Alberta Spreafico:

Firstly, rare diseases are rare individually, not collectively. Up to 36 million people in the European Union live with a rare disease, across an estimated 6,000–8,000 conditions.

Many are progressive, begin in childhood, and require lifelong multidisciplinary care. Yet, patients continue to face prolonged diagnostic journeys. A large European Rare Barometer study found that the average time from first symptoms to confirmed diagnosis was 4.7 years. For conditions in which irreversible damage can develop before treatment, those years matter.

But beyond the significant clinical and societal burden, rare diseases present a particularly compelling case for European-level action. Their very characteristics – small and geographically dispersed patient populations, limited data, concentrated specialist expertise, and complex care needs – make cross-border collaboration essential. No single country can always mobilise the patient populations, data, or expertise needed to advance research and deliver optimal care.

In many ways, rare diseases are a stress test for European health systems, but also an opportunity to pioneer solutions that can benefit healthcare more broadly. They challenge us to rethink how we conduct multinational clinical research, generate evidence from small populations, connect specialist expertise, and translate innovation into patient access.

Europe has important foundations to build upon: world-class science, the European Reference Networks, and an established regulatory framework for orphan medicines. Yet, these assets do not automatically translate into timely diagnosis or equitable access to care and innovation across Member States.

Making rare diseases a strategic European priority is therefore not only about addressing a major unmet need. It is also about strengthening Europe's capacity to innovate, attract research and investment, and develop more integrated, evidence-driven, digitally-enhanced models of care. Success in rare diseases could demonstrate what a more connected, innovative, and competitive European health ecosystem can achieve.

There are genuine scientific, therapeutic, and access gaps: most rare diseases still lack an approved treatment. We should not reduce these challenges to a data problem.

But across the care journey, the way information is generated, recognised, and shared is frequently a limiting factor. At diagnosis, early symptoms may be individually non-specific and appear across different specialties, making it difficult to recognise the underlying pattern unless clinical observations and specialist expertise are brought together. Disease-specific coding is not consistently implemented, and referral pathways vary across healthcare systems.

Lysosomal storage disorders illustrate this particularly well. Some have established disease-modifying therapies, yet timely diagnosis, progressive multisystem involvement, and the need for coordinated, long-term multidisciplinary care remain important challenges. Episodic consultations may not fully capture what happens between visits, while patient-reported symptoms, daily functioning, and caregiver burden are not always systematically documented. Meanwhile, registries, electronic health records, and research cohorts can remain disconnected across centres and countries.

So, the challenge is not simply a shortage of information. It is how we connect and translate dispersed clinical observations into meaningful knowledge, timely decisions, and evidence that can further inform care, research, and access.

There are multiple opportunities across the rare disease care journey. One is earlier recognition and diagnosis. AI offers promising capabilities to analyse complex and often dispersed clinical information, from electronic health records and laboratory findings to imaging and genomic data.

By identifying patterns and associations that may be difficult to recognise through conventional approaches, appropriately validated AI tools could support clinicians in identifying patients who warrant further investigation and referral to specialist expertise. This is particularly relevant in rare diseases, where symptoms may be non-specific and diagnostic expertise is often concentrated in a limited number of centres.

Another is continuity of care: teleconsultations between local clinicians and specialist teams, remote monitoring and electronic patient-reported outcomes can support patients who need lifelong, multidisciplinary follow-up, but who cannot repeatedly travel to a centre of expertise. These tools can connect information across visits and care settings, but they do not replace the clinical team.

Equally important is evidence generation: common data standards, interoperable registries, and well-governed multicentre research can help characterise natural history, identify clinically meaningful outcomes, improve trial feasibility, and evaluate long-term treatment effectiveness.

In a scoping review my co-authors and I published in JMIR in April 2026, we mapped 245 records on digital technologies relevant to lysosomal storage disorders. Research activity was substantial, but the evidence remained heterogeneous and often focused on feasibility or technical performance, rather than demonstrated clinical effectiveness and patient benefit. We need to evaluate digital interventions against meaningful clinical, patient, and health system outcomes, rather than treating predictive accuracy alone as evidence of better care.

Because rare diseases, by their very nature, require Europe to function as a connected research and care ecosystem. In individual Member States, there may simply not be enough eligible patients to adequately study a condition or generate the evidence needed to advance innovation. Pooling expertise, connecting data, and facilitating multinational research are therefore particularly important.

Europe also faces a broader competitiveness challenge. Despite continued growth in clinical research globally, Europe has experienced a decline in industry-sponsored clinical trial activity and a significant reduction in its share of global trials. This raises concerns about Europe's attractiveness for research investment and the opportunities available to European patients to participate in innovative clinical studies.

There are important policy developments that could help address these challenges. The EU Clinical Trials Regulation already provides a common framework for multinational clinical trial applications through the Clinical Trials Information System (CTIS). The proposed European Biotech Act, presented by the Commission in December 2025, seeks to further simplify regulatory processes, accelerate trial authorisations, and strengthen Europe's biotechnology ecosystem. These developments are particularly relevant for rare diseases, where cross-border research collaboration is often essential.

The EU Health Technology Assessment Regulation represents another important step towards greater European cooperation. From January 2028, Joint Clinical Assessments (JCAs) will extend to orphan medicinal products, building on the framework already in place for advanced therapies and new oncology medicines. This offers an opportunity for more coordinated clinical evidence assessment across Member States, while national authorities retain responsibility for pricing and reimbursement decisions.

The European Health Data Space is equally consequential. Having entered into force in March 2025, its provisions for the secondary use of most health-data categories will begin applying in 2029, with genomic and certain other data categories following in 2031. By enabling more secure, governed, and interoperable access to health data for research and innovation, it could make an important contribution to rare-disease research, evidence generation, and the development of new therapies.

The opportunity, however, will depend on how effectively these frameworks are implemented. For rare diseases to fully benefit, we need to start preparing now: improving disease coding, strengthening registries, promoting interoperability, harmonising clinically meaningful outcomes, and defining how synthetic data and modelling approaches can be appropriately leveraged in clinical research and evidence generation, with the active involvement of patients, researchers, and European specialist networks.

Ultimately, it is about making Europe's scientific excellence, data resources, and collaborative infrastructure work together to accelerate innovation and improve patient access.

We need to recognise rare diseases as a strategic European priority and translate that commitment into coordinated action.

This means building on Europe's existing strengths, particularly its scientific excellence and European Reference Networks, while strengthening cross-border research, data infrastructure, and the pathways that connect innovation with patient access. The emerging European policy frameworks offer an important opportunity, but their impact will depend on effective implementation and sustained collaboration among policymakers, industry, researchers, clinicians, and patients.

Rare diseases represent a valuable testing ground for health innovation. If Europe can develop effective approaches to research, evidence generation, and care for small, geographically dispersed patient populations, these capabilities can also advance precision medicine and other complex areas of healthcare.

Investing in rare diseases is therefore not only about addressing unmet needs. It is an investment in Europe's broader capacity to innovate, collaborate, and translate scientific progress into meaningful benefits for patients.