Traumatic brain injury. Rethinking pharmacological clinical trials in an orphan pathology.

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.