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.