Cited by 249Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchEthics in Clinical Research

The DOI matches its Crossref record; 102 of the 102 references it cites were found in a registry or an index.

Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials

Open access

Stein, Donald G.·2015·Brain Injury

DOI 10.3109/02699052.2015.1065344PMC PMC4667711

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials. METHODS: This paper reviews and analyses the trial structures and outcomes and discusses the implications of these failures for future drug and clinical trial development. Persistently negative trial outcomes have led to disinvestment in new drug research by companies and policy-makers and disappointment for patients and their families, failures which represent a major public health concern. The problem is not limited to TBI. Failure rates are high for trials in stroke, sepsis, cardiology, cancer and orthopaedics, among others. RESULTS: This paper discusses some of the reasons why the Phase III trials have failed. These reasons may include faulty extrapolation from pre-clinical data in designing clinical trials and the use of subjective outcome measures that accurately reflect neither the nature of the deficits nor long-term quantitative recovery. CONCLUSIONS: Better definitions of injury and healing and better outcome measures are essential to change the embrace of failure that has dominated the field for over 30 years. This review offers suggestions to improve the situation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3109/02699052.2015.1065344

Cites

102 of 102 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Two new Later Stone Age sites from the Final Pleistocene in the Falémé Valley, eastern Senegal
Ndiaye, M., Lespez, L., Tribolo, C., Rassé, M., Hadjas, I., Davidoux, S., Huysecom, É., & Douze, K. (2024) · Monash University Research Portal (Monash University) · doi:10.3929/ethz-b-000667478 · Cited by 24,214
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020124 · Cited by 10,505
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · CHANCE · doi:10.1080/09332480.2005.10722754 · Cited by 4,702 · cited 5×
“According to Schwamm [67] and Ioannidis [68], these published papers then lead to unwarranted and overenthusiastic estimations of effect sizes and are uncritically reported in the peer-review literature and accepted and used by the clinical community to go forward with clinical trials (see also Mak et al.”
BackgroundResultInfluential
Raise standards for preclinical cancer research
Begley, C. G., & Ellis, L. M. (2012) · Nature · doi:10.1038/483531a · Cited by 2,979 · cited 2×
“problem in the field of stroke, while Begley and Ellis [9] make the same claim for pre-clinical cancer research.”
Background
Higher cortical functions in man
Lurii︠a︡, A. R., Teuber, H., Pribram, K. H., & Haigh, B. (1966) · Basic Books · Cited by 2,858
BioMed Research International
Bellini, M., Charalampidis, S., Herbert, P., Bonatsos, V., Crane, J., Muthusamy, A., Dor, F., & Papalois, V. E. (2022) · BioMed Research International · doi:10.1155/2738 · Cited by 2,431
Flawed Self-Assessment: Implications for Health, Education, and the Workplace
Dunning, D., Heath, C., & Suls, J. M. (2004) · Psychological Science in the Public Interest · doi:10.1111/j.1529-1006.2004.00018.x · Cited by 1,865
Goodman and Gilman's the Pharmacological Basis of Therapeutics
Coon, J. T. (2002) · Focus on Alternative and Complementary Therapies · doi:10.1111/j.2042-7166.2002.tb05480.x · Cited by 1,748
Classification of traumatic brain injury for targeted therapies
Saatman, K. E., Duhaime, A.-C., Bullock, R., Maas, A. I. R., Valadka, A., & Manley, G. T. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2008.0586 · Cited by 1,141
Lost in translation: animal models and clinical trials in cancer treatment.
(2014) · Europe PMC (PubMed Central) · Cited by 1,033

Show all 102 references

Research works printed but not linked: 5

Luoma JI, 2011, Steroids, 76, 845
Hannay HJ, 1996, Journal of Head Trauma Rehabilitation, 1141
10.1371/journal. pmed.0020124 · DOI
Mak IW, 2014, American Journal of Translational Research, 6, 114
Goldberg SI, 2008, MIA Annual Symposium Proceedings, 2008, 242

