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In British journal of clinical pharmacology ; h5-index 58.0

AIMS : To identify, characterize, and compare all FDA and 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 EA 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. All but one (12/13) approvals were granted orphan designation. In 8/13, there were differences between regulators in approval status and valuation of evidence. Strikingly, 4 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.

Polak Tobias B, van Rosmalen Joost, Uyl-de Groot Carin A


Drug Regulation, Effectiveness, Evidence-Based Medicine, Health Policy