Re: simultaneous PK/PD

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/ > > ------------------------------------------------------------------------ > > This message and any attachments are solely for the intended recipient. If you are not the intended recipient, disclosure, copying, use or distribution of the information included in this message is prohibited --- Please immediately and permanently delete. > > ------------------------------------------------------------------------ -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford