Measuring Outcome in Traumatic Brain Injury Treatment Trials: Recommendations From the Traumatic Brain Injury Clinical Trials Network

Background:Traumatic brain injury (TBI) involves several aspects of a patient's condition, including physical, mental, emotional, cognitive, social, and functional changes. Therefore, a clinical trial with individuals with TBI should consider outcome measures that reflect their global status. Methods:We present the work of the National Institute of Child Health and Development–sponsored Traumatic Brain Injury Clinical Trials Network Outcome Measures subcommittee and its choice of outcome measures for a phase III clinical trial of patients with complicated mild to severe TBI. Results:On the basis of theoretical and practical considerations, the subcommittee recommended the adoption of a core of 9 measures that cover 2 different areas of recovery: functional and cognitive. These measures are the Extended Glasgow Outcome Scale; the Controlled Oral Word Association Test; the Trail Making Test, Parts A and B; the California Verbal Learning Test–II; the Wechsler Adult Intelligence Scale–III Digit Span subtest; the Wechsler Adult Intelligence Scale–III Processing Speed Index; and the Stroop Color-Word Matching Test, Parts 1 and 2. Conclusions:The statistical methods proposed to analyze these measures using a global test procedure, along with research and methodological and regulatory issues involved with the use of multiple outcomes in a clinical trial, are discussed.