Improving Patient Classification and Outcome Measurement in Traumatic Brain Injury (TBI)

摘要 创伤性脑损伤是一种常见的导致慢性症状和残疾的损伤。 对很多病人来说。不幸的是，有效的治疗选择可以降低脑外伤相关死亡率和 明显缺乏降低发病率的措施。先前脑损伤临床试验的失败被认为是一个 对患者异质性认识不足、缺乏客观生物标志物的后果 以及迟钝的结果衡量方法。拟议的R01研究将使用 现代定量建模方法，以(A)提高对患者模式的理解 异质性和(B)提高临床结果衡量的效率。这项研究将 对来自转化研究和临床知识的数据进行二次分析 TBI(Track-TBI)研究，积累了最大的平民患者预期样本 到目前为止，还将收集一个较小的新样本，以满足目标。这个 本研究的具体目的是：(1)确定脑外伤的最佳临床表型模型。 严重程度的连续体，通过演示不同的患者来验证模型 急性颅脑损伤血液生物标记物水平不同的急性临床表现类型和(2) 使用项目反应理论(IRT)分析，这是AIM 1中使用的建模工具的扩展 开发新的方法，以更精确的方式测量与脑损伤相关的残疾的全谱 目前的方法。这项研究将在利用先进的量化模型方面具有创新性 在其他环境中被证明是有价值的工具，以解决目前在TBI中的方法学挑战。 尽管这项工作将利用Track-TBI提供的专业知识和数据，但它将 带来新的专业知识和创新的方法，超越正在进行的工作 在任何现有的研究中。我们的调查团队非常适合领导这项工作，因为我们 将建议的分析方法应用于脑损伤、精神病学、 阿尔茨海默氏症和测量研究。这一发现可能会改变脑外伤的诊断方式， 如何选择患者进行临床和转化性研究，以及结果如何 测量，以推动精准医学治疗研究的发展，并增加 确定有效治疗脑损伤的机会。

Abstract Traumatic brain injury (TBI) is a common injury that causes chronic symptoms and disabilities for many patients. Unfortunately, effective treatment options to reduce TBI-related mortality and reduce morbidity are glaringly absent. The failure of prior clinical trials of TBI is thought to be a consequence of inadequate understanding of patient heterogeneity, lack of objective biomarkers of TBI, and blunt approaches to outcome measurement. The proposed R01 study will use modern quantitative modeling approaches to (a) advance understanding of patterns of patient heterogeneity and (b) improve the efficiency of clinical outcome measurement. The study will perform secondary analyses of data from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which has accrued the largest prospective sample of civilian patients with TBI to date, and will additionally collect a smaller new sample to address the aims. The specific aims of the study are to (1) identify the optimal clinical phenotypic model of TBI across the continuum of severity, validating the model by demonstrating that patients with distinct patterns of acute clinical presentation differ in their levels of acute TBI blood biomarkers and (2) use item-response theory (IRT) analyses, an extension of the modeling tools used in Aim 1, to develop new ways measure the full spectrum of TBI-related disability with more precision than current approaches. The study will be innovative in leveraging advanced quantitative modeling tools proven valuable in other settings to address current methodological challenges in TBI. Although this work will leverage the expertise and data available through TRACK-TBI, it will bring new expertise and an innovative approach that will go beyond the work being undertaken in any existing study. Our investigative team is uniquely suited to lead this effort given our extensive experience applying the proposed analytic approaches to TBI, psychiatric, Alzheimer’s, and measurement research. The findings could transform how TBI is diagnosed, how patients are selected for clinical and translational studies, and how outcomes are measured, to fuel the development of precision medicine treatment studies and increase the chances of identifying effective treatments for TBI.