Use of External Control Arms in Novel Drug Approvals by the U.S. Food and Drug Administration: A Targeted Review

Randomized clinical trials (RCTs) are the gold standard in clinical research, but challenges like limited patient populations, patient heterogeneity, and ethical concerns have led to exploring real-world evidence (RWE) as a complement or alternative. External control arms (ECAs), a promising type of RWE, compare treatment effects with historical or concurrent controls, potentially reducing the need for placebo-controlled trials. The U.S. Food and Drug Administration (FDA) has increasingly integrated ECAs into regulatory decision-making. This study assesses the use of ECAs in FDA novel drug approvals from 2017 to 2023, examining methodological considerations, derivation methods, and associated challenges. New Drug Applications (NDAs) from this period were identified in the FDA database. Keywords were used to search FDA labels, approval letters, and NDA review documents to find approvals involving ECAs. Approval year, disease area, and ECA sources were analyzed and categorized.

This report is a poster presentation of Axtria from ISPOR 2024.

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