Consolidated Guidelines

Annex 3. Conflict of interest assessment for Guideline Development Group and External Review Group members

Before being considered for group membership, each candidate for the Guideline Development Group (GDG) and External Review Group (ERG) was required to submit a completed declaration of interest (DOI) form. In addition, a preliminary internet search was performed to identify any obvious public controversies or interests that might lead to compromising situations for the World Health Organization (WHO) and the expert concerned.

Annex 2. GDG processes and decision-making

For every GDG meeting PICO questions were drafted by the WHO steering group and were presented to the respective GDG for discussion and modification. The WHO steering group has been making an initial list of patient-important outcomes, including desirable and undesirable effects and has solicited feedback from the Guideline Development Group to identify any other outcomes. The outcomes were further rated, according to the procedure described in WHO handbook for guideline development (2nd edition)

3.4.4. Data synthesis and meta-analysis

A standardized overall approach was specified a priori for each systematic review, to account for significant heterogeneity in results expected between studies. First, data were synthesized separately for each commercial IGRA and by the World Bank country income classification (LMIC versus high-income countries) as a surrogate for TB incidence. Second, heterogeneity was visually assessed using forest plots, and the variation in study results attributable to heterogeneity was characterized (I-squared statistic) and statistically tested (chi-squared test).

3.4.3. Studies search, selection and quality assessment

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and experts in the field as well as IGRA manufacturers were contacted to identify additional studies (published, unpublished and ongoing).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.

3.4.2. Hierarchy of reference standards

Studies evaluating the performance of IGRAs are hampered by the lack of a gold standard to distinguish the presence or absence of TB infection. Since diagnostic accuracy for TB infection could not be directly assessed, a hierarchy of reference standards was developed and agreed beforehand with the systematic reviewers, to evaluate the role of IGRAs, depending on the individual topic (i.e. not all systematic reviews necessarily used the hierarchy).