Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies

doi:10.1038/s41436-020-01012-w

. 2021 Mar;23(3):451-460.

doi: 10.1038/s41436-020-01012-w. Epub 2020 Oct 28.

Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies

Chunmei Li¹, Stacey Vandersluis², Corinne Holubowich², Wendy J Ungar^{3

4}, Elaine S Goh⁵, Kym M Boycott⁶, Nancy Sikich², Irfan Dhalla^{2

7}, Vivian Ng²

Affiliations

¹ Ontario Health (Quality), Toronto, ON, Canada. chunmei.li@ontariohealth.ca.
² Ontario Health (Quality), Toronto, ON, Canada.
³ Program of Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁵ Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.
⁶ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁷ Unity Health Toronto, Toronto, ON, Canada.

PMID: 33110268
DOI: 10.1038/s41436-020-01012-w

Free article

Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies

Chunmei Li et al. Genet Med. 2021 Mar.

Free article

. 2021 Mar;23(3):451-460.

doi: 10.1038/s41436-020-01012-w. Epub 2020 Oct 28.

Authors

Chunmei Li¹, Stacey Vandersluis², Corinne Holubowich², Wendy J Ungar^{3

4}, Elaine S Goh⁵, Kym M Boycott⁶, Nancy Sikich², Irfan Dhalla^{2

7}, Vivian Ng²

Affiliations

¹ Ontario Health (Quality), Toronto, ON, Canada. chunmei.li@ontariohealth.ca.
² Ontario Health (Quality), Toronto, ON, Canada.
³ Program of Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁵ Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.
⁶ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁷ Unity Health Toronto, Toronto, ON, Canada.

PMID: 33110268
DOI: 10.1038/s41436-020-01012-w

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: ES would likely be cost-saving if used earlier in the diagnostic pathway.

Keywords: cost-effectiveness; developmental disabilities; genome-wide sequencing; multiple congenital anomalies.

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References

1. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64. - DOI
1. Jimenez-Gomez A, Standridge SM. A refined approach to evaluating global developmental delay for the international medical community. Pediatr Neurol. 2014;51:198–206. - DOI
1. Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability. Paediatr Child Health. 2018;23:403–10. - DOI
1. Sun F, Oristaglio J, Levy SE, Hakonarson H, Sullivan N, Fontanarosa J, et al. AHRQ comparative effectiveness technical briefs. Genetic testing for developmental disabilities, intellectual disability, and autism spectrum disorder. Rockville, MD: US Agency for Healthcare Research and Quality; 2015.
1. Moeschler JB, Shevell M. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics. 2014;134:e903–18. - DOI

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[1] Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64. - DOI

[2] Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64. - DOI

[3] Jimenez-Gomez A, Standridge SM. A refined approach to evaluating global developmental delay for the international medical community. Pediatr Neurol. 2014;51:198–206. - DOI

[4] Jimenez-Gomez A, Standridge SM. A refined approach to evaluating global developmental delay for the international medical community. Pediatr Neurol. 2014;51:198–206. - DOI

[5] Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability. Paediatr Child Health. 2018;23:403–10. - DOI

[6] Bélanger SA, Caron J. Evaluation of the child with global developmental delay and intellectual disability. Paediatr Child Health. 2018;23:403–10. - DOI

[7] Sun F, Oristaglio J, Levy SE, Hakonarson H, Sullivan N, Fontanarosa J, et al. AHRQ comparative effectiveness technical briefs. Genetic testing for developmental disabilities, intellectual disability, and autism spectrum disorder. Rockville, MD: US Agency for Healthcare Research and Quality; 2015.

[8] Sun F, Oristaglio J, Levy SE, Hakonarson H, Sullivan N, Fontanarosa J, et al. AHRQ comparative effectiveness technical briefs. Genetic testing for developmental disabilities, intellectual disability, and autism spectrum disorder. Rockville, MD: US Agency for Healthcare Research and Quality; 2015.

[9] Moeschler JB, Shevell M. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics. 2014;134:e903–18. - DOI

[10] Moeschler JB, Shevell M. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics. 2014;134:e903–18. - DOI

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Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies

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Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies

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