Dear all,
I am currently trying to model the transitions from CTCAE grade 0 - 3 (4
states) for several
toxicities using a markov approach in Nonmem.
However, I am facing some problems with the data set, which I cannot solve
by myself.
The set looks like this:
C
ID
TIME
DOSE
DV
EVID
CMT
AMT
MDV
0
1
0
0
0
1
1
1
1
0
1
1
50
1
0
1
0
0
0
1
1
50
0
2
-1
0
1
0
1
1
50
0
2
-2
0
1
0
1
1
50
0
2
-3
0
1
0
1
1
50
0
2
-4
0
1
0
1
1
50
0
1
1
1
1
0
1
1
50
0
2
2
0
1
0
1
1
50
0
2
3
0
1
0
1
1
50
0
2
4
0
1
To implement the markov property the compartments are emptied and
initialized after each observation.
When I try to execute the model I get the following error message for every
record where the compartment without
a previous observation is emptied :
COMPARTMENT ASSOCIATED WITH THE PREDICTION IS OFF
In the example above this error refers to record 4 - 6.
When I remove these records the model works, but then I am violating the
markovian assumption, if I am not mistaken.
Am I missing something important? Any help is highly appreciated!
Here are the relevant parts of the control file:
$DES
K01_F = K01 * EXP(-GAM*T) + DOSE*SLP
K02_F = K02 * EXP(-GAM*T) + DOSE*SLP
K03_F = K03 * EXP(-GAM*T) + DOSE*SLP
K12_F = K12 * EXP(-GAM*T) + DOSE*SLP
K23_F = K23 * EXP(-GAM*T) + DOSE*SLP
KB10 = KB * EXP(-BA*DOSE)
KB21 = KB * EXP(-BA*DOSE)
KB32 = KB * EXP(-BA*DOSE)
KB20 = KB * EXP(-BA*DOSE)
KB30 = KB * EXP(-BA*DOSE)
DADT(1) = A(2)*KB10 + A(3)*KB20 + A(4)*KB30 - A(1) * (K01_F + K02_F +
K03_F) ; No grade
DADT(2) = A(1)*K01_F - A(2) * (K12_F + KB10)
; Grade 1
DADT(3) = A(2)*K12_F + A(1)*K02_F - A(3) * (K23_F + KB21 + KB20)
; Grade 2
DADT(4) = A(3)*K23_F + A(1)*K03_F - A(4) * (KB32 + KB30)
; Grade 3
$ERROR
PB0 = A(1)
PB1 = A(2)
PB2 = A(3)
PB3 = A(4)
Y = 1
IF(DV.EQ.1.AND.CMT.EQ.1) Y = A(1)
IF(DV.EQ.1.AND.CMT.EQ.2) Y = A(2)
IF(DV.EQ.1.AND.CMT.EQ.3) Y = A(3)
IF(DV.EQ.1.AND.CMT.EQ.4) Y = A(4)
$ESTIMATION SIG=3 MAXEVAL=9999 PRINT=1 METHOD=1 LAPLACIAN LIKE NOABORT
Thank you very much in advance!
Kind regards
____________________
Achim Fritsch
Pharmacist
Klinische Pharmazie
Pharmazeutisches Institut
Universität Bonn
An der Immenburg 4
53121 Bonn
Tel.: 0228 / 73 5229
Fax.: 0228 / 73 9757
[email protected]
