title: Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement.
abstract: To undertake the first prospective cost-effectiveness study of whole-exome sequencing (WES) as an early, routine clinical test for infants with suspected monogenic disorders.
  
  
  
  Cost data for diagnosis-related investigations and assessments were collected for a prospective, sequential clinical cohort of infants (N = 40) who underwent singleton WES in parallel to usual diagnostic care. We determined costs per patient, costs per diagnosis, and incremental costs per additional diagnosis for three alternative strategies for integrating WES into the diagnostic trajectory. We performed a sensitivity analysis to examine the robustness of estimates and bootstrapping (500 replications) to examine their distributions.
  
  
  
  Standard care achieved an average cost per diagnosis of AU$27,050 (US$21,099) compared with AU$5,047 (US$3,937) for singleton WES. If WES had been performed after exhaustive standard investigation, then there would have been an incremental cost per additional diagnosis of AU$8,112 (US$ 6,327). Using WES to replace some investigations decreases this incremental cost to AU$2,622 (US$2,045), whereas using it to replace most investigations results in a savings per additional diagnosis of AU$2,182 (US$1,702).
  
  
  
  Use of WES early in the diagnostic pathway more than triples the diagnostic rate for one-third the cost per diagnosis, providing strong support for reimbursement as a clinical test.Genet Med advance online publication 26 January 2017.
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Zornitza
authors.identifier: 0000-0001-8640-1371
authors.initials: Z
authors.lastname: Stark
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Faculty of Pharmacy, University of Sydney, Sydney, Australia.|Garvan Institute of Medical Research, Sydney, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Schofield
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Khurshid
authors.initials: K
authors.lastname: Alam
authors.affiliation: Melbourne Genomics Health Alliance, Melbourne, Australia.|Commonwealth Scientific and Industrial Research Organization, Sydney, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Wilson
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Melbourne Genomics Health Alliance, Melbourne, Australia.
authors.forename: Nessie
authors.initials: N
authors.lastname: Mupfeki
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Melbourne Genomics Health Alliance, Melbourne, Australia.
authors.forename: Ivan
authors.identifier: 0000-0002-0908-8542
authors.initials: I
authors.lastname: Macciocca
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, Australia.
authors.forename: Rupendra
authors.identifier: 0000-0001-5455-0735
authors.initials: R
authors.lastname: Shrestha
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.|Melbourne Genomics Health Alliance, Melbourne, Australia.
authors.forename: Susan M
authors.identifier: 0000-0001-7611-634X
authors.initials: SM
authors.lastname: White
authors.affiliation: Department of Paediatrics, University of Melbourne, Melbourne, Australia.|Melbourne Genomics Health Alliance, Melbourne, Australia.
authors.forename: Clara
authors.initials: C
authors.lastname: Gaff
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D003955:Diagnostic Tests, Routine / Q000191:economics*; D042241:Early Diagnosis; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007349:Insurance, Health, Reimbursement; D008297:Male; D011446:Prospective Studies; D000073336:Whole Genome Sequencing / Q000191:economics*