Real-World Evidence in FDA Approvals for Labeling Extension of Drugs and Biologics

Author(s)

Yung-Fang Deng, MPH, Cynthia J. Girman, DrPH, Mary Beth Ritchey, MSPH, PhD;
CERobs Consulting, LLC, Mills River, NC, USA
OBJECTIVES: The 21st Century Cures Act (2016) increased focus on real-world evidence (RWE) in FDA decision-making, but utilization in labeling extensions remains unclear. This study examined the role of RWE in labeling extensions for supplemental new drug applications (sNDAs) and biologics license applications (sBLAs), both to add new (therapeutic) indications and to expand indicated populations (e.g., pediatrics).
METHODS: Between January 2022 and May 2024, we identified sNDAs and sBLAs related to labeling extensions by reviewing FDA documents within Drugs@FDA. RWE used to support these submissions were extracted from FDA’s prescribing information and medical/statistical review documents. Since FDA does not systematically include RWE in labeling nor provide review documents for supplemental applications, we conducted additional searches on ClinicalTrials.gov and PubMed to identify relevant RWE likely available at the time of submission but not mentioned in official documents. The characteristics of identified RWE were then summarized.
RESULTS: Among 218 approved labeling extensions, 55 (25.2%) had available RWE, with 3 instances identified via FDA records and 52 via ClinicalTrials.gov or PubMed. RWE was most common in oncology (43.6%), infection (9.1%) and dermatology (7.3%) submissions. RWE was more frequently identified in sNDAs (69.1%) and for new therapeutic indications (78.2%). The proportion of approvals with RWE by year was 23.3%, 27.7%, and 23.7% in 2022, 2023, and 2024, respectively. There were 88 RWE studies, with nearly half (48.9%) addressing both safety and efficacy. Most studies were retrospective (65.9%), used a cohort design (87.5%), and assessed electronic health records (75.0%).
CONCLUSIONS: RWE is increasingly incorporated into the regulatory decision-making process. However, limited documentation from FDA for supplemental approvals implies a substantially smaller use of RWE in labeling extensions than information obtained from study registration and published literature. Enhancing transparency of FDA review documents could improve understanding of the extent and quality of RWE used in labeling extensions.

Conference/Value in Health Info

2025-05, ISPOR 2025, Montréal, Quebec, CA

Value in Health, Volume 28, Issue S1

Code

HPR51

Topic

Health Policy & Regulatory

Topic Subcategory

Approval & Labeling

Disease

STA: Multiple/Other Specialized Treatments

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