Sorted by citations

Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know
Gupte, R. P., Brooks, W. M., Vukas, R. R., Pierce, J. D., & Harris, J. L. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6171 · Cited by 533
Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema
Kitchen, P., Salman, M. M., Halsey, A. M., Clarke-Bland, C., MacDonald, J. A., Ishida, H., Vogel, H. J., Almutiri, S., Logan, A., Kreida, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.037 · Cited by 452
Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets
Thapa, K., Khan, H., Singh, T. G., & Kaur, A. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01841-7 · Cited by 341
Sexual dimorphism in the inflammatory response to traumatic brain injury
Villapol, S., Loane, D. J., & Burns, M. P. (2017) · Glia · doi:10.1002/glia.23171 · Cited by 320
Neuroprotective strategies for retinal disease
Pardue, M. T., & Allen, R. S. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.02.002 · Cited by 237
Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities
Xiong, Y., Mahmood, A., & Chopp, M. (2018) · Chinese Journal of Traumatology · doi:10.1016/j.cjtee.2018.02.003 · Cited by 253
How to Translate Time? The Temporal Aspect of Human and Rodent Biology
Agoston, D. V. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00092 · Cited by 226
Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions
Jarrahi, A., Braun, M., Ahluwalia, M., Gupta, R. V., Wilson, M., Munie, S., Ahluwalia, P. K., Vender, J. R., Vale, F. Ĺ., Dhandapani, K. M., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8100389 · Cited by 241
Sex-related responses after traumatic brain injury: Considerations for preclinical modeling
Späni, C. B., Braun, D. J., & Van Eldik, L. J. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.03.006 · Cited by 195
Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration
Sandsmark, D. K., Bashir, A., Wellington, C. L., & Diaz-Arrastia, R. R. (2019) · Neuron · doi:10.1016/j.neuron.2019.06.002 · Cited by 180
The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions
Osier, N. D., & Dixon, C. E. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00134 · Cited by 173
Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant
Guennoun, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155271 · Cited by 167
The potential for animal models to provide insight into mild traumatic brain injury: Translational challenges and strategies
Shultz, S. R., McDonald, S. J., Haar, C. V., Meconi, A., Vink, R., van Donkelaar, P., Taneja, C., Iverson, G. L., & Christie, B. R. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.014 · Cited by 149
Concussion As a Multi-Scale Complex System: An Interdisciplinary Synthesis of Current Knowledge
Kenzie, E. S., Parks, E. L., Bigler, E. D., Lim, M. M., Chesnutt, J. C., & Wakeland, W. W. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00513 · Cited by 164
A porcine model of traumatic brain injury via head rotational acceleration
Cullen, D. K., Harris, J. P., Browne, K. D., Wolf, J. A., Duda, J. E., Meaney, D. F., Margulies, S. S., & Smith, D. H. (2016) · Methods in Molecular Biology · doi:10.1007/978-1-4939-3816-2_17 · Cited by 142
“Unfortunately, despite reports of hundreds of treatments that have show efficacy in rodent models of TBI, none have translated to clinical use despite over 30 clinical trials based on the preclinical data [47, 48].”
Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury
Webster, K. M., Wright, D. K., Sun, M., Semple, B. D., Öztürk, E., Stein, D. G., O'Brien, T. J., & Shultz, S. R. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0457-7 · Cited by 137
Self-citation
The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome
McDonald, S. J., Sun, M., Agoston, D. V., & Shultz, S. R. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0555-1 · Cited by 134
Progesterone for acute traumatic brain injury
Ma, J., Huang, S., Qin, S., You, C., & Zeng, Y. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008409.pub4 · Cited by 116
NADPH oxidases in traumatic brain injury – Promising therapeutic targets?
Ma, M. W., Wang, J., Dhandapani, K. M., Wang, R., & Brann, D. W. (2018) · Redox Biology · doi:10.1016/j.redox.2018.03.005 · Cited by 116
