Earlier this week, the Food and Drug Administration released the latest in a series of draft guidance documents on the topic of real-world data (RWD) to support regulatory decision-making for drugs and biologics. .[1] These guidance documents are part of the Real-World Evidence (RWE) program framework. FDA developed in response to a mandate in the 21st Cures of the Century Act.[2] If necessary, the FDA has 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 meet the requirements of a post-approval study. .[3]
In September 2021, the FDA released a comprehensive draft guidance document on the use of electronic health records (EHRs) and medical claims data to support regulatory decisions about drugs and biologics.[4] The draft guidelines propose how to make appropriate selections of data sources, develop and validate definitions for study design elements, and assess data quality throughout the data lifecycle. Due to limitations inherent in the use of EHR data and medical claims, the FDA recommends that sponsors submit proposed protocols that include information on the suitability of data sources and provide sufficient details of the data sources to capture 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 The draft guidance also provides recommendations on issues such as data entry, handling of missing data, use of unstructured data, and data linkage and synthesis.
The FDA followed up in October 2021 with another draft guidance document addressing some preliminary considerations for submitting regulatory submissions containing data from studies derived from RWD sources using data standards supported by the FDA, such as specified in the Data Standards Catalog.[5] The draft guidelines propose that sponsors seeking RWD compliance with these data standards should consider any data transformations, conversions, or mappings that may be required to create study data sets in the required format. The draft guidance also provides a glossary of key terminology and provides examples of mapping certain healthcare data to traditional clinical trial data using FDA accepted standards.
In the latest draft guidance, the FDA builds on themes discussed in previous documents and describes the approach it proposes to assess the use of patient registries to support a regulatory decision. The draft guidance addresses various considerations regarding the suitability of a registry for use in regulatory decision making. Suitability for use may depend on how the data is intended to be used, the patient population recruited, the data collected, how the data sets were created, maintained, organized 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 biologic sponsors seeking to incorporate RWD to support regulatory decisions regarding their products should meet with the FDA before conducting a study that builds on this data. To have a productive meeting with the FDA, sponsors must first prepare statistical analysis protocols and plans that explain the reliability, appropriateness and completeness of the data sources as well as the methodologies used to validate the evidence. key design and maintain quality during data accumulation, retention, and transformation to the final dataset, and also consider the potential impact of linking one or more registers or data systems on the overall data integrity.
While the public can submit comments on FDA guidance documents at any time, stakeholders are encouraged to submit comments on the most recent draft guideline on the assessment of registry data on file before the deadline. February 28, 2022.
[3] See, 21 USC § 355g.
