Implementing preconception expanded carrier screening in a universal health care 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 3 ECS panels (ie, 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 with 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 was based on the following assumptions: 100% sensitivity of investigated screening strategies, 77% intervention rate of at-risk couples (ARCs), and no risk to conceive an affected child by risk-averse couples opting for medical interventions. Results: The incremental CE ratios generated by comparing each genetic screening panel with no screening were: -14,875 & PLUSMN; 1,208 euro/life years gained (LYG) for ACMG1S, -106,863 & PLUSMN; 2,379 euro/LYG for Focused Screening, and -47,277 & PLUSMN; 1,430 euro/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 3 ECS panels considered in the study would be more cost-effective than no screening. & COPY; 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.