Zornitza Stark1,2,3, Sebastian Lunke4, Gemma R Brett4,5, Natalie B Tan4, Rachel Stapleton4, Smitha Kumble4, Alison Yeung4,5, Dean G Phelan4, Belinda Chong4, Miriam Fanjul-Fernandez4,6, Justine E Marum4, Matthew Hunter7,8, Anna Jarmolowicz4,5, Yael Prawer5,7, Jessica R Riseley4, Matthew Regan7, Justine Elliott4, Melissa Martyn5,6, Stephanie Best9, Tiong Y Tan4,5,6, Clara L Gaff5,6,10, Susan M White4,5,6. 1. Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia. zornitza.stark@vcgs.org.au. 2. Melbourne Genomics Health Alliance, Melbourne, Australia. zornitza.stark@vcgs.org.au. 3. Department of Paediatrics, University of Melbourne, Melbourne, Australia. zornitza.stark@vcgs.org.au. 4. Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia. 5. Melbourne Genomics Health Alliance, Melbourne, Australia. 6. Department of Paediatrics, University of Melbourne, Melbourne, Australia. 7. Monash Genetics, Monash Children's Hospital, Melbourne, Australia. 8. Department of Paediatrics, Monash University, Melbourne, Australia. 9. Centre for Healthcare Resilience and Implementation Science, Australian Institute of Health Innovation, Macquarie University, Melbourne, Australia. 10. Department of Medicine, University of Melbourne, Melbourne, Australia.
Abstract
PURPOSE: The purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers. METHODS: Rapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed. RESULTS: Of 40 enrolled patients, 21 (52.5%) received a diagnosis, with median time to report of 16 days (range 9-109 days). A result was provided during the first hospital admission in 28 of 36 inpatients (78%). Clinical management changed in 12 of the 21 diagnosed patients (57%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. The cost per diagnosis was AU$13,388 (US$10,453). Additional cost savings from avoidance of planned tests and procedures and reduced length of stay are estimated to be around AU$543,178 (US$424,101). The clear relative advantage of rWES, joint clinical and laboratory leadership, and the creation of a multidisciplinary "rapid team" were key to successful implementation. CONCLUSION: Rapid genomic testing in acute pediatrics is not only feasible but also cost-effective, and has high diagnostic and clinical utility. It requires a whole-of-system approach for successful implementation.
PURPOSE: The purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers. METHODS: Rapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed. RESULTS: Of 40 enrolled patients, 21 (52.5%) received a diagnosis, with median time to report of 16 days (range 9-109 days). A result was provided during the first hospital admission in 28 of 36 inpatients (78%). Clinical management changed in 12 of the 21 diagnosed patients (57%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. The cost per diagnosis was AU$13,388 (US$10,453). Additional cost savings from avoidance of planned tests and procedures and reduced length of stay are estimated to be around AU$543,178 (US$424,101). The clear relative advantage of rWES, joint clinical and laboratory leadership, and the creation of a multidisciplinary "rapid team" were key to successful implementation. CONCLUSION: Rapid genomic testing in acute pediatrics is not only feasible but also cost-effective, and has high diagnostic and clinical utility. It requires a whole-of-system approach for successful implementation.
Authors: Sarah V Clowes Candadai; Megan C Sikes; Jenny M Thies; Amanda S Freed; James T Bennett Journal: J Genet Couns Date: 2019-04 Impact factor: 2.537
Authors: Alison M Elliott; Christèle du Souich; Anna Lehman; Ilaria Guella; Daniel M Evans; Tara Candido; Leah Tooman; Linlea Armstrong; Lorne Clarke; William Gibson; Harinder Gill; Pascal M Lavoie; Suzanne Lewis; Margaret L McKinnon; Sarah M Nikkel; Millan Patel; Alfonso Solimano; Anne Synnes; Joseph Ting; Margot van Allen; Jan Christilaw; Matthew J Farrer; Jan M Friedman; Horacio Osiovich Journal: Eur J Pediatr Date: 2019-06-07 Impact factor: 3.183
Authors: Zornitza Stark; Lena Dolman; Teri A Manolio; Brad Ozenberger; Sue L Hill; Mark J Caulfied; Yves Levy; David Glazer; Julia Wilson; Mark Lawler; Tiffany Boughtwood; Jeffrey Braithwaite; Peter Goodhand; Ewan Birney; Kathryn N North Journal: Am J Hum Genet Date: 2019-01-03 Impact factor: 11.025
Authors: Stephen F Kingsmore; Julie A Cakici; Michelle M Clark; Mary Gaughran; Michele Feddock; Sergey Batalov; Matthew N Bainbridge; Jeanne Carroll; Sara A Caylor; Christina Clarke; Yan Ding; Katarzyna Ellsworth; Lauge Farnaes; Amber Hildreth; Charlotte Hobbs; Kiely James; Cyrielle I Kint; Jerica Lenberg; Shareef Nahas; Lance Prince; Iris Reyes; Lisa Salz; Erica Sanford; Peter Schols; Nathaly Sweeney; Mari Tokita; Narayanan Veeraraghavan; Kelly Watkins; Kristen Wigby; Terence Wong; Shimul Chowdhury; Meredith S Wright; David Dimmock Journal: Am J Hum Genet Date: 2019-09-26 Impact factor: 11.025
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
Authors: Christopher M Richmond; Sally Campbell; Hee W Foo; Sebastian Lunke; Zornitza Stark; Amanda Moody; Elizabeth Bannister; Anthea Greenway; Natasha Brown Journal: Mol Syndromol Date: 2020-02-01
Authors: Sebastian Lunke; Stefanie Eggers; Meredith Wilson; Chirag Patel; Christopher P Barnett; Jason Pinner; Sarah A Sandaradura; Michael F Buckley; Emma I Krzesinski; Michelle G de Silva; Gemma R Brett; Kirsten Boggs; David Mowat; Edwin P Kirk; Lesley C Adès; Lauren S Akesson; David J Amor; Samantha Ayres; Anne Baxendale; Sarah Borrie; Alessandra Bray; Natasha J Brown; Cheng Yee Chan; Belinda Chong; Corrina Cliffe; Martin B Delatycki; Matthew Edwards; George Elakis; Michael C Fahey; Andrew Fennell; Lindsay Fowles; Lyndon Gallacher; Megan Higgins; Katherine B Howell; Lauren Hunt; Matthew F Hunter; Kristi J Jones; Sarah King; Smitha Kumble; Sarah Lang; Maelle Le Moing; Alan Ma; Dean Phelan; Michael C J Quinn; Anna Richards; Christopher M Richmond; Jessica Riseley; Jonathan Rodgers; Rani Sachdev; Simon Sadedin; Luregn J Schlapbach; Janine Smith; Amanda Springer; Natalie B Tan; Tiong Y Tan; Suzanna L Temple; Christiane Theda; Anand Vasudevan; Susan M White; Alison Yeung; Ying Zhu; Melissa Martyn; Stephanie Best; Tony Roscioli; John Christodoulou; Zornitza Stark Journal: JAMA Date: 2020-06-23 Impact factor: 56.272