A systematic, structured, evidence-based process for TB diagnostic policy generation was followed. The first step constituted systematic reviews and meta-analysis of available data (published and unpublished), using standard methods appropriate for diagnostic accuracy studies. The second step involved the convening of a GDG to evaluate the strength of the evidence base, evaluate the risks and benefits of using IGRAs in LMIC and identify gaps to be addressed in future research. Based on the Expert Group findings, the third and final step involved development of a WHO policy guidance, with eventual dissemination to WHO Member States for implementation.
The GRADE system,⁶ adopted by WHO for all policy and guideline development, was used by the GDG. Given the absence of studies evaluating patient-important outcomes among TB suspects randomized to treatment based on IGRA results, reviews were focused on the diagnostic accuracy of IGRAs versus the TST in detecting TB infection or TB disease. Recognizing that test results may be surrogates for patient-important outcomes, the GDG evaluated the accuracy of IGRAs while also drawing inferences on the likely impact of these tests on patient outcomes, as reflected by false negatives (i.e. cases of TB infection missed) or false positives.
Systematic reviews were undertaken following detailed protocols with predefined questions relevant to the individual topics. Summaries of methodologies followed for each topic are given in the relevant sections below.
⁶ See www.gradeworkinggroup.org.