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.

基因组测序的诊断和临床益处在多种罕见遗传病症中得到越来越多的证明。尽管临床文献不断增多，但仍缺乏健康经济学证据来为基因组测序的优先次序和实施提供信息。本研究旨在从澳大利亚医疗保健系统的角度评估儿科发病线粒体疾病 (MDs) 的基因组测序相对于传统护理是否具有成本效益和成本效益。使用了两种独立且互补的健康经济建模方法。方法 1 使用决策树来模拟与基因组测序和常规护理相关的成本和结果。方法 2 使用离散事件模拟将异质性纳入条件和临床实践中。进行了确定性和概率敏感性分析。与传统护理相比，基因组测序成本更低、更有效，每名受检儿童可节省 1997 澳元（方法 1）至 8823 澳元（方法 2），同时每名儿童可额外确诊 11 例（方法 1）至 14 例（方法 2） 100 名儿童接受了测试。基因组测序带来的增量收益的平均货币价值估计为 5890 澳元（95% CI：5730-6046 澳元）。在澳大利亚实施 MD 基因组测序可以转化为每年节省高达 70 万澳元的成本。与传统的调查方法相比，基因组测序可以节省成本，同时能够及时做出更多诊断，为儿童及其家人带来巨大的个人利益。