Re: NONMEM

From: "Stephen Duffull" stephen.duffull@stonebow.otago.ac.nz Subject: Re: [NMusers] NONMEM Nick >> If I may split the academic hair a little more ... Of course :-) >> I suspect that in fact your collaborators would have >> initially asked you for an 'optimal design' i.e. these are >> the words they would have used when asking you to help them. >> But you would have offered a 'sufficient design' as being good enough. Sometimes - but not always. Many 'sponsors' really do want the 'minimally effective' design - and don't ask for an 'optimal' design. And of course some sponsors know what they want but inadvertently use the term 'optimal' anyway. So, I don't agree with your assertion here. >> I accept that methods based on the Fisher information matrix >> (FIM) are much faster than brute force Monte Carlo (MC) >> methods but the FIM methods are limited to minimizing >> parameter precision as the objective. (Hair split - you mean maximize precision.) Not true - although I accept that this is their most common use in practice. In addition to maximizing precision, FIM based designs can be used to: 1) determine designs for model discrimination 2) determine designs with minimum bias 3) determine designs for power to reject the null hypothesis (for model building decisions only) 4) determine designs that carry the highest probability of success (GLMs) And of course any combination of the above (including with the standard maximizing parameter precision). I'm not of course advocating that FIM based methods should replace all MC methods - but I think both have a complementary role. Steve -- Professor Stephen Duffull Chair of Clinical Pharmacy School of Pharmacy University of Otago PO Box 913 Dunedin New Zealand E: stephen.duffull@otago.ac.nz P: +64 3 479 5044 F: +64 3 479 7034 Design software: www.winpopt.com