RE: Non-physiological parameters at lowest OBJ

From: Stephen Duffull <duffull@pharmacy.uq.edu.au> Subject: RE: [NMusers] Non-physiological parameters at lowest OBJ Date: 8/5/2003 6:03 PM Hi Justin, I think that this is potentially a very interesting example. Obviously all of the advice to date has been prudent - but what I am interested in is along the same lines as Ken's comment. Just how unreasonable are the parameters? It would be nice to have an idea of whether we are talking about illegal parameters (e.g. a negative CL) - in which case I find it intriguing that you would be able to find a minimum that is so much better and that produced good diagnostic plots. Or, perhaps the variance components are greatly inflated >500% - which can cause the objective function to become quite small without affecting the apparent fit of the model. Or, alternatively you might be finding that some relationship that you thought was important a priori was not being supported by your data-model interaction, for example if you knew that the drug was 90% renally cleared but that from one set of initial estimates it minimised to a model where all the clearance was considered to be non-renal? Regards Steve ========================================= Stephen Duffull School of Pharmacy University of Queensland Brisbane 4072 Australia Tel +61 7 3365 8808 Fax +61 7 3365 1688 University Provider Number: 00025B Email: sduffull@pharmacy.uq.edu.au www: http://www.uq.edu.au/pharmacy/sduffull/duffull.htm PFIM: http://www.uq.edu.au/pharmacy/sduffull/pfim.htm MCMC PK example: http://www.uq.edu.au/pharmacy/sduffull/MCMC_eg.htm