Covariate Models

From ltc_Ralf_Brueckner@wrsmtp-ccmail.army.mil Thu Jun 12 08:23:23 1997 Subject: Covariate Models Thanks to all who have replied to my inquiry re: different ways of modeling covariates. In this inquiry, I used V as an exqample, but the question is equally applicable to any other parameter one wishes to evaluate. With respect to method 1: V = THETA(1)+THETA(2)*WT If THETA(1) drops out, the models yields a simple L/Kg relationship, something I was ingrained with as a pediatrician. The argument that when WT approaches 0, a Volume (THETA(1)) exists, which is theoretically impossible, is true. However, I have also seen NONMEM results presented using the second method: V = THETA(1)+THETA(2)*(WT-70) where THETA(1) and THETA(2) have values such that a 40 kg individual is predicted to have a negative volume (e.g. when THETA(1) = 10 L, THETA(2)=0.5 L/kg, WT=40 kg, V = -5 L. These are both really just examples of extrapolating the model to individuals not used in the model determination. It seems so far, that this is a question of interpretation, and one's frame of reference (i.e. a "typical" adult and deviation from this, versus a more straightforward - to my way of thinking - relationship between V and WT). I was actually expecting some statistical answer, or something more along the lines of what Raj Pradhan alluded to in terms of computational efficiency: Further comments on this phenomenon would also be appreciated. Ralf Brueckner, MD Dept. of Clinical Pharmacology Div. of Experimental Therapeutics Walter Reed Army Institute of Research