Neuroprotective Role of Steroidal Sex Hormones: An Overview
Siddiqui, A. N., Siddiqui, N., Khan, R. A., Kalam, A., Jabir, N. R., Kamal, M., Firoz, C. K., & Tabrez, S. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12538 · Cited by 101
White matter damage after traumatic brain injury: A role for damage associated molecular patterns
Braun, M., Vaibhav, K., Saad, N., Fatima, S., Vender, J. R., Baban, B., Hoda, M. N., & Dhandapani, K. M. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.05.020 · Cited by 108
The Dynamics of Concussion: Mapping Pathophysiology, Persistence, and Recovery With Causal-Loop Diagramming
Kenzie, E. S., Parks, E. L., Bigler, E. D., Wright, D. W., Lim, M. M., Chesnutt, J. C., Hawryluk, G. W. J., Gordon, W. A., & Wakeland, W. W. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00203 · Cited by 102
Analysis of PEG-lipid anchor length on lipid nanoparticle pharmacokinetics and activity in a mouse model of traumatic brain injury
Waggoner, L. E., Miyasaki, K. F., & Kwon, E. J. (2023) · Biomaterials Science · doi:10.1039/d2bm01846b · Cited by 108
Management of Traumatic Brain Injury: From Present to Future
Crupi, R., Cordaro, M., Cuzzocrea, S., & Impellizzeri, D. (2020) · Antioxidants · doi:10.3390/antiox9040297 · Cited by 91
Progesterone neuroprotection: The background of clinical trial failure
Schumacher, M., Denier, C., Oudinet, J., Adams, D., & Guennoun, R. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.11.010 · Cited by 90
Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better?
Kline, A. E., Leary, J. B., Radabaugh, H. L., B, J. P. C. A., & Bondi, C. O. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.05.002 · Cited by 89
Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies
Baassiri, M. G. E., Raouf, Z., Badin, S., Escobosa, A., Sodhi, C. P., & Nasr, I. W. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03118-3 · Cited by 81
Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury
Howard, R. B., Sayeed, I., & Stein, D. G. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.4179 · Cited by 72
Self-citation
Traumatic brain injury in women across lifespan
Blaya, M. O., Raval, A. P., & Bramlett, H. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105613 · Cited by 69
Advances in ex vivo models and lab-on-a-chip devices for neural tissue engineering
Mobini, S., Song, Y. H., McCrary, M. W., & Schmidt, C. E. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.012 · Cited by 72
Long-acting slow effective release antiretroviral therapy
Edagwa, B., McMillan, J., Sillman, B., & Gendelman, H. E. (2017) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2017.1288212 · Cited by 69
Stress primes microglial polarization after global ischemia: Therapeutic potential of progesterone
Espinosa‐García, C., Sayeed, I., Yousuf, S., Atif, F., Sergeeva, E. G., Neigh, G. N., & Stein, D. G. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.012 · Cited by 65
Self-citation
Clinical Relevance of Behavior Testing in Animal Models of Traumatic Brain Injury
Shultz, S. R., McDonald, S. J., Corrigan, F., Semple, B. D., Salberg, S., Zamani, A., Jones, N. C., & Mychasiuk, R. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6149 · Cited by 68
From spreading depolarization to blood–brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy
van Hameren, G., Aboghazleh, R., Parker, E., Dreier, J. P., Kaufer, D., & Friedman, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00973-9 · Cited by 61
Factors Increasing Risk of Suicide after Traumatic Brain Injury: A State-of-the-Science Review of Military and Civilian Studies
McIntire, K. L., Crawford, K. M., Perrin, P. B., Sestak, J. L., Aman, K., Walter, L. A., Page, D. B., Wen, H., Randolph, B. O., Brunner, R. C., et al. (2021) · Brain Injury · doi:10.1080/02699052.2020.1861656 · Cited by 51
Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice
Jiang, C. Q., Zuo, F., Wang, Y., Wan, J., Yang, Z.-J., Lu, H., Chen, W., Zang, W., Yang, Q., & Wang, J. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.029 · Cited by 54
Theranostic Oxygen Reactive Polymers for Treatment of Traumatic Brain Injury
