title: The promise of futility trials in neurological diseases.
abstract: Double-blinded randomized controlled trials (RCTs) have contributed much important evidence to guide treatment decisions in neurology. RCTs are relatively straightforward to conduct, provided that they investigate common diseases, have clearly defined outcome measures, and are of short duration. In neurology, however, many diseases are uncommon, have no consensus outcome measures, and develop over decades. Basic research into neurological diseases continues to identify candidate therapies faster than they can be tested for their clinical utility, leading to a 'translational gap'. Futility trials were initially developed in oncology to efficiently test candidate therapies in phase II trials. As single-arm unblinded studies, futility trials are relatively easy to conduct, and they generally require smaller sample sizes than RCTs. In this article, we discuss futility models, highlighting their advantages as well as challenges to their application in several neurological diseases, including Parkinson disease, stroke and multiple sclerosis.
authors.affiliation: 1] Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada. [2] Department of Community Health Sciences, TRW Building, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada.
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Koch
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korngut
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Patry
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Agha-Khani
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: White
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Justyna R
authors.initials: JR
authors.lastname: Sarna
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Yeung
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, AB T2N 4N2, Canada.
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294-0022, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
authors.affiliation: Department of Clinical Neurosciences, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
authors.forename: Luanne
authors.initials: L
authors.lastname: Metz
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D003072:Cognition Disorders / Q000628:therapy; D006801:Humans; D018447:Medical Futility; D008954:Models, Biological; D009422:Nervous System Diseases / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size