title: Outcomes Assessment in Clinical Trials of Alzheimer's Disease and its Precursors: Readying for Short-term and Long-term Clinical Trial Needs.
abstract: An evolving paradigm shift in the diagnostic conceptualization of Alzheimer's disease is reflected in its recently updated diagnostic criteria from the National Institute on Aging-Alzheimer's Association and the International Working Group. Additionally, it is reflected in the increased focus in this field on conducting prevention trials in addition to improving cognition and function in people with dementia. These developments are making key contributions towards defining new regulatory thinking around Alzheimer's disease treatment earlier in the disease continuum. As a result, the field as a whole is now concentrated on exploring the next-generation of cognitive and functional outcome measures that will support clinical trials focused on treating the slow slide into cognitive and functional impairment. With this backdrop, the International Society for CNS Clinical Trials and Methodology convened semi-annual working group meetings which began in spring of 2012 to address methodological issues in this area. This report presents the most critical issues around primary outcome assessments in Alzheimer's disease clinical trials, and summarizes the presentations, discussions, and recommendations of those meetings, within the context of the evolving landscape of Alzheimer's disease clinical trials.
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Holly
authors.initials: H
authors.lastname: Posner
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Rosie
authors.initials: R
authors.lastname: Curiel
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Edgar
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hendrix
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Enchi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Loewenstein
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Glenn
authors.initials: G
authors.lastname: Morrison
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Leslie
authors.initials: L
authors.lastname: Shinobu
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Wesnes
authors.affiliation: Dr. Posner is with Pfizer Inc., New York, New York; Drs. Curiel, Loewenstein, and Harvey are with the University of Miami Leonard Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, Miami, Florida; Dr. Edgar is with Roche, Roche Products Ltd, Hertfordshire, United Kingdom; Dr. Hendrix is with Pentara Corporation, Salt Lake City, Utah; Dr. Liu is with Prothena Biosciences, Inc., South San Francisco, California; Dr. Morrison is with Lumos Labs, Inc., San Francisco, California; Dr. Shinobu is with Decibel, Therapeutics, Inc., Cambridge, Massachussetts; and Dr. Wesnes is with Wesnes Cognition Ltd., Streatley on Thames and Department of Psychology, Northumbria University, Newcastle, United Kingdom.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Harvey
keywords: Early Alzheimer’s disease; MCI; clinical trials; cognition; functional assessment; mild cognitive impairment