The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer’s disease treatment?

Stephanie Evans*, Kevin McRae-McKee, Mei Mei Wong, Christoforos Hadjichrysanthou, Frank De Wolf, Roy Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

To date, Alzheimer’s disease (AD) clinical trials have been largely unsuccessful. Failures have been attributed to a number of factors including ineffective drugs, inadequate targets, and poor trial design, of which the choice of endpoint is crucial. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we have calculated the minimum detectable effect size (MDES) in change from baseline of a range of measures over time, and in different diagnostic groups along the AD development trajectory. The Functional Activities Questionnaire score had the smallest MDES for a single endpoint where an effect of 27% could be detected within 3 years in participants with Late Mild Cognitive Impairment (LMCI) at baseline, closely followed by the Clinical Dementia Rating Sum of Boxes (CDRSB) score at 28% after 2 years in the same group. Composite measures were even more successful than single endpoints with an MDES of 21% in 3 years. Using alternative cognitive, imaging, functional, or composite endpoints, and recruiting patients that have LMCI could improve the success rate of AD clinical trials.

Original languageEnglish
Pages (from-to)635-644
Number of pages10
JournalEuropean Journal of Epidemiology
Volume33
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defence award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association;

Funding Information:
Data collection and sharing for this project was funded by the Alzheimer?s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defence award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer?s Association; Alzheimer?s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer?s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. R.M.A. is a non-executive board member of GlaxoSmithKline (GSK). GSK played no part in this research, its funding or the preparation of the manuscript.

Funding Information:
This study was funded by the Janssen Prevention Center.

Publisher Copyright:
© 2018, The Author(s).

Keywords

  • Alzheimer’s disease
  • Clinical trials
  • Longitudinal data analysis

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