Xu, J. M., Ypma, M., Chiarelli, P. A., Park, J. C., Ellenbogen, R. G., Stayton, P. S., Mourad, P. D., Lee, D., Convertine, A. J., & Kievit, F. M. (2016) · Advanced Functional Materials · doi:10.1002/adfm.201504416 · Cited by 54
Combination of drug and stem cells neurotherapy: Potential interventions in neurotrauma and traumatic brain injury
Zibara, K., Ballout, N., Mondello, S., Karnib, N., Ramadan, N., Omais, S., Nabbouh, A. I., Caliz, D., Clavijo, A., Hu, Z., et al. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.09.032 · Cited by 52
How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury
Agoston, D. V., Vink, R., Helmy, A. E., Risling, M., Nelson, D., & Prins, M. L. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6261 · Cited by 52
Repetitive and Prolonged Omega-3 Fatty Acid Treatment after Traumatic Brain Injury Enhances Long-Term Tissue Restoration and Cognitive Recovery
Pu, H., Jiang, X., Wei, Z., Hong, D., Hassan, S., Zhang, W., Liu, J., Meng, H., Shi, Y., Chen, L., et al. (2017) · Cell Transplantation · doi:10.3727/096368916x693842 · Cited by 49
Optimizing Outcome Assessment in Multicenter TBI Trials: Perspectives From TRACK-TBI and the TBI Endpoints Development Initiative
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 47
Altered Hippocampal Neurogenesis during the First 7 Days after a Fluid Percussion Traumatic Brain Injury
Shapiro, L. A. (2017) · Cell Transplantation · doi:10.1177/0963689717714099 · Cited by 46
Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials
Silverberg, N. D., Crane, P. K., Dams-O’Connor, K., Holdnack, J. A., Ivins, B. J., Lange, R. T., Manley, G. T., McCrea, M., & Iverson, G. L. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2016.4443 · Cited by 44
Progestagens and progesterone receptor modulation: Effects on the brain, mood, stress, and cognition in females
Bencker, C., Gschwandtner, L. P., Nayman, S., Grikšienė, R., Nguyen, B., Nater, U. M., Guennoun, R., Poromaa, I. S., Pletzer, B. A., Bixo, M., et al. (2024) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2024.101160 · Cited by 56
Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures
Schwerin, S. C., Hutchinson, E. B., Radomski, K. L., Ngalula, K. P., Pierpaoli, C. M., & Juliano, S. L. (2017) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2017.05.010 · Cited by 43
Nanoparticle-based drug delivery for the treatment of traumatic brain injury
Mohammed, F. S., Omay, S. B., Sheth, K. N., & Zhou, J. (2022) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2152001 · Cited by 42
The influence of immunological stressors on traumatic brain injury
Sun, M., McDonald, S. J., Brady, R. D., O'Brien, T. J., & Shultz, S. R. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.01.007 · Cited by 41
Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents
Turan, N., Miller, B. A., Heider, R. A., Nadeem, M., Sayeed, I., Stein, D. G., & Pradilla, G. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16665623 · Cited by 40
Self-citation
Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury
Modi, H. R., Musyaju, S., Ratcliffe, M., Shear, D. A., Scultetus, A. H., & Pandya, J. D. (2024) · Antioxidants · doi:10.3390/antiox13030303 · Cited by 44
PPARγ activation ameliorates cognitive impairment and chronic microglial activation in the aftermath of r-mTBI
Pearson, A., Koprivica, M., Eisenbaum, M., Ortiz, C., Browning, M., Vincennie, T., Tinsley, C., MULLAN, M. J., Crawford, F., & Ojo, J. O. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03173-w · Cited by 40
Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials
Pan, Z., Zhao, Y., Huang, W.-H., Xiao, Z.-Z., & Li, Z. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s192633 · Cited by 39
Safety and feasibility of minocycline in treatment of acute traumatic brain injury
Meythaler, J. M., Fath, J. J., Fuerst, D. R., Zokary, H., Freese, K., Martin, H. B., Reineke, J., Peduzzi-Nelson, J. D., & Roskos, P. T. (2019) · Brain Injury · doi:10.1080/02699052.2019.1566968 · Cited by 39
Metabolism and inflammation: implications for traumatic brain injury therapeutics
Killen, M. J., Giorgi-Coll, S., Helmy, A. E., Hutchinson, P. J., & Carpenter, K. L. H. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1582332 · Cited by 39
