Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)

描述(申请人提供)：在过去的30年里，人类免疫缺陷病毒(HIV)和与获得性免疫缺陷综合征(AIDS)相关的机会性感染(01)的治疗取得了长足的进步，导致世界各地与艾滋病相关的发病率和死亡率大幅下降。艾滋病临床试验小组(ACTG)25年多来一直站在这些努力的前列。ACTG进行的临床试验和实验室研究产生了重要的见解，这些见解构成了目前艾滋病毒-1感染及其共病和并发症临床管理指南和标准的基石。尽管取得了这一令人印象深刻的进展，但艾滋病毒治疗的关键方面仍然存在重大挑战。这些战略包括：根除艾滋病毒或实现功能性治愈的战略；结核病的诊断、治疗和预防，包括对合并感染和单一感染患者的多药耐药结核病；为治疗合并感染和单一感染患者的病毒性肝炎开发更有效、耐受性更好的治疗方案；减少治疗慢性艾滋病毒感染所伴随的持久免疫激活，防止相关的并存；开发针对艾滋病毒的新型干预措施；以及改进与艾滋病毒相关的恶性肿瘤的诊断、治疗和预防。ACTG提出了一项全面的研究议程，该议程利用一个由领先的临床和实验室艾滋病毒研究人员组成的国际联盟，与世界级的统计和数据管理中心合作，设计和进行创新的干预性临床试验，这些试验将显著减少全球因艾滋病毒、结核病和肝炎而造成的疾病负担。行动小组网络领导小组(LG)的具体目标包括： 1.ACTG领导和运营中心(LOC)。建议成立一个新重组的劳资关系委员会，以提供委员会的科学领导以及财政和组织管理。反恐执行委员会(AEC)将作为该网络的最高管理机构。变革性科学小组将监督ACTG研究议程的制定和执行，该议程将由科学议程指导委员会(SASC)协调和优先处理。协议的制定、实施、培训和网络评估将由社会与科学系统公司的网络协调中心提供便利。布里格姆妇女医院(BWH)的LOC财务管理小组将在AEC的指导下监督资源管理和协议资金的分配。LOC将确保社区参与ACTG的所有方面，并将协调网络的所有三个组成部分之间的沟通。 2.ACTG实验室中心(LC)。ACTG LC将包括病毒学专业实验室， 免疫学、药理学、分枝杆菌学和基因组学具备执行特定方案测试的能力，并通过开发新的分析方法来推进最先进的技术，以解决ACTG临床试验中出现的创新的基于发病机制的问题。该委员会还将监督所有为临床监测和主要终点确定进行测试的实验室的质量管理。LC领导层将完全融入LOC的科学委员会和治理结构，确保LC活动与整个网络的研究议程密切一致。将特别强调在资源有限的情况下在国际地点建设网络实验室的能力。 3.统计数据管理中心(SDMC)。该中心将由哈佛大学公共卫生学院生物统计和艾滋病研究中心(CBAR)的统计和数据分析中心(SDAC)和纽约阿默斯特前沿科技研究基金会(FSTRF)的数据管理中心(DMC)组成。SDMC将为ACTG临床试验和实验室研究的设计和生物统计分析提供创新的方法；领导准确收集特定方案的临床和实验室数据 通过电子数据采集；确保数据的完整性、安全性和质量；并向各地点和实验室提供培训。国家药品监督管理委员会将编制定期报告，以支持监督ACTG试验安全性的数据监测委员会的工作。国家海洋学委员会的领导将完全融入LOC的科学委员会和治理结构，确保国家海洋学委员会的活动与整个网络的研究议程密切一致。

DESCRIPTION (provided by applicant): Great strides have been made in the treatment of human immunodeficiency virus (HIV) and the opportunistic infections (01) associated with acquired immune deficiency syndrome (AIDS) over the last 30 years, resulting in substantial reductions in AIDS associated morbidity and mortality throughout the world. The AIDS Clinical Trials Group (ACTG) has been at the forefront of these efforts for more than 25 years. Clinical trials and laboratory studies conducted by the ACTG have produced major insights that form the cornerstones of current guidelines and standards of clinical management of HIV-1 infection and its co-morbidities and complications. Despite this impressive progress, substantial challenges remain in key aspects of HIV therapeutics. These include: strategies for eradicating HIV or achieving functional cure; diagnosis, treatment and prevention of tuberculosis, including multidrug-resistant (MDR) TB in co-infected and mono-infected patients; developing more effective and better tolerated regimens for the treatment of viral hepatitis in co-infected and monoinfected patients; reducing the persistent immune activation that accompanies treated chronic HIV infection and preventing the associated co-morbidities; developing novel interventions targeting HIV; and improving the diagnosis, treatment and prevention of HlV-associated malignancies. The ACTG proposes a comprehensive research agenda that draws on an international consortium of leading clinical and laboratory HIV investigators in collaboration with a world-class Statistics and Data Management Center to design and conduct innovative interventional clinical trials that will significantly reduce the global burden of diseae due to HIV, TB and hepatitis. Specific aims of the ACTG Network Leadership Group (LG) include: 1. The ACTG Leadership and Operations Center (LOC). A newly restructured LOC is proposed to provide scientific leadership and fiscal and organizational management of the ACTG. The ACTG Executive Committee (AEC) will serve as the overarching governing body of the network. Transformative Science Groups will oversee the development and execution of the ACTG research agenda, which will be coordinated and prioritized by the Scientific Agenda Steering Committee (SASC). Protocol development, implementation, training and network evaluation will be facilitated by the Network Coordinating Center at Social & Scientific Systems, Inc. The LOC financial management group at Brigham and Women's Hospital (BWH) will oversee resource management and protocol fund distribution at the direction of the AEC. The LOC will assure the engagement of Community in all aspects of the ACTG, and will coordinate communication between all three components of the network. 2. The ACTG Laboratory Center (LC). The ACTG LC will comprise Specialty Laboratories in virology, immunology, pharmacology, mycobacteriology and genomics equipped to perform protocol-specified testing and to advance the state-of-the-art by developing novel assays to address innovative pathogenesis-based questions arising from ACTG clinical trials. The LC will also oversee the quality management of all laboratories performing testing for clinical monitoring and primary endpoint determination. The LC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of LC activities with the research agenda of the network as a whole. Particular emphasis will be placed on building network laboratory capacity at international sites in resource-limited settings. 3. The ACTG Statistics and Data Management Center (SDMC). The SDMC will comprise the Statistical and Data Analysis Center (SDAC) at the Center for Biostatistics and AIDS Research (CBAR) at Harvard School of Public Health (HSPH) and the Data Management Center (DMC) at Frontier Science & Technology Research Foundation (FSTRF) in Amherst, NY. The SDMC will provide innovative approaches to the design and biostatistical analysis of ACTG clinical trials and laboratory studies; leads accurate collection of protocol specific clinical and laboratory data through electronic data capture; ensure data integrity, security and quality; and provide training to sites and laboratories. The SDMC will prepare regular reports to support the work of data monitoring committees overseeing the safety of ACTG trials. The SDMC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of SDMC activities with the research agenda of the network as a whole.