Elsevier

Genetics in Medicine

Volume 21, Issue 1, January 2019, Pages 173-180
Genetics in Medicine

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

https://doi.org/10.1038/s41436-018-0006-8Get rights and content
Under an Elsevier user license
open archive

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

Cited by (0)