Aims The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH). Methods and results We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18–40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries. The model captured coronary heart disease (CHD) morbidity/mortality over a lifetime horizon, from healthcare and societal perspectives. Risk of CHD, treatment effects, prevalence, and healthcare costs were estimated from published studies. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER), discounted 5% annually. Sensitivity analyses were undertaken to explore the impact of key input parameters on the robustness of the model. Over the lifetime of the population (4 167 768 men; 4 129 961 women), the model estimated a gain of 33 488years of life lived and 51 790 QALYs due to CHD prevention. Population genomic screening for FH would be cost-effective from a healthcare perspective if the per-test cost was ≤AU$250, yielding an ICER of <AU$28 000 per QALY gained. From a societal perspective, population genomic screening would be cost-saving. ICERs from societal perspective remained cost-saving after adaptation to other countries. Conclusion Based on our model, offering population genomic screening to all young adults for FH could be cost-effective, at testing costs that are feasible.

中文翻译：

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家族性高胆固醇血症的年轻人群体基因组筛查：成本效益分析

目的 本研究的目的是评估为澳大利亚所有年轻人提供人口基因组筛查以检测杂合子家族性高胆固醇血症 (FH) 的影响和成本效益。方法和结果 我们设计了一个决策分析马尔可夫模型，以比较澳大利亚目前对杂合子 FH 诊断的护理标准（机会性胆固醇筛查和遗传级联检测）与对 18-40 岁成年人进行人群基因组筛查以检测致病菌的替代策略LDLR/APOB/PCSK9 基因的变异。我们使用经过验证的成本调整方法来调整结果以适应八个高收入国家。该模型从医疗保健和社会角度捕获了终生范围内的冠心病 (CHD) 发病率/死亡率。冠心病风险、治疗效果、患病率、和医疗保健费用是根据已发表的研究估算的。结果包括质量调整生命年 (QALYs)、成本和增量成本效益比 (ICER)，每年折现 5%。进行敏感性分析以探索关键输入参数对模型稳健性的影响。在人口的一生中（4 167 768 名男性；4 129 961 名女性），该模型估计因预防 CHD 而增加了 33 488 年的寿命和 51 790 个 QALY。如果每次测试的成本≤250 澳元，FH 的人群基因组筛查从医疗保健的角度来看是具有成本效益的，每获得 QALY 的 ICER 小于 28 000 澳元。从社会角度来看，人口基因组筛查将节省成本。从社会角度看，ICER 在适应其他国家后仍然可以节省成本。结论 根据我们的模型，