Department of Neurosurgery, University Hospital 2650 Antwerp, Belgium.
Neurotherapeutics. 2010 Jan;7(1):115-26. doi: 10.1016/j.nurt.2009.10.022.
In this article, we review past and current experience in clinical trials of traumatic brain injuries (TBIs), we discuss limitations and challenges, and we summarize current directions. The focus is on severe and moderate TBIs. A systematic literature search of the years from 1980 to 2009 revealed 27 large phase III trials in TBI; we were aware of a further 6 unpublished trials. Analysis of these 33 trials yielded interesting observations: There was a peak incidence of trial initiations that occurred in the mid-1990s with a sharp decline during the period from 2000 to 2004. Most trials that reported a significant treatment effect were studies on a therapeutic strategy (e.g., decompressive craniectomy, hypothermia), and these were single-center studies. Increasingly, studies have been shifting toward the Far East. The currently existing trial registries permit insight into ongoing or recently conducted trials. Compared with the past decade, the number of studies on neuroprotective agents taken forward into efficacy-oriented studies is low. In contrast, the number of studies on therapeutic strategies appears to be increasing again. The disappointing results in trials on neuroprotective agents in TBI have led to a critical reappraisal of clinical trial methodology. This has resulted in recommendations for preclinical workup and has triggered extensive analysis on approaches to improve the design and analysis of clinical trials in TBI. An interagency initiative toward standardization on selection and coding of data elements across the broad spectrum of TBI is ongoing, and will facilitate comparison of research findings across studies and encourage high-quality meta-analysis of individual patient data in the future.
在本文中，我们回顾了过去和当前在创伤性脑损伤（TBI）临床试验方面的经验，讨论了局限性和挑战，并总结了当前的方向。重点是严重和中度 TBI。对 1980 年至 2009 年期间的文献进行了系统检索，发现了 27 项大型 III 期 TBI 试验；我们还了解到另外 6 项未发表的试验。对这 33 项试验的分析得出了有趣的观察结果：试验启动的发生率在 20 世纪 90 年代中期达到峰值，然后在 2000 年至 2004 年期间急剧下降。大多数报告有显著治疗效果的试验都是关于治疗策略的研究（例如，去骨瓣减压术，低温疗法），而且这些都是单中心研究。越来越多的研究转向远东。目前现有的试验登记处可以洞察正在进行或最近进行的试验。与过去十年相比，在进入疗效导向研究的神经保护剂研究数量较低。相比之下，治疗策略的研究数量似乎再次增加。TBI 中神经保护剂试验的令人失望结果导致对临床试验方法学进行了批判性重新评估。这导致了对临床前工作的建议，并引发了对改善 TBI 临床试验设计和分析方法的广泛分析。一项针对在广泛的 TBI 范围内选择和编码数据元素的标准化的机构间倡议正在进行中，这将有助于比较研究结果，并鼓励未来对个体患者数据进行高质量的荟萃分析。
