Re: sequential PK/PD

From: Liping Zhang. Subject: Re: [NMusers] sequential PK/PD Date: Wed, 8 May 2002 10:50:52 -0400 Hi, Raj, > Hello all, > I think the results from > 1. fixing population parameters (THETA, ETA, and SIGMA) and doing a simultaneous > PK-PD fitting and > 2. fixing the individual THETAs (feeding through the dataset) and doing PD fitting > will be different. What will be the criteria for the comparison? OBJ values may not > be suitable. Mats anwered your first question. > In Method 1, although we have fixed the POPULATION parameters, is there a chance > that errors due to PD model misspecification will leak into PK model because the > program is generating the individual PK parameters based on the Population values. > This problem may not be there in Method 2. I guess your interest is in getting PD models and parameter estimates since you are doing PK/PD analysis. By doing a simulation study, we have found that when the PD model is misspecified, your method 1 and method 2 behavior very similarly measured in respect to their prediciton performance, since the PD fits are still dominated by the PD model. If in method 1 there are errors in generating individual PK parameter due to PD model misspecification, the influnece in PD fits must be very minimal, if any. -- _/ _/ _/_/ _/_/_/ _/_/_/ Liping Zhang (liping@c255.ucsf.edu) _/ _/ _/ _/_ _/_/ Graduate Student in Dr. Lewis Sheiner's group _/ _/ _/ _/ _/ Biological and Medical Informatics Program _/_/ _/_/ _/_/_/ _/ Box 0626, UCSF, SF, CA, 94143-0626 415-502-1989 (v), 415-476-2796 (fax)