RE: local minimum

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: RE: [NMusers] local minimum Date: Thu, 3 Jan 2002 11:08:33 +0100 Fitting PK models with an additive residual error to log-transformed concentrations has advantages over the common approach (non-transformed concentrations and proportional or additive+proportional residual error), however the problem of local minima and the associated problem of proper selection of initial values are more serious. The probable reason is that the likelihood surface in the parameter space is more flat compared to that coming from nontransformed concentrations. I would recommend the following: initially, thy to fit the model to nontransformed concentrations, examine the results, and if they are appropriate, use the estimates as initial values for the next run where the log-transformed concentrations are involved. Best regards, Vladimir ----------------------------------------------------------------- Vladimir Piotrovsky, Ph.D. Research Fellow, Advanced PK-PD Modeling & Simulation Global Clinical Pharmacokinetics and Clinical Pharmacology (ext. 5463/151) Johnson & Johnson Pharmaceutical Research & Development Turnhoutseweg 30 B-2340 Beerse Belgium