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Cited by 109Acute Ischemic Stroke ManagementStatistical Methods in Clinical TrialsAcute Myocardial Infarction Research

The DOI matches its Crossref record; 4 of the 5 references it cites were found in a registry or an index.

Dichotomized Efficacy End Points and Global End-Point Analysis Applied to the ECASS Intention-to-Treat Data Set: Post Hoc Analysis of ECASS I

Hacke, Werner, Bluhmki, Erich, Steiner, Thorsten, Tatlisumak, Turgut, Mahagne, Marie-Helene, Sacchetti, Marisa-Luisa, Meier, Dieter·1998·Stroke
DOI 10.1161/01.str.29.10.2073
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Abstract

Background and Purpose —It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial. Methods —We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS. Results —The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS ( P =0.044; odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS ( P =0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed ( P =0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase ( P =0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group. Conclusions —Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.

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  1. 10.1001/jama.1995.03530130023023 · DOI
  2. 10.1161/str.27.11.2136 · DOI
  3. Steiner T, Höxter G, Bluhmki E, Hacke W. Multidimensional assessment of stroke outcome. Cerebrovasc Dis. 1996;6:54. Abstract.

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Metadata

Authors
Hacke, W., Bluhmki, E., Steiner, T., Tatlisumak, T., Mahagne, M.-H., Sacchetti, M.-L., & Meier, D.
Affiliations
  • Boehringer Ingelheim (Germany) (DE)
  • From the Departments of Neurology, University of Heidelberg, Heidelberg, Germany (W.H., T.S.); University of Helsinki, Helsinki, Finland (T.T.); University of Nice, Nice, France (M.-H.M.); University of Rome, Rome, Italy (M.-L.S); and Boehringer Ingelheim Pharma Deutschland, Ingelheim, Germany (E.B., D.M.).
Corresponding author
Hacke, Werner
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1998-10
Volume
29
Issue
10
Pages
2073-2075
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/01.str.29.10.2073
OpenAlex
W2102643802
Cited by
109
References
5
Citations by year
2025: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 5
FWCI
8.97
Type
journal article
Language
en
Open access
closed
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
acute ischemic stroke, alteplase, thrombolysis, intention-to-treat analysis, modified Rankin Scale, Barthel Index, NIHSS, stroke outcome measures, statistical power, post hoc analysis, stroke rehabilitation outcomes
MeSH terms
Cerebrovascular Disorders, Humans, National Institutes of Health (U.S.), Tissue Plasminogen Activator, Plasminogen Activators, Recombinant Proteins, Retrospective Studies, United States, Outcome Assessment, Health Care

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