While clinical trials are the gold standard for generating clinical data to use as evidence of your medical device’s safety and effectiveness, they are by no means the only way to gather clinical evidence.

Real-world data (RWD), which typically come from routine healthcare delivery or noninterventional studies like registries, is another potential source of clinical evidence. By collecting and analyzing RWD, you may be able to generate real-world evidence (RWE) that can support claims of safety and effectiveness.

Given the potential importance of these data to regulatory decision-making, it’s important to understand where real-world data come from, when they can be used, and how real-world evidence can support your regulatory and clinical activities.

What’s the difference between real-world data and real-world evidence?

The U.S. Food and Drug Administration (FDA) defines real-world data as “data relating to patient health status and/or the delivery of healthcare routinely collected from a variety of sources.” This is a fairly broad definition, but some examples of real-world data include:
• Data from electronic health records
• Data from medical claims
• Data from product or disease registries
• Data from other sources, like digital health technologies, that provide information on health status

Real-world data can also come from routine healthcare delivery, such as the use of a device in a clinical setting. The FDA notes that devices are often used in routine clinical practice that aren’t within their approved indications for use. If those data were systematically captured and analyzed, it could constitute suitable RWD that might support expanding the indication for use or inform new innovation.

The FDA defines real-world evidence as “the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of real-world data.” In other words, RWE is what you get once you’ve collected and analyzed your RWD. Real-world evidence can then be used to support claims of safety and effectiveness for your device.

How can medtech companies use real-world evidence?

Under the right circumstances, RWD and its associated RWE may constitute valid scientific evidence that can be used to support FDA regulatory decisions. Though RWD collected during clinical care or at home might not have the same quality controls as data collected during clinical trials, it could still be used by manufacturers to demonstrate compliance with regulations or support safety and effectiveness claims.

In 2017, the FDA put out a guidance document covering the use of RWE to support regulatory decision-making for medical devices. The guidance describes how the agency evaluates whether the RWD that manufacturers collect (and their associated RWE) are sufficient for use in FDA decision-making.

How does the FDA evaluate the suitability of real-world data?

In the guidance, the FDA notes there are many factors that go into assessing the suitability of RWD, but the two main factors the agency will consider are the relevance and reliability of the data. When it comes to relevance, the FDA will consider whether:
• The RWD contain sufficient detail to capture the use of the device, exposures, and the outcomes of interest in the appropriate population (i.e., the data apply to the question at hand)
• The data elements available for analysis are capable of addressing the specified question when valid and appropriate analytical methods are applied (i.e., the data are amenable to sound clinical and statistical analysis)
• The RWD and RWE they provide are interpretable using informed clinical/scientific judgment

When it comes to assessing the reliability of RWD and its sources, the primary factors the FDA will use to evaluate the RWD are:
• Data accrual, or how the data were collected (e.g., using a common data capture form, timeliness of data entry, or preparedness of sites for complete and accurate collection)
• Data assurance, or whether the people and processes in place provide adequate assurance that the data are high-quality and high-integrity (e.g., data consistency across sites, completeness of data for specific analyses, or adherence to source verification procedures)

In essence, the FDA wants to know that the data are relevant to your device and specific questions about it, and that the data were captured in a reliable manner that ensures their quality. And while this may seem like a tall order for data capture outside of clinical trials, with an electronic data capture (EDC) solution like Greenlight Guru Clinical, you can collect high-quality data from surveys, patient reported outcomes, and even valuable ad hoc sources—all of which are potential sources of RWD.

Use cases for real-world evidence

If they collect high-quality RWD, medtech companies can potentially use the RWE a product generates throughout the total product life cycle. There are uses for RWE starting during prototyping and clinical trials all the way through market release, postmarket surveillance, and continued innovation.

Potential uses for RWE include:
• Generating hypotheses for a prospective clinical trial
• Informing the design of prospective clinical trials
• Using RWE as a control arm for a clinical trial
• Building a data collection framework for postmarket evidence generation, such as post-approval studies
• Supporting the petition for reclassification of a device
• Public health surveillance
• Generating evidence to support expanding indications for use and future product innovations

Keep in mind that the FDA does recommend using its presubmission process to connect with the agency if a manufacturer is considering developing a study using RWD. And if you’d like to see actual examples of how RWE has been used in FDA regulatory decision-making, you can check out this FDA resource that lists 90 examples from 2012 to 2019.

What are the pros and cons of using real-world evidence?

The use of RWE can be an excellent way to support your device’s claims of safety and effectiveness. But RWD can have issues that might not make them ideal for use as clinical evidence.

The benefits of using RWE include:
• Learning about the performance of the device under real-world circumstances
• Collecting certain outcomes that aren’t always feasible in traditional trials
• Having opportunities to partner with patients in different ways, such as using wearable devices or apps for patient reported outcomes (PRO)
• Reducing the time and/or cost of answering important questions about the device
• Gaining valuable information for future device modifications or the development of new technology

The potential drawbacks that manufacturers often come across while attempting to use RWD include:
• Data may be confounding due to comparisons between biased populations
• Data may be of low quality or there could be missing data
• A lack of standard formats for documenting datasets, protocols, and tools to ensure reproducibility
• Study endpoints may not be reliable and/or clinically meaningful

These are potentially serious issues with RWD. However, in many cases you will be able to mitigate potential biases simply by creating a study protocol and data analysis plan prior to collecting and analyzing your RWD. In fact, the FDA’s guidance states that this planning is necessary whether RWD are being retrospectively or prospectively collected.

We need to collect more quantifiable data. Quantifiable data are important when applying statistical methods to collect data. But people often end up collecting a lot of free text and other misleading data that doesn’t really help.

An eCRF is not an EHR! By designing better forms that control the workflow and guide people through the “fill out” process, you’ll achieve improved compliance and less misleading data.

Users won’t have to wonder whether certain fields are relevant, and won’t be shown irrelevant information. This last action ended up becoming an inspiration for Greenlight Guru’s e-book on how to design an eCRF.

Whether you need to carry out clinical studies or collect real-world data from patients and clinicians, the captured data must be of the highest possible quality and integrity. At Greenlight Guru, we built our EDC solution specifically for medtech companies because we knew the industry needed a single, easy-to-use toolbox for collecting data from any source.

With Greenlight Guru Clinical, you can build customized eCRFs for clinical trials, but you can also collect data in a wide variety of ways, like ePROs, surveys, and ad hoc sources—all while staying compliant with regulatory requirements in the U.S. and EU. Check out a free demo here.

Published Sept. 19, 2024, in the Greenlight Guru blog.