Implementing preconception expanded carrier screening in a universal healthcare system: a model-based cost-effectiveness analysis

Purpose: The limited evidence available on the cost-effectiveness (CE) of expanded carrier screening (ECS) prevents its widespread use in most countries, including Italy. Herein, we aimed to estimate the CE of three ECS panels (i.e., American College of Medical Genetics and Genomics (ACMG) Tier 1 screening; "Focused Screening", testing 15 severe highly penetrant conditions, and ACMG Tier 3 screening) compared to no screening, the health care model currently adopted in Italy. Methods: The reference population consisted of Italian couples seeking pregnancy with no increased personal/familial genetic risk. The CE model was developed from the perspective of the Italian universal health-care system and based on the following assumptions: 100% sensitivity of investigated screening strategies; 77% intervention rate of at-risk couples (ARCs); no risk to conceive an affected child by risk-averse couples opting for medical interventions. Results: The incremental CE ratios (ICER) generated by comparing each genetic screening panel with no screening were: -14,875±1,208€/life years gained (LYG) for ACMG1S, -106,863±2,379€/LYG for Focused Screening and -47,277±1,430€/LYG for ACMG3S. ACMG1S and Focused Screening were dominated by ACMG3S. The parameter uncertainty did not significantly affect the outcome of the analyses. Conclusion: From a universal health care system perspective, all the three ECS panels considered in the study would be more cost-effective than no screening.