Health economic evaluation of screening and treating children with familial hypercholesterolemia early in life: Many happy returns on investment?


      • The cost-effectiveness of screening children for familial hypercholesterolemia (FH) and treatment is unknown.
      • A Markov model was developed to simulate the lifetime progression of ten-year-olds.
      • Cascade screening children for FH and treating are likely to be cost saving.


      Background and aims

      There are no studies that have specifically investigated the cost-effectiveness of cascade screening of children for heterozygous familial hypercholesterolemia (FH) and treatment of affected individuals with statins to prevent coronary heart disease (CHD). This study explores the cost-effectiveness of this strategy from the perspective of the Australian public healthcare system.


      A lifetime Markov model with four health states (Alive without CHD, Alive with CHD, Dead from fatal CHD, and Dead from other causes) was developed to simulate the progression of ten-year-old children screened for FH and treated immediately with statins if found to have FH. The underlying prevalence of FH in this target population was assumed to be 56.8%, and the sensitivity and specificity of testing were 100%. The comparator was usual care, which assumed that subjects started statins spontaneously at a later point or when they experienced a cardiovascular event. The effect of reducing low-density lipoprotein cholesterol (LDL-C) on the risk of a first event at each age assumed that risk was proportional to total lifetime exposure and was implemented using Mendelian randomisation analysis data. Cost and other outcome data were sourced from published sources. Outcome of interests were costs in Australian dollars (AUD), life years gained (LYG) and quality-adjusted life years (QALYs) gained, as well as incremental cost-effectiveness ratios (ICERs) of costs per LYG and per QALY gained. All future costs and outcomes were discounted by 5% annually.


      Undiscounted results showed that compared with usual care, cascade screening of ten year-old children for FH and initiation of treatment of affected individuals saved 7.77 LYG and 7.53 QALYs per person over a lifetime. With 5% annual discounting, there were 0.97 LYG and 1.07 QALYs gained per person, at net reduction cost of -$1134. The cascade screening of ten-year-old children for FH and initiation of treatment compared to usual case was a cost saving approach. In 51.2% of iterations, screening and initiation with statin were cost saving and in 48.8% of iterations were cost-effective. In most of the one-way sensitivity and scenario analyses, the ICER stayed within the accepted Australian threshold.


      Compared to usual care, cascade screening of ten-year-old children for FH and treating affected individuals are likely to be cost saving.

      Graphical abstract


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        • Watts G.F.
        • Shaw J.E.
        • Pang J.
        • Magliano D.J.
        • Jennings G.L.R.
        • Carrington M.J.
        Prevalence and treatment of familial hypercholesterolemia in Australian communities.
        Int. J. Cardiol. 2015; 185: 69-71
        • Pang J.
        • Martin A.C.
        • Mori T.A.
        • Beilin L.J.
        • Watts G.F.
        Prevalence of familial hypercholesterolaemia in adolescents: potential value of universal screening?.
        J. Pediatr. 2016; 170: 315-316
        • Watts G.F.
        • Gidding S.
        • Wierzbicki A.S.
        • et al.
        Integrated guidance on the care of familial hypercholesterolaemia from the international FH foundation.
        Int. J. Cardiol. 2014; 171: 309-325
        • Wiegman A.
        • Gidding S.S.
        • Watts G.F.
        • et al.
        Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.
        Eur. Heart J. 2015; 36: 2425-2437
        • Norman R.
        • Watts G.F.
        • Weintraub W.
        • Gidding S.S.
        Challenges in the health economics of familial hypercholesterolemia.
        Curr. Opin. Lipidol. 2016; 27: 563-569
        • Ademi Z.
        • Watts G.F.
        • Juniper A.
        • Liew D.
        A systematic review of economic evaluations of the detection and treatment of familial hypercholesterolemia.
        Int. J. Cardiol. 2013; 167: 2391-2396
        • Ference B.A.
        • Yoo W.
        • Alesh I.
        • et al.
        Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart DiseaseA mendelian randomization analysis.
        J. Am. Coll. Cardiol. 2012; 60: 2631-2639
        • Health Do
        Guidelines for Preparing Submissions to the Pharmaceutical Benefits Advisory Committee (PBAC).
        2016 (Australia)
        • Pang J.
        • Martin A.C.
        • Bates T.R.
        • et al.
        Parent-child genetic testing for familial hypercholesterolaemia in an Australian context.
        J. Paediatr. Child Health. 2018; 54: 741-747
        • Luirink I.K.
        • Wiegman A.
        • Kusters D.M.
        • et al.
        20-Year follow-up of statins in children with familial hypercholesterolemia.
        N. Engl. J. Med. 2019; 381: 1547-1556
        • Briffa T.G.
        • Hobbs M.S.
        • Tonkin A.
        • et al.
        Population trends of recurrent coronary heart disease event rates remain high.
        Circ.Cardiovasc. Qual. Outcomes. 2011; 4: 107-113
        • Humphries S.E.
        • Cooper J.A.
        • Seed M.
        • et al.
        Coronary heart disease mortality in treated familial hypercholesterolaemia: update of the UK Simon Broome FH register.
        Atherosclerosis. 2018; 274: 41-46
        • Australian Institute of Health and Welfare AIoHa
        General Record of Incidence of Mortality.
        GRIM) books, Canberra, Australia2018
        • Braamskamp M.J.
        • Kusters D.M.
        • Avis H.J.
        • et al.
        Long-term statin treatment in children with familial hypercholesterolemia: more insight into tolerability and adherence.
        Paediatric drugs. 2015; 17: 159-166
      1. Pharmaceutical benfit Scheme.
        (Available through)
        • Ademi Z.
        • Watts G.F.
        • Pang J.
        • et al.
        Cascade screening based on genetic testing is cost-effective: evidence for the implementation of models of care for familial hypercholesterolemia.
        J. Clin. Lipidol. 2014; 8: 390-400
        • Independent Hospital Pricing Authority
        The national hospital cost data collection, public hospitals cost report, round 20 (financial year 2015-16).
        • Cobiac L.J.
        • Magnus A.
        • Barendregt J.J.
        • Carter R.
        • Vos T.
        Improving the cost-effectiveness of cardiovascular disease prevention in Australia: a modelling study.
        BMC Publ. Health. 2012; 12: 398
        • Australian Institute of Health and Welfare
        Table E2: total health price index and industry-wide indexes.
        • McCaffrey N.
        • Kaambwa B.
        • Currow D.C.
        • Ratcliffe J.
        Health-related quality of life measured using the EQ-5D-5L: south Australian population norms.
        Health Qual. Life Outcome. 2016; 14: 133
        • Matza L.S.
        • Stewart K.D.
        • Gandra S.R.
        • et al.
        Acute and chronic impact of cardiovascular events on health state utilities.
        BMC Health Serv. Res. 2015; 15: 173
        • Edney L.C.
        • Haji Ali Afzali H.
        • Cheng T.C.
        • Karnon J.
        Estimating the reference incremental cost-effectiveness ratio for the Australian health system.
        Pharmacoeconomics. 2018; 36: 239-252
        • Bogsrud M.P.
        • Graesdal A.
        • Johansen D.
        • et al.
        LDL-cholesterol goal achievement, cardiovascular disease, and attributed risk of Lp(a) in a large cohort of predominantly genetically verified familial hypercholesterolemia.
        J. Clin. Lipidol. 2019; 13: 279-286
        • Lazaro P.
        • Perez de Isla L.
        • Watts G.F.
        • et al.
        Cost-effectiveness of a cascade screening program for the early detection of familial hypercholesterolemia.
        J. Clin. Lipidol. 2017; 11: 260-271
        • Kerr M.
        • Pears R.
        • Miedzybrodzka Z.
        • et al.
        Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK.
        Eur. Heart J. 2017; 38: 1832-1839
        • Pelczarska A.
        • Jakubczyk M.
        • Jakubiak-Lasocka J.
        • et al.
        The cost-effectiveness of screening strategies for familial hypercholesterolaemia in Poland.
        Atherosclerosis. 2018; 270: 132-138
        • Chen C.X.
        • Hay J.W.
        Cost-effectiveness analysis of alternative screening and treatment strategies for heterozygous familial hypercholesterolemia in the United States.
        Int. J. Cardiol. 2015; 181: 417-424
        • McKay A.J.
        • Hogan H.
        • Humphries S.E.
        • Marks D.
        • Ray K.K.
        • Miners A.
        Universal screening at age 1-2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: a cost-utility analysis.
        Atherosclerosis. 2018; 275: 434-443
        • Ference B.A.
        • Cannon C.P.
        • Landmesser U.
        • Luscher T.F.
        • Catapano A.L.
        • Ray K.K.
        Reduction of low density lipoprotein-cholesterol and cardiovascular events with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an analysis of FOURIER, SPIRE, and the Cholesterol Treatment Trialists Collaboration.
        Eur. Heart J. 2018; 39: 2540-2545
        • Bogsrud M.P.
        • Langslet G.
        • Wium C.
        • Johansen D.
        • Svilaas A.
        • Holven K.B.
        Treatment goal attainment in children with familial hypercholesterolemia: a cohort study of 302 children in Norway.
        J. Clin. Lipidol. 2018; 12: 375-382
        • Zomer E.
        • Si S.
        • Hird T.R.
        • et al.
        Cost-effectiveness of low-dose rivaroxaban and aspirin versus aspirin alone in people with peripheral or carotid artery disease: an Australian healthcare perspective.
        Eur. J. Prevent. Cardiol. 2019; 26: 858-868
        • Russell L.B.
        Is Prevention Better than Cure?.
        Brookings Institution, 1986: 134
      2. Guidelines for preparing submissions to the pharmaceutical benefits advisory committee (PBAC).
        (Version 5.0 September 2016. Available through)
        • Hendricks-Sturrup R.M.
        • Mazor K.M.
        • Sturm A.C.
        • Lu C.Y.
        Barriers and facilitators to genetic testing for familial hypercholesterolemia in the United States: a review.
        J. Personalized Med. 2019; 9: 32