Clara L Gaff1,2, Susan M White3,4, Zornitza Stark3,5,4, Deborah Schofield3,6,7, Melissa Martyn5,4, Luke Rynehart3, Rupendra Shrestha6, Khurshid Alam3,4,8, Sebastian Lunke3, Tiong Y Tan3,5,4. 1. Melbourne Genomics Health Alliance, Melbourne, Australia. clara.gaff@melbournegenomics.org.au. 2. Department of Paediatrics, University of Melbourne, Melbourne, Australia. clara.gaff@melbournegenomics.org.au. 3. Murdoch Children's Research Institute, Melbourne, Australia. 4. Department of Paediatrics, University of Melbourne, Melbourne, Australia. 5. Melbourne Genomics Health Alliance, Melbourne, Australia. 6. Faculty of Pharmacy, University of Sydney, Sydney, Australia. 7. Garvan Institute of Medical Research, Sydney, Australia. 8. School of Population and Global Health, The University of Western Australia, Perth, Australia.
Abstract
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.
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.
Authors: Zornitza Stark; Tiffany Boughtwood; Peta Phillips; John Christodoulou; David P Hansen; Jeffrey Braithwaite; Ainsley J Newson; Clara L Gaff; Andrew H Sinclair; Kathryn N North Journal: Am J Hum Genet Date: 2019-07-03 Impact factor: 11.025
Authors: Tiong Yang Tan; Sebastian Lunke; Belinda Chong; Dean Phelan; Miriam Fanjul-Fernandez; Justine E Marum; Vanessa Siva Kumar; Zornitza Stark; Alison Yeung; Natasha J Brown; Chloe Stutterd; Martin B Delatycki; Simon Sadedin; Melissa Martyn; Ilias Goranitis; Natalie Thorne; Clara L Gaff; Susan M White Journal: Eur J Hum Genet Date: 2019-07-18 Impact factor: 4.246
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Authors: Lauren S Akesson; Stefanie Eggers; Clare J Love; Belinda Chong; Emma I Krzesinski; Natasha J Brown; Tiong Y Tan; Christopher M Richmond; David R Thorburn; John Christodoulou; Matthew F Hunter; Sebastian Lunke; Zornitza Stark Journal: Eur J Hum Genet Date: 2019-07-29 Impact factor: 4.246
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Authors: Zornitza Stark; Rebecca E Foulger; Eleanor Williams; Bryony A Thompson; Chirag Patel; Sebastian Lunke; Catherine Snow; Ivone U S Leong; Arina Puzriakova; Louise C Daugherty; Sarah Leigh; Christopher Boustred; Olivia Niblock; Antonio Rueda-Martin; Oleg Gerasimenko; Kevin Savage; William Bellamy; Victor San Kho Lin; Roman Valls; Lavinia Gordon; Helen K Brittain; Ellen R A Thomas; Ana Lisa Taylor Tavares; Meriel McEntagart; Susan M White; Tiong Y Tan; Alison Yeung; Lilian Downie; Ivan Macciocca; Elena Savva; Crystle Lee; Ain Roesley; Paul De Fazio; Jane Deller; Zandra C Deans; Sue L Hill; Mark J Caulfield; Kathryn N North; Richard H Scott; Augusto Rendon; Oliver Hofmann; Ellen M McDonagh Journal: Am J Hum Genet Date: 2021-07-29 Impact factor: 11.025