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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Cost-Benefit Analysis / economics
  • Exome / genetics
  • Exome Sequencing / economics*
  • Genetic Testing / economics
  • Genomics
  • Humans
  • Infant
  • Rare Diseases / diagnosis*
  • Rare Diseases / economics*
  • Rare Diseases / epidemiology
  • Rare Diseases / genetics*