Risk Factors for High Symptom Burden Three Months after Traumatic Brain Injury and Implications for Clinical Trial Design: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.
Risk Factors for High Symptom Burden Three Months after Traumatic Brain Injury and Implications for Clinical Trial Design: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.
复制标题
创伤性脑损伤后三个月高症状负担的危险因素以及临床试验设计的意义：创伤性脑损伤研究中的转化研究和临床知识。
DOI：
10.1089/neu.2022.0113
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发表时间：
2022
影响因子：
4.2
通讯作者：
TRACK-TBIInvestigators
中科院分区：
文献类型：
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作者：
Temkin,Nancy;Machamer,Joan;Dikmen,Sureyya;Nelson,LindsayD;Barber,Jason;Hwang,PhillipH;Boase,Kim;Stein,MurrayB;Sun,Xiaoying;Giacino,Joseph;McCrea,MichaelA;Taylor,SabrinaR;Jain,Sonia;Manley,Geoff;TRACK-TBIInvestigators
在美国的一级创伤中心，超过75%的患者怀疑TBI，需要进行临床计算机断层扫描，3个月后报告损伤相关症状。目前还没有批准的治疗方法，也很少有临床试验评估可能的治疗方法。有效的试验将需要受试者纳入和排除标准，以平衡具有成本效益的招募与有更高机会从干预措施中受益的入组个体。使用来自创伤性脑损伤转化研究和临床知识（TRACK-TBI）研究的数据，我们检查了3个月症状与损伤前、人口统计学和急性特征的关系，以及2周症状和血液生物标志物，以识别和评估可用于临床试验样本富集的因素。文献中报道的许多TBI症状的危险因素得到了支持，但每个因素的效应量都很小或中等（< 0.5）。在预测3个月症状负担时，唯一具有较大效应量的因素是创伤后应激相关（即脑震荡后）和2周时创伤后应激症状水平（各自的效应量分别为1.13和1.34）。TBI严重程度与3个月症状负担无显著相关性（p= 0.37）。使用模拟数据来评估富集的效果，我们表明，与纳入未富集的样本相比，仅纳入2周时症状负担高的人可以使试验减少一半的样本量，而筛选的增加最少。旨在减轻创伤性脑损伤后症状的临床试验可以通过增加报告早期症状负担高的人的纳入样本来有效地进行。
More than 75% of patients presenting to level I trauma centers in the United States with suspicion of TBI sufficient to require a clinical computed tomography scan report injury-related symptoms 3 months later. There are currently no approved treatments, and few clinical trials have evaluated possible treatments. Efficient trials will require subject inclusion and exclusion criteria that balance cost-effective recruitment with enrolling individuals with a higher chance of benefiting from the interventions. Using data from theTransformingResearchandClinicalKnowledge inTraumaticBrainInjury (TRACK-TBI) study, we examined the relationship of 3-month symptoms to pre-injury, demographic, and acute characteristics as well as 2-week symptoms and blood-based biomarkers to identify and evaluate factors that may be used for sample enrichment for clinical trials. Many of the risk factors for TBI symptoms reported in the literature were supported, but the effect sizes of each were small or moderate (< 0.5). The only factors with large effect sizes when predicting 3-month symptom burden were TBI-related (i.e., post-concussive) and post-traumatic stress symptom levels at 2 weeks (respective effect sizes 1.13 and 1.34). TBI severity was not significantly associated with 3-month symptom burden (p= 0.37). Using simulated data to evaluate the effect of enrichment, we showed that including only people with high symptom burden at 2 weeks would permit trials to reduce the sample size by half, with minimal increase in screening, as compared with enrolling an unenriched sample. Clinical trials aimed at reducing symptoms after TBI can be efficiently conducted by enriching the included sample with people reporting a high early symptom burden.