Source : 'The Pink Sheet'
Drug development during COVID-19 has forced the US Food and Drug Administration and sponsors to accelerate their understanding and adoption of real-world evidence, given the challenges in conducting clinical trials under social distancing guidelines, FDA principal deputy commissioner Amy Abernethy said during a Friends of Cancer Research meeting 22 September.
One “silver lining” of COVID-19 is that the pandemic has “forced us to get comfortable” with real-world data technologies like remote monitoring, telemedicine, and the ability to use RWD to fill in clinical trial datasets “and how they can work in action,” Abernethy said during the two-day meeting. The first day reviewed the results of the FOCR’s Pilot 2.0 project on real-word evidence. Abernethy spoke during the second day, which focused on the policy implications of RWE.
While COVID-19 has accelerated the understanding of how to apply real-world evidence to traditional clinical trials, operating during the pandemic has also highlighted how much more work is needed. Those learnings, Abernethy says, will help inform the next round of user fee negotiations and new FDA guidance to industry that will start to be released in 2021.
While advancing the science of real-world evidence was generally expected to be part of the PDUFA VII negotiations before COVID-19, the pandemic forced regulators and the drug development community to “get familiar with these new datasets” much more quickly “than the usual many-year process that we normally have encountered,” Abernethy said.
That meant technology like remote monitoring, which had been used on a limited basis, has “become a demand,” under COVID-19, “as patients could not come to the clinic,” she said. “That’s just one example. There has been a number of digital technologies that have been put into play that we’ll be able to understand better, so everything from biosensors and home pulse ox[imeter] monitoring to ultimately the incorporation of real-world data.”
Some of those technologies are “here to stay,” she said, while others will need to be “right-sized.” As the pandemic ends, a “huge task” for the RWD community will be “to step back and study in detail the impact of these technologies and understand how can we use them safely, what happens to the integrity of the dataset, and how to they perform as we expect and where to we need to edit how we incorporate them into our clinical design.”
For real-world data technologies to go forward post-COVID, Abernethy said, three criteria will need to be met:
Sponsors, who design, pay for and execute the trials “need to be willing to incorporate these technologies,”
Regulators need to have the “confidence to review datasets and provide feedback on what does and does not work,” and
Clinical sites and patients need to ensure that RWD fits “in the way that they conduct clinical trials and they know how to use the technologies.”
“One of my lessons learned, and one of my main pieces of advice,” Abernethy said, is the importance of the “familiarly” that “all three actors start to gain” with respect to RWE during the pandemic. “It allows sponsors to be more comfortable, FDA and other regulators around the world to say ‘OK, I understand how this is going to perform,’” and “site investigators and patient participants to be able to figure out how to do this.”
Mark McClellan, director of the Duke-Margolis Center for Health Policy, said he hopes the PDUFA VII user fee agreement will include funding for more real-world evidence pilot programs that can provide concrete examples of how real-world data can fill in evidence gaps left by clinical trials. But the onus is on industry to buy in, he said, and be transparent about their experiences.
“Looking ahead to PDUFA VII, I’d like to see the next phase take us into actual applications,” McClellan said during a panel discussion at the FOCR meeting. The next user fee agreement should include “more pilot projects done in conjunction with industry. Not just academic projects, but real, actual applications,” he said. “The expectation should be in industry for this next round if we really want to accelerate progress.”
That progress will come only if sponsors are “a bit more transparent than they are used to being,” and “view this as a pre-competitive activity in a number of key areas where there are questions about how RWE could be used for label expansions or assistance with trial designs or other regulatory purposes that really matter.” Sponsors also need to share their experiences so others can understand what FDA guidance on RWE “is likely to mean in actual applications.”
“The particular pilot applications themselves might not be the most dramatic transformation of evidence, but if we are really opening up this whole area of work to another degree of relevance for understanding the totality of the evidence, that seems like it’s worth some resources being committed by industry, or by being part of the next round of ‘21st Century Cures’ to take us from understanding the framework and getting a lot more sense of the potential to really starting to do this on a larger scale.”
“Cures 2.0,”as envisioned in a concept paper released this spring by congressional sponsors, includes a provision calling for FDA to issue guidance on utilizing RWE in Breakthrough Therapies and Accelerated Approval products as part of post-approval commitments. ()
Novartis AG global head of RWE and Data Science Adrian Cassidy agreed that “more concrete aspects” of real-world data should be a focus of PDUFA VII, along with greater transparency in how the data are used. “Being able to share the learnings more broadly would be hugely helpful, and really understanding the depth of the evidence generated, as well as how FDA is using it to make decisions.”
“The demonstration projects in PDUFA VI were highly relevant and innovative. Unfortunately, there was quite limited involvement from the pharmaceutical industry itself,” he acknowledged. “I would personally like to see those elements addressed within PDUFA VII and also the opportunity to collectively partner to develop pathways that enable patients to access effective therapies.”
CDER Office of Medical Policy Initiatives deputy director John Concato agreed that RWE pilot projects are “invaluable” and can help significantly accelerate understanding of real-world evidence in a “virtually risk-free” setting. “Important advances really come from the pilot work, and would otherwise need to be addressed in the future which would delay overall progress in the space.”
“The idea is that experiences gained can be replicated or modified, and shared. There are proven considerations for design, conduct and interpretation of RWE studies from different data sources,” Concato said. “They are really invaluable. They are transparent, and really low-risk, or virtually risk-free. So the bottom line is that return on investment on these pilot activities is going to be considerable – if not immeasurable."
By Kate Rawson