Editorial
Screening for Familial Hypercholesterolemia in Children and its Cost-Effectiveness
2025 Volume 32 Issue 8 Pages 926-928
Details
2025 Volume 32 Issue 8 Pages 926-928
See article vol. 32: 962-981
In their report, Matsunaga et al. specifically estimated the cost-effectiveness of screening (universal screening＋reverse-cascade screening: RCS) for familial hypercholesterolemia (FH) in children of 9–10 years of age based on the “Kagawa model” with an incremental cost-effectiveness ratio (ICER) of JPY 150,000 ($1,042)/quality-adjusted life years (QALY)1). This value was below the willingness-to-pay threshold of JPY 5,000,000 ($34,722)/QALY for medical technology in Japan. These results are beneficial for the development of FH screening systems in Japan.
Two indicators are used to evaluate cost-effectiveness in healthcare: quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). The QALY is used as a preference-based measure for the outcome of health-care activities in health economic evaluative studies. It reflects both the quantity and the quality of life. One QALY is equal to 1 year of life in perfect health. The ICER is a way of investigating whether an intervention yields sufficient value to justify its cost. It is a measure that evaluates the additional cost to gain one QALY compared to existing treatments. The commonly cited cost-effectiveness thresholds are $50,000-100,000/QALY in the United States2), and £20,000–30,000/QALY in the United Kingdom by The National Institute for Health and Clinical Excellence (NICE).
An early diagnosis of FH in childhood is important for the following reasons. First, patients with FH have high serum low-density lipoprotein (LDL)-cholesterol levels from birth and reach the threshold for developing coronary artery disease (CAD) at an early age. Second, early treatment can prevent the development of CAD. Finally, after identifying a patient with FH, cascade screening can be used to identify other patients with FH in families who do not have CAD and treatment can be initiated accordingly. Nevertheless, an early diagnosis of FH in childhood is difficult. This is because children with FH, except homozygous FH, have no clinical findings, such as xanthomas and corneal rings. Moreover, a family history of FH may not be evident if parents have not reached the age at which CAD typically develops.
The introduction of FH screening in childhood may serve as a beneficial method for improving the low FH diagnostic rate and enabling early treatment. Screening for FH meets all 10 emerging screening criteria proposed over the past 40 years3) shown in Table 1. The optimal FH screening strategy varies depending on the characteristics of each country’s healthcare system (preventive programs for children, diagnostic test availability, healthcare level, and regulatory framework)4, 5). Two main screening strategies, universal screening and cascade screening, have been studied in many countries to detect FH in children and adolescents4, 5). Universal screening is a method in which all individuals who have reached a predetermined age undergo blood lipid testing (and possibly additional genetic testing), regardless of other risk factors. Cascade screening is a method used to identify individuals within a family who may be at risk of inheriting specific genetic conditions, and usually involves genetic testing.
| ・The screening program should respond to arecognized need. |
| ・The objectives of screening should be defined at the outset. |
| ・There should be a defined target population. |
| ・There should be scientific evidence of screening program effectiveness. |
| ・The program should integrate education, testing, clinical services and program management. |
| ・There should be quality assurance, with mechanisms to minimize potential risks of screening. |
| ・The program should ensure informed choice, confidentiality and respect for autonomy. |
| ・The program should promote equity and access to screening for the entire target population. |
| ・Program evaluation should be planned from the outset. |
| ・The overall benefits of screening should outweigh the harm. |
Various screening methods have been recommended for different age groups in childhood. The American Academy of Pediatrics recommends universal screening in children of 9–11 years of age and rescreening at 17–21 years of age6). In Slovenia, universal screening for FH is performed in 5-year-old children7). In the United Kingdom, it was performed in 1–2-year-old children during routine vaccination visits8) or in 2–6-year-old children during routine check-ups by the pediatrician9). The validity, feasibility, specificity, and cost-effectiveness of these approaches are currently under evaluation. In Japan, there are no national standardized guidelines for screening FH in childhood. Although some local governments measure serum cholesterol levels as a screening test for lifestyle-related diseases in 10-year-old children, its cost-effectiveness has yet to be determined.
In a systematic review of the cost-effectiveness of screening strategies for FH, 21 studies were identified, most of which concluded that any screening (cascade screening, opportunistic screening, systematic screening, and population-wide screening) for FH was more cost-effective than no screening10). Of the 21 studies in the review, six evaluated screening in children. The general characteristics and results of the six studies, as well as Matsunaga’s study1) are summarized in Table 2. All studies concluded that screening for FH in children is cost-effective10). The results of FH screening in 10-year-old children, the same age group as the participants in Matsunaga’s study, were reported in the Netherlands11) and Australia12). A report from the Netherlands, cascade case findings, and early preventive treatment were modeled to simulate the disease progression and costs of 10-year-old children suspected of having FH over their lifetime. This model was constructed to simulate the progression of FH in 1000 hypothetical 10-year-old children from a healthcare perspective. The results showed that the program would gain an ICER of €9,220 ($10,050)/QALY, and it was within the cost-effectiveness threshold of €20,000 ($21,800)/QALY calculated by this mode. The program resulted in lifetime cost savings compared with no cascade screening for FH11).
| Year | County | Age of the target children | Screening strategy | Ascertainment | Comparator | Study design | Cost effective? |
ICER (discounted) original costs /health gain |
|---|---|---|---|---|---|---|---|---|
| 2018 13) | UK | 1-2 years | US followed by cascade |
Cholesterol screening and genetic testing＋ RCT |
No US |
Decision tree ＋Markov |
Yes |
£12,480/QALY (＜£20,000/QALY threshold) |
| 2018 14) | Poland | 6 years | US | US based on genetic diagnosis | No screening |
Decision tree ＋Markov |
Yes |
ICUR/QALY: €4,555/QALY |
| 2020 12) | Australia |
10 years (＋1st degree relatives with FH) |
Cascade |
Cholesterol＋genetic testing at the same time |
No screening |
Decision tree ＋Markov |
Yes | Dominant＊ (cost saving) |
| 2022 15) | Australia | 1-2 years |
Opportunistic, followed by cascade |
Cholesterol screening and genetic testing |
Satandard of care |
Decision tree ＋Markov |
Yes | AU$3,979/QALY |
| 2023 16) | Argentina | 6 years | US followed by cascade | Cholesterol screening | Standard of care | Decision tree | Yes | $1,365/QALY |
| 2023 11) | The Netherlands | 10 years | Cascade | Genetic | No screening |
Decision tree ＋Markov |
Yes |
€9,220 ($10,050)/QALY (＜€20,000 ($21,800)/QALY threshold) |
| 2025 1) | Japan | 9-10 years | US＋RCS |
Cholesterol screening and genetic testing |
No screening |
Decision tree ＋Markov |
Yes |
US＋RCS: JPY 150,000 ($1,042) /QALYUS only: JPY 2,720,000 ($18,889) /QALY (＜JPY 5,000,000(($34,722) /QALY threshold) |
ICER: incrementalc ost-effectiveness ratio, QALY: quality adjusted life years, ICUR: incremental cost utility ratio, UK: United Kingdom, US: Universal screening, RCT: Reverse cascade testing, RCS: Reverse cascade screening. Reference numbers are indicated in brackets. ＊Dominant refers to an alternative screening or treatment option is both less costly and results in better health outcomes than the comparator screening or treatment.
Based on the results of these studies, including those of Matsunaga et al., screening for FH during childhood is cost-effective. Conversely, there are many issues regarding screening implementation according to the “Kagawa model” in many municipalities, including urban areas of Japan. Thus, cooperation between children’s parents, schools, medical institutions, and the government agencies is important.
None.
