Evaluating the cost-effectiveness of next-generation sequencing strategies for familial hypercholesterolemia cascade screening in Thailand

Abstract Background: Genetic cascade screening of familial hypercholesterolemia (FH) effectively prevents cardiovascular complications, but it remains unclear how health systems should roll out genetic testing over time. We developed a policy-relevant, forward-looking framework for stepwise economic evaluation on genetic testing, using FH cascade testing in Thailand as a case study. Methods: We constructed a decision tree-Markov hybrid model for a cohort of 35-year-old probands with low-density lipoprotein cholesterol above 4.9 mmol/L and their first- and second-degree relatives. We performed stepwise evaluations on conventional three-gene panel testing, whole-exome sequencing (WES), and onward to emerging long-read sequencing (LRS), compared with standard of care from a societal perspective. Conventional economic evaluation compared panel testing and WES using currently available evidence, while early economic evaluation was applied to LRS to identify target product profiles and explore uncertainties. Results: The analyses show that panel- and WES-based cascade screening are cost-effective versus standard of care, with incremental cost-effectiveness ratios (ICERs) of Thai baht (THB) 81,494 (€2,146/$2,371) and THB 74,641 (€1,966/$2,172) per quality-adjusted life-year (QALY), respectively. Compared with panel testing, WES generates 0.055 incremental QALYs at an ICER of THB 50,703 (€1,335/$1,475)/QALY. LRS is also cost-effective versus standard of care under target costs and yields 0.04 incremental QALYs/person versus WES, but requires cost reductions of 16.33% to THB 33,468/proband and 46.05% to THB 21,580/proband to surpass WES and dominate the market, respectively. Conclusions: This forward-looking, stepwise evaluation demonstrates that next-generation sequencing for FH cascade testing can be economically viable in Thailand while advancing precision health under universal healthcare.