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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search of the years from 1980 to 2009 revealed 27 large phase III trials in TBI; we were aware of a further 6 unpublished trials.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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Self-citationVillapol, S. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.177720 · Cited by 38
“Yet there exist more that 30 clinical trials for TBI that fail despite successful experimental data (Maas et al., 2010).”
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“Currently, <20% of the management guidelines for TBI are supported by either Class I or Class II evidence (Maas et al., 2010b).”
Can Mesenchymal Stem Cells Act Multipotential in Traumatic Brain Injury?
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“The most important of secondary damage mechanisms include cell death, microglia activation, and neurotoxicity (Maas et al. 2010).”
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“Also, numerous pharmacological treatments have been identified, with at least 20 compounds and therapeutic interventions being the subject of more than 50 clinical trials over the last three decades [135].”
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“Data included demographics, clinical care, genetic and proteomic markers, neuroimaging and outcome measures to represent a range of TBI data including data relevant to all TBI studies, highly heterogeneous datasets and measures for which no consensus or validation has been achieved [35,36] .”
BackgroundAutoantibodies in traumatic brain injury and central nervous system trauma
Raad, M., Nohra, E. A., Chams, N., Itani, M., Talih, F. R., Mondello, S., & Kobeissy, F. H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.08.045 · Cited by 36
“Currently, there are few effective therapies targeted against the latent manifestations of TBI (Beauchamp et al., 2008; Loane and Faden, 2010; Maas et al., 2010; Wheaton et al., 2011) exacerbated by the fact that there are no diagnostic approaches that can identify those who will develop severe…”
Nudi, E., Jacqmain, J., Dubbs, K., Geeck, K., Salois, G., Searles, M. A., & Smith, J. S. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3618 · Cited by 34
Behavioral Assessment of Patients with Disorders of Consciousness
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“57 Despite its widespread use, the psychometric strength of the GCS is moderate, 58,59 which may be attributed to the lack of standardized procedures for administration and scoring (though new online materials provide some additional guidance; https://www. glasgowcomascale.org).”
Lin, C., He, H., Li, Z., Liu, Y., Chao, H., Ji, J., & Liu, N. (2015) · Scientific Reports · doi:10.1038/srep13442 · Cited by 35
Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury
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“Many therapeutic strategies for TBI tested clinically have focused on attenuating acute damage due to glutamate excitotoxicity, free radical accumulation, or calcium influx [1].”
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“…success in experimental TBI models, however, more than 30 phase III clinical trials have failed to show successful results in clinical setting (Maas et al., 2010; Schouten, Address correspondence and proofs to: Dong Sun, M.D., Ph.D., Department of Neurosurgery, P.O.Box 980631, Medical College…”
BackgroundUp‐regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
Zhao, P., Li, C., Chen, B., Sun, G., Chao, H., Tu, Y., Bao, Z., Fan, L., Du, X., & Ji, J. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15406 · Cited by 34
Chou, A., Espin, A. T., Huie, J. R., Krukowski, K., Lee, S., Nolan, A., Guglielmetti, C., Hawkins, B. E., Chaumeil, M. M., Manley, G. T., et al. (2022) · Neurotrauma Reports · doi:10.1089/neur.2021.0061 · Cited by 32
“Despite the abundance of pre-clinical TBI studies, randomized controlled clinical trials have consistently failed.(5,6) One significant challenge for the development of effective treatments is the heterogeneity of injuries and the varied pathological biology captured by the broad definition of TBI: a”
BackgroundSelf-citationLei, J., Gao, G., Mao, Q., Feng, J., Wang, L., You, W., & Jiang, J. (2014) · Contemporary Clinical Trials · doi:10.1016/j.cct.2014.11.008 · Cited by 32
“Evidence from clinical trials and systematic reviews indicates that no intervention shows substantial efficacy [5,6].”
BackgroundMunoz, M. J., Kumar, R. G., Oh, B., Conley, Y. P., Wang, Z., Failla, M. D., & Wagner, A. K. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00044 · Cited by 30
“However, individual biomarker studies have limitations with predicting therapeutic treatment response (Maas et al., 2010), which may be due to the focus of current research on single biomarker relationships, rather than the interactions of several.”
