Re: NONMEM SE and CI

From:Nick Holford Subject:Re: [NMusers] NONMEM SE and CI Date:Tue, March 12, 2002 4:15 pm Leonid, Thanks for your remarks about perspective. My perspective is that the NONMEM SEs are not reliable for making CI predictions. When you really want a CI then you do not know if you can trust the CI predicted from SE (e.g. in your aripiprazole example, you would not have known that you could predict CL but not KA). Because of this uncertainty I maintain they are of little worth for making CI predictions *when you really need* this prediction. Remember also that your models were quite straightforward with essentially linear parameters. I would be reluctant to generalize your observations comparing the performance of SE, profiling and bootstrap to other models e.g. when estimating Emax. There is another use of SE that I sometimes hear about. It is claimed that if the $COV step runs then this somehow means that the model is alright. But I have had runs finish with a successful $COV but then re-running with slightly different initial estimates the run terminates or minimizes successfully at a lower obj function value but unable to run $COV. In this case I dont think the initial $COV success is any confirmation of the model. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/