FDA Releases Finalized Guidance on Use of Real-World Data in New Drug and Biological Product Submissions

Recently, the United States Food and Drug Administration (FDA) finalized two guidance documents that outline how sponsors can use and submit real-world data (RWD) in their new drug and biological product submissions with the agency.

The first guidance, Data Standards for Drug and Biological Product Submissions Containing Real-World Data, describes the agency’s criteria for converting data that is derived from RWD sources to FDA-supported data standards for new drug applications and biologics license applications. The second guidance, Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products, looks at the use of registries as a source of RWD for regulatory submissions.

Data Standards

In the guidance that discussed data standards for RWD submissions, the FDA addressed concerns about mapping RWD to FDA-supported data standards. This includes RWD pulled from electronic health records, medical claims data, data from product and disease registries, and data gathered from mobile devices.

The guidance notes that when seeking to conform RWD to data standards that are supported by the FDA, sponsors “should consider the relevant data transformations, conversions, or mappings22 that may be needed to produce study datasets in required formats in an applicable drug submission.” Along those lines, sponsors are recommended to discuss “as early as possible” with the FDA review division “any planned submission of study data derived from RWD sources in an applicable submission and their approaches to mapping and transformation of data,” and that conversation should include approaches for taking data from its original RWD format to intermediary format(s), including those used for analysis, and to the study data set ultimately prepared for submission to FDA.

This guidance also addressed challenges in standardizing RWD and processes for managing RWD. Additional factors that may challenge the standardization of RWD include the potential of using more than one RWD source in a study, such as combining electronic health records and claim data, or the fact that some data (such as physician and health care provider notes) only exist in a non-structured format. Sponsors also often have varying levels of access to data sources in the study, which further complicates the standardization of using RWD.

This final guidance is an update of a 2021 draft guidance and FDA notes that it did consider public comment in formulating the final guidance document.

Assessing Registries

In the other guidance that discussed using registries to support regulatory decisions surrounding the safety and effectiveness of drugs and biologics, the guidance covers a registry’s fitness-for-use considerations when linking it to another data source, such as electronic health records, medical claims, or digital health technologies.

The guidance document notes that in instances where the registry does not include all necessary information to answer the question of interest, sponsors “may consider obtaining supplemental information from another source. For example, sponsors may consider linking the data on a patient in the registry to the same patient in another data system or systems, such as another registry, an EHR, a medical claims database, or a digital health technology.”

The final guidance includes new language that notes that sponsors that propose to use registry data to support regulatory decision-making are also responsible for ensuring that attributes of the registry support the collection of relevant and reliable data – even in situations where the registry data is not managed by the sponsor.

The guidance document also notes that sponsors should have a plan to address missing assessments, including “outreach to patients who do not maintain contact with the registry or have difficulty doing so (e.g., text messages, phone calls, emails, offers of transportation assistance).

The guidance is an update of a 2021 draft guidance as well.

Califf Statement

In the announcement of the release of the guidance documents, FDA Commissioner Robert M. Califf, M.D., notes that “the FDA is supporting research (or “demonstration”) projects that seek to improve the quality of RWD and RWE. Strengthening systems for generating and gathering new and better data and analyzing those data to provide reliable evidence to inform and improve the many decisions we make as consumers, patients, families, clinicians and regulators, is key.” He also noted that in 2024, we can expect “an emphasis across our U.S. Health and Human Services agencies on [Real World Evidence, or] RWE, including point of care prospective clinical trials, in the post-market and health policy arenas.”