title: Impact of uncertainty on cost-effectiveness analysis of medical strategies: the case of high-dose chemotherapy for breast cancer patients.
abstract: OBJECTIVE
  The object of this study was to determine, taking into account uncertainty on cost and outcome parameters, the cost-effectiveness of high-dose chemotherapy (HDC) compared with conventional chemotherapy for advanced breast cancer patients.
  
  
  METHODS
  An analysis was conducted for 300 patients included in a randomized clinical trial designed to evaluate the benefits, in terms of disease-free survival and overall survival, of adding a single course of HDC to a four-cycle conventional-dose chemotherapy for breast cancer patients with axillary lymph node invasion. Costs were estimated from a detailed observation of physical quantities consumed, and the Kaplan-Meier method was used to evaluate mean survival times. Incremental cost-effectiveness ratios were evaluated successively considering disease-free survival and overall survival outcomes. Handling of uncertainty consisted in construction of confidence intervals for these ratios, using the truncated Fieller method.
  
  
  RESULTS
  The cost per disease-free life year gained was evaluated at 13,074 Euros, a value that seems to be acceptable to society. However, handling uncertainty shows that the upper bound of the confidence interval is around 38,000 Euros, which is nearly three times higher. Moreover, as no difference was demonstrated in overall survival between treatments, cost-effectiveness analysis, that is a cost minimization, indicated that the intensive treatment is a dominated strategy involving an extra cost of 7,400 Euros, for no added benefit.
  
  
  CONCLUSIONS
  Adding a single course of HDC led to a clinical benefit in terms of disease-free survival for an additional cost that seems to be acceptable, considering the point estimate of the ratio. However, handling uncertainty indicates a maximum ratio for which conclusions have to be discussed.
authors.affiliation: University of Mediterranée, INSERM U379, France. marino@marseille.inserm.fr
authors.forename: Patricia
authors.initials: P
authors.lastname: Marino
authors.forename: Carole
authors.initials: C
authors.lastname: Siani
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Moatti
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000191:economics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics*; D003362:Cost-Benefit Analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006296:Health Services / Q000706:statistics & numerical data; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011994:Recombinant Proteins; D033581:Stem Cell Transplantation; D035501:Uncertainty
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D000069585:Filgrastim; D005472:Fluorouracil