RE: Decrease in OFV with a fixed effect

From: "Kowalski, Ken" Ken.Kowalski@pfizer.com Subject: RE: [NMusers] Decrease in OFV with a fixed effect Date: Mon, August 23, 2004 11:46 am Hi Pete, To expand on Mats' comments you should be careful not to over-interpret a variance component that is estimated near zero to mean that there is no interindividual variability. It may be that there is insufficient information in the design to accurately estimate this variance component (I note that you indicate that for some subjects you only had 2 observations). Also, if there is model misspecification in omega by using a diagonal omega structure when there is a true non-zero correlation between parameters (say CL and V) it may be that NONMEM will partition the interindividual variability into only one of these components. I have observed that variance components estimated near zero (say for V) for a diagonal omega will no longer be estimated near zero when fitting a block omega that allows for the covariance to be estimated (say between CL and V). Based on these observations I have a couple of suggestions/questions: 1) If you fit a block omega structure does NONMEM still want to estimate the variance components for V1, Q2, and V2 near zero? 2) For the model fit you describe below with a 21 point drop in OFV did you ee a reduction in the omega for CL relative to the estimate when you did not include the WT effect on V1? It may be that some of the interindividual variability is getting partitioned into the random effect for CL due to misspecification of omega. If so, then I would expect that the fixed effect for WT on V1 would to some extent reduce the omega estimate for CL. Ken