title: Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.
abstract: BACKGROUND
  Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections.
  
  
  OBJECTIVE
  We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing.
  
  
  METHODS
  The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d.
  
  
  RESULTS
  In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved.
  
  
  CONCLUSIONS
  Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.
authors.affiliation: 1 Emergency Medicine Service, and.|2 Department of Medicine.|3 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
authors.forename: Ephraim L
authors.identifier: http://orcid.org/0000-0002-6417-2042
authors.initials: EL
authors.lastname: Tsalik
authors.affiliation: 4 Duke Clinical Research Institute, and.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 Department of Medicine.|3 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Hudson
authors.affiliation: 2 Department of Medicine.|4 Duke Clinical Research Institute, and.
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Chu
authors.affiliation: 2 Department of Medicine.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Himmel
authors.affiliation: 5 Department of Surgery, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Limkakeng
authors.affiliation: 6 Department of Medicine, University of North Carolina Health Care, Chapel Hill, North Carolina; and.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Katz
authors.affiliation: 7 Department of Emergency Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Seth W
authors.initials: SW
authors.lastname: Glickman
authors.affiliation: 8 Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina.|2 Department of Medicine.|3 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
authors.forename: Micah T
authors.initials: MT
authors.lastname: McClain
authors.affiliation: 8 Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina.|2 Department of Medicine.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Welty-Wolf
authors.affiliation: 2 Department of Medicine.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.affiliation: 2 Department of Medicine.|3 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.affiliation: 8 Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina.|2 Department of Medicine.|3 Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.affiliation: 2 Department of Medicine.|4 Duke Clinical Research Institute, and.
authors.forename: Shelby D
authors.initials: SD
authors.lastname: Reed
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis; D016638:Critical Illness; D003428:Cross Infection / Q000175:diagnosis* / Q000191:economics*; D003661:Decision Support Techniques; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis* / Q000191:economics*; D011446:Prospective Studies; D019057:Quality-Adjusted Life Years; D055815:Young Adult
keywords: cost-benefit analysis; cross infection; early diagnosis; ventilator-associated pneumonia