Systematic Reviews and Review Types: What is a Network Meta-Analysis?

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Other names for a Network Meta-Analysis

NMA, MTC Meta-Analysis, Multiple Treatment Meta-Analysis, Mixed Treatments Comparison, Multiple Treatments Comparison, Pair-Wise Meta-Analysis, Indirect Treatment Comparison, Multiple Treatment Comparison Meta-Analysis, Live Cumulative Network Analysis (New type)

What is a Network Meta-Analysis?

“Network meta-analysis compares multiple interventions simultaneously by analyzing studies making different comparisons in the same analysis.”

Source: M. Petticrew et al. (2013)

Network meta-analyses are best designed for:

  • Conditions with multiple interventions
  • Many combinations of direct or indirect interactions 
  • To answer more relevant clinical questions
  • To make treatment estimates for an entire treatment network instead of scanning each individual pair-wise comparison
  • To give the “full picture” to clinicians
  • Gain precision by considering all available evidence, not just (A vs. B comparisons)
  • Potential to more explicitly “rank” treatments using summary outputs

What is a Network Meta-Analysis? Outline of Stages

Timeframe: 12-18+ months.  Same as a traditional systematic review.  *Varies beyond the type of review. Depends on many factors such as but not limited to: resources available, the quantity and quality of the literature, and the expertise or experience of reviewers” (Grant et al. 2009)

Question: Addresses PICO for multiple interventions or treatments (3 or more).  These may be broad or narrow.  Combines indirect (triangular approach) or direct comparisons (pairwise approach). 

Sources and searches: Requires a large search to locate all of the trials using transparent & reproducible methods.

Selection: Same as a systematic review–based upon clear inclusion/exclusion criteria.  Requires a lot more screening of trials.

Appraisal: Formal quality assessment of all studies.  Still includes Risk of Bias and quality of evidence assessments.

Synthesis: Statistical analysis when possible (heterogeneity a potential problem with indirect comparisons)–uses different statistical methods than a systematic review. Creates a web-like analysis called a Network Diagram or Network Comparison.  May use bayesian frameworks or meta-regression analysis.

Limitations of a Network Meta-Analysis

  • Requires specialist statistical expertise and software
  • Assumes that all interventions included in the “network” are equally applicable to all populations and contexts of the studies included.
  • May introduce study selection bias.
  • Ease of software may lead researchers to undertake this type of review even though it may not be the most appropriate study design for their research question.
  • Complex methodological approaches
  • Still an evolving method

Source: M. Petticrew et al. (2013) and Li T. et al. (2011)

Example of a published Treatment Network for the Drugs Considered in the Example Multiple Treatment Comparison on Generalized Anxiety Disorder

a network diagram for a network analysis

Source: 

Mills, Edward J., John P. A. Ioannidis, Kristian Thorlund, Holger J. Schünemann, Milo A. Puhan, and Gordon H. Guyatt. 2012. How to use an article reporting a multiple treatment comparison meta-analysis. Jama 308 (12): 1246-53.  http://jamanetwork.com/journals/jama/fullarticle/1362030

Resources:

Assessing the Feasibility of a Network Meta-Analysis (VIDEO

Petticrew M, Rehfuess E, Noyes J, et al.  Synthesizing evidence on complex interventions:

how meta-analytical, qualitative, and mixed method approaches can contribute.  

J Clin Epid. 2013;66:1230-1243.

Li T, Puhan MA, Swaroop SV, Dickersin K, et al.  Network meta-analysis-highly attractive

but more methodological research is needed.  BMC Medicine.  2011.  

Reporting Standards-PRISMA NMA for Network Meta-Analyses 

Cochrane Network Meta-analysis Toolkit 

Link to Published Network Meta-Analyses 

Graphical Tools for Network Meta-Analysis in STATA 

ISPOR Task Force on Indirect Comparisons and Network Meta-Analysis

This link opens to a PDF document.

What is a Live Cumulative (NMA) Network Meta-Analysis:

An NMA that is updated at regular intervals via crowdsourcing of a research community.

Resources:

http://livenetworkmetaanalysis.com

Créquit P, Trinquart L, Ravaud P.  Live cumulative network meta-analysis: protocol for second-line treatments in advanced non-small-cell lung cancer with wild-type or unknown status for epidermal growth factor receptor.  BMJ Open 2016;6:e011841. 

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