Ethical challenges in preclinical Alzheimer's disease observational studies and trials

Alzheimers Dement. 2016 Mar 14. pii: S1552-5260(16)00076-5. doi: 10.1016/j.jalz.2016.01.009. [Epub ahead of print]

Ethical challenges in preclinical Alzheimer's disease observational studies and trials: Results of the Barcelona summit.

Molinuevo JL1, Cami J2, Carné X3, Carrillo MC4, Georges J5, Isaac MB6, Khachaturian Z7, Kim SY8, Morris JC9, Pasquier F10, Ritchie C11, Sperling R12,Karlawish J13.

Author information

• 1Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain. Electronic address: jlmolinuevo@fpmaragall.org.
• 2Pompeu Fabra University and Pasqual Maragall Foundation, Barcelona, Spain.
• 3Clinical Pharmacology Department, Hospital Clinic and IDIBAPS, Barcelona, Spain.
• 4Medical & Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
• 5Alzheimer Europe, Luxembourg, Luxembourg.
• 6European Medicines Agency (EMA).
• 7The Campaign to Prevent Alzheimer by 2020 (PAD2020), Potomac, MD, USA.
• 8Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
• 9Washington University School of Medicine, St Louis, MO, USA.
• 10Inserm 1171, Université Lille2, CHU, Memory Centre Lille, France.
• 11Centre for Clinical Brain Sciences, University of Edinburgh, UK.
• 12Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
• 13Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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.