title: Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.
abstract: BACKGROUND
  The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective.
  
  
  METHODS
  This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses.
  
  
  RESULTS
  Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67-77% of simulations, depending on the country. The cost per QALY gained for ZOL versus placebo was below € 30,000 per QALY gained threshold in approximately 93-94% of multivariate sensitivity analyses simulations.
  
  
  CONCLUSIONS
  The present analysis suggests that ZOL saves costs and increases QALYs compared to placebo in French, German, and UK RCC patients with bone metastases. Additional prospective research may be needed to confirm these results in a larger sample of patients.
authors.affiliation: Health Economics, Pharmerit International, 4530 East-West Highway, #430, Bethesda, MD 20814, USA. mbotteman@pharmerit.com
authors.forename: M F
authors.initials: MF
authors.lastname: Botteman
authors.forename: M
authors.initials: M
authors.lastname: Meijboom
authors.forename: I
authors.initials: I
authors.lastname: Foley
authors.forename: J M
authors.initials: JM
authors.lastname: Stephens
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Kaura
mesh_terms: D050071:Bone Density Conservation Agents / Q000191:economics* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology*; D003362:Cost-Benefit Analysis; D004164:Diphosphonates / Q000191:economics* / Q000627:therapeutic use; D005260:Female; D005380:Financing, Government; D005602:France; D005858:Germany; D006801:Humans; D007093:Imidazoles / Q000191:economics* / Q000627:therapeutic use; D008297:Male; D018803:Models, Economic; D009367:Neoplasm Staging; D019057:Quality-Adjusted Life Years; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D006113:United Kingdom; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
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