From: Alison_Carter@eisai.com> Subject: [NMusers] Date: Tuesday, July 30, 2002 12:23 PM Dear NONMEM users, I am having a frustrating time trying to fit a simple 2-compartment model to population data. I can fit the individual subjects with 2-compartments fairly easily, but when I try them together, I get the message: R MATRIX ALGORITHMICALLY NON-POSITIVE-SEMIDEFINITE BUT NONSINGULAR COVARIANCE STEP ABORTED I know from the manual that this means the apparent minimum might be a saddle point and that I should not trust the final estimates. My problem is what to do to correct the situation. I have tried various error models and ranges of initial estimates, but I am out of ideas. Does anyone have any suggestions? Does this indicate the data might be better fit with a 1-compartment model? Thanks very much! Alison Carter, PhD ------------------ From: "Venkatesh Atul Bhattaram"
Subject: [NMusers] Date: Tue, 30 Jul 2002 13:01:09 Hello Alison This could be due to overparameterization. I would check the estimates of eta and their correlations and try to minimize them in the model. I found this to work well. Also did you try other estimation methods. Venkatesh Atul Bhattaram Post-doctoral Fellow University of Florida Gainesville-32610 ------------------