Industry cites outdated standards as flaw in FDA’s real-world data draft guidance

Regulatory NewsRegulatory News | 11 February 2022 |  By 

The US Food and Drug Administration (FDA) should adopt updated data standards that accommodate the “evolving and emerging” nature of real-world data not currently reflected in the Data Standards Catalogue, according to industry comments on the agency’s draft guidance.
Overall, comments from industry generally supported the principles in FDA’s draft guidance on data standards for drug and biological products submissions containing RWD (RELATED: FDA drafts data standards guidance for RWD, Regulatory Focus, 22 October 2021). The guidance addresses considerations for using data standards currently supported by FDA in applicable drug submissions containing data from RWD sources.
The guidance was issued as part of the agency’s larger real-world evidence (RWE) program and to fulfill a requirement outlined in the 21st Century Cures Act and Prescription Drug User Fee Act.
The Biotechnology Innovation Organization (BIO) summed up the situation in its comments. “The current guidance seeks to align modern data sets to data standards (those existing within the FDA) created for a different era in healthcare research. BIO recommends that the agency consider providing guidance for a more far-reaching approach to data standards and create a new data standard approach tailored for RWD, given the evolving and emerging nature of RWD assets that can be at the FDA’s disposal to facilitate data use for 21st century research problems,” the organization wrote.
The draft guidance specifies that sponsors use clinical and nonclinical study data using formats developed by the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model, and specifies that RWD submissions adhere to these standards set out FDA’s Study Data Technical Conformance Guide, last updated in 2018, when submitting such data to FDA.
Commentors noted that the guidance provides some needed direction on submitting RWD. The Pharmaceutical Research and Manufacturers of America (PhRMA) said it “appreciates that the agency is providing much needed clarity to sponsors and RWD vendors regarding acceptable data standards for regulatory submissions with the publication of this draft guidance.” Janssen Research & Development noted that “the guidance outlines important information regarding RWD management and considerations for sponsors as they conform to data standards currently supported by FDA.”
Data standards need to be revised
Yet there was overwhelming consensus that FDA needs to revise its data standards specified in the guidance.
BIO said that “while the FDA is applauded for seeking guidance for developing data standards to study data derived from RWD sources, the push to apply current FDA data standards to evolving and emerging data sets is somewhat challenging. Mainly, the data standards of existing data sets were created when the healthcare data ecosystem was not as diversified, heterogeneous, and technologically advanced.” The group recommends the agency “seek industry feedback in updating the catalog with additional standards for data using RWD sources.”
Regeneron Pharmaceuticals concurred. “While CDISC is a recognized and supported data standard, we recommend that the agency should also acknowledge other industry standards more suitable to map RWD, such as OMOP (Observational Medical Outcome Partnership) and FHIR (Fast Healthcare Interoperability Resources) common data model. There is a need for complex reformatting/mapping and transformation to get RWD into the CDISC format, which is not user intuitive.”
Flatiron Health, a health IT and electronic health record vendor, noted that “in some cases, complete mapping of RWD sources to Clinical Data Interchange Standards Consortium (CDISC) format may not be feasible. Flatiron appreciates the need for FDA to have access to source data in a standardized format to facilitate analysis of study results, including studies utilizing RWD. There are many challenges faced by efforts to apply current CDISC data standards to evolving and emerging data sets using RWD, as these standards were created when the healthcare data ecosystem was not as technologically advanced.”
More clarity on documenting processes for managing RWD
Some industry comments asked for more information on documenting processes for managing RWD.
The guidance states that “during data curation and data transformation, adequate processes should be in place to increase confidence in the resultant data. Documentation of these processes may include but are not limited to electronic documentation (i.e. metadata-driven audit trials, quality control procedures, etc.) of data additions, deletions, or alternations from the source data system to the final study analytics data set(s).”
The Pharmaceutical Research and Manufacturers of America (PhRMA) said that “the draft guidance is limited regarding the documentation needed during data curation and data transformation steps. To help sponsors understand FDA’s recommendations, PhRMA requests the agency define the term ‘metadata-driven audit trail’ as used in the draft guidance.”
Regeneron said many of the recommendations in this section “are generally outside of the control of the sponsors because they concern processes that may be considered proprietary by the companies that curate these data” and are not available to sponsors.


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Tags: data, FDA, real-world

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