title: Economic Comparison of an Empirical Versus Diagnostic-Driven Strategy for Treating Invasive Fungal Disease in Immunocompromised Patients.
abstract: OBJECTIVE
  Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective.
  
  
  METHODS
  An empirical strategy with conventional amphotericin B deoxycholate (C-AmB), liposomal amphotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling.
  
  
  RESULTS
  Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000; empirical strategy, 125 of 1000), with similar survival rates.
  
  
  CONCLUSIONS
  This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers.
authors.affiliation: Cardiff University, University Hospital of Wales, Cardiff, United Kingdom. Electronic address: barnesra@cf.ac.uk.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Barnes
authors.affiliation: RTI Health Solutions, Research Triangle Park, North Carolina, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Earnshaw
authors.affiliation: Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.affiliation: Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.
authors.forename: Orla
authors.initials: O
authors.lastname: Morrissey
authors.affiliation: Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Slavin
authors.affiliation: CancerCare Manitoba and the University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Bow
authors.affiliation: RTI Health Solutions, Research Triangle Park, North Carolina, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: McDade
authors.affiliation: Pfizer International Operations, Paris, France.
authors.forename: Claudie
authors.initials: C
authors.lastname: Charbonneau
authors.affiliation: Pfizer International Operations, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Weinstein
authors.affiliation: Pfizer International Operations, Paris, France.
authors.forename: Michal
authors.initials: M
authors.lastname: Kantecki
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: Haran
authors.initials: H
authors.lastname: Schlamm
authors.affiliation: Universitaire Ziekenhuizen Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
mesh_terms: D000666:Amphotericin B / Q000191:economics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000191:economics* / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics*; D001230:Aspergillus / Q000302:isolation & purification; D000077336:Caspofungin; D017046:Cost Savings; D003663:Decision Trees; D003840:Deoxycholic Acid / Q000191:economics / Q000627:therapeutic use; D004338:Drug Combinations; D054714:Echinocandins / Q000191:economics / Q000627:therapeutic use; D064147:Febrile Neutropenia / Q000382:microbiology; D005690:Galactose / Q000031:analogs & derivatives; D017048:Health Care Costs; D006295:Health Resources / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D016867:Immunocompromised Host; D055666:Lipopeptides; D008351:Mannans / Q000032:analysis; D015996:Survival Rate; D065819:Voriconazole / Q000191:economics / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D055666:Lipopeptides; D008351:Mannans; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; C012990:galactomannan; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D000077336:Caspofungin; D065819:Voriconazole; D005690:Galactose
keywords: antifungal therapy; aspergillosis; cost benefit; fungal infection