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search of the years from 1980 to 2009 revealed 27 large phase III trials in TBI; we were aware of a further 6 unpublished trials.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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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 [36]
The Introduction reports encouraging preclinical results and says no multicenter phase III trial of a neuroprotective agent had convincingly shown benefit. But the trial-results discussion reports significant effects in 7 of 10 trials of therapeutic strategies and 3 of 23 trials of neuroprotective agents; the paper does not say that more than 30 trials failed. Its reviewed trials primarily measured clinical outcome, not specifically secondary-injury outcome measures. (LLM, conf=0.90)
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Prognostic Value of Major Extracranial Injury in Traumatic Brain Injury
van Leeuwen, N., Lingsma, H. F., Perel, P., Lecky, F. E., Roozenbeek, B., Lü, J., Shakur‐Still, H., Weir, J., Steyerberg, E. W., & Maas, A. I. R. (2011) · Neurosurgery · doi:10.1227/neu.0b013e318235d640 · Cited by 109 · see citing works
Self-citationProgesterone in the clinical treatment of acute traumatic brain injury
Stein, D. G., & Wright, D. W. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.489549 · Cited by 108 · see citing works
“In Europe, close to 7 million disabled people are living with the consequences of TBI [1], and in China over 3 million people a year are reported to suffer a brain injury [2-6].”
BackgroundChen, J., HU, J. L., Liu, H., Xiong, Y., Zou, Y., Huang, W., Shao, M., Wu, J., Yu, L., Wang, X., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5271 · Cited by 106 · see citing works
Kota, D. J., Prabhakara, K. S., Furman, N. E. T., Bhattarai, D., Chen, Q., DiCarlo, B., Smith, P., Triolo, F., Wenzel, P. L., Cox, C. S., et al. (2017) · Stem Cells · doi:10.1002/stem.2603 · Cited by 105 · see citing works
Neuroprotection for traumatic brain injury
Loane, D. J., Stoica, B. A., & Faden, A. I. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52892-6.00022-2 · Cited by 104 · see citing works
“Although preclinical studies have suggested many promising pharmacologic agents, more than 30 phase III prospective clinical trials have failed to show significance for their primary end point (Narayan et al., 2002; Schouten, 2007; Maas et al., 2010).”
BackgroundNielson, J. L., Cooper, S. R., Yue, J. K., Sorani, M. D., Inoue, T., Yuh, E. L., Mukherjee, P., Petrossian, T. C., Paquette, J., Lum, P. Y., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169490 · Cited by 100 · see citing works
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“1 | Combination of antioxidant agents for TBI treatment Generally, the favorable results obtained from preclinical studies of TBI assessing effects of antioxidant agents have not fully been confirmed in clinical trials [274, 275].”
BackgroundHaus, D. L., López-Velázquez, L., Gold, E. M., Cunningham, K. M., Perez, H. D., Anderson, A. J., & Cummings, B. J. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.04.008 · Cited by 99 · see citing works
“Considering that many pharmacologic interventions for TBI have been shown to be ineffective in clinical trials (Xiong et al., 2009; Maas et al., 2010; Lu et al., 2012), new treatment options must be explored.”
BackgroundNeurotransmitter changes after traumatic brain injury: an update for new treatment strategies
McGuire, J. L., Ngwenya, L. B., & McCullumsmith, R. E. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0239-6 · Cited by 101 · see citing works
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“Although numerous clinical trials have been conducted for moderate-to-severe TBI, no therapeutic intervention has proven effective in improving functional outcome (Maas et al., 2010; Narayan et al., 2002).”
Investigational agents for treatment of traumatic brain injury
Xiong, Y., Zhang, Y.-L., Mahmood, A., & Chopp, M. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1021919 · Cited by 82 · see citing works
“Over the past 40 years, > 100 RCTs in TBI were conducted [11,23,34-41].”
