difficulty with FOCE

From: "Jing Li" jli29@jhmi.edu Subject: [NMusers] difficulty with FOCE Date: Thu, 13 Oct 2005 10:38:12 -0400 Hi, I am running a 3-compartmental PK model with a non-linear elimation (Michealis-Menten) from the central compartment. The data were from 3 trials with total patients of 224. The drug was given as 20-min iv infusion weekly or once every three weeks at different dose leves. When it was run with first order (FO) estimation, the model got converged successfully and produced very reasonable PK parameters (THETAs), inter-individual variabilities (ETAs), and relative standard errors of estimations. The fitting looks pretty good. However, when it runs with first order conditional estimation (FOCE), convergence becomes almost impossible. Iteration becomes extremely slow, and after several iterations, there is always an error message like "...Occurs during search for ETA at a nonzero value of ETA. Numerical difficulties with integration routine. Maximum No. of evaluaitons of differential equations exceeded 100000". Does anyone have some good ideas to solve this problem? I appreciate! Also, is it acceptable to report parameters produced by FO? I am wondering if there are some guidelines or references for the choice of FO and FOCE. Thanks you in advance for any help! Sincerely, Jing