RE: Something wrong in US FDA guidance?

From: "Bachman, William (MYD)" bachmanw@iconus.com Subject: RE: [NMusers] Something wrong in US FDA guidance? Date: Fri, November 19, 2004 8:03 am Kyun-Seop, I am not surprised that two different method gives two different answers. For an explanation of the differences between NONMEM and P-Pharm you may want to read: "J Biopharm Stat. 1995 Jul;5(2):141-58. A two-step iterative algorithm for estimation in nonlinear mixed-effect models with an evaluation in population pharmacokinetics. Mentre F, Gomeni R. INSERM U194, Service de Biostatistique et Informatique Medicale, CHU Pitie-Salpetriere, Paris, France. This article proposes an EM-like algorithm for estimating, by maximum likelihood, the population parameters of a nonlinear mixed-effect model given sparse individual data. The first step involves Bayesian estimation of the individual parameters. During the second step, population parameters are estimated using a linearization about those Bayesian estimates. This algorithm (implemented in P-PHARM) is evaluated on simulated data, mimicking pharmacokinetic analyses and compared to the First-Order method and the First-Order Conditional Estimates method (both implemented in NONMEM). The accuracy of the results, within few iterations, shows the estimation capabilities of the proposed approach." Perhaps someone at the FDA or elsewhere has repeated the analysis with NONMEM and will share their results? nmconsult@globomaxnm.com GloboMax The Strategic Pharmaceutical Development Division of ICON plc 7250 Parkway Drive, Suite 430 Hanover, MD 21076 Voice: (410) 782-2205 FAX: (410) 712-0737