Regulatory News | 05 August 2024 | Jeff Craven
Sponsors thinking of incorporating real-world evidence (RWE) into their submissions should consider RWE as just another form of clinical evidence, according to a recent presentation from a US Food and Drug Administration (FDA) official at the Orange County Regulatory Affairs Discussion Group annual conference.
“[R]eal world evidence is just clinical evidence. There aren’t two things that we should be thinking about differently,” Felipe Aguel, deputy director in the Office of Clinical Evidence and Analysis at the Center for Devices and Radiological Health (CDRH), told attendees at the meeting.
Aguel said FDA has encountered misconceptions around RWE both internally and externally over the last few years. One of the most common misconceptions is that published literature is considered RWE. While Aguel acknowledged some published literature can be RWE, like when literature reports on RWE studies, it is not true of all published literature. For example, if published literature is a report of one or more clinical trials, that is not considered RWE, he explained.
“The distinction between clinical data and real-world data isn’t the availability or the ownership of the data or the availability of line-level data,” Aguel said, it is in how it was collected, noting a difference between data collected during routine clinical practice and data collected while following a protocol.
“Clinical trials that are published, whether or not there’s access to the line-level data, is not considered real-world evidence in CDRH,” he said. “If the data was collected via routine clinical practice and a study’s collected, or a case series is published, that is all considered real-world evidence whose relevance and reliability would have to be assessed.”
Two other misconceptions around RWE are that the standard for marketing authorization is relevance and reliability if a marketing submission uses RWE, and that CDRH must accept RWE if it exists “because that is least burdensome, and FDA is seeking to increase the use of real-world evidence.” Both of these statements are untrue, Aguel said.
“The standard for marketing authorization remains substantial, equivalent safety and effectiveness,” he explained, “it’s just that the type of clinical evidence supporting those decisions could come from a prospective clinical trial, or from real-world evidence, or even from other data sources.”
Concerning the claim that FDA is required to accept RWE, Aguel told attendees that the agency makes benefit-risk decisions for all clinical evidence, including RWE and evidence from a prospective clinical trial.
“CDRH takes uncertainty principles into account,” he said. “Many of the questions that reviewers consider when reviewing clinical trial data pertain to the reliability and relevance of that data, and the same is true for real-world data.” To that end, the agency considers sources of bias and uncertainty in these data, he noted.
“[A]t the end of the day, what we’re trying to do is put a bound and understand the uncertainty present in the clinical data, regardless of where it’s coming from, in order to make a benefit-risk decision for that particular submission,” Aguel said.
Aguel also shed some light on misconceptions around FDA’s 2023 draft guidance released on use of RWE in regulatory decision-making for medical device (RELATED: FDA proposes updated medtech RWE guidance, Regulatory Focus 19 December 2023). While the draft guidance contains more detail than the 2017 final guidance, it was intended to elaborate on what the agency had been looking since before that final guidance had been published, he noted.
Sponsors may want to gravitate towards the changes in the 2023 draft guidance, but Aguel emphasized that the 2017 final guidance is still in effect until the draft guidance is finalized. Aguel said the agency is still reviewing comments from the 2023 draft guidance and intends to publish a finalized version of the guidance.
“When the 2023 draft guidance is finalized, the intent is not to change the bar,” he said. “The intent is to clarify and provide the details necessary for industry to provide the information that FDA needs to make the decisions on well conducted, real-world evidence studies.”