Antibacterial Resistance Leadership Group (ARLG)

描述（由申请人提供）：我们的目标是创建和实施一个抗菌药物耐药性领导小组（ARLG），该小组将开发、设计、实施和管理一个临床研究议程，以增加对耐药性重要因素的了解并减轻其影响。我们将把一支由二十多名世界顶级研究人员组成的前所未有的团队与世界上最大的学术研究组织之一杜克临床研究所（DCRI）的卓越组织相结合。由于整合如此大规模的临床研究网络的多个组成部分的复杂性，我们的提交文件通过执行委员会和双重PI方法进行集中领导。一个PI（福勒）主要侧重于业务，另一个（钱伯斯）主要侧重于科学议程。组织结构仿照ACTG，还设有科学小组委员会，致力于四个优先领域：革兰氏阴性细菌感染，管理和感染预防，革兰氏阳性细菌感染，诊断和设备。这些小组委员会由三个特别强调小组（SEP）（儿科、药代动力学和特殊人群）和一个指导核心支持。每个小组委员会、SEP和核心都有国际公认的调查员，确保专业知识。为了补充NIH和制药生物技术行业目前的研究活动，我们的ARLG与这两个社区的成员建立了合作关系。 我们的长期目标是：1）完成新抗感染药物的优效性试验（新药物 或现有药物的新给药方案）用于MDR-革兰氏阴性细菌感染; 2）定义用于常见感染的疗程较短、窄谱治疗方案，作为支持管理的主要手段; 3）测试鉴定抗菌药物的快速诊断 基于细菌中基因型标记的耐药性;和4）鉴定万古霉素用于MRSA感染的更有效的替代物。研究议程反映了我们的总体战略，即在早期研究中采取现实的、渐进的步骤，在此基础上进行更复杂的转型试验，这些试验将改变临床实践并减少抗菌药物耐药性的影响。

DESCRIPTION (provided by applicant): Our goal is to create and implement an Antibacterial Resistance Leadership Group (ARLG) that will develop, design, implement, and manage a clinical research agenda that will increase knowledge of and mitigate the important factors that drive resistance. We will pair an unprecedented team of over two dozen of the world's top investigators with the organizational excellence of the Duke Clinical Research Institute (DCRI), one of the world's largest Academic Research Organizations. Because of the complexity of integrating multiple components of such a large-scale clinical research network, our submission features centralized leadership through an Executive Committee and a dual PI approach. One PI (Fowler) focuses primarily on operations and the other (Chambers) focuses largely on scientific agenda. The organizational structure, modeled after that of the ACTG, also features Scientific Subcommittees devoted to four priority areas: Gram-negative bacterial infections, Stewardship and infection prevention, Gram-positive bacterial infections, and Diagnostics and devices. These Subcommittees are supported by three Special Emphasis Panels (SEPs) (Pediatrics, Pharmacokinetics, and Special Populations) and a Mentoring Core. Each Subcommittee, SEP, and Core contains internationally recognized investigators, ensuring expertise. To complement the current research activities of both NIH and the pharmaceutical biotechnology industry, our ARLG has established collaborative ties with members of both communities. Our long-term goals are 1) to complete a superiority trial of new anti-infectives (either new agent or new dosing regimen of existing agent) for MDR-Gram negative bacterial infections; 2) to define shorter course, narrow-spectrum therapeutic regimens for common infections as a principal means to support stewardship; 3) to test a rapid diagnostic that identifies antimicrobial resistance based on genotypic markers in bacteria; and 4) to identify a more effective alternative to vancomycin for MRSA infections. The research agenda reflects our overall strategy of making realistic, incremental steps in early phase studies upon which to build toward more complex transformational trials that will change clinical practice and reduce the impact of antibacterial resistance.