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

摘要 创伤性脑损伤（TBI）是一种常见的损伤，可导致慢性症状和残疾 对于许多患者来说。不幸的是，降低TBI相关死亡率的有效治疗方案， 降低发病率是令人遗憾的。先前TBI临床试验的失败被认为是一个原因。 对患者异质性理解不足，缺乏客观生物标志物的后果 以及对结果测量的生硬方法。拟议的R 01研究将使用 现代定量建模方法（a）促进对患者模式的理解 异质性和（B）提高临床结果测量的效率。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，该研究积累了最大的平民患者前瞻性样本 与TBI迄今为止，并将另外收集一个较小的新样本，以解决的目标。的 研究的具体目的是（1）确定TBI的最佳临床表型模型， 严重程度的连续性，通过证明具有不同严重程度的患者 急性临床表现的模式在急性TBI血液生物标志物的水平上不同，以及（2） 使用项目反应理论（IRT）分析，目标1中使用的建模工具的扩展， 开发新的方法来测量TBI相关残疾的全方位， 目前的做法。这项研究将在利用先进的定量建模方面具有创新性 工具在其他环境中被证明是有价值的，以解决TBI当前的方法学挑战。 虽然这项工作将利用TRACK-TBI提供的专业知识和数据， 带来新的专业知识和创新方法，超越正在开展的工作 任何现有的研究。我们的调查小组是唯一适合领导这项工作，因为我们的 将所提出的分析方法应用于TBI，精神病学， 老年痴呆症和测量研究。这些发现可能会改变TBI的诊断方式， 如何选择患者进行临床和转化研究，以及结果如何 测量，以推动精确医学治疗研究的发展，并增加 为TBI确定有效治疗方法的机会。

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.