Clinical trials in traumatic brain injury: cellular therapy and outcome measures

Area of Science:

• Neuroscience
• Regenerative Medicine
• Clinical Trial Design

Background:

• Despite extensive research, clinical trials for traumatic brain injury (TBI) have not yielded effective neuroprotective or neurorestorative therapies.
• Cellular therapies show promise, with ongoing Phase II and III trials for neurological conditions like TBI and stroke.
• Past clinical failures highlight issues with preclinical data translation, often due to heterogeneous study designs and patient populations.

Purpose of the Study:

• To advocate for novel outcome measures in TBI clinical trials that are clinically meaningful and avoid global functional scores.
• To propose measuring early physiological outcomes (intracranial pressure, edema, therapeutic intensity) and later structural outcomes in specific regions of interest.
• To facilitate earlier therapeutic approval and subsequent testing through patient registries.

Main Methods:

• Critically evaluating existing clinical trial methodologies for TBI and other neurological diseases.
• Proposing a shift from global functional scores to specific, physiologically relevant outcome measures.
• Linking proposed outcome measures to the putative mechanisms of action for cell-based therapies.

Main Results:

• Current approaches in TBI clinical trials, if unchanged, are likely to perpetuate past failures.
• The proposed outcome measures offer a more precise and clinically relevant assessment of therapeutic efficacy.
• Early identification of successful therapeutics can accelerate their adoption and further evaluation.

Conclusions:

• Rethinking outcome measures is crucial for advancing TBI therapeutics.
• Focusing on early physiological and later structural outcomes can improve the success rate of clinical trials.
• Implementing these changes may lead to more effective treatments for patients with traumatic brain injury.