Evaluation and implementation of genomic technologies in the Italian national healthcare service: current status, challenges, and future perspectives

This thesis addresses how genomic technologies can be responsibly and sustainably integrated into the Italian National Healthcare Service (NHS). Despite rapid advances in human and pathogen genomics and falling sequencing costs, implementation in publicly funded health systems remains patchy and uneven. This is because bringing genomics into everyday care means moving from scattered pilots to a coordinated programme that aligns governance, funding, service design, and evaluation. Italy is no exception: early national policies on public health genomics and omics have not translated into coordinated, well-resourced programmes, and regional autonomy further amplifies variability in capacity and access. At the same time, the evaluation of genomic applications is methodologically complex, as it must capture not only analytic and clinical performance, but also long, multi-step care pathways, non-health outcomes, and system-level impacts. The overall aim of the research was to support the integration of genomic technologies into the Italian NHS by (i) mapping the current stage of implementation at national level and (ii) addressing key challenges in their health technology assessment (HTA), with particular attention to economic evaluation, in order to propose a robust, standardized framework for decision-making. A combination of methods was adopted. First, a national self-assessment of genomic implementation was conducted using a structured maturity-level model and an expert consultation to describe strengths, gaps, and priority domains for action. Second, a series of evidence syntheses examined the evaluation of genomic technologies: an overview of methodological challenges in HTA, a systematic review of HTA reports on genetic and genomic applications, two systematic reviews of economic evaluations focusing on polygenic risk scores (PRS) and on genome/exome sequencing (GS/ES), and a comparative analysis of genomic-specific evaluation frameworks against the EUnetHTA HTA Core Model®, one of the most thorough and methodologically robust HTA frameworks. The mapping study showed that Italy is at an early stage of genomic implementation. Regulatory and legal foundations, particularly for data protection and consent, are relatively advanced, but are not matched by coherent governance, dedicated funding, or homogeneous infrastructure. Major gaps concern workforce genomic literacy across professional groups, citizen and patient engagement, data and computing infrastructure compliant with FAIR (i.e., Findability, Accessibility, Interoperability, and Reusability) principles, national guidance on sequencing and interpretation, and mechanisms to support multicentre research and data sharing. These findings point to the need for an updated national genomic strategy with explicit priorities, financing, and coordination across Regions. Across the HTA-focused components, recurring barriers were identified along all evaluative domains. Existing assessments often suffer from a lag between rapid technological innovation and slower evidence generation, a lack of standardized outcome sets and clearly defined care pathways, and incomplete evaluation of analytical and clinical validity, safety, organizational aspects, ethical legal-social implications, and equity. Personal and non-health outcomes, including “personal utility”, are rarely captured. Economic evaluations of PRS and ES/GS suggest that these technologies can be cost-effective in selected indications and under specific assumptions on test performance, uptake, costs, and downstream interventions, but are limited by heterogeneous methods, narrow perspectives, simplified delivery models, and incomplete consideration of indirect and long-term costs. Lastly, the comparative analysis of evaluative frameworks confirmed substantial methodological fragmentation. Frameworks based on ACCE (i.e., Analytical validity, Clinical validity, Clinical Utility, Ethical, legal, social implications) model and other genomic-specific frameworks improve the focus on application and clinical issues but incompletely cover organizational, personal, and societal dimensions and have seen limited adoption and validation. In contrast, the HTA Core Model® emerged as a comprehensive and rigorous framework capable of encompassing genomic applications, and it is already embedded in the implementation of the European Union HTA Regulation. The thesis proposes anchoring the evaluation of genomic technologies in the HTA Core Model®, enhanced where necessary with genomics-specific issues and applied pragmatically through conditional programme-centred assessments. Overall, the work conducted provides an integrated picture of Italy’s readiness for genomics, clarifies methodological priorities for HTA of genomic technologies, and discuss a concrete, policy-relevant pathway to align implementation and evaluation within the Italian NHS and the evolving European HTA landscape.