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Bianciardi, M., Izzy, S., Rosen, B. R., Wald, L. L., & Edlow, B. L. (2021) · Neurology · doi:10.1212/wnl.0000000000012192 · Cited by 26
Relating Quality of Life to Glasgow Outcome Scale Health States
Kosty, J. A., Macyszyn, L. J., Lai, K., McCroskery, J., Park, H.-R., & Stein, S. C. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.2222 · Cited by 30
“, 2005); however, improvement has slowed since the mid-1990s, and all large multi-center phase III randomized controlled trials (RCTs) conducted since 1980 have failed to show a benefit of any neuroprotective agent or therapeutic practice (Maas et al., 2010; Stein et al., 2010).”
Novgorodov, S., Voltin, J. R., Wang, W., Tomlinson, S., Riley, C. L., & Gudz, T. I. (2019) · Journal of Lipid Research · doi:10.1194/jlr.m091132 · Cited by 20
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“Feasibility will be assessed by compliance with a tier-based treatment algorithm, including (1) ability to identify SDs in real time and adjust treatment tiers as prescribed, (2) the degree to which therapeutic goals prescribed at each tier are pursued and achieved, and (3) the difference in therapeutic intensity with…”
BackgroundMethodInfluentialCerebrolysin Asian Pacific Trial in Acute Brain Injury and Neurorecovery: Design and Methods
Poon, W. S., Vos, P. E., Muresanu, D. F., Vester, J., Wild, K. V., Hömberg, V., Wang, E., Lee, T. M. C., & Matula, C. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3558 · Cited by 28
“82 To control the heterogeneity of the study population and to increase the statistical power, all multidimensional comparisons (Wei-Lachin procedure) will be performed within predefined baseline strata of prognostic risk (for the basic procedure, see Lachin, 2000).”
Maria, N. S. S., Reger, M. L., Cai, Y., Baquing, M. A. T., Buen, F., Ponnaluri, A. V. S., Hovda, D. A., Harris, N. G., & Giza, C. C. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2016.4747 · Cited by 28
“31 One reason NMDAR antagonists may have failed is that by the time the antagonists are administered, the NMDARs are already downregulated following TBI, missing the critical window of hyperactivity of these receptors.”
A mathematical model of neuroinflammation in severe clinical traumatic brain injury
Vaughan, L. E., Ranganathan, P. R., Kumar, R. G., Wagner, A. K., & Rubin, J. E. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1384-1 · Cited by 30
“anisms, and (4) emergent co-pathologies [3, 6, 7].”
Todorov, H., Searle-White, E., & Gerber, S. (2020) · PLoS ONE · doi:10.1371/journal.pone.0230798 · Cited by 28
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Albert-Weißenberger, C., Mencl, S., Hopp, S., Kleinschnitz, C., & Sirén, A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00345 · Cited by 26
“Despite promising results from these experimental TBI models, more than 30 phase III trials of TBI in humans have failed to generate favorable results in terms of developing potential therapeutic strategies (Doppenberg et al., 2004; Maas et al., 2010).”
BackgroundBridging the gap: Mechanisms of plasticity and repair after pediatric TBI
Maria, N. S. S., Sargolzaei, S., Prins, M. L., Dennis, E. L., Asarnow, R. F., Hovda, D. A., Harris, N. G., & Giza, C. C. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.016 · Cited by 32
“NMDAR inhibition also failed to translate clinically, in some cases even leading to worsened outcome (Albers et al., 2001; Ikonomidou and Turski, 2002; Maas et al., 2010; Morris et al., 1999; Muir, 2006; Naranyan et al., 2002).”
