bias and good fit vs centering

From: musor000@optonline.net Subject: [NMusers] bias and good fit vs centering Date: Thu, 18 Aug 2005 20:38:13 -0400 Hello NONMEM Users, We are trying to fit a model which combines 2 studies (IV injection - 1 compartment and SC injection - 2 compartments). We use METHOD=1, POSTHOC, LAPLACIAN). Plots all subjects look very good, but there is a problem. Populations estimates are quite different from the means of individual estimates. For example, population estimate of absorbtion constant (Ka) is 5 times as big as mean of Ka for individuals. It is larger than the largest individual Ka!!! I tried CENTERING option. In this case there is no bias, but fit is much worse (objective function) and plots do not look good. We do not have any confidence in the results. What do we have to use? Population estimates or means of individual estimates? How do experienced and sophisticated NONMEM users deal with issue like that? Thank you, Pavel Kovalenko