BackgroundAntagonism of purinergic signalling improves recovery from traumatic brain injury
Choo, A. M., Miller, W. J., Chen, Y., Nibley, P., Patel, T. P., Goletiani, C. J., Morrison, B., Kutzing, M. K., Firestein, B. L., Sul, J., et al. (2013) · Brain · doi:10.1093/brain/aws286 · Cited by 90 · see citing works
“Traumatic brain injury is a complex and evolving disease, and some treatments have progressed recently to human clinical trials (Maas et al., 2010).”
BackgroundKuriakose, M., Younger, D., Ravula, A., Alay, E., Rao, K. V. R., & Chandra, N. (2019) · Scientific Reports · doi:10.1038/s41598-019-44147-w · Cited by 81 · see citing works
Pre-Clinical Testing of Therapies for Traumatic Brain Injury
DeWitt, D. S., Hawkins, B. E., Dixon, C. E., Kochanek, P. M., Armstead, W. M., Bass, C. R., Bramlett, H. M., Büki, A., Dietrich, W. D., Ferguson, A. R., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5778 · Cited by 85 · see citing works
“14,69,70 Maas and associates 71 observed that most of the trials that reported beneficial effects of the therapy tested were single-center RCTs.”
Nairuz, T., Sangwoo-Cho, & Lee, J.-H. (2024) · Cells · doi:10.3390/cells13110966 · Cited by 84 · see citing works
“Given the considerable challenges encountered in developing pharmaceutical interventions for conditions like stroke [169] and TBI [170], where progress has been largely elusive despite substantial investments, there is a compelling case for a broader exploration of PBM’s potential.”
BackgroundTraumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents
Malkesman, O., Tucker, L. B., Ozl, J., & McCabe, J. T. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00157 · Cited by 82 · see citing works
Randomized controlled trials in adult traumatic brain injury
Lü, J., Gary, K. W., Neimeier, J. P., Ward, J., & Lapane, K. L. (2012) · Brain Injury · doi:10.3109/02699052.2012.722257 · Cited by 80 · see citing works
“The search results were then compared against the review articles related to trials targeting the acute phase [6] and post-acute phase of TBI [7, 8].”
BackgroundResultInfluentialErdman, J. W., Oria, M. P., & Pillsbury, L. (2011) · Cited by 79 · see citing works
Is aggressive treatment of traumatic brain injury cost-effective?
Whitmore, R. G., Thawani, J. P., Grady, M. S., Levine, J. M., Sanborn, M. R., & Stein, S. C. (2012) · Journal of neurosurgery · doi:10.3171/2012.1.jns11962 · Cited by 76 · see citing works
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The NLRP3 inflammasome: a potential therapeutic target for traumatic brain injury
Ishrat, T., Ismael, S., Ahmed, H. A., Adris, T., Parveen, K., & Thakor, P. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.286951 · Cited by 74 · see citing works
“More than thirty prospective clinical trials for treating TBI have not shown significant promise, as these trials focused on single mechanisms of secondary injury while the mechanisms involved in TBI are clearly multifactorial in nature (Maas et al., 2010).”
BackgroundStanley, R., Bonsu, B. K., Zhao, W., Ehrlich, P., Rogers, A., & Xiang, H. (2012) · Pediatrics · doi:10.1542/peds.2011-2074 · Cited by 67 · see citing works
Kuriakose, M., Rao, K. V. R., Younger, D., & Chandra, N. (2018) · Scientific Reports · doi:10.1038/s41598-018-26813-7 · Cited by 73 · see citing works
Microglia Receptors in Animal Models of Traumatic Brain Injury
Younger, D., Murugan, M., Rao, K. V. R., Wu, L., & Chandra, N. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1428-7 · Cited by 69 · see citing works
Novel Therapeutic Strategies for Traumatic Brain Injury: Acute Antioxidant Reinforcement
Fernández-Gajardo, R., Matamala, J. M., Carrasco, R. A., Gutiérrez, R., Melo, R., & Rodrigo, R. (2014) · CNS Drugs · doi:10.1007/s40263-013-0138-y · Cited by 68 · see citing works
“have failed to display significance for their primary outcome [258–260].”