BackgroundTucker, L. B., Fu, A. H., & McCabe, J. T. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2021.0025 · Cited by 25
“Poorer performance on visible platform trials following multiple CHIMERA injuries has been reported in another recent study, which also found impaired performance on a visual cliff task and reduced visual evoked potentials, providing further evidence for behavioral and physiological visual dysfunction.38 Like many oth…”
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Role of regulatory non-coding RNAs in traumatic brain injury
Li, S., Qiu, N., Ni, A., Hamblin, M. H., & Yin, K. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105643 · Cited by 26
Mouse Brain PSA-NCAM Levels Are Altered by Graded-Controlled Cortical Impact Injury
Budinich, C. S., Chen, H., Lowe, D., Rosenberger, J. G., Bernstock, J. D., & McCabe, J. T. (2012) · Neural Plasticity · doi:10.1155/2012/378307 · Cited by 25
“However, in spite of decades of research and promising results in preclinical animal studies, no single effective therapy has successfully and consistently transferred to human clinical trials [7, 8].”
Li, Q., Shen, Y., Ahmad, A., Shen, Y.-J., Zhang, Y., Xu, P.-K., Chen, W., & Yu, Y. (2018) · World Neurosurgery · doi:10.1016/j.wneu.2018.05.202 · Cited by 24
Cyclosporine as Therapy for Traumatic Brain Injury
Hansson, M. J., & Elmér, E. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01414-z · Cited by 23
“Following a number of unsuccessful interventional clinical trials, large natural history initiatives over the past few decades have sought to improve the precision of TBI classification and diagnosis, standardize data collection, and develop and validate relevant clinical outcome measures [15–17].”
BackgroundInfluentialComparative Effectiveness of Surgery for Traumatic Acute Subdural Hematoma in an Aging Population
van Essen, T. A., Dijkman, M. D., Cnossen, M. C., Moudrous, W., Ardon, H., Schoonman, G. G., Steyerberg, E. W., Peul, W. C., Lingsma, H. F., & de Ruiter, G. C. W. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5869 · Cited by 23
Gardner, R. C., Cheng, J., Ferguson, A. R., Boylan, R. D., Boscardin, W. J., ZAFONTE, R. D., Manley, G. T., The Citicoline Brain Injury Treatment Trial Investigators, ZAFONTE, R. D., Bagiella, E., et al. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6167 · Cited by 22
“Severe disability / death 1 month 10 3.00 (1.15) 2–6 3 month 11 2.00 (1.34) 1–5 6 month 11 1.00 (0.00) 1–1 granular delineation of 6 month functional outcome trajectories among patients with complicated mild to severe TBI.”
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“[49,97] Numerous clinical trials involving NMDA receptor antagonists such as aptiganel, dextromethorphan, dizocilpine, eliprodil, gavestinel, licostinel, and selfotel were initiated, but some were discontinued prematurely or failed to demonstrate their efficacy in stroke or TBI trials.”
BackgroundProteomics: in pursuit of effective traumatic brain injury therapeutics
Lizhnyak, P. N., & Ottens, A. K. (2015) · Espert Review of Proteomics · doi:10.1586/14789450.2015.1000869 · Cited by 19
Roquilly, A., Lasocki, S., Moyer, J.-D., Huet, O., Perrigault, P. F., Dahyot‐Fizelier, C., Séguin, P., Sharshar, T., Geeraerts, T., Remérand, F., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-018035 · Cited by 21
“Finally, the adjustment to predefined covariates(23) will mitigate the effects of heterogeneity resulting from the use of broad inclusion criteria (Glasgow Coma Scale 3–13).(34)”
Rajagopalan, V., Das, A., Zhang, L., Hillary, F. G., Wylie, G. R., & Yue, G. H. (2018) · Brain Imaging and Behavior · doi:10.1007/s11682-018-9892-2 · Cited by 21
Nelson, L. D., Brett, B., Magnus, B. E., Balsis, S., McCrea, M., Manley, G., Temkin, N., & Dikmen, S. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6719 · Cited by 15
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“…are certain barriers to the effective treatment of TBI and associated comorbidities, including misconceptions and stigma (Redpath et al., 2010; Zhou et al., 2014), in addition to the limited, effective treatments available (Maas et al., 2010; Marguiles and Hicks, 2009; Tolias and Bullock, 2004).”
