Related Experiment Video
Updated: Jul 14, 2026
Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging
Published on: April 6, 2014
Traumatic brain injury. Rethinking pharmacological clinical trials in an orphan pathology
1Direzione Scientifica, Phase I Clinical Trials Unit and Experimental Therapy, Fondazione IRCCS Policlinico, San Matteo, Pavia, Italy.
Introduction:
Every year more than 50 million people in the world experience a traumatic brain injury (TBI). In its more severe form the mortality is high, and survivors can be very disabled. Nevertheless, there are currently no approved pharmacological treatments that definitely improve the prognosis in humans, and given the consistently disappointing results, pharmaceutical companies are reluctant to invest further.
Areas Covered:
We reviewed relevant PubMed-indexed studies on pharmacological trials conducted during the acute phase of TBI. The potential reasons for the observed lack of efficacy are discussed, including the vast heterogeneity within the TBI population, the limitations of randomization in balancing prognostic factors, and challenges posed by current clinical endpoints used to assess treatment outcomes.
Expert Opinion:
The search for new pharmacological treatments of TBI patients must continue, but a change of paradigm should be accepted by scientists and regulatory authorities. In the unique context of TBI patients, randomization and patients stratification are not sufficient to create homogeneous and comparable groups. Current clinical outcomes are too influenced by variables and too 'hard.' Alternative endpoints, i.e. relevant pathophysiological variables (e.g. ICP, biomarkers, MRI), if accepted could encourage pharmaceutical companies to develop drugs in TBI.
Insights
Developing new drugs for traumatic brain injury (TBI) requires a paradigm shift. Exploring alternative clinical endpoints beyond traditional measures may encourage pharmaceutical investment in TBI treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Traumatic brain injury (TBI) affects over 50 million people globally each year, with severe cases leading to high mortality and disability.
- Currently, no approved pharmacological treatments definitively improve outcomes in human TBI patients, leading to pharmaceutical industry reluctance in investment.
Purpose of the Study:
- To review pharmacological trials in the acute phase of TBI.
- To discuss reasons for the lack of treatment efficacy.
- To propose a change in research paradigm for TBI drug development.
Main Methods:
- Review of PubMed-indexed studies on pharmacological trials in acute TBI.
- Analysis of factors contributing to treatment inefficacy.
- Discussion of alternative clinical endpoints.
Main Results:
- Existing pharmacological trials for TBI have shown a consistent lack of efficacy.
- Heterogeneity in the TBI population and limitations in randomization challenge study design.
- Current clinical endpoints are too variable and "hard" to reliably assess treatment effects.
Conclusions:
- Continued search for TBI pharmacological treatments is essential.
- A paradigm shift is needed, accepting that randomization and stratification are insufficient for TBI patient homogeneity.
- Adoption of alternative, pathophysiological endpoints (e.g., ICP, biomarkers, MRI) could incentivize pharmaceutical development for TBI.
More Related Videos
09:29Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells
Published on: July 10, 2019
07:21Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
