title: Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease.
abstract: BACKGROUND
  Regulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.
  
  
  METHODS
  The Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data.
  
  
  RESULTS
  The literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011.
  
  
  CONCLUSIONS
  We summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.
authors.affiliation: IXICO Ltd., London, UK.
authors.forename: Derek L G
authors.initials: DLG
authors.lastname: Hill
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Isaac
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Spiros
authors.initials: S
authors.lastname: Vamvakas
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Hemmings
authors.affiliation: Alzheimer's Association, Chicago, IL, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA; The University of Texas School of Public Health, Houston, TX, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: University of California, Davis, CA, USA.
authors.forename: Laurel
authors.initials: L
authors.lastname: Beckett
authors.affiliation: IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boccardi
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Brewer
authors.affiliation: Coalition Against Major Diseases, Critical Path Institute, Tucson, AZ, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Brumfield
authors.affiliation: Wellnessmanagments.com, Livingston, NJ, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Cantillon
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Cole
authors.affiliation: UCL Institute of Neurology, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Fox
authors.affiliation: IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Jack
authors.affiliation: Bristol Myers Squibb, Wallingford, CT, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelleher
authors.affiliation: Bristol Myers Squibb, Wallingford, CT, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.affiliation: Janssen Pharmaceutical Research and Development, Titusville, NJ, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Novak
authors.affiliation: Novartis, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Maguire
authors.affiliation: Novartis, NJ, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Meibach
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Patterson
authors.affiliation: Independent science writer, Elverson, PA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bain
authors.affiliation: CHDI Foundation Inc., Princeton, NJ, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.affiliation: ICON Medical Imaging, Warrington, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Raunig
authors.affiliation: Bristol Myers Squibb, Wallingford, CT, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.affiliation: SYNARC Inc., Newark, CA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Suhy
authors.affiliation: University of California, Davis, CA, USA.
authors.forename: Huanli
authors.initials: H
authors.lastname: Wang
authors.affiliation: IXICO Ltd., London, UK; Department of Computing, Imperial College London, London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Wolz
authors.affiliation: Coalition Against Major Diseases, Critical Path Institute, Tucson, AZ, USA. Electronic address: DStephenson@c-path.org.
authors.forename: Diane
authors.initials: D
authors.lastname: Stephenson
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000628:therapy*; D002986:Clinical Trials as Topic; D060825:Cognitive Dysfunction; D016208:Databases, Factual / Q000706:statistics & numerical data; D018450:Disease Progression; D005060:Europe; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D059906:Neuroimaging; D016016:Proportional Hazards Models; D012372:ROC Curve
keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; Hippocampal volume; Mild cognitive impairment