Population Genomic Screening for Three Common Hereditary Conditions A Cost-Effectiveness Analysis

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 $100000-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.

Automated summary

The cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH) in the U.S. population is estimated using a decision analytic Markov model. Results show that screening individuals younger than 40 years can reduce cancer and cardiovascular disease incidence, improve quality-adjusted survival, but at a relatively high cost.