Abstract for: System Dynamics Modelling of Genetic Testing Policies for Familial Hypercholesterolaemia in Singapore

Familial hypercholesterolaemia (FH) is an inherited lipid disorder characterised by elevated cholesterol levels and increased risk of premature cardiovascular disease. While early detection and treatment can prevent severe cardiovascular complications, scaling up FH genetic screening presents complex logistical and resource allocation challenges. Genetic testing capacity is limited, particularly by shortage of specialised personnel needed for genetic counselling. Singapore is committed to introducing population-level genetic testing to identify and treat appropriately, individuals with FH as early as possible. We developed a System Dynamics Model for FH testing by incorporating local population dynamics and age-specific cholesterol level distributions by FH status. We explored several potential implementation policies including: varying the referral threshold from the current standard of care (LDL>4.9mmol/L), cascade testing of family members, prioritising cascade testing, applying age-differentiated referral thresholds and identifying the optimal permutation(s), including referrals from mandatory pre-enlistment cholesterol screening (applicable to all 18-year-old resident males), and lastly, combinations of the abovementioned policies. Higher referral thresholds yield rapid early detection of FH but quickly deplete testing-eligible individuals, leading to plateaued diagnoses and underutilised testing capacity. Across 625 threshold permutations, a nonlinear trade-off emerged between FH diagnoses and testing queue size, with optimal age-differentiated thresholds maximising yield without disproportionately increasing backlog. Cascade testing consistently increased detection, while prioritisation provided additional benefit only under substantial queue pressure. Calibrating referral thresholds is essential to balance diagnostic yield, testing capacity, and programme sustainability. Earlier screening and age-differentiated thresholds shift detection to younger individuals, improving long-term health gains while managing queues. Cascade testing should be widely implemented, with prioritisation reserved for high-demand settings. Integrating pre-enlistment screening may further enhance detection through family-based spillover effects, demonstrating the value of system dynamics modelling in guiding resource-constrained precision medicine strategies. AI tools were used for grammar checking and language refinement