Addressing effect modification in network meta-analysis

Network meta-analysis (NMA) is a key tool for researchers and decision makers that allows the efficacy and safety of any number of healthcare interventions to be compared simultaneously. However, a central assumption to the application of NMA relates to the comparability of the included trials, in terms of study design and patient characteristics, and an understanding of how these parameters may modify the effect of an intervention. The exploration of effect modification in NMA is important because the presence of unaccounted treatment-covariate interactions can invalidate the assumptions which underlie NMA causing confounding and bias.

A recently published meta-epidemiological study evaluated the current state of handling of effect modification in NMA (1). In summary, the study identified 77 NMA articles published in 2013 and of these, approximately 25% failed to explore potential effect modifiers. Of those that did, 21% did not apply any methods to adjust for them, while the following approaches were reported:

  • 52% performed sensitivity analyses
  • 38% performed subgroup analyses
  • 35% performed meta-regression analyses

The reporting of methods and results addressing effect modification were also incomplete across approximately 50% of the NMAs. Overall, the study highlights deficiencies in current reporting practices for addressing effect modification. It also raises concerns over the potential impact that the failure of the reporting of steps to address effect modification may have on the interpretation and validity of NMA results.

At Mtech Access we understand the importance of addressing effect modification in NMA, fully reporting the methods employed and providing a clear interpretation of the results. We have extensive experience of dealing with effect modification in NMA across a range of indications, using approaches such as sensitivity analyses, subgroup analyses and network meta-regression.

For further information on any aspects of systematic review and NMA please contact our in-house experts at Mtech Access.


  1. Kovic B, Zoratti MJ, Michalopoulos S, Silvestre C, Thorlund K, Thabane L. Deficiencies in addressing effect modification in network meta-analyses: a meta-epidemiological survey. Journal of clinical epidemiology. 2017;88:47-56.

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