背景:关于涉及意识障碍(DoC)的研究的最佳临床试验设计的数据有限,只有少数疗法在高质量的临床试验中得到了测试。为了解决这个问题,治愈昏迷运动临床试验工作组对DoC临床试验的现状进行了差距分析,以确定涉及DoC患者的研究的最佳临床设计.
方法:治愈昏迷运动临床试验工作组分为三个亚组,以(1)审查涉及DoC患者的临床试验,(2)确定涉及DoC患者的临床试验设计中的独特挑战,(3)推荐DoC的最佳临床试验设计。
结果:筛选了3055项研究,66例纳入本综述.确定了一些知识差距和独特的挑战。缺乏高质量的临床试验,关于DoC患者的大多数数据是基于针对创伤性脑损伤和心脏骤停患者的观察性研究。缺乏结构化的长期结果评估,在方法上具有显著的异质性,结果的定义,和进行研究,尤其是长期随访。进行临床试验的另一个主要障碍是缺乏资源,特别是在低收入国家。根据现有数据,我们建议合并使用主协议的试验设计,序贯多重评估随机试验,和比较有效性研究。使用多臂的自适应平台试验,多阶段法具有显著优势,应利用生物标志物评估治疗反应,以提高试验效率.最后,完善的基础设施和国际合作对于促进在DoC患者中进行试验至关重要.
结论:在DoC患者中进行试验应利用主方案和适应性设计,并建立包含标准化评估工具的国际注册中心。这将允许建立基于证据的实践建议,并减少护理方面的差异。
BACKGROUND: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC.
METHODS: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC.
RESULTS: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC.
CONCLUSIONS: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.