OBJECTIVES : To perform a comparative assessment of the formal registry requirements in Germany and Brazil for orphan therapies with limited clinical evidence in order to pinpoint the future role of real-world evidence (RWE) in health technology assessments (HTAs).

METHODS : This study conducted a targeted policy and literature review of the orphan drug registry requirements of the G-BA (Federal Joint Committee) in Germany and CONITEC (National Committee for Health Technology Incorporation) in Brazil, two HTA bodies with differential priorities for market access decision-making. To understand the impact of the formally generated real-world evidence, CBPartners also prepared an analogue assessment of recent orphan therapies that went through these registry pathways.

RESULTS : In early 2019, the G-BA obtained the authority to implement registries for any orphan drug with a conditional approval; the collected data would then be used for a re-assessment of that drug’s added benefit rating. To-date, no changes to the initial benefit assessment outcomes have occurred. That said, given the G-BA’s direct role in designing these registries, all data produced are likely to be considered in the re-assessment. In Brazil, for recent orphan drug approvals, CONITEC has recommended the implementation of patient registries as part of conditional public funding. However, while the data collected will trigger a re-assessment after three years, no orphan drugs have been negatively impacted thus far. Because CONITEC has less rigorous requirements, there may be more heterogeneity of impact for the real-world evidence that is ultimately produced.

CONCLUSIONS : RWE from formal registries is unlikely to have a significant positive impact on future HTA decisions but may contribute to worsened outcomes if efficacy or safety perform worse than expected. Manufacturers will need to be more cautious about producing RWE outside of formal registries, as HTA bodies with more experience may be highly selective on what data they accept.