Using Real-World Evidence for Clinical Development to Address the Gap Between Marketing Authorisation and Reimbursement in European Countries: Insights From Literature Review

Abstract

Background

Health Technology Assessment (HTA) agencies require evidence relevant to elements like the ‘added value’ of the drug, efficacy and safety in real life, or data regarding the drugs' effects on different subgroups of interest. Using Real-World Evidence (RWE) during drug clinical development can provide the information required for HTA approval.

Objective

Two targeted literature reviews (TLRs) were conducted to narratively describe the reasons for the gap between EMA market authorisation and market access in France and Germany; the possible importance of RWE studies to provide relevant clinical evidence for HTA approval and, therefore, their role to support drug clinical development programmes in Europe.

Methods

Relevant studies were identified by searching Embase using predefined search strategy via the Ovid platform. Additional studies were included from external keyword searches on Google Scholar and PubMed that address the objective of the review. Further searches were conducted in the Haute Autorité de Santé (HAS) and the Gemeinsamer Bundesausschuss (GBA) websites to identify examples of reimbursement submissions.

Results

The average time to access drugs was 128 days in Germany and 508 days in France. Delays in patient access to new drugs resulted in diminished patient benefits. The delays in the approval of new drugs were attributed to several clinical factors, including: (i) lack of safety and efficacy data from the submitted clinical trial; (ii) absence of clinically relevant comparators; (iii) lack of demonstration of added value and (iv) inability to contextualise data to the local population. RWE can be valuable in supporting clinical evidence generation by providing a complementary set of information to address gaps in knowledge regarding the drug's effectiveness and safety. It can also offer an external arm for comparison when randomisation is not feasible. Furthermore, RWE can support the demonstration of a drug's added benefit over existing therapies and help define its role in disease management. However, RWE studies also face several limitations, including variability in data quality, challenges in addressing specific research questions, methodological constraints and concerns about the credibility of analyses.

Conclusion

Access to medication is usually delayed due to the HTA agency's requirements for scientifically robust clinical evidence about the drug's effectiveness and safety assessed in specific subpopulations, with relevant and valid endpoints. The utilisation of RWE is revolutionising the whole clinical development process that supports HTA submissions. Early engagement among stakeholders during the drug's clinical development on how providing high-quality, relevant clinical data might be addressed is crucial for ensuring the robustness, reliability and acceptance of RWE.