Hereditary hemochromatosis screening: effect of mutation penetrance and prevalence on cost-effectiveness of testing algorithms

Authors

  • G Gagné,

    1. Center for the Development, Evaluation and Rational Implementation of New Diagnostic Tools in Medicine (CEDERINDT), Québec City
    2. Centre de Recherche Hôpital St-François d’Assise du Centre hospitalier universitaire de Québec
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  • D Reinharz,

    1. Center for the Development, Evaluation and Rational Implementation of New Diagnostic Tools in Medicine (CEDERINDT), Québec City
    2. Centre de Recherche Hôpital St-François d’Assise du Centre hospitalier universitaire de Québec
    3. Département de médecine sociale et préventive, Faculty of Medicine, Laval University, Québec City
    4. Direction régionale de santé publique de la capitale nationale, Québec City
    5. The CanGèneTest research consortium on genetic laboratory services (www.cangenetest.org)
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  • N Laflamme,

    1. Centre de Recherche Hôpital St-François d’Assise du Centre hospitalier universitaire de Québec
    2. The CanGèneTest research consortium on genetic laboratory services (www.cangenetest.org)
    3. Institut National de Santé Publique du Québec and
    4. Department of Medical Biology, Faculty of Medicine, Laval University, Québec City
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  • PC Adams,

    1. Department of Medicine, University Hospital, London, Ontario, and
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  • F Rousseau

    Corresponding author
    1. Center for the Development, Evaluation and Rational Implementation of New Diagnostic Tools in Medicine (CEDERINDT), Québec City
    2. Centre de Recherche Hôpital St-François d’Assise du Centre hospitalier universitaire de Québec
    3. The CanGèneTest research consortium on genetic laboratory services (www.cangenetest.org)
    4. Department of Medical Biology, Faculty of Medicine, Laval University, Québec City
    5. Unité de Recherche en génétique humaine et moléculaire, du CHUQ, Québec, Canada
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François Rousseau MD, FRCPC, Titular Professor, Department of Medical Biology, Faculty of Medicine, Unité de recherche en génétique humaine et moléculaire, Medical biochemistry and laboratory genetics Services, Centre hospitalier universitaire de Québec & Université Laval 10, rue de l’Espinay, Québec, Québec, Canada, G1L3L5.
Tel.: (418) 525-4470;
fax: (418) 525-4195;
e-mail: francois.rousseau@mac.com

Abstract

Screening for hereditary hemochromatosis, although largely discussed, is not yet implemented in clinical practice. We evaluated the cost-effectiveness of 165 hemochromatosis population-screening algorithms involving two or three of several screening tests by developing a computer program that simulates all possible screening scenarios. Input data comprised government estimates of health services data and costs and a virtual population with user-defined demographic characteristics (including variable HFE mutation frequencies and penetrance values). We show that when C282Y homozygote prevalence is set at 3:1000, population screening appears cost-effective when penetrance of the biochemical phenotype is >0.70. When only hepatocellular carcinoma and cirrhosis are considered as the cost-driving complications, population-based screening is not significantly more cost-efficient than no screening, but life expectancy of individuals identified with hereditary hemochromatosis and treated is still improved by 7 years. Among the 165 screening algorithms tested in 91 different virtual populations of one million individuals, biochemical tests usually perform better as the initial test than genetic testing. Indeed, the genetic testing is most cost-effective as the final confirmatory test. Finally, for most combinations of prevalence and penetrance of HFE, one screening algorithm – unbound iron-binding capacity + transferrin saturation – appeared robust enough to be always within the top 5 most cost-effective strategies.

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