Original Title: Coste-efectividad del cribado neonatal de la atrofia muscular espinal y la inmunodeficiencia combinada grave

Authors' objectives: MAIN OBJECTIVE: • To evaluate the efficiency of joint neonatal screening for SMA and SCID in the population. SECONDARY OBJECTIVES: • To analyze the cost-effectiveness of the SMA neonatal screening program, based on published studies. • To analyze the cost-effectiveness of the SMA and SCID neonatal screening program, based on published studies. • To analyze the cost-effectiveness of joint neonatal screening for SMA and SCID from the perspective of the Spanish NHS. • To estimate the budgetary impact that the incorporation of these two diseases jointly into the neonatal screening program would have on the Spanish NHS.

Authors' results and conclusions: RESULTS: SYSTEMATIC REVIEW OF COST-EFFECTIVENESS STUDIES The search identified and included seven economic evaluations that addressed neonatal screening for SMA and one that addressed combined neonatal screening for SMA and SCID. All included studies were model-based economic evaluations, with three of them funded by manufacturers of disease-modifying therapies. The healthcare system perspective was the most common, although there were also two studies reporting results from a societal perspective. Studies that addressed neonatal screening for SMA generally showed heterogeneity in terms of the SMA genotype in the screened cohort, the health states considered, and the treatments adopted for the disease. In this regard, the treatment strategy had a considerable influence on the results obtained for the ICER. The identified studies also showed limitations regarding the evidence of long-term treatment efficacy. Among the studies reporting results in terms of cost per QALY gained, three European studies, funded by the manufacturers of the treatments, obtained a dominance result (cost savings and greater effect) of screening versus no screening. Another European study obtained an ICER below the threshold or dominance in favor of screening for the base case and for most of the scenarios analyzed except one (equal treatment distribution between alternatives and health system perspective). In a study conducted in the USA, in which only patients were treated with nusinersen, markedly high ICERs were obtained, above €150,000/QALY. In a study carried out in Australia, the ICER varied between non-cost-effective and cost-saving depending on the treatment strategy. When screening was compared with no screening, treatment in both cases with nusinersen, an ICER of over €350,000/QALY was obtained. Cost savings were found when screening and treatment with OA was compared to not screening and treatment with nusinersen. The only identified study addressing co-screening for SMA and SCID is of acceptable quality and was conducted in Australia from the payer perspective (the Australian government), with a time horizon of 5 and 60 years. The SMA part of the model was based on the authors' previously published model, which is included in this systematic review of economic evaluations. The major limitation, acknowledged by the authors in the discussion, is the lack of scientific evidence on the long-term effect of SMA treatments, having to assume that the short-term effect found so far is maintained in the long term. For a 5-year time horizon, the result is not cost-effective with an ICER (expressed in 2022 euros) of €338,800/QALY, but with high uncertainty reflected in a confidence interval ranging from a dominance situation to a very high ratio of €651,342/QALY. For a 60-year time horizon, screening is dominant, with a confidence interval between dominance and €31,967/QALY. The parameters that most affect the results are the incidence of the two diseases and the cost of SMA treatment. The transferability analysis performed for the abovementioned Australian study indicates that the conclusions of its economic evaluation cannot be considered directly transferable to the Spanish context. This is due to the uncertainty related to one of the key factors, the relative costs and prices presented in the model and the corresponding ones in Spain. In particular, the costs by type of SMA and by health status associated with SCID, as incorporated in the model, are not available for Spain, which would require the use of foreign data, introducing uncertainty in the cost-effectiveness results thus obtained. COST-EFFECTIVENESS ANALYSIS AND BUDGETARY IMPACT Both the results of the economic evaluation of newborn screening for SMA and SCID (separately) show that screening is more costly and more effective than not screening, in terms of LYG and QALY. The estimated ICERs are €50,540/QALY for SMA and €29,210/QALY for SCID, both being above the cost-effectiveness threshold of €25,000/QALY. The results of the deterministic sensitivity analysis suggest that if we assume a discount rate for the effects of 1.5%, a value recommended by some authors/institutions to discount future benefits in public health interventions, the ICER comparing screening for SCID versus not screening for SCID would be below the willingness to pay threshold of €25,000/QALY. The ICER for joint neonatal screening for SMA and SCID remains above the threshold with a value of €42,938/QALY. It should be noted that the result presented for SMA, and used in the analysis of joint screening, corresponds to what we call the ‘reference case’, which is the most favorable to screening among the most realistic scenarios of all those analyzed for this disease. The sensitivity analysis shows that the cost of the screening kit has little effect on the ICER, affecting the cost of SMA treatments to a greater extent, although most of the results remain above the cost-effectiveness threshold. Among the main limitations of the cost-effectiveness analysis carried out are the following: the different possible treatment strategies with some of the drugs approved for SMA; the use of clinical effectiveness measures based on different outcome measures reported in the trials for each SMA treatment; the uncertainty about the long-term effect of SMA treatments; the uncertainty about the costs associated with the two diseases; and the different structure of the SMA and SCID models that could condition the aggregate results of both. The budgetary impact analysis, which shares some of the limitations of the cost-effectiveness analysis, shows that the net cost after five years per newborn is estimated at €17.33, which is equivalent to €28.5 million for all newborns born in Spain in that period. CONCLUSIONS: • The evidence available in the scientific literature for neonatal screening for SMA shows a wide variability of results (from non-cost-effective to dominant) depending on the treatment strategy considered and the cost of the available treatments. Other parameters that introduce uncertainty in the estimated ICERs are the incidence of SMA and the values considered for the utilities of the different health states. • The only economic evaluation identified in the literature for joint neonatal screening for SMA and SCID shows a result of non-cost-effectiveness in the short term and dominance in the long term, although this study has limitations regarding the effect of SMA treatments in the long term and the costs associated with the two diseases. • The economic evaluation performed for Spain, comparing joint neonatal screening for SMA and SCID with the alternative of not screening, resulted in an ICER (€42,938/QALY) higher than the threshold of €25,000/QALY, from the perspective of the Spanish NHS. This result is consistent in the vast majority of deterministic sensitivity analyses performed. However, the limitations of the analysis performed are diverse, based primarily on data availability, and could condition this result. The main factors affecting the results are the use and price of SMA disease-modifying drugs and the applied discount rate. • If differentiated discount rates were applied for costs (3%) and effects (1.5%) and if a cost-effectiveness threshold higher than that estimated for Spain (€25,000/QALY) were used as a decision-making criterion because it is a rare disease, then joint neonatal screening for SMA and SCID could be considered cost-effective, although at present the Spanish guidelines do not make a clear recommendation on the modification of these parameters. • It is estimated that the introduction of joint neonatal screening for SMA and SCID would have a net budgetary impact over five years of at least 28.5 million euros for the Spanish NHS, with a greater contribution to the total cost from treatment with SMA disease-modifying drugs.

