Double-blind clinical trials have always been the gold standard of clinical research, but that does not mean they don’t also have significant limitations. Insufficient patient participation, representation of ethnic and racial diversity in the study population, and the cruel reality that some study participants will only receive a placebo are some of the biggest frustrations with the randomized controlled trial. They are also part of the reason why some 80% of clinical trials fail to meet enrollment timelines and requirements. 

Recently, advances in analytics have made it possible to augment — and, in some cases, bypass altogether — the randomized controlled trial with real-world evidence (RWE) gathered from data sources like Komodo’s Healthcare Map™ of real-world patient journeys.  By tracking the patient from the moment they present with a first symptom to their trajectory over time across different specialists, lab tests, procedures, and therapies, Life Sciences teams can now identify patterns of behavior and health outcomes — previously captured only through a clinical trial — without ever fielding a study or dispensing a placebo.

RWE Makes Inroads in Regulatory Process
This approach recently allowed Pfizer to win a label expansion for its breakthrough breast cancer therapy, Ibrance. It also helped Astellas receive FDA approval for its immunosuppressant drug, Prograf, based on a non-interventional study that used RWE from the U.S. Scientific Registry of Transplant Recipients. 

The U.S. Food and Drug Administration (FDA) has made no secret of its interest in leveraging RWE. The agency’s Advancing Real-World Evidence Program aims to improve the quality and acceptability of RWE-based approaches to support new intended labeling claims and satisfy post-approval study requirements. In fact, the FDA has been a pioneer in adopting RWE since the publication of its landmark framework for real-world evidence program in 2018.

How is this growing interest in RWE playing out in the trenches, where Life Sciences teams are developing new therapies and creating the best ways to incorporate RWE into their regulatory submissions? And could RWE eventually replace the traditional clinical trial?

The Future of Regulatory-Grade RWE 
These are two critical questions that Edd Fleming, Executive Vice President, Commercialization at Enavate Sciences, posed to Tracy Mayne, an industry leader, at Komodo’s recent The One Day Summit. In a wide-ranging “fireside chat,” the two shared their experiences with RWE in the regulatory setting.

“There are some holes in randomized clinical trials. They are still the gold standard, but there are some things that you cannot account for and things that do not always work,” said Mayne. “Looking at the rare disease fast-track program as an example, there are some unintended consequences. Most commonly, if a patient is seeing no effect and suspects they are getting the placebo, they will often drop out of the trial and go on the drug because the drug is already on the market.” 

Mayne explained that, in his former role at Intercept, his team conducted a series of studies using RWE alongside a randomized controlled trial to test for managing bias and found that, as bias hazard ratios improved in the trial population, so did the ratios in the RWE population. “What this showed us is that we were seeing the true treatment effect in the RWE,” he said.

When asked how this type of approach might influence regulatory approvals in the future, Mayne explained, “This is precedent-setting science and policy, and the FDA has a very big ship to steer, so we need to understand that this is a process, an evolution.

“The FDA treats RWE the same way they treat a clinical trial. They are looking for hard endpoints, like hospitalization, death, transplant. If you’re going to use RWE as part of the regulatory submission process, you need to be able to present hard, quantifiable, explainable data with the same level of rigor and confidence you would data from a clinical trial.”

Fleming closed the discussion by noting that we’re still at the beginning of the journey with RWE and that future advances will create even more transformative impacts. “This is just the beginning,” he said, “...the potential of bringing wearable health tech into the equation to interface directly with the EHR, and Komodo taking all of that integrated data and surfacing all of the insights to create real-world studies. This really is such an amazing moment in time.”

For more information about the conversations we had during The One Day Summit, read "Reducing the Burden of Disease: 'One Day' Starts Now."

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