Extracted key information about interventional study methods and results using Evibase , NGC s purpose-built software. Evibase produces summary evidence tables, including critical appraisal ratings. Key information about non-interventional study methods and results was manually extracted onto standard evidence tables and critically appraised separately (evidence tables are included in appendix F). Generated summaries of the evidence by outcome. Outcome data were combined, analysed and reported according to study design: o Randomised data were meta-analysed where appropriate and reported in GRADE profile tables. o Data from non-randomised studies were presented as a range of values in GRADE profile tables or meta-analysed if appropriate. o Prognostic data were meta-analysed where appropriate and reported in GRADE profile tables. o Diagnostic data studies were meta-analysed where appropriate or presented as a range of values in adapted GRADE profile tables o Qualitative data were synthesised across studies and presented as summary statements with accompanying GRADE CERQual ratings for each review finding. A sample of a minimum of 10% of the abstract lists of the first 3 sifts by new reviewers and those for complex review questions (for example, prognostic reviews) were double-sifted by a senior research fellow and any discrepancies were rectified. All of the evidence reviews were quality assured by a senior research fellow. This included checking: o papers were included or excluded appropriately o a sample of the data extractions o correct methods were used to synthesise data o a sample of the risk of bias assessments. 4.3.1 Inclusion and exclusion criteria The inclusion and exclusion of studies was based on the criteria defined in the review protocols, which can be found in appendix A. Excluded studies by review question (with the reasons for their exclusion) are listed in appendix I. The committee was consulted about any uncertainty regarding inclusion or exclusion. 