Authors' methods: SYSTEMATIC REVIEW OF COST-EFFECTIVENESS STUDIES The systematic review of cost-effectiveness studies was based on the adaptation and update of the systematic review conducted by the Irish Health Technology Assessment Agency (HIQA) on newborn screening for SMA. In January 2023, they performed a search in MEDLINE, Embase and the Cochrane Library, complemented by a search of gray literature. Our search update was conducted between January 2023 and July 2024 using the same search strategy, but with the addition of the Cost-Effectiveness Analysis Registry database. Two reviewers independently selected the studies. Completed economic evaluations were selected that compared population-based screening for SMA or combined screening for SMA and SCID versus no screening in newborns. To be included, outcome measures had to be the incremental cost-effectiveness ratio (ICER) or the costs and effectiveness of the alternatives in comparison. The methodological quality of the included studies was assessed using the CHEC questionnaire. To analyze the transferability of the only identified economic evaluation of joint screening for SMA and SCID, the tool of Welte et al. was used, and its methodological quality was assessed using the 10 criteria of Drummond et al. ECONOMIC EVALUATION A complete economic evaluation was carried out, evaluating the costs and health outcomes of joint neonatal screening for SMA and SCID versus no screening. To do this, the results of two mathematical decision models were merged for each of the two diseases separately, based on common characteristics defined for both models. A de novo model consisting of a decision tree and a Markov model was designed for the modelling of neonatal screening for SMA. In the absence of a single base case, different scenarios were analyzed based on different treatment strategies and duration of treatment effectiveness. For SCID, the results of a previous model for Spain carried out by SESCS-RedETS were updated, which in turn was an adaptation of the model provided by Dr Chilcott of the University of Sheffield. The study population corresponds to all newborns born in Spain in a year. The main time horizon, common to both diseases, was the patient's entire life (maximum 100 years), but other time horizons were tested (2, 5 and 60 years). A 3% discount rate was applied to both costs and effects. The analysis was performed from the perspective of the Spanish National Health System (NHS), where only direct healthcare costs were included and were expressed in 2022 euros. The outcome measures were life years gained (LYG) and quality-adjusted life years (QALY). The results were combined using the ICER, which was compared with the cost-effectiveness threshold estimated for Spain by Vallejo et al. between €20,000 and €25,000/QALY. For the analysis of joint screening for SMA and SCID, the results were merged into absolute values (costs and years of life gained, adjusted or not for quality of life) and not average values, and the common screening costs were taken into account to avoid duplicating costs. Deterministic sensitivity analyses were performed on the results of the most favourable scenario for neonatal screening for SMA. In addition, a five-year budget impact analysis was performed, which reports the cost that the incorporation of SMA and SCID into the national neonatal screening program in Spain would entail for the NHS.

Project Status: Ongoing

Anticipated Publish Date: 2024

URL for published report: https://sescs.es/coste-efectividad-cribado-neonatal-ame-idcg/

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