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 accessAbstract
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.
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“This has been attributed in part to inadequate preclinical efforts to recapitulate the complexity of the human injury.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [19]
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“Moreover, results are not always analyzed by sex.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [19]
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Cited by
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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
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Metadata
- 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
- 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
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