title: Two-dimensional dose finding in discrete dose space.
abstract: The objective of a Phase I trial with two agents is to find a set of maximum-tolerated dose combinations that yield a prespecified toxicity rate. In this article, we consider the case where several doses of one agent are fixed and the goal is to find the maximum-tolerated dose of the other agent to be used in combination with each of the doses of agent one. We propose a Bayesian design that uses a parsimonious working model for the dose-toxicity relationship. We show that the new design is more effective in identifying the maximum-tolerated combinations than one-dimensional designs applied at each dose level of one of the agents.
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7420, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
mesh_terms: D001499:Bayes Theorem; D001699:Biometry; D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D006801:Humans; D020714:Maximum Tolerated Dose