title: An adaptive design for identifying the dose with the best efficacy/tolerability profile with application to a crossover dose-finding study.
abstract: Proof-of-concept in clinical trials has traditionally focused on the identification of a maximum tolerated dose with the assumption that the higher doses provide better efficacy. However, adverse events associated with a maximum tolerated dose may have a negative effect on efficacy. We present an efficient adaptive dose-finding strategy that concentrates patient assignments at and around the dose which has the best efficacy/tolerability profile based on a utility function. The strategy is applied within the setting of a crossover design. While the strategy may also be applied to parallel studies, a crossover design provides more power for a given sample size for comparisons between the optimal dose versus placebo and/or active control when it is reasonable to assume no carryover effects.
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, USA. aivanova@bios.unc.edu
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: Ken
authors.initials: K
authors.lastname: Liu
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.forename: Duane
authors.initials: D
authors.lastname: Snavely
mesh_terms: D000465:Algorithms; D056808:Biostatistics; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003198:Computer Simulation; D018592:Cross-Over Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D004364:Pharmaceutical Preparations