Maas Andrew I R, Marmarou Anthony, Murray Gordon D, Teasdale Sir Graham M, Steyerberg Ewout W
Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands.
J Neurotrauma. 2007 Feb;24(2):232-8. doi: 10.1089/neu.2006.0024.
Traumatic brain injury (TBI) is a major health and socio-economic problem throughout the world. Many randomized controlled trials (RCTs) have been performed to investigate the effectiveness of new therapies, but none have convincingly demonstrated benefit. Clinical trials in TBI pose complex methodological challenges and meeting these requires new approaches. The challenges are related to the heterogeneity of head injuries, to optimum analysis of outcome and to aspects of the design of trials. To address these, we have created the IMPACT database on TBI through merging individual patient data from eight RCTs and three observational surveys. This database forms a culture medium in which innovative approaches to improving trial design and analysis are being explored. We hypothesize that the statistical power of TBI trials may be increased by adjusting for heterogeneity with covariate adjustment and/or prognostic targeting, by exploiting the ordinal nature of the Glasgow Outcome Scale and by relating the outcome obtained in individual patients to their baseline prognostic risk. Extensive prognostic analysis was required as a first step towards our aim of optimizing the chance of demonstrating benefit of new therapies in future trials. The fruits of this analysis are reported in detail in the subsequent reports in this issue of the Journal of Neurotrauma. The results will lead to the development and validation of new prognostic models, which will be applied to deal with heterogeneity. The findings will be synthesized into recommendations for the design and analysis of future RCTs, with the expectation of increasing the likelihood of demonstrating the benefit of a truly effective new therapy or therapeutic agent in victims of a head injury.
创伤性脑损伤（TBI）是全球范围内的一个重大健康和社会经济问题。已经开展了许多随机对照试验（RCT）来研究新疗法的有效性，但没有一项试验令人信服地证明其益处。TBI的临床试验带来了复杂的方法学挑战，应对这些挑战需要新的方法。这些挑战与头部损伤的异质性、结局的最佳分析以及试验设计的各个方面有关。为了解决这些问题，我们通过合并来自八项RCT和三项观察性调查的个体患者数据，创建了TBI的IMPACT数据库。该数据库形成了一种培养基，正在其中探索改进试验设计和分析的创新方法。我们假设，通过协变量调整和/或预后靶向来调整异质性、利用格拉斯哥预后量表的序数性质以及将个体患者获得的结局与其基线预后风险相关联，可以提高TBI试验的统计效力。作为朝着我们在未来试验中优化证明新疗法益处机会这一目标迈出的第一步，需要进行广泛的预后分析。本期《神经创伤杂志》后续报告中详细报道了这一分析的成果。结果将导致新预后模型的开发和验证，这些模型将用于处理异质性。研究结果将综合成未来RCT设计和分析的建议，期望增加在头部受伤受害者中证明真正有效的新疗法或治疗药物益处的可能性。