Estrogen Formation and Inactivation Following TBI: What we Know and Where we Could go
Duncan, K. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00345 · Cited by 39
Cannabis sativa subsp. sativa’s pharmacological properties and health effects: A scoping review of current evidence
Lim, X. Y., Tan, T. Y. C., Rosli, S. H. M., Sa’at, M. N. F., Ali, S. S., & Mohamed, A. F. S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0245471 · Cited by 38
Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo controlled study
Aminmansour, B., Ashari, A. A., Rezvani, M., Ghaffarpasand, F., Noorian, S. M. A., Saboori, M., & Abdollahzadeh, P. (2015) · Journal of Spinal Cord Medicine · doi:10.1080/10790268.2015.1114224 · Cited by 36
Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study
Mondello, S., Sandner, V., Goli, M., Czeiter, E., Amrein, K., Kochanek, P. M., Gautam, S., Cho, B. G., Morgan, R. D., Nehme, A., et al. (2022) · EClinicalMedicine · doi:10.1016/j.eclinm.2022.101494 · Cited by 35
Pre-Clinical Common Data Elements for Traumatic Brain Injury Research: Progress and Use Cases
LaPlaca, M. C., Huie, J. R., Alam, H. B., Bachstetter, A. D., Bayır, H., Bellgowan, P. S. F., Cummings, D. M., Dixon, C. E., Ferguson, A. R., Ferland‐Beckham, C., et al. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7328 · Cited by 34
Intranasal administration of progesterone: A potential efficient route of delivery for cerebroprotection after acute brain injuries
Guennoun, R., Fréchou, M., Gaignard, P., Lière, P., Slama, A., Schumacher, M., Denier, C., & Mattern, C. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.006 · Cited by 34
Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system
Mulcahey, M. J., Jones, L., Rockhold, F. W., Rupp, R., Kramer, J. L. K., Kirshblum, S., Blight, A. R., Lammertse, D. P., Guest, J. D., & Steeves, J. D. (2020) · Spinal Cord · doi:10.1038/s41393-020-00547-8 · Cited by 33
Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role
Allen, R. S., Sayeed, I., Oumarbaeva, Y., Morrison, K. C., Choi, P., Pardue, M. T., & Stein, D. G. (2016) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-160672 · Cited by 32
Self-citation
Neuroprotective effect of minocycline against acute brain injury in clinical practice: A systematic review
Strickland, B. A., Bakhsheshian, J., Emmanuel, B., Amar, A. P., Giannotta, S. L., Russin, J. J., & Mack, W. J. (2021) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2021.01.005 · Cited by 31
Circulating microRNAs as biomarkers in traumatic brain injury
Toffolo, K., Osei, J., Kelly, W., Poulsen, A., Donahue, K., Wang, J.-F., Hunter, M., Bard, J., Wang, J.-X., & Poulsen, D. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.08.028 · Cited by 32
Progesterone Effects in the Nervous System
Theis, V., & Theiß, C. (2019) · The Anatomical Record · doi:10.1002/ar.24121 · Cited by 32
What the replication crisis means for intervention science
Hillary, F. G., & Medaglia, J. D. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2019.05.006 · Cited by 33
Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats
Yousuf, S., Atif, F., Sayeed, I., Wang, J., & Stein, D. G. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.06.002 · Cited by 30
Self-citation
Preclinical modelling of militarily relevant traumatic brain injuries: Challenges and recommendations for future directions
Černak, I., Stein, D. G., Elder, G. A., Ahlers, S., Curley, K. C., DePalma, R. G., Duda, J. E., Ikonomović, M. D., Iverson, G. L., Kobeissy, F. H., et al. (2017) · Brain Injury · doi:10.1080/02699052.2016.1274779 · Cited by 30
Self-citation
Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic brain injury via synaptic regulation
Zhou, J.-H., Liu, T., Cui, H.-J., Fan, R., Zhang, C., Peng, W.-J., Yang, A., Zhu, L., Wang, Y., & Tang, T. (2017) · OncoTarget · doi:10.18632/oncotarget.18895 · Cited by 31
Sex‐dependent effects of tranexamic acid on blood‐brain barrier permeability and the immune response following traumatic brain injury in mice
Daglas, M., Galle, A., Draxler, D. F., Ho, H., Liu, Z., Sashindranath, M., & Medcalf, R. L. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15015 · Cited by 29
Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury
Geddes, R. I., Peterson, B. L., Stein, D. G., & Sayeed, I. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146419 · Cited by 29
Self-citation
Gender difference in the effect of progesterone on neonatal hypoxic/ischemic brain injury in mouse
Dong, S., Zhang, Q., Kong, D., Zhou, C., Zhou, J., Han, J., Zhou, Y., Jin, G., Hua, X., Wang, J., et al. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.05.013 · Cited by 28
Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats
Robinson, S., Winer, J. L., Chan, L. A. S., Oppong, A. Y., Yellowhair, T. R., Maxwell, J. R., Andrews, N. A., Yang, Y., Sillerud, L. O., Meehan, W. P., III, et al. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00451 · Cited by 28
Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus
Meletti, S., Lucchi, C., Monti, G., Giovannini, G., Bedin, R., Trenti, T., Rustichelli, C., & Biagini, G. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14550 · Cited by 28
Progesterone: Synthesis, Metabolism, Mechanism of Action, and Effects in the Nervous System
Schumacher, M., Zhu, X., & Guennoun, R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00054-7 · Cited by 30
Intranasal delivery of mitochondria targeted neuroprotective compounds for traumatic brain injury: screening based on pharmacological and physiological properties
Pandya, J. D., Musyaju, S., Modi, H. R., Okada-Rising, S. L., Bailey, Z. S., Scultetus, A. H., & Shear, D. A. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-04908-2 · Cited by 33
Progesterone improves long-term functional and histological outcomes after permanent stroke in older rats
Wali, B., Ishrat, T., Stein, D. G., & Sayeed, I. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.02.024 · Cited by 27
Self-citation
Mild and Mild-to-Moderate Traumatic Brain Injury-Induced Significant Progressive and Enduring Multiple Comorbidities
Hou, J., Nelson, R., Wilkie, Z., Mustafa, G., Tsuda, S., Thompson, F. J., & Bose, P. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4851 · Cited by 27
Barriers to clinical research in trauma
Miskimins, R. J., Pati, S., & Schreiber, M. A. (2018) · Transfusion · doi:10.1111/trf.15097 · Cited by 27
Nanomedicine for Acute Brain Injuries: Insight from Decades of Cancer Nanomedicine
Kandell, R. M., Waggoner, L. E., & Kwon, E. J. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00287 · Cited by 27
Repurposing and repositioning neurosteroids in the treatment of traumatic brain injury: A report from the trenches
Stein, D. G., & Sayeed, I. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.04.006 · Cited by 26
Self-citation
Why Does Brain Trauma Research Fail?
Alves, J. L., Rato, J. R., & da Silva, V. M. M. (2019) · World Neurosurgery · doi:10.1016/j.wneu.2019.06.212 · Cited by 26
The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage
Pradilla, G., Barrow, J., Turan, N., Wangmo, P., & Roy, A. (2018) · Surgical Neurology International · doi:10.4103/sni.sni_88_18 · Cited by 25
Diagnosing the GOSE: Structural and Psychometric Properties Using Item Response Theory, a TRACK-TBI Pilot Study
Ranson, J., Magnus, B. E., Temkin, N. R., DIKMEN, S. S., Giacino, J. T., Okonkwo, D. O., Valadka, A. B., Manley, G. T., Nelson, L. D., The TRACK-TBI Investigators, et al. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.5998 · Cited by 25
Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury to the adult zebra finch brain
Pedersen, A. L., Brownrout, J., & Saldanha, C. J. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.10.013 · Cited by 25
Revisiting the critical roles of reactive microglia in traumatic brain injury
Zhao, J., Zhou, Y., Zhou, C.-W., Zhan, K., Yang, M., Wen, M., & Zhu, L. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000002420 · Cited by 30
Biomechanical simulation of traumatic brain injury in the rat
Finan, J. D. (2018) · Clinical Biomechanics · doi:10.1016/j.clinbiomech.2018.01.015 · Cited by 22
Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence
Lengel, D., Huh, J. W., Barson, J. R., & Raghupathi, R. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113329 · Cited by 24
Major publications in the critical care pharmacotherapy literature in 2015
