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Stark Z, Schofield D, Martyn M, et al. Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness. Genet Med. 2018;21(1):173-180doi: 10.1038/s41436-018-0006-8.
Stark, Z., Schofield, D., Martyn, M., Rynehart, L., Shrestha, R., Alam, K., Lunke, S., Tan, T. Y., Gaff, C. L., & White, S. M. (2019). Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness. Genetics in medicine : official journal of the American College of Medical Genetics, 21(1), 173-180. https://doi.org/10.1038/s41436-018-0006-8
Stark, Zornitza, et al. "Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness." Genetics in medicine : official journal of the American College of Medical Genetics vol. 21,1 (2019): 173-180. doi: https://doi.org/10.1038/s41436-018-0006-8
Stark Z, Schofield D, Martyn M, Rynehart L, Shrestha R, Alam K, Lunke S, Tan TY, Gaff CL, White SM. Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness. Genet Med. 2019 Jan;21(1):173-180. doi: 10.1038/s41436-018-0006-8. Epub 2018 May 15. PMID: 29765138.
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Genet Med. 2019 Jan;21(1):173-180. doi: 10.1038/s41436-018-0006-8. Epub 2018 May 15.

Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness.

Genetics in medicine : official journal of the American College of Medical Genetics

Zornitza Stark, Deborah Schofield, Melissa Martyn, Luke Rynehart, Rupendra Shrestha, Khurshid Alam, Sebastian Lunke, Tiong Y Tan, Clara L Gaff, Susan M White

Affiliations

  1. Murdoch Children's Research Institute, Melbourne, Australia.
  2. Melbourne Genomics Health Alliance, Melbourne, Australia.
  3. Department of Paediatrics, University of Melbourne, Melbourne, Australia.
  4. Faculty of Pharmacy, University of Sydney, Sydney, Australia.
  5. Garvan Institute of Medical Research, Sydney, Australia.
  6. School of Population and Global Health, The University of Western Australia, Perth, Australia.
  7. Melbourne Genomics Health Alliance, Melbourne, Australia. [email protected].
  8. Department of Paediatrics, University of Melbourne, Melbourne, Australia. [email protected].

PMID: 29765138 DOI: 10.1038/s41436-018-0006-8

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.

Keywords: cost-effectiveness; QALY; reanalysis; whole-exome sequencing

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