Tobias Polak

Chapter 5 84 ABSTRACT Aims To identify, characterize, and compare all Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals that included real-world data on efficacy from expanded access programs. Methods Cross-sectional study of FDA (1955-2018) and EMA (1995-2018) regulatory approval documentation. We automated searching for terms related to expanded access in 22,506 documents using machine learning techniques. We included all approvals where expanded access terms appeared in the regulatory documentation. Our main outcome was the inclusion of expanded access data as evidence of clinical efficacy. Characterization was based on approval date, disease area, orphan designation and whether the evidence was supportive or pivotal. Results Expanded access terms appeared in 693 out of 22,506 (3.1%) documents, which referenced 187 approvals. For 39 approvals, data from expanded access programs were used to inform on clinical efficacy. The yearly number of approvals with expanded access data increased from 1.25 for 1993-2013 to 4.6 from 2014-2018. In 13 cases, these programs formed the main evidence for approval. Of these, patients in expanded access programs formed over half (median 71%, IQR: 34 - 100) of the total patient population available for efficacy evaluation. Almost all (12/13) approvals were granted orphan designation. In 8/13, there were differences between regulators in approval status and valuation of evidence. Strikingly, four treatments were granted approval based solely on efficacy from expanded access. Conclusions Sponsors and regulators increasingly include real-world data from expanded access programs in the efficacy profile of a treatment. The indications of the approved treatments are characterized by orphan designation and high unmet medical need.

RkJQdWJsaXNoZXIy MTk4NDMw