RE: sequential PK/PD

From: Leonid Gibiansky Subject: RE: [NMusers] sequential PK/PD Date: Thu, 02 May 2002 11:01:56 -0400 Sriram, I think concentration DV should not influence your PK/PD model if you use F in Emax model expression. However, the objective function will differ with and without those observations simply because you have err1 term that is not fixed, but chosen by NONMEM based on the concentration DV. With you control stream, objective function is the combination of the PK fit OF and PD fit OF with the PD model is not connected with the PK model in any way. Effectively, you are fitting two models in step 2: PK/PD model, and error model for the PK part. These two models are not connected. Since PK model does no change when you change parameters of the PD model, the results (parameters of the PD model) should be identical with and without PK observations, although run time should be different. Have you observed this in your experiments ? There may be different opinions and situations how to choose between simultaneous and sequential PK/PD modeling. But if you prefer sequential modeling as described in your message, I would suggest to exclude all the concentration DV and modify step 2: >$ERROR >Y=Emax*F/(EC50+F)+err(1) (Y here is PD observation) Leonid