Wong, A., Erdman, M. J., Hammond, D. A., Holt, T., Holzhausen, J. M., Horng, M., Huang, L. L., Jarvis, J., Kram, B., Kram, S. J., et al. (2017) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp160144 · Cited by 24
Cognitive and neural effects of exercise following traumatic brain injury: A systematic review of randomized and controlled clinical trials
Sharma, B., Allison, D., Tucker, P., Mabbott, D., & Timmons, B. W. (2019) · Brain Injury · doi:10.1080/02699052.2019.1683892 · Cited by 24
Current advances in in vitro models of central nervous system trauma
Omelchenko, A., Singh, N. K., & Firestein, B. L. (2020) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2020.05.002 · Cited by 22
A Population-Based Study of Pre-Existing Health Conditions in Traumatic Brain Injury
Dell, K. C., Grossner, E. C., Staph, J., Schatz, P., & Hillary, F. G. (2021) · Neurotrauma Reports · doi:10.1089/neur.2020.0065 · Cited by 26
Multiple mild traumatic brain injury in the rat produces persistent pathological alterations in the brain
Brooks, D. M., Patel, S. A., Wohlgehagen, E. D., Semmens, E. O., Pearce, A. J., Sorich, E., & Rau, T. F. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.07.015 · Cited by 24
Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage
Turan, N., Miller, B. A., Huie, J. R., Heider, R. A., Wang, J., Wali, B., Yousuf, S., Ferguson, A. R., Sayeed, I., Stein, D. G., et al. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.10.118 · Cited by 21
Self-citation
Progesterone Treatment Does Not Decrease Serum Levels of Biomarkers of Glial and Neuronal Cell Injury in Moderate and Severe Traumatic Brain Injury Subjects: A Secondary Analysis of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III Trial
Korley, F. K., Pauls, Q., Yeatts, S. D., Jones, C. M. C., Corbett-Valade, E., Silbergleit, R., Frankel, M., Barsan, W. G., Cahill, N. D., Bazarian, J. J., et al. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7072 · Cited by 21
Progesterone improves neurocognitive outcomes following therapeutic cranial irradiation in mice
Yousuf, S., Brat, D. J., Shu, H. G., Wang, Y., Stein, D. G., & Atif, F. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.08.004 · Cited by 20
Self-citation
Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury
Waggoner, L. E., Madias, M. I., Hurtado, A. A., & Kwon, E. J. (2021) · The AAPS Journal · doi:10.1208/s12248-021-00626-5 · Cited by 22
Time-Course Evaluation of Brain Regional Mitochondrial Bioenergetics in a Pre-Clinical Model of Severe Penetrating Traumatic Brain Injury
Pandya, 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
Prevalence of comorbidities post mild traumatic brain injuries: a traumatic brain injury model systems study
Sudhakar, S., Sridhar, S., Char, S., Pandya, K., & Mehta, K. (2023) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2023.1158483 · Cited by 19
Results from a randomized trial evaluating a hospital–school transition support model for students hospitalized with traumatic brain injury
Glang, A. E., Todis, B. J., Ettel, D., Wade, S. L., & Yeates, K. O. (2018) · Brain Injury · doi:10.1080/02699052.2018.1433329 · Cited by 19

Authors: Stein, D. G.
Affiliations: Emory University (US)
Corresponding author: Stein, Donald G.
Venue: Brain Injury
Publisher: Informa UK Limited
Published: 2015-08-14
Volume: 29
Issue: 11
Pages: 1259-1272
ISSN: 0269-9052 (ISSN-L)
1362-301X
DOI: 10.3109/02699052.2015.1065344
PMC: PMC4667711
OpenAlex: W1757695926
Cited by: 249
References: 102
Citations by year: 2026: 17 · 2025: 16 · 2024: 19 · 2023: 26 · 2022: 14 · 2021: 20 · 2020: 25 · 2019: 25 · 2018: 30 · 2017: 24 · 2016: 27 · 2015: 5
FWCI: 3.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Brain Injury (publishedVersion)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Keywords: traumatic brain injury, progesterone, clinical trial failure, drug development, outcome measures, preclinical to clinical translation, stroke, sepsis
MeSH terms: Brain Injuries, Humans, Progestins, Progesterone, Treatment Outcome, Outcome Assessment, Health Care, Treatment Failure, Clinical Trials, Phase III as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks