The cost-effectiveness of genotyping versus sequencing for prenatal cystic fibrosis carrier screening

Objective: We investigated the cost-effectiveness of three sequential prenatal cystic fibrosis (CF) carrier screening strategies: genotyping both partners, genotyping one partner then sequencing the second, and sequencing both partners. Method: A decision-analytic model compared the strategies in a theoretical cohort of four million pregnant couples in the US population and five racial/ethnic sub-populations. Inputs were obtained from literature and varied in sensitivity analysis. Outcomes included cost per quality-adjusted life year (QALY), missed carrier couples, affected newborns, missed prenatal diagnoses, terminations, and procedure-related losses. The cost-effectiveness threshold was $100,000/QALY. Results: Sequencing both partners identified 1099 carrier couples that were missed by genotyping both partners, leading to 273 fewer missed prenatal diagnoses, 152 more terminations, and 152 fewer affected newborns. A similar trend was observed in the genotyping followed by sequencing strategy. The incremental cost-effectiveness ratio of genotyping followed by sequencing compared to genotyping both partners was $180,004/QALY and the incremental cost-effectiveness ratio of sequencing both partners compared to genotyping followed by sequencing was $17.6 million/QALY. Sequencing both partners was cost-effective below $339 per test, genotyping/sequencing between $340 and $1837, and genotyping both partners above $1838. Sequencing was not cost-effective among five racial/ethnic sub-populations. Conclusion: Despite improved outcomes, sequencing for prenatal CF carrier screening was not cost-effective compared to genotyping. The clinical significance of the incremental cost-effectiveness of CF carrier screening is a matter of deliberation for public policy debate.