Citation

Bragge P, Synnot A, Maas A, Menon D, Cooper DJ, Rosenfeld JV, Gruen RL. J. Neurotrauma 2015; 33(16): 1461-1478.

Affiliation

Monash University and The Alfred Hospital, Centre of Excellence in Traumatic Brain Injury Research, National Trauma Research Institute, Melbourne, Victoria, Australia ; Russell.gruen@monash.edu.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2015.4233

PMID

26711675

Abstract

Moderate to severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomised controlled trials (RCTs) evaluating interventions for acute management of moderate / severe TBI; synthesise key RCT characteristics and findings; and determine their implications on clinical practice and future research. RCTs were identified through comprehensive database and other searches. Key characteristics, outcomes, risk of bias, and analysis approach were extracted. Data were narratively synthesised, with a focus on robust (multicentre, low risk of bias, n > 100) RCTs, and 3-dimensional graphical figures were also used to explore relationships between RCT characteristics and findings. 207 RCTs were identified. The 191 completed RCTs enrolled 35,340 participants (median 65.5). Most (72%) were single centre and enrolled under 100 participants (69%). There were 26 robust RCTs across 18 different interventions. For 74% of 392 comparisons across all included RCTs there was no significant difference between groups. Positive findings were broadly distributed with respect to RCT characteristics. Less than one third of RCTs demonstrated low risk of bias for random sequence generation or allocation concealment; less than a quarter used covariate adjustment and only 7% employed an ordinal analysis approach. Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-centre RCTs and methodological shortcomings. More sophisticated RCT design, large multicentre RCTs in priority areas, increased focus on pre-clinical research and alternatives to RCTs such as comparative effectiveness research and precision medicine are needed to fully realise the potential of acute TBI research to benefit patients.

Language: en