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Cited by 913Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

Clinical trials in head injury

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Narayan, Raj K., Michel, Mary Ellen, Ansell, Beth, Baethmann, Alex, Biegon, Anat, Bracken, Michael B., Bullock, M. Ross, Choi, Sung C. +38 more·2002·Journal of Neurotrauma
DOI 10.1089/089771502753754037PMC PMC1462953
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Abstract

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

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  • More than 30 phase-III clinical trials have failed to improve secondary injury outcome measures after TBI despite preclinical evidence for successful pharmacologic intervention.

    “Despite preclinical studies providing evidence for successful pharmacologic intervention, more than 30 phase-III clinical trials have failed to improve secondary injury outcome measures after TBI (35–37).”

    From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [35]

    The Introduction says several TBI trials failed to demonstrate significant improvement in outcomes despite promising preclinical data. It does not establish that more than 30 of those trials were phase III or that they failed specifically on secondary-injury outcome measures; its figure of over 200 refers to randomized TBI therapy trials generally. (LLM, conf=0.86)

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Authors
Narayan, R. K., Michel, M. E., Ansell, B., Baethmann, A., Biegon, A., Bracken, M. B., Bullock, M. R., Choi, S. C., Clifton, G. L., Contant, C. F., Coplin, W. M., Dietrich, W. D., Ghajar, J., Grady, S. M., Grossman, R. G., Hall, E. D., Heetderks, W., Hovda, D. A., Jallo, J., Katz, R. L., Knoller, N., Kochanek, P. M., Maas, A. I., Majde, J., Marion, D. W., Marmarou, A., Marshall, L. F., McIntosh, T. K., Miller, E., Mohberg, N., Muizelaar, J. P., Pitts, L. H., Quinn, P., Riesenfeld, G., Robertson, C. S., Strauss, K. I., Teasdale, G., Temkin, N., Tuma, R., Wade, C., Walker, M. D., Weinrich, M., Whyte, J., Wilberger, J., Young, A. B., & Yurkewicz, L.
Affiliations
  • Temple University Hospital (US)
  • National Institute of Neurological Disorders and Stroke (US)
  • National Institutes of Health (US)
  • Ludwig-Maximilians-Universität München (DE)
  • Lawrence Berkeley National Laboratory (US)
  • Yale University (US)
  • Virginia Commonwealth University (US)
  • The University of Texas Health Science Center at Houston (US)
  • Baylor College of Medicine (US)
  • Wayne State University (US)
  • University of Miami (US)
  • Brain Trauma Foundation (US)
  • Hospital of the University of Pennsylvania (US)
  • Pfizer (United States) (US)
  • University of California, Los Angeles (US)
  • Temple University (US)
  • United States Food and Drug Administration (US)
  • Sheba Medical Center (IL)
  • University of Pittsburgh (US)
  • Academisch Ziekenhuis Rotterdam (NL)
  • Office of Naval Research (US)
  • University of California San Diego (US)
  • University of California Davis Medical Center (US)
  • University of California, San Francisco (US)
  • Southern General Hospital (GB)
  • University of Washington (US)
  • Allegheny General Hospital (US)
  • Albert B. Chandler Hospital (US)
ORCID
Venue
Journal of Neurotrauma
Publisher
SAGE Publications
Published
2002-05
Volume
19
Issue
5
Pages
503-557
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
DOI
10.1089/089771502753754037
PMC
PMC1462953
OpenAlex
W2045663952
Cited by
913
References
0
Citations by year
2026: 11 · 2025: 16 · 2024: 20 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 35 · 2019: 43 · 2018: 43 · 2017: 40 · 2016: 42 · 2015: 55 · 2014: 49 · 2013: 56 · 2012: 61
FWCI
20.60
Type
journal article
Language
en
Open access
Licence
www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Deep Blue (University of Michigan) (submittedVersion, public-domain)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • National Institutes of Health (7r01ns038654-04)
  • National Institute of Neurological Disorders and Stroke (R01-NS038654)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
traumatic brain injury, clinical trial design, closed head injury, penetrating head injury, translational research, treatment failure, long-term disability
MeSH terms
Brain Injuries, Clinical Trials as Topic, Humans

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