Population Genomic Screening for Three Common Hereditary Conditions

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.