Original Title: Efectividad, seguridad y coste-efectividad del cribado neonatal de hipercolesterolemia familiar

Authors' objectives: The main objective of this Health Technology Assessment (HTA) report is to evaluate the safety, effectiveness, cost-effectiveness, and ethical, legal, organizational, social, and environmental aspects of neonatal FH screening. The findings will support the decision on whether to include this screening in the NHS common service portfolio.

Authors' results and conclusions: RESULTS --- EFFECTIVENESS AND SAFETY No studies meeting the predefined selection criteria were identified to assess the diagnostic performance, effectiveness, or safety of neonatal FH screening. COST-EFFECTIVENESS The systematic review found no published economic evaluations meeting the selection criteria. In the de novo economic evaluation, for a cohort of 300,000 newborns, the cost per person of FH neonatal screening was higher than no screening (€22.48 per person from the NHS perspective, €21.63 from the societal perspective). However, both QALYs and LYG were slightly higher with screening. The estimated ICERs suggest that including FH screening in the current neonatal screening program could be cost-effective, as it falls below the €25,000/QALY threshold. However, probabilistic sensitivity analysis revealed high uncertainty, with ICERs ranging from €12,633/QALY (cost-effective) to €154,239/QALY (not cost-effective). The budget impact analysis estimated that implementing FH neonatal screening would require an additional €12.99 million over the first five years, assuming 100% participation. The additional cost of reverse cascade screening for family members was estimated at €3.4 million. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL, AND ENVIRONMENTAL ASPECTS Six studies were included, showing strong acceptability of neonatal screening among families of FH patients. However, no studies assessed acceptability among the general population or healthcare professionals. Findings highlighted educational and informational needs for managing FH and notifying family members about cascade screening. Organizational challenges related to implementing this process in the NHS were not explored in detail and require further investigation. --- CONCLUSIONS --- Based on the SR on safety, effectiveness and cost-effectiveness, economic evaluation, budget impact analysis, and ethical and organizational assessments, the following conclusions were drawn regarding the inclusion of FH neonatal screening in Spain: • No scientific evidence was found on the diagnostic performance, effectiveness, or safety of neonatal FH screening. • No published economic evaluations met the predefined inclusion criteria for assessing cost-effectiveness. • The de novo economic evaluation suggests that FH neonatal screening would generate higher costs but also improved health benefits, potentially making it a cost-effective option from both NHS and societal perspectives. However, results are highly sensitive to small changes in test specificity. • Implementing FH screening would require an additional €12.99 million over five years for the NHS. • Reverse cascade screening for first-degree relatives of diagnosed newborns could cost an additional €3.4 million over five years. • No ethical, legal, organizational, social, or environmental barriers were identified. While neonatal screening is highly acceptable among affected families, its acceptability among the general population and healthcare professionals remains unknown. Educational and informational support for affected families would be essential.

Authors' methods: EFFECTIVENESS AND SAFETY A systematic review (SR) of the literature published up to July 2024 was conducted in databases such as MEDLINE, Embase, and CENTRAL. A comprehensive search strategy was developed, including controlled vocabulary and free-text terms. Additionally, manual searches of bibliographic references from included studies and citation tracking via Google Scholar were performed. An alert system was set up for new publications. Original studies published in English or Spanish that evaluated the effectiveness and safety of FH population screening were included. This included measuring lipid profiles (total cholesterol and LDL cholesterol) from dried blood samples taken from newborns' heels, followed by genetic confirmation. Comparisons included screening based on cardiovascular risk factors or FH screening at different life stages (childhood, adolescence, or adulthood). Randomized controlled trials (RCTs) were prioritized, but non-randomized trials and observational studies with control groups were also considered. If no such studies were found, an evaluation of the diagnostic accuracy of FH neonatal screening was conducted. Key outcomes included coronary disease-related mortality, changes in cardiovascular risk stratification, morbidity (premature coronary disease, cardiovascular events such as unstable angina, heart attacks, strokes, or peripheral artery disease), and health-related quality of life. In the absence of effectiveness data, diagnostic performance metrics such as sensitivity and specificity were assessed. Risk of bias was evaluated using RoB-2 for RCTs, ROBINS-I for non-randomized studies, and QUADAS-2 for diagnostic studies. A meta-analysis was planned using RevMan 5.4.1 if feasible. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. COST-EFFECTIVENESS A systematic review of economic evaluations of neonatal FH screening was conducted. Economic studies (both trial-based and model-based) were included if they reported incremental cost-effectiveness ratios (ICER), costs in monetary units, and benefits in terms of quality-adjusted life years (QALYs) or life-years gained (LYG). The methodological quality of studies was assessed using Drummond's checklist, and data were synthesized narratively with tabulated results. In addition, a full de novo economic evaluation was conducted comparing the costs and health outcomes of including FH diagnosis in newborns within the National Congenital Disorders Screening Program, previously known as the Neonatal Screening Program for Endocrine and Metabolic Diseases. The analysis used a decision tree combined with a Markov model with annual cycles and four health states: no cardiovascular event (CVE), CVE, post-CVE, and death. The primary perspective was that of the NHS, considering direct medical costs. A secondary societal perspective also included productivity losses due to disease. Costs were expressed in 2024 euros, and health outcomes were measured in QALYs and LYGs. A 3% annual discount rate was applied. ICERs were compared against Spain’s cost-effectiveness threshold of €22,000–€25,000 per QALY. A base-case analysis using expected parameter values was conducted, along with deterministic and probabilistic sensitivity analyses to assess model robustness. Additionally, a budget impact analysis estimated the financial burden of incorporating FH neonatal screening into the NHS. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL, AND ENVIRONMENTAL ASPECTS This assessment was based on the same population, intervention, and comparator as the effectiveness and cost-effectiveness evaluations. Manual searches were conducted using categories from HTA frameworks such as EUnetHTA’s Core Model 3.0, GRADE’s Evidence to Decision framework, and VALIDATE. Searches were performed in Google, Google Scholar, and PubMed, using terms related to ethics, acceptability, patient perspectives, implementation barriers, facilitators, and equity. A narrative review summarized finding, with study limitations assessed using CASPe (for qualitative studies), SANRA (for narrative reviews), and OSTEBA (for observational studies).

Project Status: Completed

Year Published: 2025

URL for published report: https://sescs.es/en/neonatal-screening-familial-hypercholesterolemia/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es