title: Calculating additive treatment effects from multiple randomized trials provides useful estimates of combination therapies.
abstract: OBJECTIVE
  Many clinicians and decision makers want to know the combined effects of treatments that have not been evaluated in combination. It is possible to determine such treatment effects by making assumptions about the additive effects. We discuss here the prerequisites and methods of applying additivity assumptions in synthesizing the evidence from randomized trials and multiple treatment meta-analyses.
  
  
  METHODS
  Using statistical approaches, we demonstrate the utility of additivity of both pairwise randomized trials and multiple treatment comparison meta-analyses.
  
  
  RESULTS
  We present illustratively an example on estimating the treatment effects of drug combinations for chronic obstructive pulmonary disease. We confirm the additive treatment effects by comparing with direct combination treatment trial results.
  
  
  CONCLUSIONS
  Additive effects may be a useful tool to estimate the effectiveness of treatment combinations.
authors.affiliation: Faculty of Health Sciences, University of Ottawa, 43 Templeton Street, Ottawa, Ontario, Canada. Edward.mills@uottawa.ca
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.forename: Kristian
authors.initials: K
authors.lastname: Thorlund
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D035843:Biomedical Research / Q000379:methods*; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D015201:Meta-Analysis as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic