ABSTRACT
PURPOSE: To undertake the first end-to-end cost-effectiveness analysis of exome sequencing (ES) in rare disease diagnosis. METHODS: A cohort of 80 infants who underwent ES and usual diagnostic care in parallel were used to model incremental cost and health outcomes (quality adjusted life-years, QALYs) attributable to ES diagnosis over a 20-year horizon. Three models were developed: (1) outcomes in patients only, (2) outcomes in patients and first-degree relatives as a result of cascade testing, and (3) outcomes in patients and first-degree relatives including parental reproductive outcomes. RESULTS: When the directly observed cost and health outcomes of the cohort participants were projected, the use of ES resulted in a gain of 7.39 QALYs and an incremental cost-effectiveness ratio (ICER) of AU$31,144.35 (i.e., cost per additional QALY gained). When cascade testing in first-degree relatives was added, cost-effectiveness increased, to a gain of 11.62 QALYs and an ICER of AU$20,839.57. When parental reproductive outcomes were added, cost-effectiveness increased again, with 36.00 QALYs gained and an ICER of AU$14,235.28. CONCLUSION: Use of ES in suspected monogenic disorders becomes increasingly cost-effective as the benefits of ES data reanalysis, cascade testing in first-degree relatives, and parental reproductive outcomes are incorporated into modeling.
Subject(s)
Exome Sequencing/economics , Rare Diseases/diagnosis , Rare Diseases/economics , Computer Simulation , Cost-Benefit Analysis/economics , Cost-Benefit Analysis/methods , Exome/genetics , Female , Humans , Infant , Infant, Newborn , Male , Quality-Adjusted Life YearsABSTRACT
PURPOSE: To systematically investigate the longer-term clinical and health economic impacts of genomic sequencing for rare-disease diagnoses. METHODS: We collected information on continuing diagnostic investigation, changes in management, cascade testing, and parental reproductive outcomes in 80 infants who underwent singleton whole-exome sequencing (WES). RESULTS: The median duration of follow-up following result disclosure was 473 days. Changes in clinical management due to diagnostic WES results led to a cost saving of AU$1,578 per quality-adjusted life year gained, without increased hospital service use. Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Further usual diagnostic investigations in those with ongoing suspicion of a genetic condition yielded no new diagnoses, while WES data reanalysis yielded four. Reanalysis at 18 months was more cost-effective than every 6 months. The parents of diagnosed children had eight more ongoing pregnancies than those without a diagnosis. Taking the costs and benefits of cascade testing and reproductive service use into account, there was an additional cost of AU$8,118 per quality-adjusted life year gained due to genomic sequencing. CONCLUSION: These data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis.
Subject(s)
Exome Sequencing/economics , Rare Diseases/diagnosis , Rare Diseases/economics , Rare Diseases/genetics , Child , Cost-Benefit Analysis/economics , Exome/genetics , Genetic Testing/economics , Genomics , Humans , Infant , Rare Diseases/epidemiologyABSTRACT
The original PDF version of this Article omitted to list Clara L Gaff as a corresponding author and the affiliations were incorrectly labelled as Present Addresses. Furthermore, Tables 1 and 2 have been updated to clarify that the Australian dollar is used for the values. These errors have now been corrected in the PDF and HTML versions of the Article.