Re: Obj. function is infinite (error=136)

From: Nick Holford Subject:Re: [NMusers] Obj. function is infinite (error=136) Date:Mon, 02 Jun 2003 21:12:46 +1200 Justin, 1. FO and FOCE use different objective functions. You should not compare FO and FOCE objective function values as a means of assessing relative goodness of fit. 2. If you put some biologically obvious covariates e.g. allometric model using weight on CL and V then maybe some other features or the model will become more stable. An unusual weight distribution could be giving NONMEM the wobblies when it tries to estimate the random effects. With meaningful covariates in the model you may be able to remove fixed effect sources of variability and leave random effects that are a bit more like a simpler distribution such as log-normal and NONMEM may behave better. 3. Try avoiding obsessional compulsion about getting NONMEM to produce its semi-worthless asymptotic standard errors. 4. If company policy requires you to get some measure of estimation error then you can always bootstrap your data to get a more reliable perspective of the uncertainty of your estimates (instead of such things as relying on the naive assumption of normality to obtain confidence intervals in your estimates based on standard errors). 5. The key question is how does your model perform? Have you tried some kind of predictive check to see if your model works well enough to describe the variability of your data, predict concentrations at particular times etc? Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/