Strengthening acute stroke trials through optimal use of disability end points.
OBJECTIVE
Suboptimal choices of primary end point for acute stroke trials may have contributed to inconclusive results. The Barthel Index (BI) and Rankin Scale (RS) have been widely used and analyzed in various ways. We sought to investigate the most powerful end point for use in acute stroke trials.


METHODS
Data from the Glycine Antagonist in Neuroprotection (GAIN) International Trial were used to simulate 24 000 clinical trials exploring various patterns and magnitudes of treatment effect and thus to estimate the statistical power for a range of end points based on the BI or RS.


RESULTS
RS end points were more powerful than BI end points. End points dichotomized toward the favorable extreme of either scale or adjusted according to baseline prognosis ("patient-specific" end point) were among the most powerful. Combining RS and BI in a "global" end point was also successful. Improvements in statistical power indicated that using a RS end point instead of BI > or =60 could reduce the sample size by up to 84% (95% CI, 80% to 87%), 73% (95% CI, 68% to 79%) for a patient-specific BI end point, or 81% (95% CI, 76% to 85%) for a global end point.


CONCLUSIONS
The RS and global end points are preferable to BI end points; the position of the cut point is also important. Better choices of end point substantially strengthen trial power for a given trial size or allow reduced sample sizes without loss of statistical power.
Young
Fiona B
FB
Division of Cardiovascular and Medical Sciences, University of Glasgow, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, Scotland. Fby1w@clinmed.gla.ac.uk
Lees
Kennedy R
KR
Weir
Christopher J
CJ
D000208:Acute Disease; D003198:Computer Simulation; D004185:Disability Evaluation; D023381:Endpoint Determination / Q000706:statistics & numerical data*; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012107:Research Design; D020521:Stroke / Q000628:therapy*