Establishing a Public Resource for Acceptable Surrogate Endpoints to Support FDA Marketing Applications

Area of Science:

• Regulatory Science
• Drug Development
• Clinical Pharmacology

Background:

• The U.S. Food and Drug Administration (FDA) established a Surrogate Endpoints (SEs) Table to provide clarity on endpoints used in drug marketing applications.
• This initiative was a direct response to the 21st Century Cures Act legislation, aiming to improve transparency and efficiency in drug approvals.
• The SE Table is publicly accessible and updated biannually to reflect the latest scientific understanding and regulatory thinking.

Purpose of the Study:

• To describe the considerations and methodology behind the creation of the FDA's Surrogate Endpoints (SEs) Table.
• To address misconceptions regarding the FDA's reliance on a limited number of SEs for drug approvals.
• To highlight the frequent utilization of SEs in drug development across diverse therapeutic areas.

Main Methods:

• Development of clear criteria for table headings and content to ensure succinctness and consistency.
• Systematic review of surrogate endpoints used in FDA drug marketing applications.
• Categorization of SEs based on the degree of scientific understanding and validation.

Main Results:

• The Surrogate Endpoints (SEs) Table demonstrates that the FDA frequently utilizes SEs in drug approvals.
• SEs are employed in over 100 different disease/use and patient population combinations, countering previous misconceptions.
• The table provides a structured overview reflecting the scientific basis for each listed SE.

Conclusions:

• The SEs Table serves as a valuable resource for stakeholders involved in drug development and regulatory submissions.
• It clarifies the FDA's approach to surrogate endpoints, fostering a better understanding of drug approval pathways.
• The table's regular updates ensure it remains a relevant and accurate reflection of current regulatory science and practice.