Original Research9 May 2023
A Cost-Effectiveness Analysis
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    Visual Abstract. Population Genomic Screening for Three Common Hereditary Conditions

    The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention Tier 1 genomic conditions is unknown. This study estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome, hereditary breast and ovarian cancer syndrome, and familial hypercholesterolemia.

    Abstract

    Background:

    The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.

    Objective:

    To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).

    Design:

    Decision analytic Markov model.

    Data Sources:

    Published literature.

    Target Population:

    Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.

    Time Horizon:

    Lifetime.

    Perspective:

    U.S. health care payer.

    Intervention:

    Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.

    Outcome Measures:

    Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.

    Results of Base-Case Analysis:

    Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).

    Results of Sensitivity Analysis:

    Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.

    Limitations:

    Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.

    Conclusion:

    Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.

    Primary Funding Source:

    National Human Genome Research Institute.

    References