Re: NONMEM Tips #16 - April 2, 2003 - Modeling a "baseline" componentand an additive "drug" component

From:Mats Karlsson Subject:Re: [NMusers] NONMEM Tips #16 - April 2, 2003 - Modeling a "baseline" componentand an additive "drug" component Date:Fri, 04 Apr 2003 20:45:11 +0200 Dear all, Just a couple of thoughts on Lewis alternatives 1 and 3 (2 seems to have no advantages over 3). Alt. 3 will differ from 1 in at least a few aspects: 1) For the FO method, Model 3 seems advatageous as the linearization would occur closer to the individuals' predictions. This could be of value whenever residual error is heteroscedastic (instead of the homoscedastic error in the simple example below). Also when BSL comes into the model in a more complex form such that it influences the predicted profiles in another way than mere scaling, this could be advantageous. 2) If there is a correlation between baseline and any other parameter, this would be incorporated into model 1 as an estimated covariance, whereas in model 3 as a covariate relationship between BSL and the parameter in question. The latter will provide a wider range of shapes for the relation than a mere correlation. This difference may well also have other implications. 3) Model 3 does not assume any distribution of BSL in the population (as Lewis points out). On the other hand simulation from the final model will rely on the empirical distribution of BSL values. Model 1 on the other hand will estimate (with imprecision estimates) the features of BSL and any covariate relations that influence BSL. If Model 3 is used, such a model could of course be developed separately but with less information speaking to BSL (all data point speak to some extent to BSL) and with additional/other assumptions about error structure. 4) Some modellers like, for indirect effect models, to estimate Kin and Kout, as true physiological parameters, rather than BSL. Model 3 would not allow such parametrisation. Best regards, Mats _______________________________________________________