• Gregory F Guzauskas, Shawn Garbett, Zilu Zhou, Jonathan S Schildcrout, John A Graves, Marc S Williams, Jing Hao, Laney K Jones, Scott J Spencer, Shangqing Jiang, David L Veenstra, and Josh F Peterson.
• The CHOICE Institute, Department of Pharmacy, University of Washington, Seattle, Washington (G.F.G., S.J.).
• Ann. Intern. Med. 2023 May 1; 176 (5): 585595585-595.

BackgroundThe cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.ObjectiveTo estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).DesignDecision analytic Markov model.Data SourcesPublished literature.Target PopulationSeparate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.Time HorizonLifetime.PerspectiveU.S. health care payer.InterventionPopulation 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 MeasuresIncident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.Results Of Base Case AnalysisScreening 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 AnalysisScreening 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.LimitationsPopulation averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.ConclusionPopulation 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 SourceNational Human Genome Research Institute.

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