Covariate Model Selection

From: "Bonate, Peter, HMR/US" <Peter.Bonate@hmrag.com> Subject: Covariate Model Selection Date: 10 Mar 1998 15:24:39 -0500 I am building a 1-compartment oral model at steady-state on data that had 1-2 observations per subject. One was specifically taken at trough. In inclusion of a covariate on V such that TVV = theta(1) +theta(2)*BSA V = TVV*exp(eta(1)) I had a drop in my objective function of 35 points. The CV on my parameter estimates do not change much compared to the base model without covariate and they are all precisely estimated (CV < 10%). However, I am modeling residual error using an additive and proportional error model Y = Y + eps(1) + Y*exp(eps(2)). With the covariate included in the model my estimates of eps(1) and eps(2) double in magnitude. There is no difference in residual plots or observed vs. predicted plots. Is the covariate model deemed a better model than the base model without covariates? Surprisingly I have encountered a wide diversity in opinion regarding 'yes' or 'no'. I would be interested in the comments from the users group. Thank you. Peter L. Bonate, Ph.D. Hoechst Marion Roussel Clinical Pharmacokinetics P.O. Box 9627 (F4-M3112) Kansas City, MO 64134 fax: 816-966-6999 phone: 816-966-3723