Open Access Open Badges Research article

A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer

Shannon Cope1*, Jie Zhang2, Stephen Saletan2, Brielan Smiechowski3, Jeroen P Jansen4 and Peter Schmid5

Author Affiliations

1 Mapi, 33 Bloor Street East, Suite 1300, Toronto, Ontario M4W 3H1, Canada

2 Novartis Pharmaceuticals Corporation, One Health Plaza, BLDG 337, A10.4C, East Hanover, NJ 07936, USA

3 Mapi, 180 Canal Street, Suite 503, Boston, MA 02114, USA

4 Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA

5 Barts Cancer Institute, Queen Mary University of London, Old Anatomy Building, Charterhouse Square, London EC1M6BQ, UK

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BMC Medicine 2014, 12:93  doi:10.1186/1741-7015-12-93

Published: 5 June 2014



The aim of this study is to outline a general process for assessing the feasibility of performing a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative treatments for a specific disease population.


Several steps to assess the feasibility of an NMA are proposed based on existing recommendations. Next, a case study is used to illustrate this NMA feasibility assessment process in order to compare everolimus in combination with hormonal therapy to alternative chemotherapies in terms of progression-free survival for women with advanced breast cancer.


A general process for assessing the feasibility of an NMA is outlined that incorporates explicit steps to visualize the heterogeneity in terms of treatment and outcome characteristics (Part A) as well as the study and patient characteristics (Part B). Additionally, steps are performed to illustrate differences within and across different types of direct comparisons in terms of baseline risk (Part C) and observed treatment effects (Part D) since there is a risk that the treatment effect modifiers identified may not explain the observed heterogeneity or inconsistency in the results due to unexpected, unreported or unmeasured differences. Depending on the data available, alternative approaches are suggested: list assumptions, perform a meta-regression analysis, subgroup analysis, sensitivity analyses, or summarize why an NMA is not feasible.


The process outlined to assess the feasibility of an NMA provides a stepwise framework that will help to ensure that the underlying assumptions are systematically explored and that the risks (and benefits) of pooling and indirectly comparing treatment effects from RCTs for a particular research question are transparent.

Advanced breast cancer; Everolimus; Chemotherapy; Network meta-analysis; Progression-free survival; Systematic literature review; Feasibility assessment