Graphic reanalysis of the two NINDS-tPA trials confirms substantial treatment benefit.
OBJECTIVE
Multiple statistical analyses of the 2 NINDS-tPA trials have confirmed study findings of benefit of fibrinolytic therapy. A recent graphic analysis departed from best practices in the visual display of quantitative information by failing to take into account the skewed functional importance of NIH Stroke Scale raw scores and by scaling change axes at up to 20 times the range achievable by individual patients.


METHODS
Using the publicly available datasets of the 2 NINDS-tPA trials, we generated a variety of figures appropriate to the characteristics of acute stroke trial data.


RESULTS
A diverse array of figures all visually delineated substantial benefits of fibrinolytic therapy, including: bar charts of normalized gain and loss; stacked bar, bar, and matrix plots of clinically relevant ordinal ranks; a time series stacked line plot of continuous scale disability weights; and line plot, bubble chart, and person icon array graphs of joint outcome table analysis. The achievable change figure showed substantially greater improvement among tPA than placebo patients, median 66.7% (interquartile range, 0 to 92.0) versus 50.0% (interquartile range, -7.1 to 80.0), P=0.003.


CONCLUSIONS
On average, under 3 hour patients treated with tPA recovered two-thirds while placebo patients improved only half of the way toward fully normal. Graphical analyses of the 2 NINDS-tPA trials, when performed according to best practices, is a useful means of conveying details about patient response to therapy not fully delineated by summary statistics, and confirms a valuable treatment benefit of under 3 hour fibrinolytic therapy in acute stroke.
Saver
Jeffrey L
JL
Stroke Center and Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Calif 90095, USA. jsaver@ucla.edu
Gornbein
Jeffrey
J
Starkman
Sidney
S
D002545:Brain Ischemia / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator