FDA’s Califf: Expect to see more RWE-based regulatory decisions

WASHINGTON – Use of electronic health records (EHR) to collect real-world evidence (RWE) that can then be used to expand a product’s indication is going to become more common, according to Robert Califf, commissioner of the US Food and Drug Administration (FDA).

Earlier this summer, Johnson and Johnson obtained an expanded indication from FDA for its ThermoCool SmartTouch SF ablation catheter to treat patients with persistent atrial fibrillation (AFib). While the device was already on the market for paroxysmal AFib, it was the first time the agency expanded the indication for a product based on real-world data (RWD) from a prospective, multi-center study. More specifically, the decision was based on EHR data from two hospital systems and coordinated through the National Evaluation System for health Technology (NEST) Coordinating Center, which is part of the Medical Device Innovation Consortium (MDIC).

Califf discussed the matter with Jijo James, MD, J&J’s chief medical officer, during a prerecorded conversation at the MDIC 2023 Annual Public Forum on 19 September 2023. He said that using RWE to expand product indications has been a sound theory, but it has taken a long time to make it a reality.

“I’m optimistic we’re going to make a real run at it in this upcoming year, across the whole federal government, not just within the FDA,” said Califf. “I believe that we’re moving very rapidly now to a place where more and more of the data we use for evidence is going to come from the so-called real-world clinical environment.”

“After all, the reason we do a randomized trial is to take a sample of people and reach a causal inference that allows us to extrapolate to the population,” he added.

On top of trying to obtain quality RWD, Califf also noted that researchers need to be careful about the methods they apply to the data, which includes how they design their prospective studies and analyze the data. He added that there has been a lot of progress in terms of the methods that researchers can use to analyze the data, which in some instances have been funded by FDA (RELATED: FDA finalizes guidance on real-world evidence in drug approval, Regulatory Focus 31 August 2023).

Another issue researchers need to be aware of, according to Califf, is the “time-zero problem” in prospective studies. That is a problem of determining when to start tracking data in follow-up studies so that they are meaningful and do not lead to biased conclusions.

Califf also noted that the rest of the research community should pay attention to how RWD from EHRs was used by Israel and the United Kingdom during the COVID-19 pandemic to observe how vaccines and different treatments affected patients in real-time. That data was used by FDA in its regulatory decision-making to allow vaccines and drugs on the market to fight the virus.

Looking across the room of attendees who represented a wide spectrum of stakeholders, including regulators, industry representatives, and patient advocates, the commissioner asked everyone to support the use of unique device identifiers (UDI) so that product data can be captured in EHRs.

“Without the device identifiers, we’re often lost in terms of being able to use the data,” he said.

The commissioner said that while the Center for Devices and Radiological Health (CDRH) has been leading on the issue of using RWE and RWD, other centers at FDA have taken notice and stakeholders should expect greater engagement and new guidances in the future.

“Even within [the Centers for Medicare and Medicaid Services (CMS)], … the Inflation Reduction Act on the drug side has made this a big deal because real-world evidence will be used in the price negotiations,” said Califf. “We’re in intense discussions with CMS about not the price negotiations… but what should the criteria be for the quality of the information that companies are submitting.”

Califf also said that he thinks industry is closer than ever today to successfully using remote monitoring sensor data to gather RWD that can be used for regulatory decisions. But there are still certain technological limitations, such as missing sensor data and being able to tie results to clinical outcomes, that researchers need to address to make their data meaningful, he said.

“The problem, I think, is that most of the companies that deal with sensors either don’t know about human clinical research that much or they’re too small to do these sort of methodologic studies that cost money,” Califf said.

Source: https://www.raps.org/News-and-Articles/News-Articles/2023/9/FDA%E2%80%99s-Califf-Expect-to-see-more-RWE-based-regulato