Cost-effectiveness of alternative cascade screening strategies for familial hypercholesterolemia with realistic cascade screening acceptance rates and use of high-cost drugs

BackgroundCascade screening (CS) for familial hypercholesterolemia (FH) is cost-effective in many countries. However, most existing economic evaluation studies (i) ignored or overstated first-degree relative (FDR) participation rate (as 60-100%), (ii) did not consider novel and expensive therapies, e.g. PCSK9 inhibitors (PCSK9i), (iii) were conducted outside of Asia. In Singapore, FDR participation rate is about 25% among probands who have known pathogenic variants. AimsTo evaluate and identify drivers of cost-effectiveness of CS protocols for FH MethodsFour CS protocols, which vary in the application of genetic testing, were examined using a hybrid decision tree-Markov model. Sensitivity analysis and scenario analyses were conducted to identify drivers of cost-effectiveness. ResultsAll CS protocols are likely to be cost-effective (probabilities of being cost-effective: 85%-95% when no access to PCSK9i; 73%-99% when PCSK9i are provided). The most cost-effective protocol differs depending on whether PCSK9i are provided. Cascade acceptance rates are key drivers of cost-effectiveness. Other drivers include timeliness of starting treatment post-screening, age of proband, health-related quality of life loss with cardiovascular disease, prevalence of FH mutation among probands, conventional treatment effect and cost of PCSK9i. ConclusionCS for FH is cost-effective across most scenarios and assumptions. For better cost-effectiveness, health systems need to look for ways to improve probands willingness to share contact of their relatives and relatives willingness to be screened. Other ways to improve cost-effectiveness include to select age groups for proband screening, improve screening detection rate among probands, and start timely treatment post-screening.