title: A population approach to initial dose selection.
abstract: Before a drug can be marketed, an initial dose must be established. Sheiner et al. argue that a population approach leads to the most informed and rational decision making. We discuss the choice of an initial dose from both a predictive and estimative viewpoint. Our criteria are based upon evaluating the probabilities that a patient from the specified population obtains a response that is at least of a specified size. We demonstrate the approach using a simulation study and compare estimation of population parameters and initial dose using Bayesian and likelihood-based methods.
authors.affiliation: Department of Epidemiology and Public Health, Imperial College School of Medicine at St. Mary's, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Wakefield
authors.forename: S
authors.initials: S
authors.lastname: Walker
mesh_terms: D001499:Bayes Theorem; D003198:Computer Simulation; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D016013:Likelihood Functions; D008954:Models, Biological; D012107:Research Design