Public call for diagnostic accuracy data on nucleic acid amplification tests for TB detection and resistance to selected anti-TB agents

Nucleic acid amplification assays (NAATs) promise technologies for rapid and accurate TB detection and resistance to selected anti-TB agents. In December 2020, the World Health Organization (WHO) will convene a meeting of the Guidelines Development Group (GDG) to update its diagnostic guidelines on the use of NAATs to detect TB and resistance to selected anti-TB agents. Ahead of this meeting, the WHO will commission reviews of relevant evidence of diagnostic accuracy for several NAAT tests.

The following NAAT tests or NAAT test classes will be discussed in the GDG:

Centralized tests offering ultimate solutions for the detection of TB and resistance to rifampicin and isoniazid (cDST: Index test 1);

Technology based on the cartridge for the detection of isoniazid and other lines of drug resistance (XDR cartridge: Index test 2);

Hybridization technology for pyrazinamide resistance detection (PZA LPA: Index test 3).

To facilitate this process, the WHO is issuing a public call for data, urging industry, researchers, national tuberculosis programs and other agencies to provide appropriate evidence for the effectiveness of these technologies. The data obtained are essential to facilitate the WHO update process.

Please send relevant data by August 1, 2020 to [email protected], For more information on data set parameters, variables, and processes, see below:

Annex 1: Data requirements

Index test 1: Centralized trials representing the ultimate solutions for TB detection and resistance to rifampicin and isoniazid (cDST platforms).

Desirable test characteristics: (a) The sample preparation process is included; (b) automated DNA extraction; (c) Automated preparation for PCR; (d) automated interpretation of results; (c) Driving capacity: ≥24 tests; (d) Time from sample to complete diagnosis of MDR-TB: <12 hours; (e) Detection of minimum desirable drug resistance: at least according to INH and RIF.

Type of study: Clinical evaluation trials to confirm diagnostic efficacy on clinical specimens

Study population: Random sample of unselected patients with signs and symptoms of TB, requiring assessment of TB and / or resistance to isoniazid and rifampicin at sites intended for administration.

Reference standard: In any case, the results of individual sputum culture and phenotypic DST, wherever possible (liquid or solid, with specification), should be included for each result Index test 1, The use of genotypic sequencing results if available will have added value for confirming the presence of mutations in addition to phenotypic DST results.

Index test 2: Cartridge-based technology for detecting isoniazid and other drug resistance lines (XDR cartridge);

Desirable test characteristics: (a) automated real-time PCR; (b) automated interpretation of results; (b) driving capacity: ≥ 4 tests; (c) Time test results: <4 hours; (d) Detection of minimum desirable drug resistance: at least according to INH and FQ.

Type of study: (a) Analytical validation tests that measure the accuracy, precision, and reproducibility of a test in fitted samples or plates, and include all key mutations on isoniazid and second-line drugs. (b) Clinical evaluation studies to confirm diagnostic efficacy on clinical specimens.

Study population: Patients with detected TB, requiring assessment of resistance to isoniazid and other anti-TB drugs at sites intended for use.

Reference standard: In any case, the result of one phenotypic DST sputum (liquid or solid, with specification) should be included for each result Index test 2, The use of genotypic sequencing results if available will have added value for confirming the presence of mutations in addition to phenotypic DST results.

Index Test 3: Hybridization-Based Technology for Detection of Pyrazinamide Resistance (PZA LPA).

Desirable test characteristics: (a) Automated or manual hybridization methodology; (b) Automated or manual interpretation of results (c) Time from sample to test results: <24 hours; (d) Detection of minimum desirable drug resistance: at least according to PZA.

Type of study: (a) Analytical validation studies to measure the accuracy, precision and reproducibility of the test in fitted samples or plates, covering all key pyrazinamide mutations; (b) clinical evaluation studies to confirm diagnostic efficacy on clinical specimens;

Study population: Patients with detected TB and rifampicin resistance, who require assessment of pyrazinamide resistance at sites intended for use;

Reference standard: At a minimum, the result of one phenotypic DST sputum (liquid or solid, with specification) should be included for each result Index test 3, The use of genotypic sequencing results if available will have added value for confirming the presence of mutations in addition to phenotypic DST results.