title: Ethical challenges in preclinical Alzheimer's disease observational studies and trials: Results of the Barcelona summit.
abstract: Alzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants.
authors.affiliation: Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain. Electronic address: jlmolinuevo@fpmaragall.org.
authors.forename: José L
authors.initials: JL
authors.lastname: Molinuevo
authors.affiliation: Pompeu Fabra University and Pasqual Maragall Foundation, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Cami
authors.affiliation: Clinical Pharmacology Department, Hospital Clinic and IDIBAPS, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Carné
authors.affiliation: Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: Alzheimer Europe, Luxembourg, Luxembourg.
authors.forename: Jean
authors.initials: J
authors.lastname: Georges
authors.affiliation: European Medicines Agency (EMA), London, UK.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Isaac
authors.affiliation: The Campaign to Prevent Alzheimer by 2020 (PAD2020), Potomac, MD, USA.
authors.forename: Zaven
authors.initials: Z
authors.lastname: Khachaturian
authors.affiliation: Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Scott Y H
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Inserm 1171, Université Lille2, CHU, Memory Centre Lille, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Ritchie
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Karlawish
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D002986:Clinical Trials as Topic / Q000191:economics / Q000941:ethics*; D003245:Consensus Statements as Topic; D030881:Disclosure; D006801:Humans; D008137:Longitudinal Studies; D012307:Risk Factors; D013030:Spain; D013997:Time Factors
keywords: Alzheimer's disease; Asymptomatic; Ethics; Preclinical AD