Table 1.

Overview of Recommendations for TB Triage Test Diagnostic Accuracy Evaluations Grouped by QUADAS Domains

Topic	Recommendation
General Study Design	• Use a cross-sectional or cohort study enrolling a consecutive series or random sample of patients who require evaluation for TB (avoid using patients with known severe disease or healthy controls, because this introduces spectrum bias and can overestimate test accuracy) • Banked specimens may play an important role to supplement data collected from prospective evaluations (while recognizing the possibility of spectrum bias) • Consider how many reference standard positive and negative samples are required to obtain a precise estimate of the sensitivity and specificity respectively (sample size calculations should take into account factors including TB prevalence) • Refer to the STARD (Standards for Reporting of Diagnostic Accuracy) guidelines in addition to the more detailed advice pertaining to TB triage test evaluation in this article
Population and Setting	• Avoid selecting patients in whom TB has already been diagnosed by another test or who have already started on TB treatment • For initial studies focus on adults, including PLHIV, who have respiratory symptoms suggestive of TB; subsequent evaluation should include other key groups such as children and people being evaluated for extrapulmonary TB • Studies should potentially enroll patients in the primary settings of intended use, ie, L0: community health outposts, L1: primary healthcare centers, and L2: district hospitals • Perform testing (particularly for reference standard because triage test may be a point-of-care assay) in quality assured laboratories; followed by testing in settings of intended use • Provide stratified accuracy estimates for key subpopulations (by HIV-status, smear-status, presence of comorbidities such as chronic lung disease that may present with TB symptoms such as cough)
Index Test	• Studies should report the specifics of the triage test under investigation (administration, interpretation, and setting) • Indeterminate or invalid results and instrument failures should be reported • If a test has a nonautomated readout, blinding is essential to make sure the index test is interpreted independently of the reference test or comparators
Reference Standard and Comparators	• Use automated liquid mycobacterial culture as the primary reference standard • Studies may also compare triage tests to the confirmatory test used in practice at the setting where the test is being evaluated (eg, Xpert or other WHO-endorsed molecular diagnostic tests), but this should optimally be done in addition to culture • Avoid partial or differential verification bias; ie, all those who received the index test should also receive the same reference standard • Include clinical case definition, additional measures, as well as follow-up, to understand discordant (triage-test-positive, culture-negative) results • Studies may compare triage tests to other comparator triage tests such as CXR or CRP, but these should be done in addition to the reference standard
Flow and Specimen Issues	• Studies should carefully design and report the sample flow and specimen processing • The triage test and reference standard should ideally be performed on the same day (and same specimen if the triage test is sputum-based) • For tests that use machine learning techniques, test results may be based on probability thresholds. Prespecification of thresholds (whether a single or multiple) is essential for late-stage studies aiming to provide unbiased estimates of sensitivity and specificity
Key Issues Beyond Accuracy	• Test characteristics other than diagnostic accuracy, such as cost, feasibility, acceptability, and scalability, are often not captured by evaluations that solely evaluate accuracy but are critical and need to be evaluated systematically • Implementation studies should evaluate factors such as the testing infrastructure, which includes access to confirmatory testing, and whether this requires transporting patients or specimens, as well as test performance in different environments (temperature, humidity, dust) • Implementation studies should include process indicators that may be affected by the use of triage testing • The potential clinical and population level impact of new triage tests needs to be assessed through empirical studies, cost-effectiveness evaluations, and modeling, which should compare complete algorithms (eg, with triage test versus without triage test)

Abbreviations: CRP, C-reactive protein; CXR, chest x-ray; HIV, human immunodeficiency virus; PLHIV, people living with HIV; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; TB, tuberculosis; WHO, World Health Organization.