title: Additional considerations are required when preparing a protocol for a systematic review with multiple interventions.
abstract: OBJECTIVE
  The number of systematic reviews that aim to compare multiple interventions using network meta-analysis is increasing. In this study, we highlight aspects of a standard systematic review protocol that may need modification when multiple interventions are to be compared.
  
  
  METHODS
  We take the protocol format suggested by Cochrane for a standard systematic review as our reference and compare the considerations for a pairwise review with those required for a valid comparison of multiple interventions. We suggest new sections for protocols of systematic reviews including network meta-analyses with a focus on how to evaluate their assumptions. We provide example text from published protocols to exemplify the considerations.
  
  
  CONCLUSIONS
  Standard systematic review protocols for pairwise meta-analyses need extensions to accommodate the increased complexity of network meta-analysis. Our suggested modifications are widely applicable to both Cochrane and non-Cochrane systematic reviews involving network meta-analyses.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece. Electronic address: anna.chaimani@parisdescartes.fr.
authors.forename: Anna
authors.initials: A
authors.lastname: Chaimani
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Caldwell
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, E6011, Baltimore, MD 21205, USA.
authors.forename: Tianjing
authors.initials: T
authors.lastname: Li
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
authors.forename: Julian P T
authors.initials: JPT
authors.lastname: Higgins
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece; Institute of Social and Preventive Medicine (ISPM), University of Bern, Finkenhubelweg 11, Bern 3012, Switzerland; Institute of Primary Health Care (BIHAM), University of Bern, Gesellschaftsstrasse 49, Bern CH-3012, Switzerland.
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
mesh_terms: D035843:Biomedical Research / Q000379:methods; D057186:Comparative Effectiveness Research / Q000379:methods; D019317:Evidence-Based Medicine / Q000379:methods* / Q000592:standards; D006801:Humans; D015201:Meta-Analysis as Topic; D000078202:Systematic Reviews as Topic
keywords: Comparative effectiveness review; Eligibility criteria; Indirect comparison; Mixed treatment comparison; Network meta-analysis; Transitivity