‘Clinical Trials System is Broken,’ FDA Drug Chief Says

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By Jeannie Baumann

The nation’s clinical trial system is “broken” and needs to be changed to generate better evidence that leads to better patient outcomes, the head of the FDA’s drug center said.

“I personally believe, like many other people, that the clinical trial system we have right now is broken. It isn’t working to meet the objectives that we need it for,” Janet Woodcock, director of the Center for Drug Evaluation and Research at the Food and Drug Administration, said Sept. 20. “Our inability to generate the needed evidence efficiently and in a cost-effective manner will continue to be a barrier to innovation and to the quality of care around the world.”

The shortcomings in the current system are wasting hundreds of millions of dollars, said Robert M. Califf, the immediate past FDA commissioner who now holds data science positions at Duke University and Verily Life Sciences LLC, which is part of Google‘s parent company Alphabet Inc. Both 21st Century Cures ( Pub. L. 114-255), the biomedical innovation law to spur new drugs and devices, and the latest user fee law ( Pub. L. 115-52) to set fees the FDA collects to review medical products direct the agency to consider ways of folding real-world evidence into its regulatory decision making. Both Califf and Woodcock made clear that the drive to factor more real-world evidence into the FDA’s regulatory decisions isn’t just a legal mandate, but also that the agency’s upper echelon is putting its full weight behind this push.

FDA Committed

“FDA’s committed to exploring the use of real-world evidence in regulatory decision making,” Woodcock said. Both she and Califf made their remarks during a two-day workshop organized by the National Academies and sponsored by the FDA on examining the impact of real-world evidence on medical product development. FDA Commissioner Scott Gottlieb echoed those thoughts during remarks delivered the previous day.The idea behind this movement is to harness existing data sources such as electronic medical records to make decisions about the safety and efficacy of medical products that more accurately reflect how patients actually use them. It’s also a move to curb the cost and time of developing a new drug that has soared to more than $2.5 billion and 12 years, in large part due to expensive and increasingly complex randomized controlled clinical trials. But concerns linger that a shift away from traditional methods will lower the agency’s rigorous standards.

In an FDA device guidance released Aug. 31, the agency defined “real-world data” as information relating to patient health status and the delivery of health care routinely collected from a variety of sources such as electronic health records or mobile apps. Real-world evidence is the clinical evidence regarding the usage, and potential benefits or risks, of a medical product derived from analysis of real-world data.

The drug center would use real-world evidence in the same way the device center does, Woodcock said, including for planning clinical trial endpoints and developing biomarkers. These factors are excruciatingly important for the success of development programs, Woodcock said. A new drug candidate has about a 10 percent chance of getting through the clinical trial process, with a 42 percent chance of failing in the large, expensive phase III clinical trial stage, according to an analysis from the Biotechnology Innovation Organization.

The Big Kahuna

Incorporating real-world evidence into investigational drug review would be the “big kahuna,” Woodcock said, adding this will require a hybrid approach.

The NIH Collaboratory succeeded with this hybrid in establishing pragmatic clinical trials, she noted. In this environment, research takes place directly in the hospital, clinic, or other everyday health-care setting instead of being isolated in a randomized, controlled trial. Investigators and physicians work together to generate knowledge to create a learning health-care system that is constantly generating knowledge to improve care.

“We need to bring the clinical trial universe and the health-care universe as close together as possible so that much of the work is done in the actual process of care,” Woodcock said. Significant work would be required to establish these new trial platforms, she acknowledged, but the payoff could be significant. “There’s no reason this type of trial could not be done for regulatory purposes.”

These new drug development platforms also could help address objections to real-world evidence. “Randomization is completely possible, and yet you can still have most of the desirable elements of real-world evidence,” Woodcock said.

Bloated and Burdened

In what he described as “a mistaken understanding of the theory and purpose of clinical trials,” Callif said the regulated clinical trials industry and academic investigators have diverted enormous resources to increase data precision instead of ensuring these data are reliable. The traditional system has done a lot of good, Califf said, but it has become “bloated and burdened” with expensive practices that are increasing cost without improving quality.

“But I don’t think the right thing to do is to tear down the temple,” Califf said. “My main point is not that the system has failed. My main point is that I believe we’re in the new era where we can shed the old system and move onto something new, that’s quite different. And I believe we really should.”

The National Academies workshop was the first of a three-part series on real-world evidence. The second workshop will explore what types of data are appropriate for what specific purposes, and the third workshop will examine and suggest approaches for operationalizing the collection and use of real-world evidence.

To contact the reporter on this story: Jeannie Baumann in Washington at jbaumann@bna.com

To contact the editor responsible for this story: Randy Kubetin at RKubetin@bna.com

For More Information

More information on the National Academies workshop is available at http://www.nationalacademies.org/hmd/Activities/Research/DrugForum/2017-SEP-19.aspx.

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