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Valcárcel-Nazco et al. Rare Dis Orphan Drugs J 2023;2:19 https://dx.doi.org/10.20517/rdodj.2023.14 Page 5 of 11

NBS’s impact on health service utilization and health outcomes might be lifelong. However, the effect of
screening on early identification of conditions is mainly based on extrapolated short-term outcomes and
data quantification in adulthood is inadequate. Consequently, CEAs are restricted to short timeframes based
on the available information or, alternatively, incorporate an appropriate time horizon relying on
assumptions. Specific aspects such as incidence, prevalence and costs are likely to be different between
countries, not only for NBS itself, but also for all subsequent treatment and follow-up activities. Therefore,
the transferability to different contexts of CEAs on NBS is limited and requires review, revision, and
[44]
adaptation on the basis of local data .
Since 2006, an HTA perspective, including CEA, has been required by the Spanish Ministry of Health for
[39]
decision-making on the potential extension of the national NBS programme (available from ).
Unfortunately, as epidemiological, clinical, and economic data relating to NBS are in short supply and
unreliable, CEA studies are limited. From 2006 to 2022, RedETS provided evidence of the effectiveness and
cost-effectiveness of an expanded NBS programme at the national level. RedETS drew up CEAs comparing
costs and outcomes for 16 different disorders from both societal and national health system perspectives.
The first CEA report carried out in 2006 determined the cost-effectiveness of MS/MS to screen PKU and
medium chain 3-hydroxyacyl-CoA dehydrogenase deficiency (MCADD) in Spain, with an incremental
[22]
cost-effectiveness ratio (ICER) below €6000/LY . Following this report, RedETS estimated the ICER of
adding five new disorders to the NBS national programme (based on MS/MS for PKU and MCADD):
homocystinuria, long chain 3-hydroxyacyl- CoA dehydrogenase deficiency (LCHADD), maple syrup urine
disease, isovaleric acidaemia and glutaric aciduria type 1 (GA-I) . The incorporation of this set of diseases
[44]
yielded an ICER of €28,000/LY approximately. Subsequently, other reports were prepared in which the cost-
effectiveness of neonatal screening for different diseases, not all of which subject to MS/MS, was estimated:
sickle cell disease, cystic fibrosis, biotinidase deficiency, congenital adrenal hyperplasia, galactosaemia,
methylmalonic and propionic acidaemia, tyrosinaemia type I, primary carnitine deficiency (CUD), very
long-chain acyl-CoA dehydrogenase deficiency (VLCAD), and severe combined immunodeficiency (SCID)
[39]
(available from ). It should be noted that the results of these reports showed that adding propionic and
methylmalonic acidaemia, VLCAD, and CUD to the national NBS programme is a cost-effective alternative
in Spain (ICER: €21,405/QALY, €10,723/LY and €14,217/LY, respectively). In sharp contrast, the ICER for
tyrosinaemia type 1 was €30,034/QALY. In addition, other diseases whose screening was shown to be a cost-
effective technology were biotinidase, congenital adrenal hyperplasia, or cystic fibrosis (all of them yielded
ICERs of below €30,000/LY). Finally, sickle cell disease screening would be cost-effective if the cost per
newborn screened did not exceed €2.5 and SCID screening would be below the Spanish cost-effectiveness
[39]
[43]
threshold of €25,000 per QALY as long as the cost of the screening test does not exceed €4 per newborn .
From the evidence generated in this set of HTA reports, a set of seven disorders were included in the
national NBS programme in 2014 (hypothyroidism, PKU, cystic fibrosis, sickle cell disease, MCADD,
[44]
LCHADD, and GA-I ) and four additional diseases were added in 2022 (biotinidase deficiency, maple
syrup urine disease, homocystinuria, and congenital adrenal hyperplasia ). The Spanish NBS programme
[39]
could be expanded in the near future, depending upon new scientific evidence, the development of new
detection biomarkers, enhanced knowledge of the natural history, and new therapies that may possibly
emerge for the respective disorders.

STAKEHOLDER PARTICIPATION TO SUPPORT DECISION-MAKING ON NEWBORN
SCREENING IN SPAIN
Beyond cost-effectiveness, several other previously mentioned factors influence policy-making in NBS.
Differences in the interpretation and management of uncertainties in these factors might explain observed