BackgroundJehan, F., Azim, A., Rhee, P., Khan, M., Gries, L. M., O’Keeffe, T., Kulvatunyou, N., Tang, A. L., & Joseph, B. A. (2017) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0000000000001658 · Cited by 21
“In the United States, the annual cost burden of TBIs is more than US $60 billion.(3) According to the Centers for Disease Control and Prevention, the number of TBI-related emergency room visits has increased, whereas the number of hospitalizations and deaths has remained stable over the last decade.”
BackgroundLow-Value Clinical Practices in Adult Traumatic Brain Injury: An Umbrella Review
Moore, L., Tardif, P., Lauzier, F., Berube, M., Archambault, P. M., Lamontagne, F., Chassé, M., Stelfox, H. T., Gabbe, B. J., Lecky, F. E., et al. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7044 · Cited by 19
“[4,5] Treatment options for TBI are multiple, but many lack robust evidence of their effectiveness.[6,7]”
BackgroundPandya, J. D., Leung, L. Y., Hwang, H. M., Yang, X., Deng‐Bryant, Y., & Shear, D. A. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7379 · Cited by 19
Biofidelic dynamic compression of human cortical spheroids reproduces neurotrauma phenotypes
Shoemaker, A. R., Jones, I. E., Jeffris, K., Gabrielli, G., Togliatti, A. G., Pichika, R., Martin, E., Kiskinis, E., Franz, C. K., & Finan, J. D. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048916 · Cited by 19
“A total of 191 clinical trials (Bragge et al., 2016), including at least 33 large multicenter phase III trials, have been conducted for TBI but we remain without a US Food and Drug Administration (FDA)-approved treatment for this disorder (Maas et al., 2010).”
Semple, B. D., & Noble‐Haeusslein, L. J. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.02.002 · Cited by 19
“…receptors; Neuroprotection; Pioglitazone; Traumatic brain injury Despite an abundance of laboratory and clinical research over the last three decades, an effective neuroprotective agent for the treatment of traumatic brain injury (TBI) remains elusive (Narayan et al., 2002; Maas et al., 2010).”
BackgroundBrain Death and True Patient Care
Nguyen, D. (2016) · The Linacre Quarterly · doi:10.1080/00243639.2016.1188472 · Cited by 19
“Concomitant multi-organ injury (e.g., in road accidents) or multi-organ failure (e.g., in post-cardiac arrest syndrome) produce multiple physiological instabilities such as hypotension, pyrexia, and coagulopathy, among others (Maas, Roozenbeek, and Manley 2010, 115; Neumar et al. 2008, 2456).”
BackgroundHypothermia and the complexity of trials in patients with traumatic brain injury
Maas, A. I. R., & Stocchetti, N. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70312-4 · Cited by 19
Self-citationRoles of Astrocytic Endothelin ETB Receptor in Traumatic Brain Injury
Michinaga, S., Hishinuma, S., & Kōyama, Y. (2023) · Cells · doi:10.3390/cells12050719 · Cited by 18
Lei, J., Gao, G., & Jiang, J. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2548 · Cited by 18
“73 Maas and colleagues, 70 who analyzed 33 large phase III RCTs covering the period from 1980 to 2009, found that no intervention for the treatment of acute TBI showed convincing benefit in the overall population, highlighting the need for improvement in study design and analysis.”
