Clinical Coordinating Center for the Network of Excellence in Neuroscience Clinical Trials (NEXT - CCC)

项目概要 神经科学临床试验卓越网络 (NeuroNEXT) 计划的长期目标是通过与政府、学术界、私人基金会和行业的合作，有效地将神经科学的进步转化为治疗患有神经系统疾病的成人和儿童。基础神经科学的最新发现直接导致了对神经系统疾病过程理解的重大突破，其中许多神经系统疾病给个人、家庭和社区带来了巨大的负担。然而，在多中心临床试验中测试这些新疗法存在一些组织和后勤方面的挑战，包括监管和机构审批效率低下、招募和保留不同研究参与者的障碍，以及缺乏经过培训成为多中心临床研究试验领导者的个人。 NeuroNEXT (NN) 的中心目标是通过提供有效的方法、组织、统计和后勤支持，促进从最初构思到最终分析的高质量早期临床试验和生物标志物多中心研究，并做出明确的进行/不进行决策。 NeuroNEXT 还将作为针对极其罕见的神经系统疾病进行基因治疗早期临床试验的工具。如果研究人群的性质有保证，例如罕见疾病，将使用适应性 2-3 期试验和平台试验。 NeuroNEXT 由 25 个临床中心、临床协调中心 (CCC) 和数据协调中心 (DCC) 组成。目标 1 是与 DCC 创建一个协作且可访问的 CCC 和临床研究网络，以针对罕见和常见的成人和儿童神经系统疾病高效开展高质量的 2 期临床试验、生物标志物研究和基因治疗试验。目标 2 是扩大经验丰富的临床研究者和研究人员的人才库和多样性，让他们做好成为多中心临床研究试验领导者的准备。目标 3 是与临床试验的主要利益相关者（包括政府组织、学术界、基金会、行业合作伙伴和以患者为中心的团体）建立战略合作，通过 NN 组织针对神经系统疾病的高影响力临床试验。 NeuroNEXT 的创新将包括建立一个试验网络，该网络需要使用单一机构审查委员会、所有网络资助研究的主合同流程、集中药学和实验室测试、用于安全审查的单一数据安全监测委员会、标准操作程序和知识的广泛共享、最先进的早期开发试验设计方法以及使用通用数据元素进行数据收集。寻求使用该网络的申请人可以是新手，也可以是经验丰富的试验人员，从而大大扩大了受过培训并准备领导多中心试验的经验丰富的临床研究人员的库和多样性。将通过几种新的推广方法积极寻求新的协议。 NN 的前 11 年资助了 11 项涉及工业界、基金会、学术界和政府合作的研究。 CCC 将扩展这些先前成果，进一步推进和加速神经系统疾病的治疗开发。

Project Summary The long-term objective of the Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT) initiative is to efficiently translate advances in neuroscience into treatments for adults and children with neurological disorders through partnerships with government, academia, private foundations, and industry. Recent discoveries in basic neuroscience have directly led to major breakthroughs in the understanding of disease processes in neurological disorders, many of which impose an enormous burden on individuals, families, and communities. Yet there are several organizational and logistical challenges to testing these new therapies in multicenter clinical trials, including inefficiencies in regulatory and institutional approvals, barriers to recruitment and retention of diverse study participants, and a dearth of individuals trained to be the leaders of multicenter clinical research trials. A central goal of NeuroNEXT (NN) is to facilitate, from initial conception through final analysis, high-quality early phase clinical trials and biomarker multisite studies with clear go/no-go decisions by providing efficient methodological, organizational, statistical, and logistical support. NeuroNEXT will also serve as the vehicle for the conduct of early clinical trials of gene therapy for ultra-rare neurological disorders. If warranted by the nature of the studied population, such as rare diseases, adaptive phase 2-3 trials and platform trials will be used. NeuroNEXT is comprised of 25 clinical sites, a Clinical Coordinating Center (CCC), and a Data Coordinating Center (DCC). Aim 1 is to create a collaborative and accessible CCC and clinical research network with the DCC, to efficiently conduct high-quality Phase 2 clinical trials, biomarker studies, and gene therapy trials in rare and common adult and pediatric neurological disorders. Aim 2 is to expand the pool and diversity of experienced clinical Investigators and research staff who are prepared to be leaders of multicenter clinical research trials. Aim 3 is to form strategic collaborations with key stakeholders in clinical trials, including government organizations, academia, foundations, industry partners, and patient-centered groups to organize high-impact clinical trials through NN for neurological disorders. NeuroNEXT innovations will include establishing a trial network that requires the use of a single institutional review board, a master contract process for all network- funded studies, centralized pharmacy and laboratory testing, a single Data Safety Monitoring Board for safety review, broad sharing of Standard Operating Procedures and knowledge, state-of-the-art early development trial design approaches, and the use of the common data elements for data collection. Applicants who seek to use the network can be novice or experienced trialists, thereby greatly expanding the pool and diversity of experienced clinical investigators trained and prepared to lead multicenter trials. New protocols will be proactively sought through several new outreach approaches. Eleven studies involving partnerships with industry, foundations, academia, and the government were funded in the first 11 years NN. The CCC will expand on these prior achievements to further advance and accelerate therapeutic development for neurological disorders.