(040) Using Real-World Evidence for Clinical Drug Development to Address the Gap Between Marketing Authorization and Reimbursement in European Countries

Background: In order for a new drug to gain acceptance, Health Technology Assessment (HTA) agencies require evidence regarding the “added value” of the drug’s efficacy and safety in real life, or data regarding the drug’s effects on different subgroups of interest. Generating Real-World Evidence (RWE) during drug clinical development can provide the information required by HTA agencies.

Objectives: Two targeted literature reviews (TLRs) were conducted: 1) to narratively describe the possible reasons for the gap between market authorization and reimbursement of medicines; and 2) the possible role of RWE studies to provide clinical evidence and support the drug clinical development programs in Europe.

Methods: Relevant studies were identified by searching Embase using predefined search strategies 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: Between 2018 and 2021, average time to access a drug was 128 days in Germany and 508 days in France. Delay in accessing new drugs has a profound impact on patients' health. The main clinical reasons identified for delaying the approval of new drugs were (i) lack of appropriate control; (ii) lack of safety and efficacy data; (iii) inability to contextualize the evidence to the local population; (iv) lack of data demonstrating impact on healthcare; and (v) absence of locally relevant comparators. The review identified several positive aspects of using RWE to provide a complementary set of information regarding the drug’s effectiveness and safety or providing a valid external arm in cases of single arm trial. Data from Electronic Health Records (EHRs) were useful to address various safety issues, especially long-term safety data that are often missing from limited duration in clinical trials. Moreover, RWE could document the added benefit of the drug over existing therapies and determine its place in disease management. RWE studies also face several limitations such as addressing unprecise research questions, using poor methodology, using poor data quality, and lacking transparency and credibility.

Conclusions: Access to drugs might experience delays as a result of the HTA agency's need for additional clinical evidence supporting the added value of the drug. The utilization of RWE is revolutionizing the whole clinical development process that support HTA submissions. Early engagement among stakeholders during drug’s clinical development on how such challenges might be addressed is crucial for ensuring the accuracy and acceptance of RWE.