Optimizing Real-World Evidence in Medical Device Development

The Evolution of RWE Generation for Medical Devices

The use of real-world data to generate RWE for medical devices by industry has become more prominent in recent years, and more attractive to a variety of stakeholders. It is used frequently to understand the use of the device in the larger clinical setting, but more recently it is also being used for regulatory decision making. Over the last few years, the use of RWE for medical devices has evolved for use in pre-approval trials for hypothesis generation, historical or synthetic controls, or supplemental data as part of the investigational device exemption, and post-approval trials for labelling expansion and post-market surveillance, particularly to satisfy the 522-mandate (Section 522 of the Federal Food, Drug, and Cosmetic Act).

Growing Adoption of RWD and RWE

In 2016, the signing of the 21^st Century Cures Act marked the pivotal moment that the U.S. Food and Drug Administration embraced the modernization of clinical trials and outcome assessments to help accelerate medical product development. Around the same time, the FDA’s Center for Devices and Radiological Health released strategic priorities to increase the use of RWD for generating the types of RWE that can be used in FDA regulatory decision making for medical devices. These included the implementation of the National Evaluation System for health Technology, which leverages RWD to identify safety issues faster and to better understand the risk-benefit profile of devices when used in the larger clinical care setting. Between 2016 and 2017, the Center for Devices and Radiological Health’s strategic priorities accomplishments noted that the number of pre-market and post-market regulatory decisions that used RWE increased by 193 percent.

As RWD and RWE continue to rise in popularity and adoptability, it’s important to understand the benefits and applicability to stakeholders beyond just FDA.

Benefits of RWE

• Regulators: increases the body of evidence to assess device safety; used to support labelling expansion and generate data on a broader patient population
• Medical device manufacturers: decreases time to market, identifies any technical training required for providers, identifies challenges and opportunities in clinical practice, captures patient and provider experience; provides information on routine clinical practice use of devices that are not within the approved indication for use (i.e. off-label uses)
• Patients: determines how the product will work for patients given their age, gender, or comorbidities, and their quality of life and other patient-reported outcomes
• Providers: provides outcomes in clinical practice
• Facilities: improves understanding of patient and provider outcomes
• Employers: helps employers better understand the effects on care utilization and absenteeism
• Payors (including CMS): determines peri/post-procedural complications or other device-related issues, assesses long-term outcomes, evaluates provider and facility outcomes, and the total cost of care delivery

HealthCore has a strong history of collaborating with other organizations to advance the use of RWE generation. The following are several examples of successful RWE use cases outlining some of the efforts to maximize the value of RWE generation in medical devices.

Successful RWE Use Cases

In the late 1990s, New England Research Institutes (now HealthCore) formed a unique collaboration with the Society for Vascular Surgery, the FDA, the Centers for Medicare and Medicaid Services, the National Heart, Lung, and Blood Institute, ten medical device manufacturers in the field, and clinicians to create the Lifeline Registry for Endovascular Aneurysm Repair that standardized the collection of outcomes, definitions, and data elements in the treatment of abdominal and thoracic aortic aneurysm. The Registry was established before any endovascular aneurysm repair devices were given marketing approval, with the express intent of instituting a standard protocol applicable to multiple patient populations both in pre-approval studies and post-approval studies. It collected baseline, procedural, and long-term follow-up data (up to five years) on 323 surgical controls and 2,664 patients treated with endovascular aneurysm repair both under investigational device exemption trials as well as post-market surveillance. The learnings of the Lifeline Registry and collection of standardized endpoints and definitions still resonate today in clinical practice, making the extraction of RWD more consistent.

Since that time, HealthCore has expanded the use of RWD in medical devices considerably. Our Health Economics and Outcomes Research team has published nine research studies. Additionally, there are several studies currently being conducted that have not yet been published. Our Translational Research team has utilized our data ecosystem on several collaborations with the National Evaluation System for health Technology as well as industry evaluating the devices resulting in six presentations and publications. HealthCore’s Clinical Research team continues to conduct clinical trials, including pragmatic clinical trials such as BEST-CLI (NCT0206030) and PRESERVE (NCT02381509), and the BEST-CLI Registry (NCT04191746). In addition to generating RWE with these studies, the BEST-CLI trial is collaborating with the FDA to provide further insights on our trial population for which paclitaxel-coated balloons and paclitaxel-eluting devices were used due to recent safety concerns.

Certainly there are some challenges to generating RWE for medical devices. The following list is not exhaustive, but includes many of the common challenges faced by stakeholders across the healthcare research industry.

The Challenges/Barriers to Obtaining RWD

• Inability to assess the incremental value of the device in instances where multiple medical devices or surgical techniques are used during a single procedure
• Difficulty generalizing study findings across providers who may not be utilizing the same standard of care or the same treatment patterns
• Lack of standardization of collection of relevant endpoints, common data elements, event definitions
• Inconsistencies in claims, pharmacy, billing, and electronic health/medical records (EHR/EMR)
• Inability to identify specific medical devices due to lack of unique device identifiers
• Pediatric patients may have Medicaid which is governed state by state

HealthCore is working to solve these challenges, but especially lack of unique device identifiers and limited access to Medicaid data. Unique device identifiers enable us to identify specific medical devices, and Medicaid data allows us to identify pediatric patients. We’re actively contributing to the National Evaluation System for health Technology Coordinating Center with data from over 90 hospitals and 90 clinics across the U.S. with more than 65 million patient records providing claims, unique device identifiers, and registry data as well as participating in the National Evaluation System for health Technology Coordinating Center test cases to further explore the feasibility for a medical device ecosystem for stakeholders. New England Research Institutes (now HealthCore) has also participated as an early collaborator for the Pediatric Cardiovascular Device Consortium under Boston Children’s Hospital. The continued advances in these initiatives are promising.

The use of RWD to generate RWE in devices is expanding and now more widely accepted by our industry. This is seen through FDA’s continued commitment through public meetings and funding initiatives, as well as industry’s demonstrated use of RWE in regulatory decision making. Let’s continue the conversation!