Backgroundvan Erp, I. A. M., Michailidou, I., van Essen, T. A., van der Jagt, M., Moojen, W. A., Peul, W. C., Baas, F., & Fluiter, K. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01306-8 · Cited by 69 · see citing works
“Despite the vast amount of research performed to improve our understanding of the pathophysiology in TBI, the field has repeatedly experienced collective failures to translate research from animals to successful therapeutic application in humans [11, 12].”
BackgroundGao, Y., Li, J., Wu, L., Zhou, C., Wang, Q., Li, X., Zhou, M., & Wang, H. (2016) · Journal of Surgical Research · doi:10.1016/j.jss.2016.07.014 · Cited by 66 · see citing works
Targeting mTOR as a novel therapeutic strategy for traumatic CNS injuries
Don, A. S. A., Tsang, C., Kazdoba, T. M., D'Arcangelo, G., Young, W., & Zheng, X. F. S. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.04.010 · Cited by 70 · see citing works
Kontos, A. P., Collins, M. W., Holland, C. L., Reeves, V. L., Edelman, K. L., Benso, S., Schneider, W., & Okonkwo, D. O. (2018) · Military Medicine · doi:10.1093/milmed/usx172 · Cited by 66 · see citing works
Pleiotropic neuroprotective and metabolic effects of Actovegin's mode of action
Machicao, F. E., Muresanu, D. F., Hundsberger, H., Pflüger, M., & Guekht, A. B. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.07.069 · Cited by 64 · see citing works
“However, what is clear from clinical trials in neuroprotection is that the suppression subtractive strategywith chemical drugs does notwork [2,3].”
Past, Present, and Future of Traumatic Brain Injury Research
Hawryluk, G. W. J., & Bullock, M. R. (2016) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2016.05.002 · Cited by 65 · see citing works
“Paralleling this basic science advancement is recognition of the methodologic shortcomings of the approximately 35 phase III TBI trials undertaken to date, which likely contributed to their failure.(3) There is thus great optimism that victims of TBI may soon benefit from novel and efficacious therapeutics that have b…”
BackgroundResultInfluentialFolweiler, K. A., Sandsmark, D. K., Diaz-Arrastia, R. R., Cohen, A. S., & Masino, A. J. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6705 · Cited by 63 · see citing works
Traumatic brain injury: Changing concepts and approaches
Maas, A. I. R. (2016) · Chinese Journal of Traumatology · doi:10.1016/j.cjtee.2016.01.001 · Cited by 62 · see citing works
Self-citationThe Influence of Dietary Factors in Central Nervous System Plasticity and Injury Recovery
Gómez‐Pinilla, F., & Gomez, A. G. (2011) · PM&R · doi:10.1016/j.pmrj.2011.03.001 · Cited by 60 · see citing works
Towards a roadmap in brain protection and recovery
Muresanu, D. F., Buzoianu, A. D., Florian, I. Ş., & von Wild, T. (2012) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2012.01605.x · Cited by 58 · see citing works
“[4], the only drug that showed significant results was progesterone, which is also a non-suppressive, multimodal agent with pleiotropic neuroprotective effect [32].”
BackgroundTRIVEDI, R. B., & Humphreys, K. N. (2015) · Contemporary Clinical Trials · doi:10.1016/j.cct.2015.07.009 · Cited by 56 · see citing works
“Among neurological disorders, the IMPACT (International Mission on Prognosis and Clinical Trial Design in TBI) multidisciplinary group was formed with the mission to develop better approaches to phase III TBI trials [9,28].”
MethodDynamic neural and glial responses of a head-specific model for traumatic brain injury in Drosophila
Saikumar, J., Byrns, C. N., Hemphill, M. A., Meaney, D. F., & Bonini, N. M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003909117 · Cited by 53 · see citing works
Muresanu, D. F., Florian, I. Ş., Hömberg, V., Matula, C., von Steinbüchel, N., Vos, P. E., Wild, K. V., Bîrle, C., Mureșanu, I. A., Slăvoacă, D., et al. (2020) · Neurological Sciences · doi:10.1007/s10072-019-04181-y · Cited by 56 · see citing works
“According to an in-depth review performed in 2010, the majority of randomized controlled trials (RCTs) used a single outcome measure model with arbitrary dichotomization of continuous variables and had other essential flaws, notably not adjusting the research design to the complexity of TBI [4].”
