@article{cddff550b0a64d1fa64771f60ac7f189,
title = "Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease",
abstract = "Background: The promise of Alzheimer's disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer's disease and thus represents the most rational target for an initial effort at standardization. Methods and Results: The authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer's Disease Centers-Alzheimer's Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer's Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark. Conclusions: Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers.",
keywords = "Alzheimer's disease, Biomarker standards, Biomarkers, Hippocampus, Magnetic resonance imaging",
author = "Jack, {Clifford R.} and Frederik Barkhof and Bernstein, {Matt A.} and Marc Cantillon and Cole, {Patricia E.} and Charles Decarli and Bruno Dubois and Simon Duchesne and Fox, {Nick C.} and Frisoni, {Giovanni B.} and Harald Hampel and Hill, {Derek L.G.} and Keith Johnson and Mangin, {Jean Franois} and Philip Scheltens and Schwarz, {Adam J.} and Reisa Sperling and Joyce Suhy and Thompson, {Paul M.} and Michael Weiner and Foster, {Norman L.}",
note = "Funding Information: C.R.J., Jr. serves as a consultant for Janssen, Lilly, General Electric (GE), Johnson and Johnson, Eisai, and {\'E}lan. He is an investigator in clinical trials sponsored by Pfizer, Allon and Baxter, Inc. He receives research funding from the NIA (R01-AG11378 [PI], P50-AG16574 [Co-I], R21-AG38736 [Co-I], and U01 AG024904-01 [Co-I]), and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Foundation. He owns stock in Johnson and Johnson. F.B. has received compensation for consulting from Roche, Lundbeck, Janssen Alz Immunotherapy, and GE Medical Systems; M.A.B. receives research contract funding from Pfizer Inc., and Baxter Allon; M.C. is an employee of Coalition Against Major Diseases. P.E.C. reports no conflicts; C.D.C. reports no conflicts; B.D. has served on the advisory boards of GE healthcare and Eisai/Pfizer; S.D. reports no conflicts; N.C.F. served on the scientific advisory boards of Alzheimer{\textquoteright}s Research Forum, Alzheimer{\textquoteright}s Society and Alzheimer{\textquoteright}s Research Trust, and editorial boards of Alzheimer{\textquoteright}s Disease and Associated Disorders; Neurodegenerative Diseases and BioMed Central—Alzheimer{\textquoteright}s Research and Therapy. He holds a patent for QA Box that may accrue revenue. In the last 5 years, his research group has received payment for consultancy or for conducting studies from Abbott Laboratories, Elan Pharmaceuticals, Eisai, Eli Lilly, GE Healthcare, Information extraction from imaging company (IXICO), Lundbeck, Pfizer Inc, Sanofi-Aventis, and Wyeth Pharmaceuticals. He receives research support from Medical Research Council (MRC) (G0801306 [PI], G0601846 [PI]), National Institutes of Health (NIH) (U01 AG024904 [Co-investigator{sub contract}]), Alzheimer Research Trust (ART/RF/2007/1 [PI]), National Institute for Health Research (NIHR) (Senior Investigator), and Engineering and Physical Sciences Research Council (EPSRC) (GR/S48844/01 [PI]); G.B.F. serves/has served on the advisory boards for Lilly, Bristol-Myers Squibb, Bayer, Lundbeck, Elan, Astra Zeneca, Pfizer, Taurx, and Wyeth. He is a member of the editorial boards of Lancet Neurology, Aging Clinical & Experimental Research, Alzheimer{\textquoteright}s Disease & Associated Disorders, and Neurodegenerative Diseases. He serves as the Imaging Selection Editor of Neurobiology of Aging. He has received grants from Wyeth Int{\textquoteright}l, Lilly Int{\textquoteright}l, Lundbeck Italia, and the AA ; H.H. disclosed no conflicts; D.L.G.H. is an employee and stock holder in IXICO Ltd; K.J. reports no conflicts; J.-F.M. reports no conflicts; P.S. serves/has served on the advisory boards of Genentech, Novartis, Roche, Danone, Nutricia, Baxter, and Lundbeck. He has been a speaker at symposia organized by Lundbeck, Merz, Danone, Novartis, Roche, and Genentech. For all his activities, he receives no personal compensation. Funding Information: He serves on the editorial board of Alzheimer{\textquoteright}s Research & Therapy and Alzheimers Disease and Associated Disorders, is a member of the scientific advisory board of the European Union Joint Programming Initiative and the French National Plan Alzheimer. The Alzheimer Center receives unrestricted funding from various sources through the VUmc Fonds; A.J.S. is an employee and shareholder of Eli Lilly and Company; R.S. has been a consultant for Pfizer, Janssen, Elan, Bristol-Myers-Squibb, Bayer, and Avid (unpaid). She is a site investigator for clinical trials for Bristol-Myers-Squibb, Pfizer, Janssen, and Avid; J.S. is an employee of Synarc; P.M.T. reports no conflicts; M.W. serves/has served on the advisory boards of Elan/Wyeth, Novartis, Banner, Veterans Affairs Central Office, Lilly, Araclon and Insitut Catala de Neurociencies Aplicades, Biogen Idec, and Pfizer. He serves/has served as a consultant for Elan/Wyeth, Novartis, Forest, Ipsen, Daiichi Sankyo, Inc., Astra Zeneca, Araclon, Medivation/Pfizer, TauRx Therapeutics Ltd, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, Alzheimer's Association (SA), Servier, Synarc, and Pfizer. Funding for his travel has been provided by Elan/Wyeth, AA, Forest, University of California, Davis, Tel-Aviv University Medical School, Colloquium Paris, Ipsen, Wenner-Gren Foundations, Social Security Administration, Korean Neurological Association, National Institutes of Health, Washington University at St. Louis, Banner Alzheimer{\textquoteright}s Institute, Clinical Trials on Alzheimer's Disease (CTAD), Veterans Affairs Central Office, Beijing Institute of Geriatrics, Innogenetics, New York University, NeuroVigil, Inc., Centre Hospitalier Regional (CHRU)-Hospital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego – ADNI, Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Pfizer, Paul Sabatier University, and Novartis. He serves on the editorial advisory boards of Alzheimer{\textquoteright}s and Dementia and MRI. He has received honoraria from American Academy of Neurology, Ipsen, NeuroVigil, Inc., and Insitut Catala de Neurociencies Aplicades. He receives research support from Merck and Avid. He owns stock in Synarc and Elan; N.L.F. disclosed no conflicts.",
year = "2011",
month = jul,
doi = "10.1016/j.jalz.2011.04.007",
language = "English (US)",
volume = "7",
pages = "474--485.e4",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "4",
}