Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's disease

David McGhee, Alexander Parker, Shona Fielding, John Zajicek, Carl Counsell

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6 Citations (Scopus)
8 Downloads (Pure)

Abstract

BACKGROUND: Simple, robust, sensitive and clinically meaningful outcome measures are required for neuroprotective trials in Parkinson's disease (PD). We explored the feasibility of a composite binary outcome measure, 'dead or dependent', in such trials using data from a prospective follow-up study of an incident cohort of PD patients.

METHODS: Two hundred incident patients had an annual follow-up, including assessment of the Hoehn-Yahr stage (H-Y) and Schwab and England Activities of Daily Living Scale (S&E). Annual scores were converted into binary variables (H-Y <3 vs H-Y ≥3, and S&E ≥80% vs S&E <80%). A new outcome of 'dead or dependent' was also created, with dependence in activities of daily living defined as S&E <80%. Using these data, sample sizes were calculated for a hypothetical three-year randomised trial in which the trial outcome was defined by a binary clinical variable, all-cause mortality, or PD-related mortality.

RESULTS: At 3 years, 18.0% of patients were dead and 38.4% were dead or dependent. At 80% power, large sample sizes were required if PD-related mortality (n=1938 per study arm) or all-cause mortality (n=734) were used as the outcome, even for large treatment effects (30% reduction in relative risk). The new outcome of 'death or dependency' required the smallest sample sizes of all the outcome measures (n=277 for 30% reduction in relative risk, 627 for a 20% reduction).

CONCLUSIONS: 'Death or dependency' is a feasible and potentially useful outcome measure in PD trials of neuroprotective agents, but further work is required to validate its use and define dependency.

Original languageEnglish
Pages (from-to)180-185
Number of pages6
JournalJournal of Neurology, Neurosurgery & Psychiatry
Volume86
Issue number2
Early online date22 May 2014
DOIs
Publication statusPublished - Feb 2015

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Parkinson Disease
Outcome Assessment (Health Care)
Clinical Trials
Sample Size
Mortality
Activities of Daily Living
Neuroprotective Agents
England
Therapeutics

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Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's disease. / McGhee, David; Parker, Alexander; Fielding, Shona; Zajicek, John; Counsell, Carl.

In: Journal of Neurology, Neurosurgery & Psychiatry, Vol. 86, No. 2, 02.2015, p. 180-185.

Research output: Contribution to journalArticle

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N2 - BACKGROUND: Simple, robust, sensitive and clinically meaningful outcome measures are required for neuroprotective trials in Parkinson's disease (PD). We explored the feasibility of a composite binary outcome measure, 'dead or dependent', in such trials using data from a prospective follow-up study of an incident cohort of PD patients.METHODS: Two hundred incident patients had an annual follow-up, including assessment of the Hoehn-Yahr stage (H-Y) and Schwab and England Activities of Daily Living Scale (S&E). Annual scores were converted into binary variables (H-Y <3 vs H-Y ≥3, and S&E ≥80% vs S&E <80%). A new outcome of 'dead or dependent' was also created, with dependence in activities of daily living defined as S&E <80%. Using these data, sample sizes were calculated for a hypothetical three-year randomised trial in which the trial outcome was defined by a binary clinical variable, all-cause mortality, or PD-related mortality.RESULTS: At 3 years, 18.0% of patients were dead and 38.4% were dead or dependent. At 80% power, large sample sizes were required if PD-related mortality (n=1938 per study arm) or all-cause mortality (n=734) were used as the outcome, even for large treatment effects (30% reduction in relative risk). The new outcome of 'death or dependency' required the smallest sample sizes of all the outcome measures (n=277 for 30% reduction in relative risk, 627 for a 20% reduction).CONCLUSIONS: 'Death or dependency' is a feasible and potentially useful outcome measure in PD trials of neuroprotective agents, but further work is required to validate its use and define dependency.

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