The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
Clinical Trials in Traumatic Brain Injury: Past Experience and Current Developments
Open accessAbstract
In this article, we review past and current experience in clinical trials of traumatic brain injuries (TBIs), we discuss limitations and challenges, and we summarize current directions. The focus is on severe and moderate TBIs. A systematic literature search of the years from 1980 to 2009 revealed 27 large phase III trials in TBI; we were aware of a further 6 unpublished trials. Analysis of these 33 trials yielded interesting observations: There was a peak incidence of trial initiations that occurred in the mid-1990s with a sharp decline during the period from 2000 to 2004. Most trials that reported a significant treatment effect were studies on a therapeutic strategy (e.g., decompressive craniectomy, hypothermia), and these were single-center studies. Increasingly, studies have been shifting toward the Far East. The currently existing trial registries permit insight into ongoing or recently conducted trials. Compared with the past decade, the number of studies on neuroprotective agents taken forward into efficacy-oriented studies is low. In contrast, the number of studies on therapeutic strategies appears to be increasing again. The disappointing results in trials on neuroprotective agents in TBI have led to a critical reappraisal of clinical trial methodology. This has resulted in recommendations for preclinical workup and has triggered extensive analysis on approaches to improve the design and analysis of clinical trials in TBI. An interagency initiative toward standardization on selection and coding of data elements across the broad spectrum of TBI is ongoing, and will facilitate comparison of research findings across studies and encourage high-quality meta-analysis of individual patient data in the future.
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“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 [36]
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Cites
Moderate and severe traumatic brain injury in adults
Maas, A. I., Stocchetti, N., & Bullock, R. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70164-9 · Cited by 2,123
Self-citationThe Incidence and Economic Burden of Injuries in the United States
Finkelstein, E. A., Corso, P. S., & Miller, T. R. (2006) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195179484.001.0001 · Cited by 936
Clinical trials in head injury
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., et al. (2002) · Journal of Neurotrauma · doi:10.1089/089771502753754037 · Cited by 913
Self-citationPrevention of secondary ischemic insults after severe head injury
Robertson, C. S., Valadka, A. B., Hannay, H. J., Contant, C. F., Gopinath, S. P., Cormio, M., Uzura, M., & Grossman, R. G. (1999) · Critical Care Medicine · doi:10.1097/00003246-199910000-00002 · Cited by 748
Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury
Oertel, M. F., Kelly, D. F., McArthur, D. A., Boscardin, W. J., Glenn, T. C., Lee, J. H., Gravori, T., Obukhov, D., McBride, D. Q., & Martin, N. A. (2002) · Journal of neurosurgery · doi:10.3171/jns.2002.96.1.0109 · Cited by 482
Xiao, G., Wei, J., Yan, W., Wang, W., & Lu, Z. (2008) · Critical Care · doi:10.1186/cc6887 · Cited by 463
Cooper, D. J., Myles, P. S., McDermott, F. T., Murray, L., Laidlaw, J. D., Cooper, G., Tremayne, A. B., Bernard, S., Ponsford, J. L., & For the HTS Study Investigators For the HTS Study Investigators (2004) · JAMA · doi:10.1001/jama.291.11.1350 · Cited by 461
Prognosis and Clinical Trial Design in Traumatic Brain Injury: The IMPACT Study
Maas, A., Marmarou, A., Murray, G., Teasdale, G., & Steyerberg, E. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2006.0024 · Cited by 366
Self-citationA multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury
Marshall, L. F., Maas, A. I. R., Marshall, S. B., Bricolo, A., Fearnside, M. R., Iannotti, F., Klauber, M. R., Lagarrigue, J., Lobato, R., Persson, L., et al. (1998) · Journal of neurosurgery · doi:10.3171/jns.1998.89.4.0519 · Cited by 336
Self-citation
Research works printed but not linked: 2
- Maas, 1999, Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy?, Neurosurgery, 44, 1286
- Gaab, 1994, “Ultrahigh” dexamethasone in acute brain injury, Zentralbl Neurochir, 55, 135
Cited by
Sorted by citations
Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research
Maas, A. I. R., Menon, D. K., Adelson, P. D., Andelic, N., Bell, M. J., Belli, A., Bragge, P., Brazinova, A., Büki, A., Chesnut, R. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30371-x · Cited by 2,609
Self-citationDecompressive Craniectomy in Diffuse Traumatic Brain Injury
Cooper, D. J., Rosenfeld, J. V., Murray, L., Arabi, Y. M., Davies, A. R., D’Urso, P., Kossmann, T., Ponsford, J. L., Seppelt, I., Reilly, P. L., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102077 · Cited by 1,661
Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets
Ng, S. Y., & Lee, A. Y. W. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00528 · Cited by 906
“The L-type voltage-sensitive calcium channel antagonist nimodipine was also found to have beneficial effect for memory impairment in rats, though clinical trials were terminated because of its hypotensive effects and the lack of improvement in intracranial pressure observed in TBI survivors (Bailey et al., 1991; Veng…”
BackgroundMicroglia in the TBI brain: The good, the bad, and the dysregulated
Loane, D. J., & Kumar, A. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.08.018 · Cited by 846
“Historically, broad-spectrum anti-inflammatory therapies for TBI have translated poorly to the clinic for human head injury (Kumar and Loane, 2012; Maas et al., 2010), whichmay in part reflect loss of beneficialM2-like effects inmicroglia.”
BackgroundNeuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention
Kumar, A., & Loane, D. J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.008 · Cited by 710
“However, translation of promising experimental neuroprotective treatments to human injury have been very disappointing, with none of the pharmacological treatments resulting in any consistent improvements in outcome in the clinic (Maas et al., 2010).”
Metadata
- Authors
- Maas, A. I. R., Roozenbeek, B., & Manley, G. T.
- Affiliations
- Antwerp University Hospital (BE)
- Erasmus MC (NL)
- University of California, San Francisco (US)
- Corresponding author
- Maas, Andrew I.R.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 7
- Issue
- 1
- Pages
- 115-126
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC5084118
- OpenAlex
- W2112462557
- Cited by
- 291
- References
- 44
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 12 · 2023: 13 · 2022: 21 · 2021: 10 · 2020: 17 · 2019: 20 · 2018: 26 · 2017: 19 · 2016: 24 · 2015: 24 · 2014: 20 · 2013: 16 · 2012: 28
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- traumatic brain injury, clinical trials, neuroprotective agents, decompressive craniectomy, therapeutic hypothermia, clinical trial registries, clinical trial design, data element standardization, individual patient data meta-analysis
- MeSH terms
- Brain Injuries, Clinical Trials as Topic, Humans
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