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

Area of Science:

• Genomic Medicine
• Health Economics
• Preventive Cardiology

Background:

• The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions remains unknown.
• CDC Tier 1 conditions include Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).

Purpose of the Study:

• To estimate the cost-effectiveness of simultaneous genomic screening for LS, HBOC, and FH.
• To evaluate the impact of screening on cancer and cardiovascular events, quality-adjusted survival, and healthcare costs.

Main Methods:

• A decision analytic Markov model was developed using published literature data.
• The model simulated simultaneous genomic screening for LS, HBOC, and FH in separate age-based cohorts of U.S. adults (ages 20-60).
• Interventions included clinical sequencing, cascade testing of first-degree relatives, and preventive interventions.

Main Results:

• Screening 100,000 30-year-olds reduced cancer and cardiovascular events, increasing quality-adjusted life-years (QALYs) by 495 at an incremental cost of $33.9 million, with an ICER of $68,600/QALY.
• Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of simulations, respectively, at a $100,000/QALY threshold.
• Key influential parameters included variant prevalence and adherence to preventive interventions.

Conclusions:

• Population genomic screening for 3 CDC Tier 1 conditions is likely cost-effective in U.S. adults younger than 40.
• Cost-effectiveness is contingent on relatively low testing costs and proband access to preventive interventions.
• Further research is needed to validate findings across diverse ancestries and healthcare environments.