Additional considerations are required when preparing a protocol for a systematic review with multiple interventions

J Clin Epidemiol. 2017 Mar:83:65-74. doi: 10.1016/j.jclinepi.2016.11.015. Epub 2017 Jan 11.


Objectives: 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.

Study design and setting: 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.

Conclusion: 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.

Keywords: Comparative effectiveness review; Eligibility criteria; Indirect comparison; Mixed treatment comparison; Network meta-analysis; Transitivity.

MeSH terms

  • Biomedical Research / methods
  • Comparative Effectiveness Research / methods
  • Evidence-Based Medicine / methods*
  • Evidence-Based Medicine / standards
  • Humans
  • Meta-Analysis as Topic
  • Systematic Reviews as Topic*