Re: NONMEM

From: Mark Sale - Next Level Solutions mark@nextlevelsolns.com Subject: Re: [NMusers] NONMEM Date: Thu, 14 Sep 2006 14:55:07 -0700 >I would suggest that using a information theoretic technique you would get >> rid of the simulation component completely and do this more efficiently >> using an FIM approach. I do not advocate simulation where quicker methods >> are available. Absolutely, the only problem is the quicker method often don't answer the question you want answered (they tell you how to get the smallest SE of model parameters, not how to do the cheapest/most powerful study/fastest). >> If you use simulation then: >> 1) how do you know what designs to choose? You optimize, based on user defined criteria (1-alpha >=0.9, 1-beta >>=0.9, minimal cost, shortest duration) >> 2) how do you determine when you have a minimally effective design - could >> there be another design around the corner that you didn't think of which is >> more efficient? That what optimization does, I can reference you to a text. GA (unlike FIM) does NOT guarantee the "best" answer, the textbooks always say "near optimal solution". But, some analysis more sophisticated than I understand, done mostly at Illinois University has examined "GA deceptive searches", and you can be pretty sure that properly done GA is truly optimal - but not guaranteed. Also, as an aside I have combined search algorithms and greatly increased the "robustness" of the search, specifically addressing the problem you mention. >> Why not just let an FIM search do its business, get the answer for the most >> efficient-sufficient design. In a sense the most efficient design is how >> you would determine 'optimal' (or 'best') - just that the design is cast >> from finding the minimum experimental effort rather than some other goal. Absolutely (again), if your goal is minimal SE of model parameters. If your goal is cheapest/most power/fastest, I'm not sure FIM will work. Mark Sale MD Next Level Solutions, LLC www.NextLevelSolns.com