On December 18, the FDA issued a draft guidance, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices. When final, this guidance will supersede Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, issued August 2017.

The new draft guidance clarifies how the FDA evaluates real-world data (RWD) to be used in the agency’s regulatory decision-making for medical devices. It also proposes expanded recommendations for sponsors considering the use of real-world evidence (RWE) to support regulatory submissions for medical devices.

The guidance covers:

• Regulatory context in which use of RWE may be appropriate, including general considerations for the use of RWE
• Guidance on assessing data relevance and reliability
• Considerations for methodologies for collection and analysis of RWD to generate RWE

FDA considers the use of RWD to be fit-for-purpose to support generation of clinical evidence for regulatory decision-making for medical devices when it concludes that the RWD used to generate the RWE are relevant to and reliable for informing or supporting a particular regulatory decision. The agency notes that it is important to understand the strengths and limitations of the underlying RWD and how these qualities impact their relevance and reliability, as well as context of the specific regulatory decision for which the RWE is being proposed. FDA noted that it does not endorse one type of RWD over another. Sponsors should select the appropriate RWD sources based on their suitability to address the specific study questions.

Data sources that may be considered RWD sources include the following:

• Registries
• EHRs
• Administrative claims data
• Patient-generated data created, reported, or gathered by patients including in-home use settings (e.g., data from digital health technologies (DHTs) such as wearables)
• Device-generated data (e.g., implantable devices, physiological monitoring devices)
• Public health surveillance data (e.g., COVID-1919 case surveillance)
• Clinically annotated biobanks
• Medical device data repositories (e.g., imaging, electrocardiography databases).

Per the new draft guidance, some purposes for which use of RWD may potentially be applicable in a regulatory submission include the following:

• To generate hypotheses to be tested in a clinical study
• As a historical control, an informative prior in a Bayesian analysis of a clinical trial, or as one source of data in a hierarchical model or a hybrid data synthesis
• As a concurrent control group or as a mechanism for collecting data to support marketing authorization when a registry, EHR, claims data, or some other systematic data collection mechanism exists
• As a mechanism for re-training artificial intelligence/machine learning-enabled medical devices
• To generate evidence to identify, demonstrate, or support the clinical validity of a biomarker or clinical outcome assessment
• To generate (primary) clinical evidence to support marketing authorization (e.g., HDE, PMA, 510(k) or De Novo request)
• To generate evidence directly by the subject device to provide new information on safety or effectiveness
• To generate evidence to support a determination on whether the subject device meets the statutory criteria for a CLIA waiver21 (e.g., CW and Duals22)
• To generate evidence to support the interpretability of the primary clinical evidence (e.g., to demonstrate that the study population for an investigation conducted outside the United States (OUS) is representative of the U.S. population, or to provide context for an adverse event observed in the clinical study)
• To generate evidence to support a petition for reclassification of a medical device under section 513(e) or (f)(3) of the FD&C Act
• To generate evidence for expanding the labeling of a device to include additional indications for use or to update the labeling to include new information on safety and effectiveness
• To generate evidence for postmarket surveillance. Through ongoing surveillance signals are at times identified that suggest there may be a safety issue with a medical device. RWE may be generated using RWD to refine these signals for purposes of informing appropriate corrective actions and communication
• To conduct post-approval studies that are imposed as a condition of device approval or to potentially preclude the need for 522 submissions
• To provide postmarket data in lieu of some premarket data, consistent with FDA’s policy on balancing premarket and postmarket data collection

Stakeholders may submit comments under docket number FDA-2023-D-4395 at www.regulations.gov by February 20, 2024.