Re: NONMEM

From: Mark Sale - Next Level Solutions mark@nextlevelsolns.com Subject: Re: [NMusers] NONMEM Date: Fri, 15 Sep 2006 09:19:59 -0700 Key phrase "If the feature of interest (such as AUC or tmax) can be written as a function of your PK parameters," I'm assuming closed form solution. But, we are still talking about precision in estimating parameters. What about the vast majority of phase II and III studies that we do using hypothesis testing? using ANOVA, Fisher exact test etc. Not infrequently we can develop models for the endpoint. Can we optimize the study (obviously, I beleive we can). We have not had a lot of success convincing people that we should move from a hypothesis testing mode to an estimation mode. BTW, the reason I'm obsessed with this - and I admit that I am, is that I think this is a real opportunity for Clin pharm/modeling to impact later phase development. Companies like Pharsight (and others) have really done an excellent job of raising awareness that modeling can contribute to phase III design. Part of the reason that this role hasn't been fully embraced everywhere, (IMHO) is that they are trying to wrest control of study design away from stats (and others). Methods to optimize phase III trials are new turf - we wouldn't have to fight anyone for it, it really is very complimentary to stats - since it requires their methods to implement. If we could actually demonstrate saving money (optimizing for lowest cost for an adequate study), I think we can seriously impact late phase development. Of course in academics, money is never an issue .... But, tools need to be developed, and we need more computers. Mark Sale MD Next Level Solutions, LLC www.NextLevelSolns.com