title: Modelling Comparative Efficacy of Drugs with Different Survival Profiles: Ipilimumab, Vemurafenib and Dacarbazine in Advanced Melanoma.
abstract: BACKGROUND
  In the absence of head-to-head data, a common method for modelling comparative survival for cost-effectiveness analysis is estimating hazard ratios from trial publications. This assumes that the hazards of mortality are proportional between treatments and that outcomes are not polluted by subsequent therapy use. Newer techniques that compare treatments where the proportional hazards assumption is violated and adjust for use of subsequent therapies often require patient-level data, which are rarely available for all treatments.
  
  
  OBJECTIVE
  The objective of this study was to provide a comparison of overall survival data for ipilimumab, vemurafenib and dacarbazine using data from three trials lacking a common comparator arm and confounded by the use of subsequent treatment.
  
  
  METHODS
  We compared three estimated overall survival curves for vemurafenib and the difference compared to ipilimumab and dacarbazine. We performed a naïve comparison and adjusted it for heterogeneity between the ipilimumab and vemurafenib trials, including differences in prognostic characteristics and subsequent therapy using a published hazard function for the impact of prognostic characteristics in melanoma and trial data on the impact of second-line use of ipilimumab.
  
  
  RESULTS
  The mean incremental life-years gained for patients receiving ipilimumab compared with vemurafenib were 0.34 (95 % confidence interval [CI] -0.24 to 0.84) using the naïve comparison and 0.51 (95 % CI -0.08 to 0.99) using the covariate-adjusted survival curve.
  
  
  CONCLUSIONS
  The analyses estimated the comparative efficacy of ipilimumab and vemurafenib in the absence of head-to-head patient-level data for all trials and proportional hazards in overall survival.
authors.affiliation: BresMed, North Church House, 84 Queen Street, Sheffield, S1 2DW, UK. dlee@bresmed.co.uk.
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.affiliation: BresMed, North Church House, 84 Queen Street, Sheffield, S1 2DW, UK.
authors.forename: J
authors.initials: J
authors.lastname: Porter
authors.affiliation: Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge, Middlesex, UK.
authors.forename: N
authors.initials: N
authors.lastname: Hertel
authors.affiliation: BresMed, North Church House, 84 Queen Street, Sheffield, S1 2DW, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hatswell
authors.affiliation: Health Economics and Health Technology Assessment, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: A
authors.initials: A
authors.lastname: Briggs
mesh_terms: D000911:Antibodies, Monoclonal / Q000191:economics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D003606:Dacarbazine / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000191:economics / Q000627:therapeutic use*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000191:economics / Q000401:mortality*; D008875:Middle Aged; D015233:Models, Statistical; D013449:Sulfonamides / Q000191:economics / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007211:Indoles; D000074324:Ipilimumab; D013449:Sulfonamides; D000077484:Vemurafenib; D003606:Dacarbazine