In December 2023, the U.S. Department of Health and Human Services, in collaboration with the Food and Drug Administration (FDA), released a groundbreaking guidance document titled “Data Standards for Drug and Biological Product Submissions Containing Real-World Data.” This guidance is a crucial milestone in the evolving landscape of medical product development, specifically addressing the integration of Real-World Data (RWD) and Real-World Evidence (RWE) into regulatory decision-making processes.
I. The 21st Century Cures Act and Real-World Data:
The guidance begins by highlighting the significance of the 21st Century Cures Act, signed into law in 2016, which aims to expedite medical product development. Section 505F of the Federal Food, Drug, and Cosmetic Act calls for the FDA to provide guidance on the use of RWE in regulatory decision-making. This led to the creation of a framework for an RWE Program to evaluate the potential use of RWD in supporting new indications for approved drugs.
II.Regulatory Background:
Under section 745A(a) of the FD&C Act, the FDA specifies electronic submission requirements for certain submission types. The guidance emphasizes the importance of adhering to the Study Data Guidance and the Data Standards Catalog when submitting RWD as study data in applicable drug submissions.
III. Applying Currently Supported Data Standards to RWD:
A.Challenges in Real-World Data Standardization:
The guidance recognizes challenges in standardizing RWD, including the diversity of sources, inconsistent formats, and differences in data captured globally. These challenges necessitate early discussions between sponsors and the FDA, allowing for a tailored approach to address specific issues.
B.Documentation of Processes for Managing Real-World Data:
Processes for data curation and transformation must be well-documented, ensuring confidence in the resultant data. Electronic documentation, such as audit trails and quality control procedures, is crucial for transparency.
C.Considerations for Conforming Real-World Data to Currently Supported FDA Study Data Standards:
Sponsors are encouraged to discuss their approaches to mapping and transforming RWD with the FDA. The use of standards like CDISC’s Study Data Tabulation Model (SDTM) or Analysis Data Model (ADaM) is highlighted, with a focus on documentation and early communication.
D.Considerations for Mapping Real-World Data To Study Data Submission Standards:
Mapping terminology from RWD sources to FDA-supported standards poses challenges, especially in data domains like race and ethnicity. The guidance recommends using Define-XML files to document the mapping decisions, ensuring traceability and transparency.
E.Considerations for Data Transformations:
Challenges in transforming RWD into standardized data are acknowledged. The guidance suggests approaches to handle semantic concepts, inconsistent coding, and missing information, emphasizing detailed documentation in Define-XML and data domain files.
The guidance provides illustrative examples of mapping non-standardized data, such as race and prescription information, to CDISC SDTM. These examples demonstrate the use of Alias elements in Define-XML to document mapping decisions.
The FDA’s guidance on Real-World Data Standards represents a significant step toward integrating RWD into the regulatory framework. Sponsors are encouraged to engage in early and transparent communication with the FDA, document their processes meticulously, and utilize standards to ensure the quality and consistency of RWD in drug and biological product submissions. As the healthcare landscape continues to evolve, this guidance paves the way for more efficient and informed decision-making processes in drug development.
