ReviewBrain injury2015
Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials.
Review in Brain injury, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
144 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- A comprehensive meta-analysis of exogenous estrogen, progesterone, and testosterone in animal models of ischemic and hemorrhagic stroke.Biology of sex differences · 2026Pooled it
- Pooled it
- Effects of Progesterone on Preclinical Animal Models of Traumatic Brain Injury: Systematic Review and Meta-analysis.Molecular neurobiology · 2022Pooled it
- Pooled it
- Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials.Drug design, development and therapy · 2019Pooled it
- Progesterone for acute traumatic brain injury.The Cochrane database of systematic reviews · 2016Pooled it
- Efficacy of Progesterone for Acute Traumatic Brain Injury: a Meta-analysis of Randomized Controlled Trials.Molecular neurobiology · 2016Pooled it
- Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment III Trial Revisited: Objective Classification of Traumatic Brain Injury With Brain Imaging Segmentation and Biomarker Levels.Critical care explorations · 2025Trial
- Trial
- Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo controlled study.The journal of spinal cord medicine · 2016Trial
- Article
- IL-3 Modulates Microglia Polarization and Attenuates Neuroinflammation in Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Longitudinal Multimodal Neuroimaging After Traumatic Brain Injury.Human brain mapping · 2026Article
- The Effects of Adenosine A1/A3 Receptors Agonist on Improving the Outcomes of TBI and Stroke: Focus on AST-004.Current neurology and neuroscience reports · 2026Review
- Editorial: Neuroprotective and therapeutic effects of progesterone, allopregnanolone, and their derivatives.Frontiers in endocrinology · 2026Article
- The Design Strategies and Applications of Engineered Nanoparticles for Traumatic Brain Injury.International journal of nanomedicine · 2026Review
- Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury.Ibrain · 2026Review
- Peptide OM-LV20 demonstrates neuroprotective effects by attenuating mitochondria-mediated neuronal apoptosis and dysfunction in mice with traumatic brain injury.Zoological research · 2025Article
- A Model of Traumatic Brain Injury Oligomerizes Tau in Cortical Organoids and Induces Clinically Relevant Pathologies that Synergize withJournal of neurotrauma · 2025Article
- Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite 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.
methodsThis 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.
resultsThis 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.
conclusionsBetter 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.