title: Model selection versus model averaging in dose finding studies.
abstract: A key objective of Phase II dose finding studies in clinical drug development is to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to support dose selection for the subsequent Phase III studies. In this paper, we compare different approaches for model selection and model averaging using mathematical properties as well as simulations. We review and illustrate asymptotic properties of model selection criteria and investigate their behavior when changing the sample size but keeping the effect size constant. In a simulation study, we investigate how the various approaches perform in realistically chosen settings. Finally, the different methods are illustrated with a recently conducted Phase II dose finding study in patients with chronic obstructive pulmonary disease. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Fakultät für Mathematik, Ruhr-Universität Bochum, Bochum, 44780, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schorning
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, 4002, Basel, Switzerland.
authors.forename: Björn
authors.initials: B
authors.lastname: Bornkamp
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, 4002, Basel, Switzerland.
authors.forename: Frank
authors.identifier: 0000-0002-2008-8340
authors.initials: F
authors.lastname: Bretz
authors.affiliation: Fakultät für Mathematik, Ruhr-Universität Bochum, Bochum, 44780, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Dette
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D018401:Sample Size
keywords: clinical trials; model averaging; model selection; simulation study