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.
Citation: Jonathan P. Roiser, Pradeep J. Nathan, Adrian P. Mander, Gabriel Adusei, Kenton H. Zavitz, Andrew D. Blackwell Assessment of cognitive safety in clinical drug development doi:10.1016/j.drudis.2015.11.003
Available online: 22 November 2015
Copyright: © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).
Conflict of interest:
Other than A.P.M. and J.P.R., all authors were employees of Cambridge Cognition Ltd at the time of writing. J.P.R. consults for Cambridge Cognition Ltd. P.J.N. is on the editorial board of Drug Discovery Today but was not involved in the review of this manuscript.
We thank Kristina Cook for assistance in figure preparation and Rebecca Landy for statistical discussions. This article was supported by Cambridge Cognition Ltd. Employees of the company made substantive intellectual contributions to the manuscript and approved the final version. A.P.M. is funded by the Medical Research Council (grant number G0800860).