title: Assessment of cognitive safety in clinical drug development.
abstract: Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks.
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, UK. Electronic address: j.roiser@ucl.ac.uk.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK; Neuroscience Center of Excellence, inVentiv Health, Maidenhead, UK; School of Psychological Sciences, Monash University, Clayton, Australia.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Mander
authors.affiliation: Cambridge Cognition Limited, Bottisham, Cambridge, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Adusei
authors.affiliation: Cambridge Cognition Limited, Bottisham, Cambridge, UK.
authors.forename: Kenton H
authors.initials: KH
authors.lastname: Zavitz
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridge Cognition Limited, Bottisham, Cambridge, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blackwell
mesh_terms: D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design