A Systematic Review of Reported Outcomes in Randomized Controlled Trials Targeting Early Interventions in...

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Randomized controlled trials (RCTs) are the cornerstone to evaluate the efficacy of an intervention. To assess the methodology of clinical research, we performed a systematic review that evaluated the different outcomes used in RCTs targeting the early phase of moderate-to-severe adult TBI from 1983 to October 31, 2023. We extracted each outcome and organized them according to the COMET and OMERACT framework (core area, broad domains, target domains, and finally outcomes). A total of 190 RCTs were included, including 52,010 participants. A total of 557 outcomes were reported and classified between the following core areas: pathophysiological manifestations [169 RCTs (88.9%)], life impact [117 RCTs (61.6%)], death [94 RCTs (49.5%)], resource use [72 RCTs (37.9%)], and adverse events [41 RCTs (21.6%)]. We identified 29 broad domains and 89 target domains. Among target domains, physical functioning [111 (58.4%)], mortality [94 (49.5%)], intracranial pressure target domain [68 (35.8%)], and hemodynamics [53 (27.9%)] were the most frequent. Outcomes were mostly clinician-reported [177 (93.2%)], while patient-reported outcomes were rarely reported [11 (5.8%)]. In our review, there was significant heterogeneity in the choice of end-points in TBI clinical research. There is an urgent need for consensus and homogeneity to improve the quality of clinical research in this area.