All studies evaluating IGRAs published up to the end of May 2010 were reviewed using predefined data search strings. In addition to database searches, bibliographies of reviews and guidelines were reviewed, citations of all included studies were screened, and experts in the field as well as IGRA manufacturers were contacted to identify additional studies (published, unpublished and ongoing). Pertinent information not reported in the original publications was requested from the primary authors of all studies included by the systematic reviewers.
Studies that evaluated the performance of currently available commercial IGRAs, published in all languages and in all LMIC, were reviewed by individual topic. Only studies evaluating IGRAs performance in LMIC were included in this analysis. Excluded were studies that evaluated noncommercial (i.e. in-house) IGRAs, older generation IGRAs (i.e. PPD-based IGRAs) and IGRAs performed in specimens other than blood; studies that were focused on the effect of anti-TB treatment on the IGRA response; studies including fewer than 10 individuals; studies reporting insufficient data to determine diagnostic accuracy measures; and conference abstracts and letters without original data, and reviews.
Study quality was assessed by relevant standardized methods, depending on the topic. For primary outcomes focused on test accuracy, quality was appraised using a subset of relevant criteria from QUADAS, a validated tool for diagnostic accuracy studies. For studies of the predictive value of IGRAs, quality was appraised with a modified version of the NewcastleOttawa Scale (NOS) for longitudinal or cohort studies. Conflicts of interest are a known concern in TB diagnostic studies; therefore, the systematic reviews added a quality item about involvement of commercial test manufacturers in published studies; they also reported whether IGRA manufacturers had any involvement with the design or conduct of each study, including donation of test materials, provision of monetary support, work or financial relationships with study authors, and participation in data analysis.
⁶ See www.gradeworkinggroup.org.