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Cost Effectiveness of Karyotyping, Chromosomal Microarray Analysis, and Targeted Next-Generation Sequencing of Patients with Unexplained Global Developmental Delay or Intellectual Disability

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Abstract

Background

Genetic diagnosis of unexplained global developmental delay and intellectual disability (GDD/ID) often ends the diagnostic odyssey and can lead to changes in clinical management.

Objective

The objective of this study was to investigate the cost effectiveness of testing scenarios involving several methods used to diagnose GDD/ID: karyotyping, chromosomal microarray analysis (CMA), and targeted next-generation sequencing (NGS).

Methods

We used decision-tree models to estimate the number of genetic diagnoses, the cost from a payers’ perspective in the USA, and the incremental cost per additional genetic diagnosis. Model parameters were taken from peer-reviewed literature and governmental fee schedules.

Results

CMA testing results in more genetic diagnoses at an incremental cost of US $2692 per additional diagnosis compared with karyotyping, which has an average cost per diagnosis of US $11,033. Performing both tests sequentially results in the same number of diagnoses, but the total cost is less when CMA testing is done first and karyotyping second. Furthermore, when CMA testing yields a variant of unknown significance, additional genetic diagnoses can be obtained at an incremental cost of US $4220 by CMA testing of both parents, and when parents are not available or the patient had a normal CMA result, targeted NGS of the patient can add diagnoses at a further incremental cost of US $12,295.

Conclusion

These results provide a cost effectiveness rationale for the use of CMA as the first-tier test for the genetic diagnosis of unexplained GDD/ID and further indicate that testing of both parents may be cost effective when a variant of unknown significance is detected in the patient.

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Acknowledgements

We thank Andre Arellano for technical assistance and Joseph Higgins and Jeff Radcliff for helpful comments on the manuscript.

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Authors and Affiliations

  1. Quest Diagnostics, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA

    Yonghong Li, Lori A. Anderson & James J. Devlin

  2. Quest Diagnostics, Marlborough, MA, USA

    Edward I. Ginns

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  1. Yonghong Li
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Correspondence to Yonghong Li.

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Conflict of interest

Yonghong Li, Lori A. Anderson, Edward I. Ginns, and James J. Devlin are employed by Quest Diagnostics.

Funding

All funding was provided by Quest Diagnostics

Ethical approval and informed consent

No patients were enrolled and nor was protected health information used in this study.

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Li, Y., Anderson, L.A., Ginns, E.I. et al. Cost Effectiveness of Karyotyping, Chromosomal Microarray Analysis, and Targeted Next-Generation Sequencing of Patients with Unexplained Global Developmental Delay or Intellectual Disability. Mol Diagn Ther 22, 129–138 (2018). https://doi.org/10.1007/s40291-017-0309-5

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  • DOI: https://doi.org/10.1007/s40291-017-0309-5

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