GAM analysis and further action

From: "Toufigh Gordi" tgordi@Depomedinc.com Subject: [NMusers] GAM analysis and further action Date: Wed, 29 Mar 2006 10:07:12 -0800 Dear all, I have modeled the pharmacokinetics of a compound in very young children using the FOCE INTERACTION option in NONMEM. Following that I looked at graphs of model parameters (CL and VC) vs. various covariates (6 of them). None of the graphs show any obvious correlations or trends. However, running a GAM analysis in Xpose I have the following results on CL (no effect on VC): Start: CL ~ 1; AIC= 29.056 Step : CL ~ HB ; AIC= 27.886 Step : CL ~ HT + HB ; AIC= 26.1178 Step : CL ~ HT + BW + HB ; AIC= 24.9265 Step : CL ~ ns(HT, df = 2) + BW + HB ; AIC= 24.3268 The analysis implies effect of HT, BW, and HB on CL, although the graphs indicate no correlations. Any comments on how to proceed next? In general, are there any recommendations on the significance of covariate with regard to the drop in AIC? Is a drop from 29 to 24 sufficient enough to justify including 3 covariates in the model? (although not all of them might be needed depending on the NONMEM results) Best regards, Toufigh Toufigh Gordi, PhD Associate Director of Pharmacokinetics 1360 O'Brien Drive Menlo Park, CA 94025-1436 USA Phone: 650-462-2752 ext. 273 Fax: 650-462-9993