsrats: Werner Wenning
>
> Sitz der Gesellschaft: Berlin | Eintragung: Amtsgericht Charlottenburg 93 HRB 283