(Stroke. 2000;31:2335.)
© 2000 American Heart Association, Inc.
Original Contributions |
Finding the Most Powerful Measures of the Effectiveness of Tissue Plasminogen Activator in the NINDS tPA Stroke Trial
From the Department of Neurology, University of Cincinnati (Ohio) (J.P.B.); Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Mich (M.L.); Borgess Research Institute, Kalamazoo, Mich (R.K.); Department of Neurology, Wayne State University School of Medicine, Detroit, Mich (S.R.L.); University of California at San Diego Stroke Center (P.D.L.); Department of Neurology, University of Virginia Health System, Charlottesville (E.C.H.); Department of Neurology, Mayo Clinic Jacksonville (Fla) (T.G.B.); Department of Neurology, University of Texas, Houston (J.G.); Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston (B.C.T.); Division of Stroke and Trauma, National Institute of Neurological Disorders and Stroke, Bethesda, Md (J.R.M.); and Department of Neurology, Emory University School of Medicine, Atlanta, Ga (M.F.).
Correspondence to Joseph Broderick, MD, University of Cincinnati, Department of Neurology, 231 Bethesda Ave, ML 0525, Cincinnati, OH 45267-0525.
Background and Purpose—We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial.
Methods—Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results.
Results—Of the 5 most powerful outcome measures for early
activity of tPA, 4 involved the National Institutes of Health Stroke
Scale (NIHSS) score at 24 hours or changes in the NIHSS score from
baseline to 24 hours. The best overall single outcome measure was an
NIHSS score 
2 at 24 hours, which provided an odds ratio of 5.4 (95%
CI, 2.4 to 12.1) and a projected sample size of 58 per treatment
group assuming an 
of 0.05 (2-sided test) and a power of 80% using
part I data. The top 2 and 3 of the top 5 outcome measures for
detecting the longer-term efficacy of tPA also involved the NIHSS
score. A Rankin score of 0 or 1 at 3 months was the third most powerful
outcome measure. Outcome measures identified by CART from part I data
were not as sensitive in detecting the effectiveness of tPA when
applied to part II data.
Conclusions—Measures using the NIHSS and a Rankin score 1 were
the most sensitive discriminators of the effectiveness of tPA in the
NINDS tPA Stroke Trial compared with the other clinical and
radiological measures. The outcome measures identified in this
exploratory analysis (eg, NIHSS score 2 at 24 hours) would be
best used as an outcome measure in future phase II trials of
recanalization begun within the first 3 hours after
stroke onset, with inclusion and exclusion criteria similar to those in
the NINDS tPA Stroke Trial.
Key Words: clinical trials • models, predictive • outcome • stroke • tissue plasminogen activator
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