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


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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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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Correspondence to John Christodoulou or Ilias Goranitis.

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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).

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