Chapter 5 96 Limitations and future research Previous literature focused on the legal and ethical implications of expanded access,4,35–39 or attempted to characterize (US) expanded access programs in terms of associated clinical holds, impact on product labeling, acceptance rates or dates of initiation.6,40–43 This study is the first to systematically identify, compare, and categorize all EMA and FDA approvals that rely on RWD from expanded access. This differs from previous literature comparing approvals, focusing on the absence of randomized controlled trials.30 Additionally, to analyze the entire history of RWD use from expanded access, no time limit was used. We are limited by the fact that the Drugs@FDA database includes only drugs and therapeutics (no other biologics) and consistently included reviews only after 1997. Using recent advances in artificial intelligence to facilitate the processing of documents, we were able to analyze a large number of approvals. As only approvals where expanded access -related appeared were assessed manually, the possibility remains that cases where expanded access data were in fact used were missed because these terms did not appear in the documentation. Although it is unlikely that such terms would not appear in relevant documents, our numbers therefore form a lower bound of the real number of cases where expanded access data were used for approvals. Future research could focus on statistical implications of combining data from expanded access programs and controlled trials. Additionally, we have only investigated the use of expanded access efficacy data for regulators. Its influence on other stakeholders such as payors or drug developers is a subject that could be pursued through further research. Conclusion Expanded access programs can generate real-world evidence prior to drug approval. EMA and FDA increasingly utilize RWD from expanded access in regulatory decision making. The treatments in these approval decisions involved orphan designations and high unmet medical need.
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