OBJECTIVES: Reimbursing orphan medicinal products (OMPs) presents both opportunities and challenges for national healthcare payers and health technology assessment (HTA) bodies because of their potential high benefits, large clinical uncertainties and high prices. To support a more structured application of potentially suitable (outcome-based) managed entry agreements (MEAs) to mitigate these OMP-related reimbursement challenges, a matrix was developed to facilitate reimbursement negotiations and, ultimately, patient access in a sustainable fashion.

METHODS:

A systematic literature review was performed, searching PubMed, Embase, and grey literature from 1 January 2000 until 1 January 2024 to globally identify uncertainties (clinical, cost-effectiveness, or financial risk) mentioned in relation to MEAs for OMPs. The data retrieved was used to develop a matrix in which OMP-specific uncertainties and reimbursement challenges are linked to suitable MEAs.

RESULTS: A total of 130 studies were included in the review, identifying 23 different types of MEAs for OMPs. The results indicated that more commonly known schemes can mitigate different reimbursement challenges, and more innovative MEAs and combinations thereof have been frequently described. The selected case study of Myozyme® illustrated how the matrix can present stakeholders with additional suitable mitigation strategies for the relevant reimbursement challenges.

CONCLUSIONS: To address reimbursement challenges for OMPs along their life cycle, it is valuable to consider both established and innovative, e.g., outcome-based MEAs. Combining reimbursement and payment models has the potential to effectively address multifaceted reimbursement challenges. The developed matrix fills a gap in providing systematic guidance for selecting MEAs tailored to OMPs, enhancing decision-making processes and ultimate patient access to OMPs targeting high unmet medical needs.