Medical device manufacturers are navigating the waters on the best ways to use real world data (RWD) to support their regulatory strategies and submissions to the U.S. Food and Drug Administration (FDA). The pathway for successfully leveraging RWD in regulatory submissions is complex and must be tailored to each scenario.

This column will discuss considerations related to real world data and the best methods to improve the chances of leveraging real world evidence (RWE) to achieve regulatory success. The FDA released its guidance document, “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,” in 2017. The agency defines RWD as “data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources,” such as data derived from electronic health records, claims or billing information, or registries. When RWD are analyzed, they are presented as RWE, which FDA defines as “clinical evidence regarding the usage, and potential benefits or risks, of a medical product.”

These definitions are broad and allow industry to apply the FDA’s recommendations to a wide range of scenarios. This can raise both challenges and opportunities, in understanding FDA’s exact recommendations, and how to use RWD to provide insights into a medical device’s safety and performance. 

Let’s explore the ways in which each of the five W questions—commonly used for project planning and problem solving—can be used to leverage RWD in a regulatory submission: Who, What, Where, When, Why (and How!). 

Who 

The medical device industry continues to learn how best to utilize RWD and follow FDA guidance, including manufacturers, consultants, health information technology companies, payers, clinician groups, and research sponsors. As regulatory consultants, we engage in many interactions with FDA on behalf of clients who want to use RWD in regulatory submissions. 

When evaluating RWD, a sponsor should consider who is captured in the dataset regarding patient and surgeon population. FDA will typically ask for sufficient demographic data to demonstrate the treated population is in line with the proposed device use indications, and that they are generalizable to the relevant U.S. population, including surgeon training level. 

FDA also will typically ask who collected the data, which is another important factor to consider when demonstrating the data are reliable. A sponsor should fully understand who collected the data, whether the collectors are prepared and qualified, and who helped ensure quality control. One practical way to demonstrate data reliability is for the sponsor to provide the qualifications of the site personnel or clinical research organization responsible for collecting and monitoring the data. It also could be beneficial to consider whether an independent reviewer can improve the dataset’s reliability and quality.

What

FDA will want to understand the level of evidence available (i.e., exactly what data are available), including data sources and types of analyses to be conducted. Creating a common set of data elements or data dictionary can be helpful for both the sponsor and FDA to understand the RWD. This is the first step in developing the regulatory strategy around utilizing the data to support a regulatory submission, then considering the precise goal of the regulatory submission and data relevancy. For example, a sponsor cannot expand the indications for use based on RWD collected from a registry if the dataset lacks sufficient evidence on indication treated or adequate follow up information. 

Lastly, the sponsor must consider the specific methods and processes for data collection and quality control that were followed. Documenting these methods will ultimately give FDA confidence that the data sources meet regulatory expectations, in line with its guidance.

Where

Where the data are sourced from is important, and it is the sponsors’ responsibility to consider if the sources are reputable. A sponsor should provide objective evidence to FDA proving the data are from reliable sources. Such credible references include a patient-level database, study or validation protocols; copies of ethics committee approvals; or copies of claims data. Each RWD source is unique but the sponsor must assure FDA that its data come from reputable sources, is routinely collected, and accurate compared to verifiable source documentation. 

The precise data location is also important—the countries, hospitals, clinical study sites, etc., should be reported to FDA and be appropriate to inform the regulatory decision. 

When

The RWD should demonstrate device safety and performance in a time period that is representative of the product’s current design and practice of medicine. For example, data collected within the last five years may be more likely to be accepted than historical data. However, there may be creative solutions to using historical data (on a prior product version), if sufficient evidence is available to demonstrate the RWD are representative of the final finished design. 

Also related to when the RWD were collected, a sponsor should ensure the data allow for sufficient patient follow-up (minimum of two years), and whether there is sufficient time to analyze the data for the regulatory submission to meet company objectives. It is generally advised to include time in the project plan for consulting with FDA in a pre-submission to ensure the RWD are appropriate.

Why 

Sponsors have many reasons for using RWD as supporting evidence in regulatory submissions. Considering why the data is needed and why it is important to the product’s marketing goal is key to leveraging information that may already be available. The data collected from routine medical device use is powerful in understanding the real-world usage and performance, and when carefully understood, collected, and analyzed, RWD can provide a least burdensome approach for sponsors to collect and submit clinical evidence. It can also be used to develop a control population for comparison to a new investigational device and may help describe the benefits and risks of a device to inform FDA’s decision making.

How

There are many questions to ask when developing a RWD strategy and planning an FDA submission: How can a sponsor prove its RWD are relevant and reliable to FDA? How stringent will FDA be in a specific scenario? How will FDA’s feedback differ based on the classification or novelty of a device? How can a specific regulatory question be answered by leveraging RWD? 

It may seem like there are more questions than answers. MCRA’s consultants continue to learn from industry and FDA in this area, and can help companies explore the best strategies to achieve success with their regulatory submissions.

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Sarah Pleaugh is director of Regulatory Affairs at MCRA, an IQVIA business, a global clinical research organization and advisory firm. pleaugh is focused primarily on U.S. regulatory submissions for orthopedic and spinal medical devices. A graduate of Michigan Technological University, she earned a bachelor’s degree in biomedical engineering and has worked in medical device regulatory affairs since 2007. For the last four years, Pleaugh has helped clients with FDA regulatory strategies and submission support, including pre-submissions for non-clinical and clinical data development, 510(k)s, Breakthrough Device Designations, and premarket approvals.