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Genomic sequencing for the diagnosis of childhood mitochondrial disorders: a health economic evaluation

European Journal of Human Genetics volume 30, pages 577–586 (2022)Cite this article

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Abstract

The diagnostic and clinical benefits of genomic sequencing are being increasingly demonstrated across multiple rare genetic conditions. Despite the expanding clinical literature, there is a significant paucity of health economics evidence to inform the prioritization and implementation of genomic sequencing. This study aims to evaluate whether genomic sequencing for pediatric-onset mitochondrial disorders (MDs) is cost-effective and cost-beneficial relative to conventional care from an Australian healthcare system perspective. Two independent and complementary health economic modeling approaches were used. Approach 1 used a decision tree to model the costs and outcomes associated with genomic sequencing and conventional care. Approach 2 used a discrete-event simulation to incorporate heterogeneity in the condition and clinical practice. Deterministic and probabilistic sensitivity analyses were performed. Genomic sequencing was less costly and more effective compared with conventional care, saving AU$1997 (Approach 1) to AU$8823 (Approach 2) per child tested, while leading to an additional 11 (Approach 1) to 14 (Approach 2) definitive diagnoses per 100 children tested. The mean monetary value of the incremental benefits of genomic sequencing was estimated at AU$5890 (95% CI: AU$5730−$6046). Implementation of genomic sequencing for MDs in Australia could translate to an annual cost-saving of up to AU$0.7 million. Genomic sequencing is cost-saving relative to traditional investigative approaches, while enabling more diagnoses to be made in a timely manner, offering substantial personal benefits to children and their families. Our findings support the prioritization of genomic sequencing for children with MDs.

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Fig. 1: Decision tree model.
Fig. 2: Discrete-event simulation model.
Fig. 3: Cost-effectiveness acceptability curves—Approach 1a.
Fig. 4: Variation in the incremental cost-effectiveness ratio (ICER) of genome sequencing (GS) relative to exome sequencing followed by mitochondrial DNA sequencing (ES ± mtDNA), depending on the cost of GS and its additional diagnostic yield (Dx)—Approach 1b: sensitivity analysis.

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Acknowledgements

Australian Genomics Health Alliance is funded by a National Health and Medical Research Council (NHMRC) grant (GNT: 1113531) and the Australian Government’s Medical Research Future Fund (MRFF), and a NHMRC research fellowship (GNT: 1102896). Philanthropic support from the Crane and Perkins families also funded this project. The research conducted at the Murdoch Children’s Research Institute was supported by the Victorian Government’s Operational Infrastructure Support Program. This work represents independent research and the views expressed are those of the authors and not necessarily those of the NHMRC or MRFF.

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Author notes

  1. These authors contributed equally: John Christodoulou and Ilias Goranitis

Authors and Affiliations

  1. Health Economics Unit, Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia

    You Wu & Ilias Goranitis

  2. Australian Genomics Health Alliance, Melbourne, VIC, Australia

    You Wu, David R. Thorburn, John Christodoulou & Ilias Goranitis

  3. Murdoch Children’s Research Institute, Melbourne, VIC, Australia

    You Wu, Rocio Rius, David R. Thorburn, John Christodoulou & Ilias Goranitis

  4. Genetic Metabolic Disorders Service, The Children’s Hospital at Westmead, Sydney, NSW, Australia

    Shanti Balasubramaniam

  5. Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Shanti Balasubramaniam & John Christodoulou

  6. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia

    Rocio Rius, David R. Thorburn & John Christodoulou

  7. Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, VIC, Australia

    David R. Thorburn

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Wu, Y., Balasubramaniam, S., Rius, R. et al. Genomic sequencing for the diagnosis of childhood mitochondrial disorders: a health economic evaluation. Eur J Hum Genet 30, 577–586 (2022). https://doi.org/10.1038/s41431-021-00916-8

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