Guidance for Studies Evaluating the Accuracy of Rapid Tuberculosis Drug-Susceptibility Tests

• Published in: The Journal of infectious diseases Vol. 220; no. Supplement_3; pp. S126 - S135
• Main Authors: Georghiou, Sophia B, Schumacher, Samuel G, Rodwell, Timothy C, Colman, Rebecca E, Miotto, Paolo, Gilpin, Christopher, Ismail, Nazir, Rodrigues, Camilla, Warren, Rob, Weyer, Karin, Zignol, Matteo, Arafah, Sonia, Cirillo, Daniela Maria, Denkinger, Claudia M
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08.10.2019
• Subjects: Antitubercular Agents - therapeutic use; Biological Assay - standards; Biomarkers - analysis; Blood Culture - standards; Diagnostic tests; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Humans; Medical diagnosis; Microbial Sensitivity Tests - standards; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Mycobacterium tuberculosis - pathogenicity; Practice Guidelines as Topic; Reference Standards; Research Design; Sensitivity and Specificity; Sputum - microbiology; Tuberculosis; Tuberculosis, Multidrug-Resistant - diagnosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology; Tuberculosis, Multidrug-Resistant - physiopathology; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - physiopathology; World Health Organization; target product profile; diagnostics; WHO End TB Strategy; drug-susceptibility testing; tuberculosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz106

Abstract The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support potential policy recommendations. The evidence necessary includes an assessment of the performance for TB and resistance detection as well as an assessment of the operational characteristics of these platforms. The performance assessment should include analytical studies to confirm the limit of detection and assay ability to detect mutations conferring resistance across globally representative strains. The analytical evaluation is typically followed by multisite clinical evaluation studies to confirm diagnostic performance in sites and populations of intended use. This paper summarizes the considerations for the design of these analytical and clinical studies.