Real-World Evidence in FDA and EMA Regulatory Reviews: Insights on Its Role in Submission Packages and Approvals
Author(s)
Ramon Hernandez, MD, PhD1, Antoine Pugeat, MBA1, Jun Collet, B.Med, MSc2, Mati Lopez-Grancha, PhD1, Mir Sohail Fazeli, MD, PhD2, Kimberly Hofer, BSc2, Jean-Paul Collet, MD, PhD2;
1Sanofi, Gentilly, France, 2Evidinno Outcomes Research Inc, Vancouver, BC, Canada
1Sanofi, Gentilly, France, 2Evidinno Outcomes Research Inc, Vancouver, BC, Canada
Presentation Documents
OBJECTIVES: This study examined the evaluation, utility, and acceptance criteria of real-world evidence (RWE) in regulatory submissions to the FDA and EMA.
METHODS: Regulatory review packages and label documents (2015-2023) from FDA and EMA websites were searched to select historical submissions that included RWE studies. Detailed extractions focused on the characteristics of RWE data sources, study design, utility for regulatory approval, and specific comments from regulatory agencies.
RESULTS: Of 1,334 submissions reviewed, 131 (73 EMA, 58 FDA) included RWE (207 instances). Most (79%) were for novel drugs, with 21% for label extensions. RWE was used across various regulatory stages: pre-marketing (79%) and post-marketing (21%). Therapeutic areas included oncology (37%), rare genetic diseases (14%), neurology and infectious diseases (11% each), hematology, dermatology, immunology, and vaccines represented 5 to 7% each, and others (4%). Orphan drug status applied to 64%, with 27% receiving accelerated approval and 32% conditional approval (EMA-specific). RWE supported external control arms for single arm trials (35%), efficacy/safety assessments (47%), disease burden documentation (39%), and post-marketing commitments (32%). Other uses included dose-response analysis and comparative effectiveness. However, only 4% of submissions relied solely on RWE. Comprehensive disease burden documentation, unmet needs analysis, robust efficacy data, and structured post-marketing plans enhanced the likelihood of approval. Regulatory feedback highlighted gaps: 8 RWE submissions were rejected, 6 had limited impact, and 40 (30%) were considered inadequate while 20 did not receive comments. Agencies often rejected for methodological reasons RWE for external controls of single-arm trials, unless supported by robust post-marketing commitments.
CONCLUSIONS: RWE plays a growing, supportive role in regulatory submissions, especially in oncology, rare diseases, and orphan drug applications. To enhance its impact, pharmaceutical companies should emphasize methodologically sound designs, high-quality data, and alignment with regulatory requirements.
METHODS: Regulatory review packages and label documents (2015-2023) from FDA and EMA websites were searched to select historical submissions that included RWE studies. Detailed extractions focused on the characteristics of RWE data sources, study design, utility for regulatory approval, and specific comments from regulatory agencies.
RESULTS: Of 1,334 submissions reviewed, 131 (73 EMA, 58 FDA) included RWE (207 instances). Most (79%) were for novel drugs, with 21% for label extensions. RWE was used across various regulatory stages: pre-marketing (79%) and post-marketing (21%). Therapeutic areas included oncology (37%), rare genetic diseases (14%), neurology and infectious diseases (11% each), hematology, dermatology, immunology, and vaccines represented 5 to 7% each, and others (4%). Orphan drug status applied to 64%, with 27% receiving accelerated approval and 32% conditional approval (EMA-specific). RWE supported external control arms for single arm trials (35%), efficacy/safety assessments (47%), disease burden documentation (39%), and post-marketing commitments (32%). Other uses included dose-response analysis and comparative effectiveness. However, only 4% of submissions relied solely on RWE. Comprehensive disease burden documentation, unmet needs analysis, robust efficacy data, and structured post-marketing plans enhanced the likelihood of approval. Regulatory feedback highlighted gaps: 8 RWE submissions were rejected, 6 had limited impact, and 40 (30%) were considered inadequate while 20 did not receive comments. Agencies often rejected for methodological reasons RWE for external controls of single-arm trials, unless supported by robust post-marketing commitments.
CONCLUSIONS: RWE plays a growing, supportive role in regulatory submissions, especially in oncology, rare diseases, and orphan drug applications. To enhance its impact, pharmaceutical companies should emphasize methodologically sound designs, high-quality data, and alignment with regulatory requirements.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
HPR82
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
No Additional Disease & Conditions/Specialized Treatment Areas