title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mapi, 33 Bloor Street East, Suite 1300, Toronto, Ontario M4W 3H1, Canada. scope@mapigroup.com.
authors.forename: Shannon
authors.initials: S
authors.lastname: Cope
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Saletan
authors.forename: Brielan
authors.initials: B
authors.lastname: Smiechowski
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Jansen
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000068338:Everolimus; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D000068338:Everolimus; D020123:Sirolimus