FDA's Califf Clarifies Real-World Data Use

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By Jeannie Baumann

Sept. 9 — It is a “total misfire” to pit randomized controlled trials against the use of real-world evidence as methods for evaluating new medical products for patients, FDA Commissioner Robert M. Califf said Sept. 8.

The commissioner of the Food and Drug Administration was addressing a move to incorporate real-world evidence, or data captured in routine medical care or from the patient directly, into the agency's regulatory decision-making process. Real-world evidence language appears in both the House-passed 21st Century Cures bill (H.R. 6) and the Senate's companion medical innovation effort to accelerate the development of new drugs and devices. The final agreement for the sixth authorization of the Prescription Drug User Fee Act (PDUFA VI) also includes incorporation of real-world evidence.

Proponents of adopting real-world evidence mechanisms, such as the Bipartisan Policy Center, say incorporating real-world data can address concerns about the $2 billion, decade-long effort it takes to develop a new drug, much of which is consumed by clinical trials. But groups like Public Citizen say moving away from the controlled clinical trial environment would mean increased risk to patients (10 LSLR 14, 7/8/16).

Califf's remarks responded to a question to identify the greatest challenges to and opportunities for using real-world evidence “to supplement, and in some cases substitute, for gold standard, randomized controlled clinical trials,” during Research!America's national health research forum.

Two Dimensions of Information

“I don’t blame you for the way you posed the question. I think it represents the way most people talk about it, and I think it’s a total misfire,” he said. “What we’re really talking about here are two dimensions of information.”

Those two dimensions, he said, are the source of the data and the experimental method being used.

“So it’s not one versus the other,” Califf said. “And I’ll just say the highest form of the arc in our view is randomization within the real world. And it’s happening. There are many successful examples developing.”

There has been a long tradition of doing clinical trials in a research clinic environment because of older information systems. Now capturing real-world data is more feasible because electronic health records are getting better, Califf said, adding that work at both the Patient-Centered Outcomes Research Institute and the National Institutes of Health has led to the development of higher-quality clinical data.

“That rarified, research clinic environment is a source of data. It’s not the method of randomization,” Califf said.

The emergence of personal devices and social media also make the use of real-world data possible to harness data that “we couldn’t even have talked about five years ago.”

“So when you talk about problems like movement disorder, there are a lot of people who believe that the old fashioned clinic detailed assessments are just completely the wrong way to do it,” Califf said. “We should be measuring motion in real life, which is entirely feasible. It couldn’t have been done without cloud computing, etc. That’s all possible now.”

Better Drug Labeling

“We can now expand into clinical practice, and it took me awhile to catch onto this,” Califf said. Drawing from his own experience running cardiology clinical trials, he said, “You can’t take a heart attack patient off to the research [clinic] and say, ‘Why don’t you have your heart attack tomorrow? We’ll make an appointment in the research clinic.' They come into the emergency room and that’s where you do your clinical trials in real life.”

The “old-fashioned, traditional clinical trial in the research setting” still has great value for early development of new medical products, as well as phase II studies, which measure efficacy and side effects, as well as phase III studies, which examine the efficacy of the investigational product and monitor for adverse reactions. But a randomized controlled trial also limits the risk-benefit profile that appears on the label once the FDA approves the product, he said.

“You can extrapolate and in general you’re right. But if you do the trials in the real populations that are going to get treated and you measure the real-world outcomes then you have a profile that gives you much better information to go into the label,” he said. “That’s the way we see it. This is going to be a rapidly growing area.”

The FDA is about to issue a “a series of writings” on real-world evidence, he said.

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 about Resesarch!America's national health research forum is at http://www.researchamerica.org/news-and-events/events/national-health-research-forum.

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