Measuring outcome after severe TBI
Kosty, J. A., & Stein, S. C. (2013) · Neurological Research · doi:10.1179/1743132813y.0000000168 · Cited by 18
Cholinergic Dysfunction and Cognitive Impairment After Traumatic Brain Injury. Part 2
Arciniegas, D. B. (2011) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0b013e31821ebfb3 · Cited by 18
Lindfors, M., Vehviläinen, J., Siironen, J. O., Kivisaari, R. P., Skrifvars, M. B., & Raj, R. (2018) · Acta Neurochirurgica · doi:10.1007/s00701-018-3670-1 · Cited by 18
Perumal, V., Ravula, A. R., Agas, A., Gosain, A., Aravind, A., Sivakumar, P. M., Sundari, S., Sambath, K., Vijayaraghavalu, S., & Chandra, N. (2023) · Brain Sciences · doi:10.3390/brainsci13030402 · Cited by 19
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“tality rates for severe TBI are largely unchanged over the last decade.(6,7) There are also still no treatments that have received a Level I recommendation for efficacy in the recent 4th edition TBI Guidelines,(8) and no treatments have been approved by the Food and”
Sears, B., Bailes, J. E., & Asselin, B. L. (2013) · PharmaNutrition · doi:10.1016/j.phanu.2013.04.002 · Cited by 17
Acute Management of Moderate-Severe Traumatic Brain Injury
Whitaker-Lea, W. A., & Valadka, A. B. (2017) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2016.12.002 · Cited by 17
Reddy, D. S., Golub, V. M., Ramakrishnan, S., Churn, S. B., Shapiro, L. A., Iannucci, J., Pitkänen, A., Galanopoulou, A. S., Maganti, R. K., & Boison, D. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100080 · Cited by 18
van Erp, I. A. M., van Essen, T. A., Lingsma, H. F., Pisică, D., Singh, R. D., van Dijck, J. T. J. M., Volovici, V., Kolias, A. G., Peppel, L. D., Heijenbrok‐Kal, M. H., et al. (2023) · Acta Neurochirurgica · doi:10.1007/s00701-023-05797-y · Cited by 16
“This could have led to a neutral treatment effect through averaging out of subgroups effects, a core characteristic of multiple “failing” studies in TBI research [13, 14].”
BackgroundSelf-citationNeuhaus, W. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00149 · Cited by 16
“However, numerous animal studies and clinical trials were unsuccessful, and 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; Xiong et al., 2009; Su et al., 2015).”
Challenges Enrolling Children Into Traumatic Brain Injury Trials: An Observational Study
Stanley, R., Johnson, M. D., Vance, C., Bajaj, L., Babcock, L., Atabaki, S., Thomas, D. G., Simon, H., Cohen, D., Rubacalva, D., et al. (2017) · Academic Emergency Medicine · doi:10.1111/acem.13085 · Cited by 16
“than 16 years of age) sites which had to obtain written informed consent took significantly longer to randomize patients and ultimately to administer study drug (3 hours versus 4 hours).(33,34)”
BackgroundMassie, C. L., Du, Y., Conroy, S. S., Krebs, H. I., Wittenberg, G. F., Bever, C. T., & Whitall, J. (2015) · Neurorehabilitation and neural repair · doi:10.1177/1545968315620301 · Cited by 18
“The traditional option to control for variability in clinical trials is to have strict inclusion/exclusion criteria, but this is statistically inefficient, increases recruitment burden, and decreases external validity.(20,21) More novel approaches implement appropriate statistical analyses that can control for inheren…”
BackgroundDesign of acute neuroprotection studies
Hawryluk, G. W. J., & Bullock, M. R. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63521-1.00047-9 · Cited by 15
“Demonstration of acceptable blood–brain barrier penetration is also important but often overlooked in preclinical studies (Tolias and Bullock, 2004; Maas et al., 2010a).”
BackgroundMethodResultInfluentialZeiler, F. A., Teitelbaum, J. S., Gillman, L. M., & West, M. A. (2014) · Neurocritical Care · doi:10.1007/s12028-014-9978-7 · Cited by 15
“The non-CO2-generating buffer capacity of tromethamine, or Tris (hydroxymethyl) aminomethane (THAM), affords it potential advantages in the setting of hypercapneic acidosis and a variety of other applications [6– 10].”
BackgroundZaghmi, A., Drouin‐Ouellet, J., Brambilla, D., & Gauthier, M. A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120461 · Cited by 17
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“Such paucity of diagnostic and therapeutic options stands in stark contrast to the intensity of research efforts and number of clinical trials that have been performed to date (Maas et al., 2010).”
Traumatic Brain Injury: Methodological Approaches To Estimate Health and Economic Outcomes
Lu, J., Røe, C., Aas, E., Lapane, K., Niemeier, J. P., Arango-Lasprilla, J., & Andelic, N. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.2891 · Cited by 13
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The Role of Decompressive Craniectomy in Diffuse Traumatic Brain Injury
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Potential for the development of light therapies in mild traumatic brain injury
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“Despite significant job-, school- and economic-related burdens associated with the medical management of mTBIs [1], there is no currently accepted gold standard treatment for mTBIs [21,22].”
