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Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials

Lookup NU author(s): Dr Nick Steen


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Objectives The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages.Methods Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated.Results There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4.Discussion We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.

Publication metadata

Author(s): Balendra R, Jones A, Jivraj N, Steen IN, Young CA, Shaw PJ, Turner MR, Leigh PN, Al-Chalabi A, UK-MND LiCALS Study Group, Mito Target ALS Study Group

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery and Psychiatry

Year: 2015

Volume: 86

Issue: 1

Pages: 45-49

Print publication date: 01/01/2015

Online publication date: 24/01/2014

Acceptance date: 30/12/2013

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Publishing Group Ltd.


DOI: 10.1136/jnnp-2013-306865


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Funder referenceFunder name
King's College London
NIHR Dementia Biomedical Research Unit at South London
The Motor Neurone Disease Association of Great Britain and Northern Ireland
Maudsley NHS Foundation Trust
National Institute for Health Research (NIHR) DeNDRoN
259867European Community
HEALTH-F2-2008-223388European Union