Preventing deaths due to tuberculosis: An assessment of global targets with a protocol for a systematic review and meta-analysis

Background: Tuberculosis (TB) is believed to have caused more deaths than any other infection since records began. The “Sustainable Development Goals”, previous “Millennium Development Goals”, World Health Organisation “End TB Strategy” and the second and third “Global Plans to Stop TB” all prioritise(d) key targets to reduce deaths due to TB. However, there seems to be limited research evidence available to inform how this may best be achieved. We therefore aim to summarise, critically appraise, and synthesise the trial evidence that interventions decrease deaths due to TB. Methods: We will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We will search the PubMed, Scopus and Web of Science databases for peer reviewed English/Spanish language publications focused on evaluating interventions to reduce deaths due to TB as primary or secondary trial outcomes. We plan to use the following search terms: tuberculosis OR TB; death OR mortality OR fatality OR survival; prevent* OR reduce* OR decrease*; AND trial. Eligible publications will be selected by two independent reviewers and a third will resolve any discrepancies. Key information will be extracted using a shared cloud-based spreadsheet, publications categorised and summarised and critically appraised. Key data will be extracted and synthesised. Meta-analysis will be carried out if there are three or more studies investigating similar interventions with a similar outcome. The quality of trial evidence and any risk of bias will be formally assessed using the Cochrane tools. Conclusions: We report a protocol for a systematic review of the published literature involving trial evidence assessing whether interventions reduce deaths due to TB and a meta-analysis of the quantitative evidence. We aim to clarify research gaps and to synthesise evidence in order to guide future policy and research. PROSPERO registration: Record number CRD42023387877