title: The cost effectiveness of a randomized controlled trial to establish the relative efficacy of vitamin K1 compared with alendronate.
abstract: The authors aimed to evaluate whether vitamin K(1) or alendronate (the recommended treatment in England and Wales for postmenopausal women with a previous fracture) appeared to be the more cost-effective treatment for fracture prevention. Furthermore, expected value of sample information (EVSI) analyses were undertaken to estimate whether a head-to-head trial of alendronate and vitamin K(1) would be considered cost effective.
  
  
  
  A published osteoporosis model structure, populated with data from literature reviews, was used to evaluate the costs and quality-adjusted life-years associated with each intervention being provided to women at high risk of fracture, given current information. A lifetime horizon and a national health service and personal social services cost perspective were used. Observed outcomes from head-to-head randomized controlled trials (RCTs) of predetermined sizes were simulated and synthesized with existing data to formulate posterior distributions, which were used to estimate the more cost-effective treatment given these additional data. The EVSI was estimated and the expected net benefit of sampling (ENBS) calculated by subtracting the proposed trial costs.
  
  
  
  Given current information, vitamin K(1) is expected to dominate alendronate. However, this was subject to a considerable degree of uncertainty; dominance was reversed when it was assumed that vitamin K(1) had no effect on hip fractures. EVSI analysis indicated that an RCT of 2000 or 5000 women per arm produced high, and comparable, ENBS. These results were maintained in sensitivity analyses.
  
  
  
  It is concluded that an RCT recruiting between 2000 and 5000 women per arm to evaluate the relative efficacy of alendronate and vitamin K(1) appears to be cost effective for informing decision making in England and Wales.
authors.affiliation: Centre for Bayesian Statistics in Health Economics, Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Matt D
authors.initials: MD
authors.lastname: Stevenson
authors.affiliation: Centre for Bayesian Statistics in Health Economics, Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: Myfanwy Lloyd
authors.initials: ML
authors.lastname: Jones
mesh_terms: D000368:Aged; D019386:Alendronate / Q000191:economics* / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000191:economics* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000191:economics* / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003657:Decision Making; D004739:England; D005260:Female; D006801:Humans; D018803:Models, Economic; D008962:Models, Theoretical; D010024:Osteoporosis / Q000188:drug therapy / Q000191:economics*; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic / Q000191:economics*; D012306:Risk; D012307:Risk Factors; D010837:Vitamin K 1 / Q000191:economics* / Q000627:therapeutic use; D014852:Wales
chemical_list: D000933:Antifibrinolytic Agents; D050071:Bone Density Conservation Agents; D010837:Vitamin K 1; D019386:Alendronate