Why the US FDA’s Growing Focus on Real-World Evidence Should Matter to You
Following the passage of the 21st Century Cures Act in 2016, the FDA developed a Real-World Evidence (RWE) Framework to outline how the agency planned to incorporate RWE in regulatory decision-making. RWE has historically been considered in the context of safety (e.g., the Sentinel Initiative), but this document also outlined how the agency would use RWE to better evaluate the effectiveness of drugs and devices. Recent FDA activities have continued to signal the importance of RWE to industry stakeholders, although some uncertainties lie ahead.
In 2024, the FDA released three guidance documents associated with the use of real-world data or RWE in agency decisions.
In March, the draft guidance document for industry titled “Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products” was released. Non-interventional studies are defined as observational studies such as cohort studies, case-control studies, and case-crossover studies used to assess the safety and/or effectiveness of a drug. This guidance describes the FDA’s current considerations for these studies related to the proposed approach, design, data sources, and analytic methods. The document in general advises study sponsors on key information that should be considered when developing an observational study protocol for agency review.
In July, FDA finalized their guidance titled “Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products”. This guidance provides considerations to industry around the use of common sources of secondary data for RWE studies and specifically focuses on how to assess the reliability and relevance of the data for the research questions and methods being proposed.
In September, the FDA issued their draft guidance titled “Integrating Randomized Controlled Trials for Drug and Biological Products into Routine Clinical Practice”. These interventional studies are sometimes called point of care trials or large simple trials, and the more accessible nature of these studies can generate results that are more generalizable than traditional randomized controlled trials. Investigators may often use sources of real-world data such as pharmacy dispensing information from claims or clinical data from electronic medical records to assess outcomes and streamline the trial design to better integrate the study into routine clinical practices.
Lastly, in December, the Center for Drug Evaluation and Research (CDER) announced the formation of the CDER Center for Real-World Evidence Innovation (CCRI) which will serve as a hub for RWE-related activities associated with regulatory decision-making within CDER. This center seeks to continue FDA’s efforts in the advancement of RWE, particularly in using this body of evidence in the development of new therapeutic options for patients.
Taken together, industry stakeholders should feel confident that FDA staff recognize the value of RWE in regulatory decision-making and these guidance documents will help de-risk studies by providing information that the agency expects sponsors to consider when initiating studies and submitting study protocols. The FDA also continues to recommend early outreach by sponsors to the agency, in order to discuss study-specific questions and considerations.
However, we must also recognize the inherent uncertainty around the upcoming priorities and initiatives of the FDA following the change in administration this January. The Department of Health and Human Services (which oversees the FDA, among other agencies) has paused all non-critical mass communications and public appearances, including those related to RWE. It is too soon to know how agency policies may change in the future, and the long and risky drug development process thrives best in an environment of regulatory and legislative stability. However, the value of RWE is well-established, and regulatory agencies and payers will still require the generation of RWE for decision-making purposes. The additional clarity provided by the FDA on relevant considerations for the execution of these studies and the centralization of efforts around RWE within the agency is welcomed and should continue.