Using 'dead or dependent' as an outcome measure in clinical trials in Parkinson's disease.
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.
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
David
D
McGhee
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Alexander
A
Parker
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Shona
S
Fielding
Clinical Neurology Research Group, University of Plymouth, Plymouth, Derriford, UK.
John
J
Zajicek
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Carl
C
Counsell
D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D015203:Reproducibility of Results; D018401:Sample Size
D018696:Neuroprotective Agents
EVIDENCE-BASED NEUROLOGY; PARKINSON'S DISEASE; RANDOMISED TRIALS