FDA and the Real-World: Key Changes from Draft to Final Guidance on RWD and RWE

As the FDA explores the complexities of using real-world data to provide evidence for regulatory decision-making, sponsors face the challenge of staying updated with the evolving definitions and standards. Recently, the FDA released its finalized “Guidance for Industry” titled “Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products”. While the August 2023 version largely retains content from the draft guidance of December 2021, we’ve highlighted the primary changes to offer a concise overview for all stakeholders.

Key Shifts in the FDA’s RWD/RWE Guidance:

Practical Data Submission Approach:

      • The draft underscored the importance of data submission and highlighted third-party agreement roles. However, the finalized guidance suggests practical methods for the FDA to access data owned by third parties. Specifically, the FDA recommends third parties to submit via a pre-investigational new drug application (pre-IND) or a Type V drug master file (DMF). They should also provide the right of reference to the Sponsor through an authorization letter. It’s crucial to note that the FDA still deems external database links unsuitable for such data.

Evolving Definitions:

  • Deepening the Meaning of “Data Integrity” perhaps to encapsulate more of the ALCOA principles.
    1. The draft defined data integrity in the RWS context as: “The property of data or information remaining unaltered or undestroyed without authorization, often encompassing the completeness, consistency, and accuracy of data.”


    2. The final guidance refines this to: “Data integrity entails the completeness, consistency, and accuracy of data. Moreover, data should be attributable, legible, recorded in real-time, and either original or a verified copy.
  • Updated Reference Points: Two definitions from the draft have been substituted with references to related guidance.
    1. The “Externally Controlled Trial” definition has been replaced with a reference to the recent guidance: “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products (February 2023).”


    2. The “Historically Controlled Trial” definition now refers to two guidances: “Rare Diseases: Natural History Studies for Drug Development (March 2019)” and “E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001).”

Reflecting on the Journey:

As the FDA rolls out the framework for an RWE program under the directives of the 21st Century Cures Act, the industry can expect further clarity and actionable solutions, as exemplified in this final guidance. Amidst these industry shifts, MMS Holdings remains a trusted partner. With our deep expertise, we simplify the complexities, ensuring stakeholders stay ahead in their regulatory pursuits.

To stay at the forefront of regulatory changes and to benefit from unparalleled expertise, continue your journey with MMS Holdings.

Authored by:
Amanda Beaster PhD, Associate Director, Regulatory Strategy.