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. 2019 Nov;21(11):2586-2593.
doi: 10.1038/s41436-019-0534-x. Epub 2019 May 21.

Long-term economic impacts of exome sequencing for suspected monogenic disorders: diagnosis, management, and reproductive outcomes

Deborah Schofield  1 , Luke Rynehart  2 , Rupendra Shresthra  1 , Susan M White  3   4   5 , Zornitza Stark  3   4   5
Affiliations
Free article

Long-term economic impacts of exome sequencing for suspected monogenic disorders: diagnosis, management, and reproductive outcomes

Deborah Schofield et al. Genet Med. 2019 Nov.
Free article

Abstract

Purpose: To undertake the first end-to-end cost-effectiveness analysis of exome sequencing (ES) in rare disease diagnosis.

Methods: A cohort of 80 infants who underwent ES and usual diagnostic care in parallel were used to model incremental cost and health outcomes (quality adjusted life-years, QALYs) attributable to ES diagnosis over a 20-year horizon. Three models were developed: (1) outcomes in patients only, (2) outcomes in patients and first-degree relatives as a result of cascade testing, and (3) outcomes in patients and first-degree relatives including parental reproductive outcomes.

Results: When the directly observed cost and health outcomes of the cohort participants were projected, the use of ES resulted in a gain of 7.39 QALYs and an incremental cost-effectiveness ratio (ICER) of AU$31,144.35 (i.e., cost per additional QALY gained). When cascade testing in first-degree relatives was added, cost-effectiveness increased, to a gain of 11.62 QALYs and an ICER of AU$20,839.57. When parental reproductive outcomes were added, cost-effectiveness increased again, with 36.00 QALYs gained and an ICER of AU$14,235.28.

Conclusion: Use of ES in suspected monogenic disorders becomes increasingly cost-effective as the benefits of ES data reanalysis, cascade testing in first-degree relatives, and parental reproductive outcomes are incorporated into modeling.

Keywords: ICER; QALY; cost-effectiveness; exome sequencing.

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Comment in

  • Economic value of exome sequencing for suspected monogenic disorders.
    Ferket BS, Veenstra DL. Ferket BS, et al. Genet Med. 2020 Nov;22(11):1909. doi: 10.1038/s41436-020-0888-0. Epub 2020 Jun 30. Genet Med. 2020. PMID: 32601385 No abstract available.
  • Response to Ferket et al.
    Schofield D, Rynehart L, Shresthra R, White SM, Stark Z. Schofield D, et al. Genet Med. 2020 Nov;22(11):1910. doi: 10.1038/s41436-020-0889-z. Epub 2020 Jul 1. Genet Med. 2020. PMID: 32606441 No abstract available.

References

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    1. Stark Z, Schofield D, Alam K, et al. Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement. Genet Med. 2017;19:867–874. - DOI

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