Implementing preconception expanded carrier screening in a universal healthcare system: insights from a cost-effectiveness analysis

Study question: Would reimbursement of expanded carrier screening (ECS) panels of different gene content be cost-effective in a universal healthcare system? Summary answer: Both tested ECS panels would be cost-effective if reim bursed by the Italian national healthcare system for a population without per sonal/familiar or racial/ethnic preconception genetic risks. What is known already: Collectively, Mendelian diseases are a significant cause of infant mortality and hospitalization. Current preconception screening strategies test a limited number of individuals based on self-reported per sonal/familiar or racial/ethnic background. Consequently, the majority of at risk couples (ARCs) remain hidden in the general population. If adopted at a population level, multiplex platforms can thus improve screening effectiveness by allowing rapid ECS for a large number of conditions. Available economic evaluations assume the perspective of private/commercial payers. However, the decision to reimburse ECS in a tax-based national healthcare system would benefit from a cost-effectiveness analysis from the perspective of the public payer. Study design, size, duration: This cost-effectiveness decision model com pared lifetime costs and effects of two preconception ECS panels (i.e., “Strategy A1” (testing Cystic Fibrosis, Spinal-Muscular-Atrophy, Beta Thalassemia, Phenylketonuria and Fragile-X-Syndrome) and “Strategy A2” (testing “Strategy A1” þ 16 common severe highly-penetrant childhood con ditions in the Mediterranean population)) with no screening (“Strategy B”). We embraced the perspective of the Italian National Healthcare System. The time horizon for each condition equals an affected child’s life expectancy. Participants/materials, setting, methods: We included couples seeking pregnancy without personal/familiar or racial/ethnic genetic risk. The cost-ef fectiveness analysis was based on a decision tree model where: i) the ECS panels sensitivity was 100%; ii) the probability for at risk couples (ARCs) to be risk-adverse was 77% based on data available from the literature; iii) all the forms of intervention that risk-adverse couples opted for lowered to zero the risk to conceive an affected child for the considered conditions. Main results and the role of chance: Unitary cost of e240 for Strategy A1 and of e270 for Strategy A2 for each couple were estimated through a market analysis simulating a public ECS provision. For risk-adverse couples, the cost of intervention was estimated as equal to e8,376. This resulted from the weighted mean of the cost of the different options available (i.e., in vitro fertilization (IVF) with preimplantation testing for monogenic disorders (PGT M) or, in case of natural conception, prenatal diagnosis and, eventually, termi nation of pregnancy). Strategy A1 was dominant versus no screening: Strategy A1 entailed savings equal to e1,395 and an incremental benefit of 0.0154 life years gained. Strategy A2 was dominant versus no screening: Strategy A2 entailed savings of e2,273 and an incremental benefit of 0.0238 life years gained. Strategy A2, when compared with Strategy A1, entailed an incremen tal cost of e649 and higher health benefits (0.7688 life years gained) (incre mental cost-effectiveness ratio (ICER): e844). Limitations, reasons for caution: This decision analytic model relies on in put parameters on costs and life expectancy associated to each Mendelian disease derived from the literature. However, the feasibility to generate ex perimental evidence to inform this type of studies is very limited. The cost-ef fectiveness profiles established are valid under the assumptions listed. Wider implications of the findings: Cost-effectiveness analyses like the one performed are useful policy tools to inform decisions regarding precon ception screening programs for detectable severe recessive highly penetrant early-onset genetic conditions. Trial registration number: not applicable