Deborah Schofield1, Luke Rynehart2, Rupendra Shresthra1, Susan M White3,4,5, Zornitza Stark3,4,5. 1. GenIMPACT: Centre for Economic Impacts of Genomic Medicine, Department of Economics, Faculty of Business and Economics, Macquarie University, Sydney, NSW, Australia. 2. GenIMPACT: Centre for Economic Impacts of Genomic Medicine, Department of Economics, Faculty of Business and Economics, Macquarie University, Sydney, NSW, Australia. luke.rynehart@mq.edu.au. 3. Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia. 4. Department of Paediatrics, University of Melbourne, Melbourne, Australia. 5. Melbourne Genomics Health Alliance, Melbourne, Australia.
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.
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.
Authors: Stephen F Kingsmore; Audrey Henderson; Mallory J Owen; Michelle M Clark; Christian Hansen; David Dimmock; Christina D Chambers; Laura L Jeliffe-Pawlowski; Charlotte Hobbs Journal: NPJ Genom Med Date: 2020-11-02 Impact factor: 8.617
Authors: Karl Johnson; Katherine W Saylor; Isabella Guynn; Karen Hicklin; Jonathan S Berg; Kristen Hassmiller Lich Journal: Genet Med Date: 2021-12-07 Impact factor: 8.822
Authors: Stephen F Kingsmore; Audrey Henderson; Mallory J Owen; Michelle M Clark; Christian Hansen; David Dimmock; Christina D Chambers; Laura L Jeliffe-Pawlowski; Charlotte Hobbs Journal: NPJ Genom Med Date: 2020-11-02 Impact factor: 8.617