Strengthening acute stroke trials through optimal use of disability end points

FB Young, KR Lees, CJ Weir, GAIN Intl Trial Steering Comm Inve

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose-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 greater than or equal to60 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.

Original languageEnglish
Pages (from-to)2676-2680
Number of pages5
JournalStroke
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2003

Keywords

  • clinical trials
  • end point determination
  • neuroprotection
  • stroke, acute
  • thrombolysis
  • RANDOMIZED CONTROLLED-TRIAL
  • ACUTE ISCHEMIC-STROKE
  • TISSUE-PLASMINOGEN ACTIVATOR
  • MODIFIED RANKIN SCALE
  • CEREBRAL INFARCTION
  • BARTHEL INDEX
  • OUTCOMES
  • NEUROPROTECTION
  • RECOMMENDATIONS

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