Chapter 15:Difficulties in Clinical Trials to Treat Traumatic Brain Injury and Stroke

Traumatic brain injury (TBI) and stroke are major causes of morbidity and mortality worldwide. Despite major advances in the comprehension of the molecular mechanisms determining brain injury in stroke and TBI, the history of clinical translation of experimentally successful trials of neuroprotective drugs is plagued with failures. Although with certain differences, the reasons for the failures of clinical trials are similar, from insufficient data on animal experiments and too many assumptions in translation to insufficient acknowledgement and control of clinical heterogeneity, poor data handling and standardization and restricted outcome measurement and analysis. Realization of these reasons with improved experimental conception and testing of the potentially active compound, including the use of different strains, sexes, models and outcome analyses, with replication of preclinical data in different laboratories, as well as better planning and analysis of clinical trials, could finally allow the development of an effective therapeutic strategy.