title: A quantitative evaluation of the regulatory assessment of the benefits and risks of rofecoxib relative to naproxen: an application of the incremental net-benefit framework.
abstract: OBJECTIVE
  To undertake a quantitative benefit-risk analysis of rofecoxib relative to naproxen using an incremental net-benefit (INB) analysis from the societal perspective, using the same data evaluated by the Health Canada and US FDA expert advisory panels.
  
  
  METHODS
  We developed a discrete event simulation model to calculate the INB of rofecoxib relative to naproxen in arthritis patients over a 1-year time horizon. All outcomes were weighted using societal utilities for each health state which facilitated the use of quality-adjusted life years (QALYs) as the outcome. Probability distributions were incorporated for each model parameter to facilitate a probabilistic analysis using second-order Monte Carlo simulation.
  
  
  RESULTS
  In the base case analysis, the mean INB (SD) of rofecoxib relative to naproxen was 0.0002 (0.415) QALYs per patient over 12 months of treatment, or 0.2 QALYs per 1000 patients treated. The probabilistic sensitivity analysis resulted in a mean INB of 0.0022 QALYs (95%CI -0.0005, 0.0051). Overall, the INB associated with rofecoxib relative to naproxen was ≥0 in 94% of the iterations of the model.
  
  
  CONCLUSIONS
  This analysis illustrates the application of the incremental net-benefit framework to quantitative benefit-risk evaluation, and suggests that the potential benefits of rofecoxib outweigh the potential harms relative to naproxen over 1 year from the societal perspective under the assumptions of this model.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. larry.lynd@ubc.ca
authors.forename: Larry D
authors.initials: LD
authors.lastname: Lynd
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Marra
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najafzadeh
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sadatsafavi
mesh_terms: D003198:Computer Simulation; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008954:Models, Biological; D009010:Monte Carlo Method; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen