Cost-effectiveness and Return on Investment of a Nationwide Case-Finding Program for Familial Hypercholesterolemia in Children in the Netherlands

Abstract

ImportanceThe Netherlands is one of the few countries that has a long-term history of active screening for familial hypercholesterolemia (FH), enabling health-economic analyses.ObjectiveTo investigate cost-effectiveness and the return on investment (ROI) of a nationwide cascade case-finding and preventive treatment program starting with identification of FH in children and treatment, from both a societal and health care perspective.Design, Setting, and ParticipantsCascade case-finding and early preventive treatment were modeled to simulate the progression of disease and costs of 10-year-olds suspected of having heterozygous FH over a lifetime. The model consisted of 3 health states: alive without coronary heart disease (CHD), alive with CHD, and deceased. Mendelian randomization analysis was used to quantify the risk of a first CHD event as a function of age and total lifetime exposure to low-density lipoprotein cholesterol. Cost-effectiveness was defined as €20 000 ($21 800) per QALYs (quality-adjusted life-years) gained, using incremental cost-effectiveness ratios (ICERs). All future benefits and costs were discounted annually by 1.5% and 4%, respectively.InterventionsThe study compared 2 strategies: (1) cascade screening and initiation of treatment with statins in children (mean age, 10 years) and (2) no screening, later detection, and treatment.Main Outcomes and MeasuresOutcome of interest included cost, detection, and successful treatment of FH in terms of life-years gained and QALYs. The clinical and cost outputs for each model in the 2 scenarios (early detection and treatment and later detection and treatment) were totaled to determine the overall cost-effectiveness and ROI attributed to implementation of the Dutch FH program.ResultsIn this model constructed to simulate the progression of FH in 1000 hypothetical 10-year-olds, from a health care perspective, the program would gain 2.53 QALYs per person, at an additional cost of €23 365 ($25 468) (both discounted). These equated to an ICER of €9220 ($10 050) per QALY gained. From the societal perspective, the detection and treatment program were cost saving over a lifetime compared with no cascade screening for FH. The ROI for the detection and treatment program for FH in children was €8.37 ($9.12).Conclusions and RelevanceThe findings of this study suggest that the early detection and treatment program for FH in children may offer a good value for investment, being both health and cost saving. The findings and interpretations are conditional on assumptions inherent in the health economic model.

Synthesized Economic Evidence on the Cost-effectiveness of Screening Familial Hypercholesterolemia: A meta-analytic review and Aggregate Distributional Cost-Effectiveness Analysis

“…44 Similar studies were conducted in Australia and the Netherlands. Ademi et al 38,45 the economic aspects of cascade screening for 10-year-old children from the perspectives of the Australian public healthcare system and Dutch healthcare and society, respectively. Results consistently showed that cascade screening for 10-year-old children was cost-effective compared to standard care in both Australia and the Netherlands.…”

“…The meta-analysis excluded literature that did not provide specific cost or outcome values 33,39,44 and literature where strategies were not comparable. 31,32,35,42,43,46 The final synthesis of results included eight studies on cascade screening 30,34,37,38,40,41,45,47 and three studies on Universal Screening. 25,34,36 These studies considered outcome measures such as QALY, LYG, adverse events averted, and deaths averted, resulting in the eventual synthesis of seven distinct groups (Table 3).…”

“…Even more, we need to calculate the return on investment of FH screening from a broader perspective, as the Netherlands has done. 38 Secondly, the choice of models emerges as a critical consideration. While Markov models are widely applied, the utilization of composite models, combining decision tree models with other approaches, can more comprehensively address the actual complexities associated with FH screening.…”

Still “on the Fence” About Universal Childhood Lipid Screening

“…Economic evaluations can guide uptake at scale, particularly if they include implementation costs and long-term outcomes. There are some economic data on the use of genetic testing to identify FH in US adults, in children outside the US, and on cascade FH screening in adults, and there is 1 recent cost analysis of childhood universal vs targeted lipid screening for hyperlipidemia; however, there are no cost-effectiveness analyses of lipid-based screening for FH in children assessing downstream health outcomes. Cost-effectiveness of childhood lipid screening is likely to vary by disease targeted (primary vs secondary lipid disorders), disease prevalence in the population, and the cost of testing and follow-up.…”

USPSTF Recommendation on Screening for Lipid Disorders in Children and Adolescents

“…However, observational and genetic data show that lowering LDL-C concentrations reduces progression of subclinical ASCVD and prevents clinical events . Cholesterol screening is critical for early diagnosis of FH and, with clinical assessment and genetic testing, cost-effectively enables cascade testing of close relatives . The International Atherosclerosis Society recently published clinical and implementation guidance on the care of FH, advocating for use of integrated screening and testing methods for FH in adult and pediatric individuals .…”