Towards accessibility for Rare Diseases RD(s) therapies from an international to local perspective

Abstract

Rare diseases (RDs) affect more than 450 million people worldwide, yet fewer than 10% have access to orphan drugs (ODs). Variation in how RDs and ODs are defined across countries affects clinical recognition, policy development, research priorities, and access to treatment. In Saudi Arabia (SA), health system transformation under Vision 2030 has progressed without an agreed national RD definition, whereas Northern Ireland (NI) faces access challenges within the wider UK policy and regulatory context. This thesis examined gaps and barriers to OD access and explored practical opportunities to improve access.

A multi-method design was used across four linked components. First, a systematic literature review (SLR) examined global definitions of RDs, ODs, ultra-rare diseases URDs, and ultra-orphan drugs UODs. Second, a national workshop in SA used polling and thematic analysis to develop a context-specific RD definition and identify OD access challenges and solutions. Third, multistakeholder semi-structured interviews in NI explored barriers and enablers affecting OD access. Finally, a sequential explanatory mixed-methods study of the Mucopolysaccharidosis type VI (MPS VI) patient journey, using electronic medical records and interviews with MPS VI patients' parents.

The SLR revealed marked heterogeneity in definitions of RD and OD, with no global consensus. In SA, 96% of workshop participants supported a hybrid qualitative-quantitative RD definition, while the access workshop highlighted the need for registries, regulatory flexibility, and sustainable funding. In NI, interviews identified diagnostic delays, fragmented procurement, and post-Brexit regulatory complexity, but also pointed to Managed Access Agreements (MAAs) and clinical networks as potential levers. The MPS VI study showed late diagnosis, fragmented referral pathways, and ongoing psychosocial burden despite government-funded enzyme replacement therapy (ERT).

Overall, equitable OD access requires clearer definitions, tailored national strategies, robust registries, flexible regulation, and sustainable funding. The findings offer practical recommendations for policymakers, clinicians, and patient advocates in SA and NI.