Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's disease
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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.
McGhee , D , Parker , A , Fielding , S , Zajicek , J & Counsell , C 2015 , ' Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's disease ' Journal of Neurology, Neurosurgery, and Psychiatry , vol 86 , no. 2 , pp. 180-185 . DOI: 10.1136/jnnp-2014-307703
Journal of Neurology, Neurosurgery, and Psychiatry
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DM was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124). The PINE study was funded by Parkinson’s UK (grant numbers G0502 and G0914), the BMA Doris Hillier Award, NHS Grampian Endowments, RS MacDonald Trust and SPRING (Special Parkinson’s Research Interest Group).