BackgroundIntegrated approaches to paediatric neurocritical care in traumatic brain injury
Maas, A. I. R., & Menon, D. K. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70272-7 · Cited by 11
Self-citationKhan, A. D., Elseth, A. J., Head, B., Rostas, J. W., Dunn, J., Schroeppel, T. J., & Gonzalez, R. P. (2017) · The American Surgeon · doi:10.1177/000313481708300832 · Cited by 10
Bodien, Y. G., Barber, J. K., Taylor, S. R., Boase, K., Corrigan, J. D., DIKMEN, S. S., Gardner, R. C., Kramer, J. H., Levin, H. S., Machamer, J., et al. (2022) · Journal of Neurotrauma · doi:10.1089/neu.2022.0141 · Cited by 10
“1 Multiple factors have been hypothesized to account for this problem.”
Self-citationKhan, F., Valliani, A., Rehman, A., & Bari, M. E. (2018) · Asian Journal of Neurosurgery · doi:10.4103/ajns.ajns_6_18 · Cited by 10
“[7] Given that performing randomized trials in patients with TBI is technically challenging,[12] results from observational studies have been given more weightage in this regard.”
BackgroundChapter 5 – Traumatic Brain Injury
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“The tangible failure in the area was often thought to be a result of poor clinical trial design, creating substantial academic skepticism [21].”
Advanced Topics in Neurological Disorders
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“In this way, understanding how two instruments correspond may help with ongoing goals of developing an efficient yet precise outcome measurement for clinical trials.(15) Recently, TBI researchers have turned their attention to advanced psychometric techniques, including item response theory (IRT), which allows for the…”
BackgroundSelf-citationRevi, N., Sankaranarayanan, S. A., & Rengan, A. K. (2022) · Materialia · doi:10.1016/j.mtla.2022.101454 · Cited by 8
Action Collaborative on Traumatic Brain Injury Care: Adapted Clinical Practice Guideline
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“78 Screening for SDoH should be conducted by health care providers or professions trained in connecting patients to community resources (eg, community health workers, case managers, patient navigators) utilizing standardized screening tools during the initial assessment and at regular follow-up…”
Self-citationAlcohol affects the outcome after head trauma
Vaaramo, K. (2013) · Cited by 7
Lissencephaly-1 mutations enhance traumatic brain injury outcomes in Drosophila
Katzenberger, R. J., Ganetzky, B., & Wassarman, D. A. (2023) · Genetics · doi:10.1093/genetics/iyad008 · Cited by 7
Amerineni, R., Sun, H., Fernandes, M. P., Westover, M. B., Moura, L. M. V. R., Patorno, E., Hsu, J., & Zafar, S. F. (2023) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0000000000001043 · Cited by 7
Reconsidering the role of hypothermia in management of severe traumatic brain injury
Honeybul, S. (2016) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2016.01.002 · Cited by 7
“Since that time the use of steroids has largely been abandoned and this has been the fate of many pharmacological agents that showed early promise in the laboratory setting [32,35–38].”
Singh, R. D., van Dijck, J. T. J. M., Maas, A. I. R., Peul, W. C., & van Essen, T. A. (2022) · World Neurosurgery · doi:10.1016/j.wneu.2021.11.092 · Cited by 7
Self-citationEthical and regulatory considerations in the design of traumatic brain injury clinical studies
Hicks, R. R. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63521-1.00046-7 · Cited by 7
Lei, J., Gao, G., & Jiang, J. (2012) · PubMed · Cited by 7
Huang, A. J., Kornguth, D. G., & Kornguth, S. E. (2019) · Brain Sciences · doi:10.3390/brainsci9050097 · Cited by 9
Underpowered trials in critical care medicine: how to deal with them?
Roozenbeek, B., Lingsma, H. F., Steyerberg, E. W., Maas, A. I. R., & the IMPACT Study Group (2010) · Critical Care · doi:10.1186/cc9021 · Cited by 7
“Th is problem is particularly relevant to the fi eld of neurocritical care after traumatic brain injury [2].”
BackgroundSelf-citation
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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