By: Jeff Shuren, M.D., J.D., Director, Center for Devices and Radiological Health (CDRH) and Daniel Caños, Ph.D., M.P.H., Director, Office of Clinical Evidence and Analysis, Office of Product Evaluation and Quality, CDRH
Among the many ways that the U.S. Food and Drug Administration protects and promotes the public health is by ensuring the safety and effectiveness of medical devices, assuring that patients have timely access to them, and advancing medical device innovation. For sponsors of medical products, providing data from prospective randomized controlled trials has long been considered the gold standard to demonstrate the safety and efficacy of a regulated product. However, for many medical devices, practical limitations related to the device or disease condition require alternative approaches to prospective randomized controlled trials and increased flexibility in trial design and statistical analysis.
Advances in the availability of real-world data (RWD) sources – such as electronic health records, registries, medical claims, pharmacy data and feedback from wearables and mobile technology – have increased the potential to generate robust real-world evidence (RWE), to support FDA regulatory decisions. RWE is the clinical evidence regarding the usage, and benefits and risks, of a medical product derived from the analysis of RWD. The real-life clinical performance of a medical product might be more clearly demonstrated through RWD/RWE because a controlled clinical trial often cannot evaluate all applications of a product in clinical practice across the full range of potential users.
The CDRH Experience with RWD and RWE
The FDA’s Center for Devices and Radiological Health (CDRH) clarified how we evaluate the relevance and reliability of RWD to determine whether they are sufficient for generating the types of RWE that can be relied on for FDA regulatory decision-making for medical devices, in a 2017 guidance on Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices.
RWE can be leveraged to bring new products to market, evaluate the safety and effectiveness of existing products for new uses, and assess the continued performance and safety of products once on the market. The experience of CDRH, exemplified by a recent analysis, illustrates the wide range of RWE that has been used in regulatory decisions. Today, CDRH published the results of that analysis, which include 90 publicly available examples of different types of regulatory submissions supported by RWE. These examples come from the full continuum of clinical and device areas throughout CDRH and across the medical device total product life cycle but do not comprise an exhaustive list of all submissions that have relied on RWE.
Many Data Sources and Opportunities to Leverage RWE
Innovations in medical devices, including mobile apps, have resulted in novel data sources, including the device itself. For example, some automatic external defibrillators (AED) collect data during use, and in several cases device-collected data from out-of-hospital use were submitted in premarket applications for AEDs (see P160012, P160032, and P160033). In another example, a De Novo classification request for a mobile software application for contraception was supported by an analysis of data from more than 15,000 women who had used the mobile application outside the U.S. (see DEN170052).
Medical device registries can provide high-quality RWE when designed properly. For example, data from the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery Registry were the primary source of clinical evidence to support a modification to the indication for a large vessel occlusion catheter (see K170411). The aggregation of data in medical device registries can also provide ongoing device safety surveillance and additional evidence for effectiveness to meet postmarket data collection requirements. As an example, conditions of approval for a premarket approval (PMA) supplement to expand the use of a portable normothermic perfusion system for donor lungs include two post-approval studies using the United Network for Organ Sharing Registry (UNOS). One study follows premarket clinical trial patients long term in the UNOS database, and the other leverages the UNOS registry to collect data on a group of patients treated post-approval (see P160013/S002).
The FDA has relied on RWE to support regulatory decisions to help speed patient access to innovations that advance public health. The FDA also continues to broaden and improve the opportunities to leverage RWE for many types of devices. The National Evaluation System for health Technology, or NEST, may help do this. The FDA is working to establish NEST to integrate data from clinical registries, electronic health records, and medical billing claims to gather more comprehensive evidence of medical device safety and effectiveness.
When reviewing the use of RWE to support a regulatory decision, the FDA relies on scientifically robust methods and approaches to determine whether the submitted RWE is of sufficient quality to support the regulatory decision. Leveraging RWE has provided CDRH with more timely access to a broader and richer set of safety information to better protect the American public and to inform our oversight of the total product life cycle. By unleashing the power of RWE, we can accelerate medical product development and bring new innovations and advances faster and more efficiently to the patients who need them, without compromising patient safety.
We invite stakeholders to review the selected examples highlighted here to gain a better appreciation of the vast applicability of how widely applicable RWE has been and can be. Please visit: Examples of Real World Evidence (RWE) used in Medical Device Regulatory Decisions.