Ethics and regulatory guidance to address the challenges encountered in research on rare diseases in a multinational dimension: the experience of a European funded programme

The rare diseases (RD) research framework presents unique challenges, impacting on ethics and regulatory compliance. Sixty-five projects funded by the European Joint Programme for Rare Diseases (EJP RD) were analysed to identify key ethics and regulatory issues encountered by researchers and to describe the ethics and regulatory guidance provided in the framework of this European-funded Programme. These projects underwent the Ethics Follow-up process throughout their lifecycle. Most of the projects (58) addressed issues related to human participants and personal data, with 28 processing genetic data, 26 handling biospecimens, 24 involving children, and 30 engaging with non-EU countries. The consistent guidance provided to researchers played a significant role in achieving a high level of ethical compliance. Only 5 projects were unable to complete the Ethics Follow-up process, and 10 showed deviations. The most common issues were delayed ethics approvals (7 projects) and missing informed consent or assent documents (6 projects). Among the 60 projects that completed the process, 50 fully adhered to all ethical provisions, while 8 did not meet at least one ethical requirement. Interestingly, regulatory procedures were predominantly overlooked, with only 2 projects reporting their implementation. This highlights a gap in researchers’ awareness of the critical role of regulatory compliance in ensuring research credibility and translational success. Our findings emphasize that while EJP RD’s guidance significantly supported ethics compliance, a more robust focus on regulatory awareness is essential. Initiatives to improve understanding of regulatory landscapes and their integration into RD research are urgently needed.