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. 2022 Sep-Oct;16(5):667-675.
doi: 10.1016/j.jacl.2022.07.014. Epub 2022 Jul 30.

Cost-effectiveness of population-wide genomic screening for familial hypercholesterolemia in the United States

Scott J Spencer  1 , Laney K Jones  2 , Gregory F Guzauskas  3 , Jing Hao  4 , Marc S Williams  5 , Josh F Peterson  6 , David L Veenstra  7
Affiliations

Cost-effectiveness of population-wide genomic screening for familial hypercholesterolemia in the United States

Scott J Spencer et al. J Clin Lipidol. 2022 Sep-Oct.

Abstract

Background: Population genomic screening for familial hypercholesterolemia (FH) in unselected individuals can prevent premature cardiovascular disease.

Objective: To estimate the clinical and economic outcomes of population-wide FH genomic screening versus no genomic screening.

Methods: We developed a decision tree plus 10-state Markov model evaluating the identification of patients with an FH variant, statin treatment status, LDL-C levels, MI, and stroke to compare the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness of population-wide FH genomic screening. FH variant prevalence (0.4%) was estimated from the Geisinger MyCode Community Health Initiative (MyCode). Genomic test costs were assumed to be $200. Age and sex-based estimates of MI, recurrent MI, stroke, and recurrent stroke were obtained from Framingham risk equations. Additional outcomes independently associated with FH variants were derived from a retrospective analysis of 26,025 participants screened for FH. Sensitivity and threshold analyses were conducted to evaluate model assumptions and uncertainty.

Results: FH screening was most effective at younger ages; screening unselected 20-year-olds lead to 111 QALYs gained per 100,000 individuals screened at an incremental cost of $20 M. The incremental cost-effectiveness ratio (ICER) for 20-year-olds was $181,000 per QALY, and there was a 38% probability of cost-effectiveness at a $100,000 per QALY willingness-to-pay threshold. If genomic testing cost falls to $100, the ICER would be $91,000 per QALY.

Conclusion: Population FH screening is not cost-effective at current willingness to pay thresholds. However, reducing test costs, testing at younger ages, or including FH within broader multiplex screening panels may improve clinical and economic value.

Keywords: Cost-effectiveness analysis; Cost-utility analysis; Familial hypercholesterolemia; Genomic screening; Population screening.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflicts of interest. The funders did not have a role in the design of the study, in the collection, analysis, or interpretation of data, in the manuscript writing, or in the decision to publish results.

Figures

Figure 1.
Figure 1.
Model Schematic
Figure 2:
Figure 2:
One Way Sensitivity Analysis for 20-year-olds and 35-year-olds
Figure 3:
Figure 3:
Base Case Results by Age of Genomic Screening
See this image and copyright information in PMC

References

    1. Khera AV, Won H-H, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. Journal of the American College of Cardiology. 2016;67(22):2578–2589. - PMC - PubMed
    1. Benn M, Watts GF, Tybjærg-Hansen A, Nordestgaard BG. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. European heart journal. 2016;37(17):1384–1394. - PubMed
    1. Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype–phenotype relationship, and clinical outcome. European heart journal. 2015;36(9):560–565. - PubMed
    1. Henderson R, O’Kane M, McGilligan V, Watterson S. The genetics and screening of familial hypercholesterolaemia. Journal of biomedical science. 2016;23(1):1–12. - PMC - PubMed
    1. Sturm AC, Knowles JW, Gidding SS, et al. Clinical genetic testing for familial hypercholesterolemia: JACC scientific expert panel. Journal of the American College of Cardiology. 2018;72(6):662–680. - PubMed

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