title: Enzyme replacement therapy in orphan and ultra-orphan diseases: the limitations of standard economic metrics as exemplified by Fabry-Anderson disease.
abstract: BACKGROUND
  Fabry-Anderson disease is an x-linked deficiency of lysosomal alpha-galactosidase A (GALA), resulting in chronic renal failure, cardiac arrhythmia, hypertrophy, valvular disease, pain (acro-paraesthesiae) and stroke, together with premature mortality. The disease has a significant impact on quality of life (QOL), as illustrated by studies using the EQ-5D. A specific treatment is available for Fabry-Anderson disease consisting of intravenous enzyme replacement therapy (ERT) of the deficient enzyme. The variable clinical efficacy and cost of ERT has resulted in reluctance by some health providers to approve it.
  
  
  METHODS
  We use the limited QOL data available in the Fabry-Anderson disease literature on ERT to derive standard economic metrics. These were derived by bootstrap estimates of the incremental net benefit (INB) statistics together with a cost-effectiveness acceptability curve relating the willingness to pay to the probability that the INB was >0. The estimates were further developed by adoption of a supplementary Bayesian approach utilising a sceptical and enthusiastic prior of the INB of ERT in Fabry-Anderson disease.
  
  
  RESULTS
  ERT for Fabry-Anderson disease is not economically viable by standard health programme evaluation metrics. Based on current ERT costs (year 2005 values), derivation of the INB distribution, and a Bayesian analysis using an enthusiastic and sceptical prior of the INB, an upper (350,000 dollars over 1 year) and lower (175,000 dollars over 1 year) economic cost, respectively, of ERT was derived.
  
  
  CONCLUSIONS
  The cost of ERT will always result in a net deficit to society under current costing and ERT efficacy as determined by the QALY metric. The rules of fair cooperation should govern decision making both for ERT in Fabry-Anderson disease and for funding therapeutic advances in other rare diseases belonging to the orphan and ultra-orphan categories.
authors.affiliation: Section of Neurology and Section of Proteomics and System Biology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Moore
authors.forename: Markus
authors.initials: M
authors.lastname: Ries
authors.forename: Evelyn L
authors.initials: EL
authors.lastname: Forget
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D000795:Fabry Disease / Q000188:drug therapy* / Q000191:economics; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015201:Meta-Analysis as Topic; D011788:Quality of Life; D035583:Rare Diseases / Q000188:drug therapy* / Q000191:economics; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*
chemical_list: D000519:alpha-Galactosidase