RE: Model building algorithm

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: RE: Model building algorithm Date: Fri, 28 Apr 2000 09:16:12 +0200 Dear NONMEM users, I received questions from two members of the list regarding my last posting, so I feel it necessary to make it clear for the entire list. My original posting was: >If you choose between two or more canditate structural models, look first at >the plots of individual weighted residuals versus time (or sqrt(time) if the >range of time is wide and models have two or more exponential terms). The >best model produces residuals that show no pattern. The minimum objective >function value or AIC are less important, especially if you have many >observations per individual. The models you test should have random effects >for every structural parameter. The form of $OMEGA matrix is not important. >It is sufficient to use just a simple diagonal form: you can optimize $OMEGA >after selecting an appropriate structural model. It is even not essential to >get the convergence: only the posthoc step is really needed. It is only applicable if you have many measurement per individual (rich data). The optimal structural model should fit individual data reasonably well, and the best way to evaluate the goodness of individual fit is visual examination of IRES (or IWRES to be exact) versus time and IPRED. If you have only sparse data, this approach will not work, of course. However, I think, having no rich data you cannot identify the right (realistic) structural model unless the sparse data are collected using an optimal, well-balanced sampling schedule which is most oftenly not the case. Suppose you know the drug has the two-exponential disposition, but you have sparse data and can fit only the one-compartment model? Will you trust parameter estimates then? Best regards, Vladimir ---------------------------------------------------------------------- Vladimir Piotrovsky, Ph.D. Janssen Research Foundation Clinical Pharmacokinetics (ext. 5463) B-2340 Beerse Belgium Email: vpiotrov@janbe.jnj.com