title: Cost effectiveness of dabrafenib as a first-line treatment in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma in Canada.
abstract: OBJECTIVE
  To evaluate the cost effectiveness of dabrafenib versus dacarbazine and vemurafenib as first-line treatments in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a Canadian healthcare system perspective.
  
  
  METHODS
  A partitioned-survival analysis model with three mutually exclusive health states (pre-progression, post-progression, and dead) was used. The proportion of patients in each state was calculated using survival distributions for progression-free and overall survival derived from pivotal trials of dabrafenib and vemurafenib. For each treatment, expected progression-free, post-progression, overall, and quality-adjusted life-years (QALYs), and costs were calculated. Costs were based on list prices, a clinician survey, and published sources. A 5-year time horizon was used in the base case. Costs (in 2012 Canadian dollars [CA$]) and QALYs were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were conducted.
  
  
  RESULTS
  Dabrafenib was estimated to yield 0.2055 more QALYs at higher cost than dacarbazine. The incremental cost-effectiveness ratio was CA$363,136/QALY. In probabilistic sensitivity analyses, at a threshold of CA$200,000/QALY, there was an 8.2% probability that dabrafenib is cost effective versus dacarbazine. In deterministic sensitivity analyses, cost effectiveness was sensitive to survival distributions, utilities, and time horizon, with the hazard ratio for overall survival for dabrafenib versus dacarbazine being the most sensitive parameter. Assuming a class effect for efficacy of BRAF inhibitors, dabrafenib was dominant versus vemurafenib (less costly, equally effective), reflecting its assumed lower daily cost. Assuming no class effect, dabrafenib yielded 0.0486 more QALYs than vemurafenib.
  
  
  CONCLUSIONS
  At a threshold of CA$200,000/QALY, dabrafenib is unlikely to be cost effective compared with dacarbazine. It is not possible to make reliable conclusions regarding the relative cost effectiveness of dabrafenib versus vemurafenib based on available information.
authors.affiliation: Policy Analysis Inc. (PAI), Four Davis Court, Brookline, MA, 02445, USA, tdelea@pai2.com.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Delea
authors.forename: Jordan
authors.initials: J
authors.lastname: Amdahl
authors.forename: Alice
authors.initials: A
authors.lastname: Wang
authors.forename: Mayur M
authors.initials: MM
authors.lastname: Amonkar
authors.forename: Marroon
authors.initials: M
authors.lastname: Thabane
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D002170:Canada; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D016527:Drug Costs; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018803:Models, Economic; D009154:Mutation; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D019057:Quality-Adjusted Life Years
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib