The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study seeks to identify and rigorously assess promising early stage tuberculosis (TB) triage and diagnostic tests (hereafter referred to as “novel diagnostics”) in clinical studies conducted in settings of intended use. Rapid diagnosis and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, analysis of care cascades and prevalence surveys indicate that 40-60% of patients with TB are not initiated on effective treatment.^{1, 2} The different types of tests required to reduce this “diagnostic gap” have been described in the form of target product profiles (TPPs). The highest- priority TPPs are for: 1) a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (a biomarker test) and 2) a simple, low-cost test that can be used by front-line health workers to rule-out TB (a triage test). The R2D2 TB Network study is a phased evaluation of promising novel TB diagnostics, with iterative assessment of early/late prototypes nested within large-scale validation of design-locked products. In all phases, the accuracy of novel diagnostics will be compared against a reference standard including sputum/urine Gene Xpert® MTB/RIF Ultra and sputum mycobacterial culture, which are standard of care for tests used routinely in patient care.