BackgroundBrett, B. L., Kramer, M. D., Whyte, J., McCrea, M., Stein, M. B., Giacino, J. T., Sherer, M., Markowitz, A. J., Manley, G. T., Nelson, L. D., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.3467 · Cited by 55 · see citing works
Self-citationStover, J. F., Belli, A., Boret, H., Bulters, D., Sahuquillo, J., Schmutzhard, E., Zavala, E., Ungerstedt, U., Schinzel, R., Tegtmeier, F., et al. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3344 · Cited by 53 · see citing works
Role of fibrinogen in cerebrovascular dysfunction after traumatic brain injury
Muradashvili, N., & Lominadze, D. G. (2013) · Brain Injury · doi:10.3109/02699052.2013.823562 · Cited by 54 · see citing works
“Traumatic brain injury (TBI) is the leading cause of death and disability, for which no effective treatment exists other than supportive care [1].”
BackgroundYuan, J., Zhang, J., Cao, J., Wang, G., & Bai, H. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00749-6 · Cited by 54 · see citing works
Nimer, F. A., Lindblom, R. P. F., Ström, M., Guerreiro‐Cacais, A. O., Parsa, R., Aeinehband, S., Mathiesen, T. I., Lidman, O., & Piehl, F. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.10.002 · Cited by 53 · see citing works
“Genetic variability may influence pathophysiological processes triggered by TBI, in turn of relevance for outcome and possibly also response to treatment (Dardiotis et al., 2010; Maas et al., 2010; McAllister, 2010; Zhou et al., 2008).”
InfluentialImatinib treatment reduces brain injury in a murine model of traumatic brain injury
Su, E. J., Fredriksson, L., Kanzawa, M., Moore, S. J., Folestad, E. B., Stevenson, T. K., Nilsson, I., Sashindranath, M., Schielke, G. P., Warnock, M., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00385 · Cited by 52 · see citing works
“However, despite numerous studies in animal models of TBI and clinical trials of various therapeutic strategies, no effective therapy for TBI patients has emerged (Grumme et al., 1995; Marmarou et al., 1999; Bramlett and Dietrich, 2004; Yurkewicz et al., 2005; Maas et al., 2006, 2010).”
BackgroundBregy, A., Nixon, R. A., Lotocki, G., Alonso, O. F., Atkins, C. M., Tsoulfas, P., Bramlett, H. M., & Dietrich, W. D. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.12.008 · Cited by 52 · see citing works
“Although a significant amount of information is now known regarding the pathophysiology of brain injury (Bigler andMaxwell, 2011; Bramlett andDietrich, 2004), the successful translation to the clinic of therapeutic interventions shown to be promising in animal models has yet to be achieved (Maas et al., 2010).”
Kumar, R. G., Rubin, J. E., Berger, R. P., Kochanek, P. M., & Wagner, A. K. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.12.008 · Cited by 52 · see citing works
“Clinical trials have not been successful to date in identifying any definitive neuroprotective treatment (Maas et al. , 2010).”
Cellular microparticles and pathophysiology of traumatic brain injury
Zhao, Z., Zhou, Y., Tian, Y., Li, M., Dong, J., & Zhang, J. (2017) · Protein & Cell · doi:10.1007/s13238-017-0414-6 · Cited by 51 · see citing works
“Cellular microparticles produced by injured tissues have been increasingly recognized as a key mediator for the interplay, promoting a transition from primary injury to secondary injury (Maas et al., 2010; Stoica and Faden, 2010).”
