Jeroen,
There is no need to defined a different EPS for PK and PD. Every
observation record has a new random instance of EPS associated with it.
So if there is only one random residual error parameter (PK or PD) then
only one EPS is needed.
In this particular case EPS(1) is always mean 0 and variance 1 but it is
scaled by THETA(8) for PK and THETA(9) for PD so that the residual error
is appropriate for the type of observation.
There is no implied correlation between the random residual error.
Nick
Elassaiss - Schaap, J. (Jeroen) wrote:
Dear Hauke,
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.
Hope this helps,
Jeroen
Modeling & Simulation Expert
Pharmacokinetics, Pharmacodynamics & Pharmacometrics (P3) - DMPK
*MSD*
PO Box 20 - AP1112
5340 BH Oss
The Netherlands
[email protected]
T: +31 (0)412 66 9320
F: +31 (0)412 66 2506
www.msd.com
------------------------------------------------------------------------
*From:* [email protected]
[mailto:[email protected]] *On Behalf Of *Hauke Rühs
*Sent:* Wednesday, 23 June, 2010 14:54
*To:* [email protected]
*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 Rühs
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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Nick Holford, Professor Clinical Pharmacology
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