title: Cost-effectiveness of activated protein C in real-life clinical practice.
abstract: BACKGROUND
  Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.
  
  
  METHODS
  We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.
  
  
  RESULTS
  In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 +/- 14.9 years, Simplified Acute Physiology Score II was 56.7 +/- 18.5, and the number of organ failures was 3.20 +/- 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (47,870 euros versus 36,717 euros, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: 20,278 euros per life-year gained and 33,797 euros per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay 50,000 euros per life-year gained. The probability was 64.3% if there were willingness to pay 50,000 euros per quality-adjusted life-year gained.
  
  
  CONCLUSIONS
  This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay 50,000 euros per life-year gained is 74.5%.
authors.affiliation: Department of Intensive Care, Cochin Port-Royal University Hospital, AP-HP, René Descartes University, Paris 5, Paris, France. dhainaut@univ-paris5.fr
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dhainaut
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Payet
authors.forename: Benoit
authors.initials: B
authors.lastname: Vallet
authors.forename: Lionel Riou
authors.initials: LR
authors.lastname: França
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Bollaert
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Tulzo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Runge
authors.forename: Yannick
authors.initials: Y
authors.lastname: Malledant
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.forename: Katell
authors.initials: K
authors.lastname: Le Lay
authors.forename: Robert
authors.initials: R
authors.lastname: Launois
mesh_terms: D000925:Anticoagulants / Q000191:economics* / Q000627:therapeutic use; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D005260:Female; D005602:France / Q000453:epidemiology; D017721:Hospital Costs / Q000706:statistics & numerical data; D006760:Hospitalization / Q000191:economics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000401:mortality; D011486:Protein C / Q000191:economics* / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis