Advances in data management and in the use of novel data sources in clinical research have cast a spotlight on the data standards FDA requires for study data submitted in marketing applications. These data standards, compiled in an FDA spreadsheet known as the Data Standards Catalog, have changed little over the past several years despite increasing focus by FDA and the clinical research community on new sources of data, such as real-world data (RWD).

As FDA has acknowledged, it can be challenging to map or transform datasets into FDA’s currently supported data standards, particularly when RWD sources are involved.  Transforming a dataset from one standard to another can be fraught because different standards represent variables (e.g., medication information) in different ways.  Accordingly, FDA typically expects detailed “mapping” information to document how the information in a dataset is maintained as it is transformed from one standard to another.  While updated data standards may not remove the need for researchers and sponsors to transform datasets from one standard to another, updated standards may be designed to handle information more flexibly than older standards. New data standards also can be designed to be more universal or interoperable, reducing the transformations needed as data moves from collection (e.g., from an electronic health record) to analysis by the sponsor or researcher and submission to FDA.

Against this backdrop, it’s notable that FDA has issued two Federal Register notices in two weeks that seek comments on updates to FDA data standards.  These updates could have a profound impact on the preparation, analysis, submission, and FDA review of study data.  Recognizing this impact, FDA has detailed procedures for adopting new data standards for drug and biological product submissions, described in guidance issued under section 745A of the Federal Food, Drug, and Cosmetic Act.  As stakeholders consider the technical implications of FDA’s proposed changes, FDA’s process and timeline for adopting any new or updated standards will be a critical consideration.

As described below, FDA is seeking comment in its two open dockets not only on the potential for updated data standards but also on the broader data ecosystem, including healthcare data interoperability, the exchange of health information through the TEFCA framework, and other aspects of information technology (IT) goals and strategy advanced by FDA and the broader Department of Health and Human Services (HHS).

Request for Comment on HL7 FHIR Standard for Submission of Study Data Derived from Real-World Data Sources

On April 23, 2025, FDA published a Federal Register notice titled “Exploration of Health Level Seven [HL7] Fast Healthcare Interoperability Resources [FHIR] for Use in Study Data Created from Real-World Data Sources for Submission to the Food and Drug Administration” to request comments on approaches to optimize the submission of structured and standardized clinical study data collected from RWD sources. 

FDA’s request for comment on the HL7 FHIR standard follow’s the Agency’s 2023 final guidance “Data Standards for Drug and Biological Product Submissions Containing Real-World Data” in which FDA pointed to several challenges involved in standardizing study data derived from RWD sources and stated that FDA would update the Agency’s Data Standards Catalog and/or issue other guidance documents to reflect standards for study data that are derived from RWD sources.  FDA states that the Agency is exploring alignment of data standards for submission of real-world clinical study data with the recently adopted HHS Health IT Alignment Policy that seeks to promote greater alignment of health IT-related activities in support of the department’s health IT and interoperability goals. 

FDA’s request for comment on the HL7 FHIR standard aligns with the work of the Assistant Secretary for Technology Policy/Office of the National Coordinator for Health (ASTP/ONC).  In 2020, ASTP/ONC published a final rule establishing the HL7 FHIR standard as the nationwide standard for access, exchange, and use of data for healthcare delivery organizations.  In 2024, ASTP/ONC then created a new standard set of data elements available through the FHIR standard in its HTI-1 final rule.  Given the existing use of the FHIR-based data elements and the overlap between healthcare data and RWD, FDA states that the Agency is exploring the possibility of receiving clinical study data collected from RWD sources using the HL7 FHIR standard.

Specifically, FDA states that the Agency is seeking input “regarding the range of challenges to be addressed when considering the use of FHIR for submission of clinical study data collected from RWD sources.”  FDA also seeks feedback on “possible approaches and challenges to structuring and standardizing study data submissions with RWD sources using FHIR while aligning with the data interoperability and exchange standards adopted by HHS through ASTP/ONC.”  While FDA’s current focus appears to be on drug and biological product submissions, FDA’s approach to the submission of RWD and alignment with ASTP/ONC standards may have implications for other types of submissions to FDA and, more broadly, for other parts of the health data ecosystem.

FDA poses five questions for comment: 

1. What challenges do you see for the pharmaceutical industry regarding the current state of submitting clinical study data collected from RWD sources to FDA?
2. What opportunities and/or challenges do you see for the pharmaceutical industry on reaching a future state of clinical study data submissions collected from RWD sources using HL7 FHIR (e.g., business processes, technical considerations)?
3. What are your suggestions on how, from a data standards perspective, FDA might reach a future state of clinical study data submissions collected from RWD sources that aligns with ASTP/ONC health IT goals for HL7 FHIR-based exchange?
4. Does USCDI version 3 provide enough information for collecting RWD for research purposes? Is there information that USCDI version 3 does not sufficiently address?
5. Under TEFCA, a variety of “Exchange Purposes” are authorized. If “Research” was added as an “Exchange Purpose,” what role could TEFCA play with using RWD for clinical research? How could TEFCA support more efficient collection and exchange of RWD for clinical research purposes? What challenges might exist with this approach?

Comments are due June 23, 2025.

Request for Comment on CDISC Dataset-JSON Version 1.1 Exchange Standard

On April 9, 2025, FDA published a Federal Register notice titled “Electronic Study Data Submission; Data Standards; Clinical Data Interchange Standards Consortium Dataset-JavaScript Object Notation” to request comments on Clinical Data Interchange Standards Consortium (CDISC) Dataset-JavaScript Object Notation (Dataset-JSON) version 1.1 as a new exchange standard to potentially replace Statistical Analysis System (SAS) version 5 XPORT Transport Format (XPT) for submission of electronic study data to the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER).

Specifically, FDA is requesting feedback on the risks and benefits of industry adopting Dataset-JSON as a new exchange standard for submitting electronic study data to FDA and any integration challenges with existing tools and systems.

Comments are due June 9, 2025.

How to Submit Comments to FDA

Stakeholders may submit comments to the CDISC Dataset-JSON Version 1.1 Exchange Standard notice (Docket No. FDA-2025-N-0129) on or before June 9, 2025, and to the HL7 FHIR Standard for Submission of Study Data Derived from Real-World Data Sources notice (Docket No. FDA-2025-N-0287) on or before June 23, 2025.  Interested stakeholders should submit comments through regulations.gov.