Adherence to tuberculosis (TB) treatment in high compared to low TB burden countries: study protocol for a systematic review and meta-analysis with a qualitative meta-synthesis of themes.

Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries. Additionally, it seeks to identify the unique facilitators and barriers to treatment adherence in these distinct settings.

Methods And Analysis: This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Statement. Using key medical subject heading terms and free-text terms related to TB treatment adherence, a systematic search of the literature will be performed in Medline, Embase, CINAHL, Scopus, Global Health and the Cochrane Databases of Systematic Reviews. A medical librarian will assist with developing the search strategy. Two independent reviewers will independently screen studies against predefined inclusion and exclusion criteria at both the title/abstract and full-text stages. Working in duplicate, the same two reviewers will independently extract relevant study and outcomes data, including study descriptors, TB burden, adherence levels and adherence measures, from eligible studies. Countries will be classified according to TB burden based on the WHO's high-burden country list from the post-2015 era (2015-2025). The quality of the included studies will be appraised using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. Qualitative data will be appraised using the Critical Appraisal Skills Programme tool. Studies will be pooled using the DerSimonian-Laird random-effects meta-analysis. Additionally, a meta-synthesis of the qualitative data from the included studies may be conducted to identify emergent themes related to facilitators and barriers of TB treatment adherence in high- vs low-TB burden countries.

Ethics And Dissemination: Ethics approval is not required for this study as it does not involve the recruitment or collection of data from participants. The findings from this systematic review and meta-analysis will be disseminated through publication in peer-reviewed journals, presentations at scientific conferences, and via social media channels to enhance visibility, particularly within programmatic and policy spheres.

Prospero Registration Number: CRD42021273336.