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A Critical Review of Stroke Trial Analytical Methodology: Outcome Measures, Study Design, and Correction for Imbalances

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Translational Stroke Research

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Despite considerable advances in understanding the pathophysiology of stroke, there has been a lack of success in identifying new therapies to improve outcome. Our work suggests that the execution of stroke trials is not the primary issue. Here, we consider the analysis of clinical trials as a potential source of error. We review several components of stroke trial analysis. We conclude that many of these trials have been plagued by inappropriate use of complex statistical analytical methods that have not considered the underlying assumptions required for their valid application. Unfortunately, many of these methods have been encouraged by publishing, regulatory, granting, and pharmaceutical entities, yet continue to generate flawed results, usually discovered when early results are not confirmed in subsequent large trials. Because these errors may be just as likely to occur when early studies appear negative and so potentially reflect a missed opportunity to identify an effective therapy, we urge a reassessment of these analytical principles and provide some alternative approaches.

Funding for the Stroke Outcomes Laboratory provided by the Institute of Clinical and Translational Research Pilot Grant Program, Baylor College of Medicine.

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Authors and Affiliations

  1. Department of Neurology and The Stroke Outcomes Laboratory (SOuL), Baylor College of Medicine and The Michael E. DeBakey VA Medical Center Comprehensive Stroke Program, 2002 Holcombe Blvd (127), Houston, TX, 77030, USA

    Pitchaiah Mandava MD, PhD, MSEE, Chase S. Krumpelman PhD, MSEE, Santosh B. Murthy MD, MPH & Thomas A. Kent MD

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  1. Pitchaiah Mandava MD, PhD, MSEE
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  2. Chase S. Krumpelman PhD, MSEE
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  3. Santosh B. Murthy MD, MPH
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  4. Thomas A. Kent MD
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Correspondence to Pitchaiah Mandava MD, PhD, MSEE .

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Editors and Affiliations

  1. , Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA

    Paul A. Lapchak

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Mandava, P., Krumpelman, C.S., Murthy, S.B., Kent, T.A. (2012). A Critical Review of Stroke Trial Analytical Methodology: Outcome Measures, Study Design, and Correction for Imbalances. In: Lapchak, P., Zhang, J. (eds) Translational Stroke Research. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9530-8_40

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