Rapid Research for Diagnostics Development in TB Network (R2D2 TB Network)

项目摘要 在高负担国家，许多结核病患者从未得到诊断或有效药物治疗 治疗方案，导致持续传播和死亡率增加。一个主要原因是目前的结核病 诊断是不够的关键问题，包括灵敏度不足，成本高，无法使用， 卫生系统水平较低和/或未能发现耐药性。没有一个单一的测试是可能解决所有 这些限制，因此世界卫生组织（WHO）已描述了最佳的测试特性 以目标产品概况（TPP）的形式针对不同的用例。推进高优先级的创新解决方案 TPP，确定有前途的技术，并将其开发人员与经验丰富的临床研究中心联系起来， 促进评价和业绩反馈至关重要。 结核病诊断开发快速研究网络（R2D2结核病网络）的总体目标 是解决对更好的结核病诊断的关键未满足需求，以缩小“诊断差距”， 从而改善患者和公共卫生结果。为了实现这一目标，R2D2 TB网络将征求， 在不同的开发阶段审查和优先考虑最相关的新型结核病诊断方法， 在奖励期间，在不同的用例中进行评估（目标1）。我们将利用我们 与生物技术孵化器建立伙伴关系，引进尚未在结核病领域工作的技术创新者， 与一个重要的非政府组织合作，该组织在开发当前的结核病诊断管道方面一直处于领先地位。临床研究 在开发的早期阶段评估测试的准确性和可用性将允许迭代测试优化 （目标2）。在可能的情况下，这些研究将嵌套在大规模、多中心评估中， 设计锁定诊断的准确性和可用性，以促进世卫组织的政策审查（目标3）。临床 研究将严格遵循世卫组织对特定用例的指导，以及对高 质量诊断评估。对于设计锁定诊断，我们将补充临床研究， 通过经验成本计算、卫生经济学和传播模型评估增值 研究（目标4），以进一步支持世卫组织和国家一级的政策审查。 为了实现这些目标，R2D2结核病网络将具有广泛知识的研究人员聚集在一起， 在10个结核病高负担地区的12个有经验的临床研究中心， 为评估结核病诊断提供相关人群的国家。负责监督 网络在协调多中心研究方面具有深厚的专业知识， 广泛的产品开发人员，在世界卫生组织的审查和认可实践方面的经验， 监管机构，以及十多年的协作领导经验。通过培养和 支持由调查人员、产品开发人员和利益相关者组成的强大协作网络， R2D2结核病网络将推动下一代结核病诊断。

PROJECT SUMMARY In high burden countries, many patients with tuberculosis (TB) are never diagnosed or treated with effective drug regimens, leading to ongoing transmission and increased mortality. A primary reason is that current TB diagnostics are inadequate with key issues including inadequate sensitivity, high costs, inability to be used at lower levels of the health system and/or failure to identify drug resistance. No single test is likely to address all these limitations and therefore the World Health Organization (WHO) has described optimal test characteristics for different use-cases in the form of target product profiles (TPPs). To advance novel solutions for high priority TPPs, identifying promising technologies and linking their developers to experienced clinical study sites to facilitate evaluation and performance feedback is essential. The overall goal of the Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) is to address the critical unmet need for better TB diagnostics in order to close the “diagnostic gap” and thereby improve patient and public health outcomes. To achieve this goal, the R2D2 TB Network will solicit, review and prioritize the most relevant novel TB diagnostics across different phases of development and across different use cases for evaluation during the award period (Objective 1). We will leverage our partnership with a biotech incubator to bring in technology innovators not already working in the TB field and with a key NGO that has been a leader in developing the current TB diagnostics pipeline. Clinical studies to assess accuracy and usability of tests in earlier phases of development will allow for iterative test optimization (Objective 2). These studies will be nested, where possible, within large-scale, multi-center assessments of the accuracy and usability of design-locked diagnostics to facilitate WHO policy review (Objective 3). The clinical studies will rigorously follow WHO guidance for specific use-cases as well as general guidelines for high- quality diagnostic evaluations. For design-locked diagnostics, we will complement the clinical studies with assessments of incremental value through empirical costing, health economic and transmission modeling studies (Objective 4) to further support WHO- and country-level policy reviews. To accomplish these objectives, the R2D2 TB Network brings together investigators with a broad range of relevant expertise related to TB diagnostic research and 12 experienced clinical study sites in 10 high-burden countries that provide access to relevant populations for evaluating TB diagnostics. The PIs overseeing the network have deep expertise in coordination of multi-center studies, a demonstrated history of working with a broad range of product developers, experience in the review and endorsement practices of the WHO and regulatory authorities, and more than a decade of collaborative leadership experience. By fostering and supporting a strong, collaborative network of investigators, product developers and stakeholders across diverse geographic sites, the R2D2 TB Network will advance the next-generation of TB diagnostics.