RE: simultaneous PK/PD
Dear Hauke,
Nonmem cannot handle random variables defined in nested conditions. See the help entry on abbreviated code:
"Random variables cannot be defined within nested conditionals, i.e.,
within a conditional structure beginning with an IF and containing
another IF. The use of ELSEIF ... THEN implies a nested conditional."
The usual way of handling this is to define a dummy variable to set the condition, but you do not even need this in your case as Brendan and Katya pointed out.
Moreover in this case, I would assign a different sigma to PK and PD. Your model actually states the belief that the variability in PK and PD are 100% correlated (unless they are always measured at different times). If you have background support for such a model it is fine, but in general I would advice to associate EPS(1) with THETA(8) for PK and EPS(2) with THETA(9) for PD.
You may even skip zero testing by request (ONLYOBS) after $ERROR if you always have positive predictions of C1 and C3 during observation records (e.g., a PK model without lagtime), see nmhelp on $ERROR.
Hope this helps,
Jeroen
Modeling & Simulation Expert
Pharmacokinetics, Pharmacodynamics & Pharmacometrics (P3) - DMPK
MSD
PO Box 20 - AP1112
5340 BH Oss
The Netherlands
jeroen.elassaiss
T: +31 (0)412 66 9320
F: +31 (0)412 66 2506
www.msd.com
Quoted reply history
________________________________
From: owner-nmusers
On Behalf Of Hauke Rhs
Sent: Wednesday, 23 June, 2010 14:54
To: nmusers
Subject: [NMusers] simultaneous PK/PD
Dear NMusers,
I want to combine my sequential PK and PD model to one simultaneous model. In both models I used an exponential error model (log-transformation). When I write the model as follows, NONMEM gives me this error message:
326 RANDOM VARIABLE IS DEFINED IN A NESTED IF STRUCTURE.
Leaving out the condition C.GT.0 will also lead to errors. Is there another way to write this?
Thanks
Hauke
$ERROR
C1=(A(1)/V1)
C3=A(3)
IPRE=0
IF (M1H2.EQ.1) THEN
IF (C1.GT.0) IPRE = LOG(C1)
IRES = DV-IPRE
W = EPS(1)*THETA(8)
Y = IPRE+W
ENDIF
IF (M1H2.EQ.2) THEN
IF (C3.GT.0) IPRE = LOG(C3)
IRES = DV-IPRE
W = EPS(1)*THETA(9)
Y = IPRE+W
ENDIF
DEL = 0
IF(W.EQ.0) DEL = 1
IWRE = IRES/(W+DEL)
$SIGMA
1 FIX
-----------------------------
Hauke Rhs
Apotheker
Pharmazeutisches Institut
- Klinische Pharmazie -
An der Immenburg 4
53121 Bonn
Tel: + 49-(0)228 73-5781
Fax: + 49-(0)228 73-9757
www.klinische-pharmazie.info http://www.klinische-pharmazie.info/
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