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.

PROJECT NARRATIVE 1.5 million patients die of TB every year partly due to delays in diagnosing the disease. The world needs faster, more accurate and/or less expensive diagnostics for TB and drug-resistant TB. We will identify, prioritize and evaluate promising new diagnostics across different use-cases in rigorous clinical studies and use the data to further develop and advance better and more reliable TB diagnostics for global use.