OBJECTIVES: Following a negative HTA decision, manufacturers often submit additional data for a reassessment of their product. Our research aims to understand the role of real-world evidence (RWE) in re-submissions and determine if it can help to improve HTA outcomes when products are reassessed by the Haute Autorité de Santé (HAS) in FRA and Gemeinsamer Bundesausschuss (G-BA) in GER.

METHODS: Therapies approved by the EMA from 2011 - 2018 were compiled (N=418) followed by analyses to identify products that initially had a poor HTA outcome (defined as ASMR IV or V in FRA and “no additional benefit” in GER) and were reassessed. Pharmaceutical therapies indicated for chronic conditions in addition to oncology therapies were prioritised for further analysis. Commentary on the submitted evidence from HTA bodies vs. the EMA was analysed to understand the role of RWE in the re-submission.

RESULTS: Only N=1 drug (FIRAZYR) improved its benefit rating based on RWE alone. Post-hoc analyses and five retrospective observational studies addressed HAS concerns and resulted in an ASMR III outcome, following an initial score of ASMR IV. N=4 drugs were able to maintain their HTA outcome through RWE, while N=4 improved their ratings through randomised controlled trials or post-hoc analysis. Generally, RWE is not of significant value alone, with most improved benefit ratings driven by post-hoc analyses in specific subpopulations or long-term studies demonstrating significant efficacy vs. competitors. Overall, FRA appears more open to RWE vs. GER which does not typically comment on RWE in the benefit assessment.

CONCLUSIONS: RWE alone is unlikely to improve HTA outcomes. However, RWE that supports clinical trials by confirming a long-term benefit could be valuable for re-submissions.