title: Phase II dose-response trials: A simulation study to compare analysis method performance under design considerations.
abstract: Phase II trials are intended to provide information about the dose-response relationship and to support the choice of doses for a pivotal phase III trial. Recently, new analysis methods have been proposed to address these objectives, and guidance is needed to select the most appropriate analysis method in specific situations. We set up a simulation study to evaluate multiple performance measures of one traditional and three more recent dose-finding approaches under four design options and illustrate the investigated analysis methods with an example from clinical practice. Our results reveal no general recommendation for a particular analysis method across all design options and performance measures. However, we also demonstrate that the new analysis methods are worth the effort compared to the traditional ANOVA-based approach.
authors.affiliation: a Institute for Medical Informatics, Biometry and Epidemiology , University of Duisburg-Essen , Germany.
authors.forename: Jan
authors.identifier: 0000-0002-5207-3864
authors.initials: J
authors.lastname: Rekowski
authors.affiliation: b Faculty of Statistics , TU Dortmund , Germany.
authors.forename: Claudia
authors.identifier: 0000-0002-0612-2637
authors.initials: C
authors.lastname: Köllmann
authors.affiliation: c Statistical Methodology , Novartis Pharma AG , Basel , Switzerland.
authors.forename: Björn
authors.initials: B
authors.lastname: Bornkamp
authors.affiliation: b Faculty of Statistics , TU Dortmund , Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ickstadt
authors.affiliation: d Clinical Epidemiology, Center for Sepsis Control and Care , University Hospital Jena , Germany.
authors.forename: André
authors.identifier: 0000-0002-9406-4704
authors.initials: A
authors.lastname: Scherag
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data
keywords: Dose finding; dose-response curve; minimum effective dose; phase II trials; proof of concept; study design