Cost-Effectiveness of Newborn Screening for Spinal Muscular Atrophy in The Netherlands

Objectives: Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and paralysis. In its most common and severe form, the majority of untreated infants die before 2 years of age. Early detection and treatment, ideally before symptom onset, maximize survival and achievement of age-appropriate motor milestones, with potentially substantial impact on health-related quality of life. Therefore, SMA is an ideal candidate for inclusion in newborn screening (NBS) programs. We evaluated the cost-effectiveness of including SMA in the NBS program in The Netherlands. Methods: We developed a cost-utility model to estimate lifetime health effects and costs of NBS for SMA and subsequent treatment versus a treatment pathway without NBS (ie, diagnosis and treatment after presentation with overt symptoms). Model inputs were based on literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess model robustness and validity of results. Results: After detection of SMA by NBS in 17 patients, the number of quality-adjusted life-years gained per annual birth cohort was estimated at 320 with NBS followed by treatment compared with treatment after clinical SMA diagnosis. Total healthcare costs, including screening, diagnostics, treatment, and other healthcare resource use, were estimated to be €12 014 949 lower for patients identified by NBS. Conclusions: NBS for early identification and treatment of SMA versus later symptomatic treatment after clinical diagnosis improves health outcomes and is less costly and, therefore, is a cost-effective use of resources. Results were robust in sensitivity and scenario analyses

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems

Rare diseases' genetic newborn screening as the gateway to future genomic medicine: the Screen4Care EU-IMI project

Following the reverse genetics strategy developed in the 1980s to pioneer the identification of disease genes, genome(s) sequencing has opened the era of genomics medicine. The human genome project has led to an innumerable series of applications of omics sciences on global health, from which rare diseases (RDs) have greatly benefited. This has propelled the scientific community towards major breakthroughs in disease genes discovery, in technical innovations in bioinformatics, and in the development of patients' data registries and omics repositories where sequencing data are stored. Rare diseases were the first diseases where nucleic acid-based therapies have been applied. Gene therapy, molecular therapy using RNA constructs, and medicines modulating transcription or translation mechanisms have been developed for RD patients and started a new era of medical science breakthroughs. These achievements together with optimization of highly scalable next generation sequencing strategies now allow movement towards genetic newborn screening. Its applications in human health will be challenging, while expected to positively impact the RD diagnostic journey. Genetic newborn screening brings many complexities to be solved, technical, strategic, ethical, and legal, which the RD community is committed to address. Genetic newborn screening initiatives are therefore blossoming worldwide, and the EU-IMI framework has funded the project Screen4Care. This large Consortium will apply a dual genetic and digital strategy to design a comprehensive genetic newborn screening framework to be possibly translated into the future health care