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

统计和数据管理中心（SDMC）、艾滋病临床试验组（ACTG）

• 批准号: 10200227
• 负责人: Michael David Hughes
• 金额: $ 65.55万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-07 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200227
• 关键词: 2019-nCoV; AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Address; Adopted; Adult; Affect; Biological Assay; Biometry; COVID-19; Cessation of life; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Clinical Trials Data Monitoring Committees; Collection; Communication; Communities; Data; Detection; Development; Disease; Drops; Endpoint Determination; Enrollment; Ensure; Evaluation; Foundations; Funding; Genomics; Goals; HIV; Hepatitis; Hospitalization; Hospitals; Immunology; Individual; Infection; Influenza; Infrastructure; International; Investigation; Laboratories; Laboratory Study; Leadership; Monitor; New Agents; Occupational activity of managing finances; Outcome; Outcome Measure; Outpatients; Participant; Pathogenesis; Pharmacology; Phase; Placebos; Protocols documentation; Public Health Schools; RNA; Randomized; Randomized Clinical Trials; Reporting; Research; Resources; Safety; Science; Security; Site; Specific qualifier value; Statistical Data Interpretation; Structure; Swab; Symptoms; System; Technology; Testing; Therapeutic Intervention; Training; Tuberculosis; United States; United States National Institutes of Health; Visit; Woman; Work; base; coronavirus disease; data integrity; data management; design; electronic data; frontier; high standard; innovation; medical specialties; novel; operation; optimal treatments; phase 2 testing; phase 3 testing; phase II trial; prevent; primary endpoint; primary outcome; protocol development; social; statistics; symptom treatment; therapeutic vaccine; virology

Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2 infection. It includes a Phase II evaluation, with a seamless transition into a larger Phase III evaluation for promising agents. The trial is a randomized, controlled platform that allows agents to be added and dropped during the course of the study for efficient testing of new agents against placebo within the same trial infrastructure. When more than one new agent is being tested concurrently, the same placebo will be used, when feasible. The primary outcome measures in the Phase II evaluation will be duration of symptoms, similar to the outcome used for outpatient influenza studies, detection of SARS-CoV-2 RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a Phase II agent will continue to be evaluation in Phase III will be made after the last participant randomized to that agent or placebo completes their day 28 Phase II visit. If continued, data collected from participants enrolled in Phase II will be included in the Phase III evaluation. The Phase III evaluation is a continuation of the Phase II trial, for those agents that meet criteria for further evaluation and for which sufficient study product is available. Enrollment of those agents advancing to Phase III will continue for a fully powered trial to determine the efficacy of each investigational agent compared to placebo to prevent hospitalization and death in non-hospitalized adults with COVID-19. 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. RELEVANCE: The expertise provided by the SDMC will help advance research concerning the treatment of HIV-infected people or of diseases such as tuberculosis and hepatitis affecting these people. It will achieve this by ensuring that ACTG clinical trials and other studies are efficiently designed and analyzed to the highest standards. This research will continue to make significant contributions in advancing optimal treatment of HIV-infected individuals both in the Unites States and internationally.

Adapt Out COVID 是评估研究性药物的安全性和有效性的主协议 用于治疗有症状、非住院成人 SARS-CoV-2 的药物 感染。它包括第二阶段评估，并无缝过渡到更大的阶段 III 对有前景药物的评估。 该试验是一个随机、受控的平台，允许添加和删除药物 在研究过程中，针对安慰剂有效测试新药 相同的试验基础设施。当同时测试不止一种新试剂时， 如果可行，将使用相同的安慰剂。 第二阶段评估的主要结果指标是症状的持续时间， 与门诊流感研究的结果相似，检测 SARS-CoV-2 通过鼻咽 (NP) 拭子检测 RNA，以及安全性。确定是否进入第二阶段 代理人将在第三阶段继续进行评估，将在最后一名参与者之后进行 随机接受该药物或安慰剂的患者完成第 28 天的 II 期访视。如果继续的话， 从第二阶段注册的参与者收集的数据将包含在第三阶段 评估。 III 期评估是 II 期试验的延续，对于那些满足以下条件的药物 进一步评估的标准以及是否有足够的研究产品可用。注册 进入第三阶段的这些药物将继续进行全功率试验以确定 每种研究药物与安慰剂相比在预防住院方面的功效 以及非住院成人感染 COVID-19 的死亡。 1. ACTG 领导和运营中心 (LOC)。建议新重组的 LOC 为 ACTG 提供科学领导以及财政和组织管理。 ACTG 执行委员会 (AEC) 将作为该网络的总体管理机构。变革科学小组将监督 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) 进行协调和优先排序。 Social & Scientific Systems, Inc. 的网络协调中心将促进协议的制定、实施、培训和网络评估。布莱根妇女医院 (BWH) 的 LOC 财务管理小组将按照社会科学系统公司的指导监督资源管理和协议资金分配。东盟经济委员会。 LOC 将确保社区参与 ACTG 的各个方面，并将协调网络所有三个组成部分之间的通信。 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能够执行协议指定的测试，并通过开发新的检测方法来解决 ACTG 临床试验中出现的基于创新发病机制的问题，从而推进最先进的技术。 LC 还将监督所有进行临床监测和主要终点确定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紧密结合。将特别强调在资源有限的国际地点建设网络实验室能力。 3. ACTG 统计和数据管理中心（SDMC）。 SDMC 将包括哈佛大学公共卫生学院 (HSPH) 生物统计和艾滋病研究中心 (CBAR) 的统计和数据分析中心 (SDAC) 以及前沿科学技术研究基金会 (FSTRF) 的数据管理中心 (DMC) ）在纽约州阿默斯特。 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方法；引导准确收集方案特定的临床和实验室数据 通过电子数据采集；确保数据完整性、安全性和质量；并为现场和实验室提供培训。 SDMC 将准备定期报告，以支持数据监测委员会监督 ACTG 试验安全性的工作。 SDMC 的领导层将完全融入 LOC 的科学委员会和治理结构，确保 SDMC 的活动与整个网络的研究议程紧密结合。 相关性：SDMC 提供的专业知识将有助于推进有关治疗 HIV 感染者或影响这些人的结核病和肝炎等疾病的研究。它将通过确保 ACTG 临床试验和其他研究按照最高标准进行有效设计和分析来实现这一目标。这项研究将继续为美国和国际上推进艾滋病毒感染者的最佳治疗做出重大贡献。