BackgroundErythropoietin Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy
Bramlett, H. M., Dietrich, W. D., Dixon, C. E., Shear, D. A., Schmid, K. E., Mondello, S., Wang, K., Hayes, R. L., Povlishock, J. T., Tortella, F. C., et al. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.4116 · Cited by 51 · see citing works
“5 There are various proposed reasons for this failure, including the complexity and heterogeneous nature of clinical TBI, as well as other limitations regarding adequate pre-clinical data to support the translation of therapies into the clinic.”
Raj, R., Mikkonen, E. D., Siironen, J. O., Hernesniemi, J. A., Lappalainen, J., & Skrifvars, M. B. (2015) · Journal of neurosurgery · doi:10.3171/2015.4.jns141746 · Cited by 50 · see citing works
Neuroprotection Trials in Traumatic Brain Injury
Chakraborty, S., Skolnick, B. E., & Narayan, R. K. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0625-x · Cited by 50 · see citing works
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Hu, B., Liu, X., Qiang, R., Jiang, Z., Xu, L., Wang, G., Li, X., & Peng, B. (2014) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2014.07.009 · Cited by 48 · see citing works
Branched Chain Amino Acids (BCAAs) and Traumatic Brain Injury: A Systematic Review
Sharma, B., Lawrence, D. W., & Hutchison, M. G. (2017) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000280 · Cited by 48 · see citing works
Bodien, Y. G., McCrea, M., DIKMEN, S. S., Temkin, N. R., Boase, K., Machamer, J., Taylor, S. R., Sherer, M., Levin, H. S., Kramer, J. H., et al. (2018) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000367 · Cited by 48 · see citing works
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Therapeutic inducers of the HSP 70/ HSP 110 protect mice against traumatic brain injury
Eroglu, B., Kimbler, D. E., Pang, J., Choi, J., Moskophidis, D., Yanasak, N. E., Dhandapani, K. M., & Mivechi, N. F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12781 · Cited by 48 · see citing works
Lagraoui, M., Sukumar, G., Latoche, J. R., Maynard, S. K., Dalgard, C. L., & Schaefer, B. C. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.12.005 · Cited by 47 · see citing works
“Given the uniform lack of success of clinical trials of TBI therapeutics to date (Maas et al., 2012, 2010), many in the TBI field now argue that multifactorial therapies are required, either in the form of multiple drugs targeting distinct aspects of the pathological response, or single drugs with…”
BackgroundMokhtari, M., Nayeb‐Aghaei, H., Kouchek, M., Miri, M., Goharani, R., Amoozandeh, A., Salamat, S. A., & Sistanizad, M. (2018) · Journal of clinical pharmacology · doi:10.1002/jcph.980 · Cited by 47 · see citing works
Validation of a prognostic score for early mortality in severe head injury cases
Gómez, P. A., de la Cruz, J., Lora, D., Roldan, L. J., Rodríguez-Boto, G., Sarabia, R., Sahuquillo, J., Lastra, R., Morera, J., Lazo-Fernández, E., et al. (2014) · Journal of neurosurgery · doi:10.3171/2014.7.jns131874 · Cited by 45 · see citing works
New considerations in the design of clinical trials for traumatic brain injury
Roozenbeek, B., Lingsma, H. F., & Maas, A. I. R. (2012) · Clinical Investigation · doi:10.4155/cli.11.179 · Cited by 44 · see citing works
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Operation Brain Trauma Therapy: 2016 Update
Kochanek, P. M., Bramlett, H. M., Dixon, C. E., Dietrich, W. D., Mondello, S., Wang, K., Hayes, R. L., Lafrenaye, A. D., Povlishock, J. T., Tortella, F. C., et al. (2018) · Military Medicine · doi:10.1093/milmed/usx184 · Cited by 44 · see citing works
Kaloostian, P., Robertson, C., Gopinath, S., Stippler, M., King, C. C., Qualls, C., Yonas, H., & Nemoto, E. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.2147 · Cited by 44 · see citing works
“Second, it is also important for injury stratification for inclusion in randomized clinical trials (RCTs; Maas et al., 2007,2010).”
- 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 › 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 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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