For many years, the US Food and Drug Administration (FDA) has used what is now known as real-world data (RWD) and realworld evidence (RWE). It does so to monitor and evaluate the post-market safety of approved drugs. Throughout history, RWE has also been used to support effectiveness, albeit on a smaller scale.
The FDA defines RWD as “data relating to patient health status and/or the delivery of healthcare routinely collected from a variety of sources”. Examples might be data derived from electronic health records, medical claims data, product or disease registries, or other sources, such as digital health technologies. The aim of each is to inform on health status.
RWE, meanwhile, refers to the “clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD”.
The FDA’s Center for Devices and Radiological Health has also provided more information on its RWE programme for medical devices specifically. Updated in 2017, this guidance notes that there is “rapidly advancing methodology for generating and interpreting RWD”, and as such it doesn’t “elaborate on the methodological approaches that can be used”.
However, it adds, “when reviewing the use of RWE to support a regulatory decision, the FDA will rely on scientifically robust methods and approaches to determine whether submitted RWE is of sufficient quality to support a particular regulatory decision”.
The ways RWD and RWE are used have changed a lot over time, and continues to do so. Much of this is in line with the FDA’s Real-World Evidence framework, which supports timely safety signal detection and potential labelling expansions.
“The FDA welcomes the adoption and implementation of post-market surveillance efforts – by industry and others in the healthcare ecosystem – that leverage RWE as one of the tools for collecting data on medical devices once they are on the market,” an FDA spokesperson tells Medical Device Developments.
“While the FDA can’t directly speak to specific efforts and regulations for leveraging RWE to inform post-market surveillance taking place in foreign countries, in general, RWE can be leveraged to deliver further understanding of the performance, clinical outcomes and benefit–risk profiles related to medical device use.”
The view on the ground
So, what do those in the industry think about the recent movements, particularly from reactive oversight to more proactive, data-driven surveillance?
“The current administration is introducing radical transparency to government processes, while also adopting a more technology-forward approach to approving new innovations in the pharmaceutical and medical device sectors,” says Marcel Botha, a product development leader with 20 years of experience.
“For this approach to remain intrinsically safe as we drive faster go-to-market strategies and increase patient access, it’s essential to double down on RWE, which is impossible without RWD. The future of both pharma and IoMT [Internet of Medical Things] requires a deep understanding of how this data is collected, segmented and tracked over time to provide valuable insights into patient use, efficacy, safety and marketed function.”
Botha adds that this RWE future is “aligned with a macro trend of care moving out of hospitals, into clinics, mobile care solutions, and patients’ homes”. This, he feels, provides opportunity for the IoMT development and innovation community to step up and develop “modern, miniaturised, data-enabled medical devices that live and provide care closer to patients’ homes”.
He also cites many reasons why IoMT is unique. For instance, it enables continuous, passive data collection; device interconnectivity (including cloud, edge and remote monitoring); and high-volume, highfrequency datasets. This might be from wearables, smart inhalers or remote sensors.
David Davidson, a board-certified health law attorney (US) in Dickinson Wright’s Fort Lauderdale office, agrees that analytics are becoming more integrated into the changing face of healthcare, both by providers and by regulators. Specifically, he notes that providers are “using datadriven compilations to improve patient care, and to gain efficiencies”.
“Regulators have used data-driven information for a longer period of time. For example, the government has used statistical extrapolation to calculate damages under the False Claims Act, at least since the 1990s, with courts approving that practice in the 2010s.”
“RWE can be leveraged to deliver further understanding of the performance, clinical outcomes and benefit–risk profiles related to medical device use.”
FDA spokesperson
Patient safety is a key issue. According to Dr Brandi Niemeier, professor of behavioural sciences at New Anglia University, the future of this element lies in moving from retrospective analysis to realtime insight.
“By integrating IoMT-generated data, electronic health records and patient registries into regulatory surveillance systems, device manufacturers and regulatory bodies will be able to detect safety-related signals earlier, refine risk–benefit profiles continuously, and even identify opportunities for expanding device indications in real time,” says Niemeier.
“Just as high-fidelity simulation allows practitioners to learn in a controlled environment, robust real-time evidence frameworks allow regulators and manufacturers to ‘course-correct’ swiftly without waiting for adverse events to accumulate.”
Niemeier also points out the proactive model, “embodied in EU MDR Article 83”, published in 2017, and then “echoed in the FDA’s RWE initiatives”. She suggests that it “marks a fundamental shift towards ensuring that medical devices remain safe, effective and trusted throughout their life cycle “by integrating technology that allows for ongoing analyses in real time”.
“Proactive, data-driven surveillance lets us detect safety-related signals early to monitor and fine-tune device performance in real time, a fundamental shift from simply reacting to problems,” she adds.
“By harnessing IoMT data, health records and patient registries, regulators can continuously safeguard patients while simultaneously unlocking new opportunities for device innovation.”
“By harnessing IoMT data, health records and patient registries, regulators can continuously safeguard patients while unlocking new opportunities.”
Dr Brandi Niemeier, New Anglia University
Global differences
Also in the US, John Ziobro has worked in the medical devices field for 40 years. To name a few areas, this has seen him focus on engineering, document control, manufacturing and regulatory. A consultant for the past 16 years, he feels that the post-market surveillance (PMS, as defined in EU regulation) requirements that stem from Article 83 of the EU MDR have been “a burden without much benefit”.
Ziobro’s global outlook has alerted him to varying attitudes between those in the EU and the rest of the world. “Most of my EU clients have added one to two people to manage the paperwork, while most of my non-EU clients have left the market. I’m unaware of a single design change that has occurred due to PMS activities,” he reveals.
Regardless of the desire to comply or implement PMS/real-world processes, he recommends using a common vocabulary and consolidating it into one shared term.
The future for the industry
Botha predicts that consumer medical brands, such as Apple and Samsung, will “step up and become more valuable”. He also thinks there will be incumbent device manufacturers needing to change their approach to innovation, that “now span multiple device stakeholder communities without compromising quality and efficacy”.
Meanwhile, according to Davidson, it’s unsurprising that more sophisticated analytics would make their way into actual investigations and analysis. “The use of enhanced analytics will likely identify potential outliers more quickly, allowing regulators to take action sooner,” he expects. “That can also help the providers, since the universe of claims at issue could be smaller, potentially making the claims easier to defend.”
“A system similar to the EU MDR Article 83 would be interesting. Post-market data could open up a whole new level of whistleblower, based on information collected by a device manufacturer,” continues Davidson.
Analytics and AI are also becoming increasingly prominent within healthcare, and Davidson personally thinks that these can act as beneficial tools to both healthcare providers and regulators.
However, he warns all parties to be careful to not blindly rely solely on data and instead prioritise clinical judgment and human regulatory analysis.
Cross-borders
Some US-based medical technology manufacturers, such as Chicago’s Novian Health, are currently in their early stages of commercialisation in Europe. This entails aspects such as signing up distributors and scheduling demos.
However, Novian Health’s VP of operations, Eugene Bajorinas, shared that the company does have post-market clinical follow-up and PMS plans. These include a registry to track longitudinal outcomes, and it is looking forward to collecting the real-world evidence.
All in all, it appears that whether they’re based in the US, EU or even elsewhere, regulators and manufacturers are attuned to such a shift in surveillance.
Having a significant impact across the industry, it’s evident that a lot has changed in the past decade or so. And owing to a rapidly changing sector and new technologies in tow, it seems likely that more changes will soon follow suit.
