FDA Alert

FDA Releases the Latest in a Series of Draft Guidance Documents on Real World Data

December 3, 2021

Earlier this week, the Food and Drug Administration released the latest in a series of draft guidance documents on the topic of real-world data (RWD) to support regulatory decision-making for drugs and biological products.[1] These guidance documents are a part of the Real-World Evidence (RWE) Program framework. FDA developed in response to a mandate in the 21st Century Cures Act.[2] As required, FDA established the program to evaluate the potential use of RWE to help support the approval of a new indication for an approved drug or to help support or satisfy post-approval study requirements.[3]

In September 2021, FDA released a comprehensive draft guidance document regarding the use of electronic health records (EHR) and medical claims data to support regulatory decisions for drugs and biologics.[4]  The draft guidance proposes how to make appropriate selections of data sources, develop and validate definitions for study design elements, and evaluate data quality throughout the course of the data life cycle. Due to the inherent limitations in using EHR and medical claims data, FDA recommends that sponsors submit proposed protocols that include information on the relevancy of the data sources and provide sufficient detail about the data sources to capture the study populations, exposures, key covariates, outcomes of interest, and other important parameters relevant to the study. The draft guidance also provides recommendations on issues such as data capture, handling missing data, use of unstructured data, and data linkage and synthesis.

FDA followed up in October 2021 with another draft guidance document addressing some preliminary considerations for making regulatory submissions containing study data derived from RWD sources using data standards supported by FDA as specified in the Data Standards Catalog.[5]  The draft guidance proposes that sponsors seeking to conform RWD to these data standards should consider the data transformations, conversions, or mappings that may be needed to create study datasets in the required format. The draft guidance also proposes a glossary of key terminology and provides examples of mapping certain health care data with traditional clinical trial data using standards accepted by FDA.

In the latest draft guidance, FDA builds on the themes discussed in the previous documents and outlines its proposed approach towards assessing the use of patient registries to support a regulatory decision. The draft guidance discusses various considerations regarding a registry’s fitness-for-use in regulatory decision-making. Fitness-for-use may depend on how the data are intended to be used, the patient population enrolled, the data collected, how the datasets were created, maintained, curated, and analyzed, and whether the data can be supplemented by linking data from other sources.

The main takeaway from the collective set of draft guidance documents is that drug and biologics sponsors seeking to incorporate RWD to support regulatory decisions involving their products should meet with FDA before conducting a study that relies on such data. To have a productive meeting with FDA, sponsors should first prepare protocols and statistical analysis plans that explain the reliability, relevance, and comprehensiveness of the data sources as well as the methodologies used to validate key design elements and maintain quality during data accrual, curation, and transformation to the final data set, and also take into consideration the potential impact of linking one or more registries or data systems on the overall integrity of the data.

While the public can submit comments on FDA guidance documents at any time, stakeholders are encouraged to submit comments on the most recent draft guidance on assessing registry data to the docket prior to February 28, 2022.



[1] FDA Draft Guidance, “Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products” (Nov. 2021), https://www.fda.gov/media/154449/download.

[2] Food & Drug Admin., Framework for FDA’s Real-World Evidence Program (Dec. 2018), https://www.fda.gov/media/120060/download.

[3] See, 21 U.S.C. § 355g.

[4] FDA Draft Guidance, “Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products” (September 2021), https://www.fda.gov/media/152503/download.

[5] FDA Draft Guidance, “Data Standards for Drug and Biological Product Submissions Containing Real World Data” (October 2021), https://www.fda.gov/media/153341/download.