Expanded Access as a source of real-world data: An overview of FDA and EMA approvals

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 (EA) programmes.

Methods: Cross-sectional study of FDA (1955-2018) and EMA (1995-2018) regulatory approval documentation. We automated searching for terms related to EA in 22,506 documents using machine learning techniques. We included all approvals where EA terms appeared in the regulatory documentation. Our main outcome was the inclusion of EA 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: EA terms appeared in 693 out of 22,506 (3.1%) documents, which referenced 187 approvals. For 39 approvals, data from EA programmes 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 programmes formed the main evidence for approval. Of these, patients in EA programmes formed over half (median 71%, interquartile range: 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, 4 treatments were granted approval based solely on efficacy from EA.

Conclusion: Sponsors and regulators increasingly include real-world data from EA programmes in the efficacy profile of a treatment. The indications of the approved treatments are characterized by orphan designation and high unmet medical need.

Keywords: drug regulation; effectiveness; evidence-based medicine; health policy.

FIGURE 1

Flowchart of automated candidate search. We searched through all FDA and EMA documentation for expanded‐access related terms (compassionate use, expanded access, early access, preapproval access, named patient and managed access). When these terms appear, the document is considered a candidate. For scanned files, optical character recognition was used

FIGURE 2

Flowchart of review process. We manually reviewed and deduplicated 187 approvals related to the candidate documents. All approvals that used expanded access (n = 39) to support clinical efficacy were analysed. For 13 approvals, the evidence from expanded access was the pivotal source of evidence

FIGURE 3

Venn‐diagram of approvals where the Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) relied on data from expanded access programmes to form the clinical efficacy profile. The level of evidence associated to these data by either regulator could be pivotal or supportive

FIGURE 4

Bar chart of dates of marketing authorization of 25 Food and Drug Administration (FDA) and 24 European Medicines Agency (EMA) approvals that relied on real‐world data from expanded access for the clinical efficacy profile