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Pink Sheet – Real-World Evidence Could Help Relax Clinical Trial Enrollment Criteria

Pink Sheet – Real-World Evidence Could Help Relax Clinical Trial Enrollment Criteria

Executive Summary

FOCR study suggests overall survival for PD-1s seen in real-world datasets is similar to results from clinical trials.


BOSTON – Results of an upcoming study on the correlation of real-world endpoints to overall survival in trials could encourage sponsors to adopt broader inclusion criteria in clinical studies, according to Friends of Cancer Research President and CEO Jeff Allen.


Many patient advocates have pushed for “ways to broaden the access to clinical trials by use of enhanced eligibility criteira,” Allen told the Drug Information Association’s recent annual meeting, where real-world evidence was a theme of many panels. “And I think what we’ll see from this pilot project is that some of the results like overall survival really aren’t that different when compared to what was achieved in the clinical trials. So there may be potential to open up clinical trials a little bit more against the fear that you will diminish your treatment effect.”


The promise of real-world evidence has often been seen as allowing faster approvals because sufficient confirmatory data could be gathered in the post-market setting, but Allen’s observation also hints at the possibility that products could get to patients quicker not just because of earlier approvals but because of broader clinical trials.


Friends of Cancer Research’s study involves an examination of six different datasets, representing a mix of electronic health records and claims data, to see whether endpoints generated from real-world data correlate with overall survival and other key measures among patients with advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors.


FOCR will present the results at a July 10 event in Washington, DC, that will include a discussion of the related policy issues with product sponsors and FDA officials.


But even as the pilot study seems to offer the possibility of getting more people into studies, Allen acknowledged “it’s becoming more and more difficult to maintain randomization in clinical trials, so we have to think about different endpoints that can be extracted.” Particularly for products that have received a Breakthrough designation from the US FDA, “conducting some of these confirmatory trials will be challenging.”

Divide And Caution

Danish Medicines Agency Chief Medical Officer Nikolai Brun suggested the pilot study might also lead to faster approvals in Europe. “This is an area where there is a transcontinental divide in terms of how studies have been conducted. The FDA has been very forthcoming in approving single-arm trials that are also based upon response rates. In Europe we are a little more hesitant.”


Europe regulators tend to “want control arms, we want at least PFS [progression-free survival] before we are willing to approve some these treatments,” Brun said. “And I think the addition of real-world data to this can maybe take some of that fear out of the equation that the trials are enrolling patients who are too healthy, not representative of the target populations. So I think this is certainly a step in the right direction and I look forward to seeing the data.”


Allen said that leveraging real-world evidence could actually help the US catch up to Europe in some respects. “I think there may be potential in demonstrating the long-term value, at least in the US – perhaps as part of the transatlantic divide – we are a little bit behind in the processes at least the government uses in evaluating value. So this type of evidence could allow value to be assessed over time in the post-market space so it doesn’t slow the premarket.”


During the panel discussion, US FDA’s Jacqueline Corrigan-Curay, director of CDER’s Office of Medical Policy, offered a note of caution about the broader applicability of real-world evidence colorations that might be found in with cancer products.


“We tend to think of [oncology] as a more objective field … and patients are fairly compliant in going to their oncologist,” she said. “But if you think about endpoints in other diseases, where maybe motivations are different and there’s a lot of variability,” real-world data may not match up as well with findings from clinical trials.…