title: Outcome markers for clinical trials in cerebral amyloid angiopathy.
abstract: Efforts are underway for early-phase trials of candidate treatments for cerebral amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for cerebral amyloid angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for cerebral amyloid angiopathy trials are probably applicable also to other small-vessel brain diseases.
authors.affiliation: Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA. Electronic address: sgreenberg@partners.org.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.affiliation: Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Rustam
authors.initials: R
authors.lastname: Al-Shahi Salman
authors.affiliation: Brain Centre Rudolf Magnus, University Medical Center of Utrecht, Utrecht, Netherlands.
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Biessels
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: van Buchem
authors.affiliation: Department of Neurology, Universite Lille Nord de France EA 1046, Lille University Hospital, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: Department of Neurology, Department of Radiology, and Department of Biomedical Engineering, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Neurology, Vall d'Hebron University Hospital and Research Institute, Autonomus University of Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Department of Pathology and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: Department of Radiology and Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Meike
authors.initials: M
authors.lastname: Vernooij
authors.affiliation: UCL Institute of Neurology, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
mesh_terms: D015415:Biomarkers; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers