Genetic testing is routine practice for individuals with unexplained developmental disabilities and multiple congenital anomalies. However, current testing pathways can be costly and time consuming, and the diagnostic yield low. Genome-wide sequencing, including exome sequencing (ES) and genome sequencing (GS), can improve diagnosis, but at a higher cost. This study aimed to assess the cost-effectiveness of genome-wide sequencing in Ontario, Canada.
A cost-effectiveness analysis was conducted using a discrete event simulation from a public payer perspective. Six strategies involving ES or GS were compared. Outcomes reported were direct medical costs, number of molecular diagnoses, number of positive findings, and number of active treatment changes.
If ES was used as a second-tier test (after the current first-tier, chromosomal microarray, fails to provide a diagnosis), it would be less costly and more effective than standard testing (CAN$6357 [95% CI: 6179–6520] vs. CAN$8783 per patient [95% CI: 2309–31,123]). If ES was used after standard testing, it would cost an additional CAN$15,228 to identify the genetic diagnosis for one additional patient compared with standard testing. The results remained robust when parameters and assumptions were varied.
ES would likely be cost-saving if used earlier in the diagnostic pathway.
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The research was conducted with in-kind support from Health Quality Ontario. The opinions expressed in this publication do not necessarily represent the opinions of Health Quality Ontario (now part of Ontario Health), a government agency that supported the completion of this work. We are grateful to June Carroll, Jordan Lerner-Ellis, Robin Hayeems, Kate Tsiplova, and Jathishinie Jegathisawaran for sharing their clinical and technical expertise during the development of this analysis. We are also thankful for Olga Gajic for conducting the model validation. Wendy J. Ungar is supported by a Canada Research Chair in Economic Evaluation and Technology Assessment in Child Health. Kym M. Boycott is supported by a Canada Research Chair in Rare Disease Precision Health. Jathishinie Jegathisawaran, Kate Tsiplova, Olga Gajic, Jordan Lerner-Ellis, Robin Hayeems, June Carroll.
K.M.B. and W.J.U. are receiving funding from the Ontario Ministry of Health and Genome Canada to examine the implementation of genome-wide sequencing (GWS) in Ontario. W.J.U. chairs the Ontario Genetics Advisory Committee but did not participate in funding deliberations on GWS. The other authors declare no conflicts of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Li, C., Vandersluis, S., Holubowich, C. et al. Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies. Genet Med (2020). https://doi.org/10.1038/s41436-020-01012-w
- developmental disabilities
- multiple congenital anomalies
- genome-wide sequencing