TY - JOUR
T1 - Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness
AU - Stark, Zornitza
AU - Schofield, Deborah
AU - Martyn, Melissa
AU - Rynehart, Luke
AU - Shrestha, Rupendra
AU - Alam, Khurshid
AU - Lunke, Sebastian
AU - Tan, Tiong Y.
AU - Gaff, Clara L.
AU - White, Susan M.
N1 - Correction to the article published in Genetics in Medicine (2019) 21:516; https://doi.org/10.1038/s41436-018-0078-5
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - cost-effectiveness
KW - QALY
KW - reanalysis
KW - whole-exome sequencing
UR - https://doi.org/10.1038/s41436-018-0078-5
UR - http://www.scopus.com/inward/record.url?scp=85046895818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/record.url?scp=85061223492&partnerID=8YFLogxK
U2 - 10.1038/s41436-018-0006-8
DO - 10.1038/s41436-018-0006-8
M3 - Article
C2 - 30158691
AN - SCOPUS:85046895818
SN - 1098-3600
VL - 21
SP - 173
EP - 180
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 1
ER -