Feasibility of disease terminology systems for mapping orphan conditions and therapeutic indications of designated orphan medicines in the European Union.

Background: In the European Union, rare diseases are defined as diseases that affect maximum 5 in 10,000 citizens. These diseases are typically associated with a high unmet medical need. To stimulate development and authorisation of medicines for rare diseases ('orphan conditions'), the European Commission (EC) can grant orphan designations. In order to enable systematic evaluation and communication of the diseases for which designated orphan medicines have (not) been developed and authorised, we aimed to investigate the feasibility of important disease terminology systems for mapping orphan conditions and therapeutic indications.

Methods: We selected all designated orphan medicines that were authorised by the EC during 2022-2023 from the EC's Union Register of medicinal products. For these medicines, we extracted orphan conditions and associated therapeutic indications at initial marketing authorisation. The orphan conditions and separate elements of therapeutic indications such as target disease or condition, severity criteria and target population were assessed for availability in six major disease terminology systems: ICD-10, ICD-11, MedDRA, MeSH, Orphanet nomenclature of rare diseases, and SNOMED CT. Descriptive statistics were used to describe the ability of each disease terminology system to map orphan conditions and elements of therapeutic indications.

Results: During 2022-2023, 37 designated orphan medicines were authorised that were designated for 40 orphan conditions (of which 37 unique) and granted 39 therapeutic indications (of which 37 unique). Overall, SNOMED CT covered most descriptions of orphan conditions (33/37, 89 %) and target diseases or conditions within therapeutic indications (28/37, 76 %). However, when allowing descriptions to be partly included and/or complemented by additional words, SNOMED CT, the Orphanet nomenclature, ICD-11 and MedDRA all had high coverage (92-97 %). Other elements than target diseases or conditions within therapeutic indications were mostly lacking.

Conclusions: Regulatory data concerning orphan conditions and therapeutic indications of designated orphan medicines seem to be best covered by SNOMED CT. However, which disease terminology system best facilitates systematic evaluation and communication about development and authorisation of designated orphan medicines also depends on the specific use case. Given the frequent use of SNOMED CT in healthcare settings, it may also facilitate interoperability between regulatory and healthcare data, while for example ICD-11 may be better suited to generate statistics concerning drug development for rare diseases.