Clinical trials in traumatic brain injury: past experience and current developments

Area of Science:

• Neurology
• Clinical Trials
• Traumatic Brain Injury Research

Background:

• Review of past and current clinical trials for moderate to severe traumatic brain injuries (TBIs).
• Analysis of 33 phase III trials conducted between 1980 and 2009, including 6 unpublished studies.
• Observation of trends in TBI trial initiations, geographic focus, and study types.

Purpose of the Study:

• To review clinical trial experience in TBI, discuss limitations, and summarize current research directions.
• To analyze trends in TBI trial design, methodology, and outcomes.
• To highlight the shift from neuroprotective agents to therapeutic strategies in TBI research.

Main Methods:

• Systematic literature search of TBI trials from 1980 to 2009.
• Analysis of 33 large phase III trials, including published and unpublished data.
• Examination of trial outcomes, therapeutic strategies, and geographic distribution.

Main Results:

• A peak in TBI trial initiations in the mid-1990s, followed by a sharp decline from 2000-2004.
• Most trials reporting significant treatment effects focused on therapeutic strategies (e.g., decompressive craniectomy, hypothermia) and were single-center studies.
• A decrease in studies on neuroprotective agents, with an increase in therapeutic strategy studies; research is increasingly shifting to the Far East.

Conclusions:

• Disappointing results from neuroprotective agent trials necessitate a critical reappraisal of TBI clinical trial methodology.
• Recommendations for preclinical workup and improved trial design/analysis are crucial for future TBI research.
• Ongoing initiatives for data element standardization will facilitate research comparison and high-quality meta-analyses in TBI.