Money, Mandate Are Keys to FDA's Drive for Use of Real-World Evidence, Gottlieb Says

Use of real-world evidence in the drug approval process will accelerate rapidly, former FDA Commissioner Scott Gottlieb, MD, said Friday, because Congress has given the agency both the money and a mandate to make this happen.

Real-world evidence, which can include data from electronic health records (EHRs) or claims, allows regulators to “fill in the blanks,” which Gottlieb said can eliminate the need for strict randomization when evaluating treatments for rare conditions or other unmet medical needs.

Gottlieb, who has returned to the American Enterprise Institute, stepped down from running FDA in April after 2 whirlwind years that saw a record pace of approvals and policy actions that covered everything from high drug prices to teen vaping. The policy agenda was still on his radar as he took the podium in Philadelphia at Patient-Centered Oncology Care^®, the annual meeting of oncology reimbursement stakeholders held by The American Journal of Managed Care^®.

He began his talk by sharing that he was in the midst of a Twitter spat with a Trump administration official who thought he’d wasted his time on tobacco regulation.

“I just got a text from someone pretty senior asking me to calm down,” he said, causing the room to erupt in laughter. Then it was down to business.

As FDA commissioner, Gottlieb advanced the use of real-world evidence with the December 2018 framework document that spelled out how the agency would comply with Congress’ directive under the 21st Century Cures Act. The $50 million that Congress authorized FDA to spend on a database of at least 10 million lives means that regulators will have to demonstrate how they are making use of that investment.

“Why this is really an inflection point,” Gottlieb said, “is now the agency has an obligation to figure out how to use practical data to answer regulatory questions.”

FDA now has money and direction from Congress, he said, “So it has to do it.”

Real-world evidence is not a complete unknown at FDA. Gottlieb said that some later indications for imatinib (Gleevec) were based on what today would be called real-world evidence. The difference now, he said, is that when a sponsor comes in with an application that makes use of EHR or claims data, regulators will be tasked with coming up with ways to incorporate that evidence in their decision-making process.

“You’re going to be pushing on an open door,” Gottlieb said. “That really, in my view, changes the equation.”

Science Leads the Way

Gottlieb is credited with creating a productive atmosphere at FDA that led to 59 approvals of novel drugs and biologics through the Center for Drug Evaluation and Research during 2018. The previous all-time high was 53 in 1996; the division’s 10-year average had been 33 approvals.

“Leadership can have an impact at the margins,” the former commissioner said, but in an indirect way. The jump in approvals, he said, “was not just because we were making policy changes or because the culture had changed,” but because Gottlieb said he took steps to “insulate” the regulatory staff from politics so they could focus on their work. “I testified 19 times on Capitol Hill,” he said, more than anyone “not facing indictment or under investigation.”

“By and large, what was influencing the review cycle was the nature of the science,” he said. Sponsors were coming in more prepared, with a better grasp of the populations that would benefit from new therapies. The agency was willing to embrace new trial methods like basket trials and the first tissue-agnostic approval (pembrolizumab for patients with unresectable or metastatic, microsatellite instability—high or mismatch repair–deficient solid tumors).

Most of all, early in clinical trial development, in small sets of patients, “We’re seeing outsize responses,” Gottlieb said. And that meant there were compelling reasons to give patients access to these therapies quickly.

More Advances to Come

Gottlieb pointed to a pair of changes that he believes will yield important dividends in the years ahead. The first is a decision to include rules for digital health tools that can aid adherence in promotional labeling instead of product labeling, so they do not slow down innovation. Sponsors have not exploited this so far, but it’s still early, he said

Second, Gottlieb sees much to gain from the movement toward “structured review,” which he said would bring more predictability in the approval process through a 52-member Office of Drug Evaluation Science, which will (1) create a platform for filing applications so time is not wasted reformatting submissions and (2) bring more uniformity to the process across divisions and reviewers.

“Right now, if you go from division to division, the nature of how they review is very different; it’s very different from person to person in a lot of ways,” he said.

Gottlieb said when it comes to incorporating real-world evidence, he knows that some might ask “what’s taking so long?”

“Actually,” he said, “It’s moving pretty quickly relative to historical precedent.”