How to Use Real-world Data Across Regions to Gain Regulatory Approval: A Case Study
Author(s)
Setareh A. Williams, PhD, Richard J. Weiss, MD.
Health Economics and Outcomes Research, Star Biopharma Consulting, LLC., Malvern, PA, USA.
Health Economics and Outcomes Research, Star Biopharma Consulting, LLC., Malvern, PA, USA.
Presentation Documents
Problem Statement: A new Marketing Authorization Application (MAA) received a negative opinion from the Committee for Medicinal Products for Human Use (CHMP). Two study sites were considered to have serious issues with conformance standards to Good Clinical Practice Guidelines. Excluding data from the sites rendered the primary endpoint non-significant. The manufacturer could not conduct another trial.
Description: This is a case study featuring the use of US RWD to secure the approval of a new drug in Europe (EU). The revised MAA incorporated data from one pivotal clinical trial, data from the FDA FARES database, and a US effectiveness and cardiovascular safety study. The execution of a robust real-world study in this instance addressed a critical data gap, ultimately leading to the EU approval.
Lessons Learned: The case study is one of the first examples of the use of RWE to support approval of a new medical intervention in Europe for a disease that is not considered to have high unmet need. Lessons learned include: (1) adhere to regulatory guidance for the given country/region in planning RWE study; (2) Engage your target audience early for input; (3) Prepare a pre-specified protocol and analysis plan, including power estimation, validated endpoints and analyses plan to minimize biases due to confounding; (4) Register in CT.gov for transparency, (5) Consider variations and generalizability in disease epidemiology and clinical practice guidelines for cross-regional comparisons.
Stakeholder Perspective: RCTs are the gold standard for assessment of clinical efficacy and safety but have limited generalizability and cannot fully characterize safety of new medications. Formal guidance on use of RWE in regulatory applications and broader availability of RWD provide the opportunity for accelerated drug approvals. This example demonstrates how data from a real-world study together with other evidence can be used cross-regionally in lieu of an additional RCT when conducting a study is not logistically or ethically feasible.
Description: This is a case study featuring the use of US RWD to secure the approval of a new drug in Europe (EU). The revised MAA incorporated data from one pivotal clinical trial, data from the FDA FARES database, and a US effectiveness and cardiovascular safety study. The execution of a robust real-world study in this instance addressed a critical data gap, ultimately leading to the EU approval.
Lessons Learned: The case study is one of the first examples of the use of RWE to support approval of a new medical intervention in Europe for a disease that is not considered to have high unmet need. Lessons learned include: (1) adhere to regulatory guidance for the given country/region in planning RWE study; (2) Engage your target audience early for input; (3) Prepare a pre-specified protocol and analysis plan, including power estimation, validated endpoints and analyses plan to minimize biases due to confounding; (4) Register in CT.gov for transparency, (5) Consider variations and generalizability in disease epidemiology and clinical practice guidelines for cross-regional comparisons.
Stakeholder Perspective: RCTs are the gold standard for assessment of clinical efficacy and safety but have limited generalizability and cannot fully characterize safety of new medications. Formal guidance on use of RWE in regulatory applications and broader availability of RWD provide the opportunity for accelerated drug approvals. This example demonstrates how data from a real-world study together with other evidence can be used cross-regionally in lieu of an additional RCT when conducting a study is not logistically or ethically feasible.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
IC6
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory), SDC: Geriatrics, SDC: Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal)