Known for its conservative and what many call risk-averse nature, the Food and Drug Administration (FDA) seems to be headed in a bold and ambitious direction under Commissioner Scott Gottlieb, MD. What will his leadership mean for cardiology?
High energy, major buzz
Always a lively forum of discussion between members of the interventional cardiology community and officialdom, the FDA Town Hall at TCT.17 in Denver created the kind of buzz typically reserved for game-changing clinical trials. The reason was not hard to divine. Six months earlier Gottlieb was sworn in as the 23rd commissioner of the FDA, and the anticipation around how he might change the arc of drug and device approval was palpable.
“Having him as commissioner will have a huge impact on how we will be performing clinical trials and clinical research for drugs and devices,” says Roxana Mehran, MD, director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai Medical Center in New York and a TCT.17 course director. “He’s very futuristic and has a great vision for our industry.”
When President Trump named Gottlieb to head up the sprawling regulatory agency, there was no small number of skeptics and detractors. To be sure, the new commissioner was well versed in national health policy, having previously served as the FDA’s deputy commissioner for medical and scientific affairs and, before that, as a senior advisor to the FDA commissioner. But in his ensuing 10 years in the private sector, Gottlieb built relationships with, and drew considerable income from, a host of large pharmaceutical and bio-tech companies as a board member or consultant. How could the public expect its new FDA chief to effectively regulate an industry to which he was so intimately tied?
At least some of those critics have since reconsidered their opinions as Gottlieb unleashed a torrent of activity and pronouncements affecting virtually all parts of his realm. He’s cracked down on dangerous stem cell clinics. Ramped up the agency’s efforts against the national opioid epidemic. Made it easier for complex generic drugs to get to market. Streamlined the process for assessing the safety and benefits of new medical devices. Opened up the communication channels between drug developers and the FDA at critical junctures of the review process.
“He’s clearly a high-energy guy who’s moving at warp speed,” says Eric Topol, MD, director of Scripps Translational Science Institute in San Diego. “I think he’s exceeded most people’s expectations.”
Impact on digital health
One area where Topol expects striking changes under Gottlieb—with manifold implications for cardiology—is digital health. Experts say the field is on the verge of explosive growth fueled by wearables and monitoring devices like the FDA-approved Kardia Band (AliveCor) for the Apple Watch that allows people to capture their own EKGs to instantly detect atrial fibrillation. “My guess is that under prior FDA [administrations] it might not have been approved for years,” says Topol of the medical-grade watch band, the first Apple Watch accessory approved by the FDA.
“As artificial intelligence and machine learning provide better learning tools for these devices, I think you’ll see more of a marriage between technology and cardiologists in their everyday practice to help diagnose and treat patients with cardiovascular disease,” says Zach Rothstein, associate vice president of technology and regulatory aff airs for the Advanced Medical Technology Association (AdvaMed). As for Gottlieb’s role, Rothstein calls the one-time venture capital partner “a true champion of these technologies,” adding, “it's exciting to think where he might take this going forward.”
Indeed, the digital medicine field has praised what Gottlieb has already done to bring the long-promised revolution a step closer. Serving notice on one of his blog posts that the FDA’s regulatory process for medical devices had remained largely unchanged for 40 years, Gottlieb acted swiftly to roll back the regulatory burden on developers. For one thing, he revealed in December new 510(k) guidance for assessing the safety and effectiveness of medical devices whose risks are already well known. In another major move unveiled in 2017, a software pilot program essentially allows companies the FDA has pre-certified to submit less information to the regulator than was previously required prior to marketing a new digital health tool.
“The pre-cert pilot is attempting to define a new regulatory paradigm for digital health software that’s more modern and more in line with how these products are developed, released and updated in the field,” observes Rothstein, whose association worked with the FDA over 18 months to help develop the pilot. Another spur to digital device innovation, he adds, may lie in the ﬂurry of new guidance from the FDA that could provide the investment community with the clarity it needs to pour money into products its members might have avoided in the past due to uncertainty over regulatory approval.
Engaging drug developers
While pharmaceuticals pose a some-what different set of regulatory dynamics than devices, the FDA under Gottlieb seems no less determined to pare cost, complexity and delays from the protracted development process. The commissioner provided a window on his thinking in December when announcing new guidance for drug developers designed to broaden the communication channels. “By engaging with product developers early, often before clinical research is underway or an application is submitted to the agency, the FDA’s scientific experts can share important advice on the proper design of clinical trials and other aspects of the development and regulatory process,” Gottlieb said in a press release.
Robert Califf, MD, who served as head of the FDA prior to Gottlieb and is now the vice chancellor for health data sciences and a practicing cardiologist at Duke Health in Raleigh-Durham, N.C., backs his successor’s road map for drug development reform. “What’s happening now is an effort to expedite, streamline and optimize the development process,” Califf says. “The industry really wanted more meetings with the FDA and more guidance so that mistakes wouldn’t be made during development which would send a product back if it was good.”
As Califf and other experts in the field see it, though, the biggest change in cardiovascular research going forward could well be the expanded use of real-world data in clinical trials. The 21st Century Cures Act, enacted by Congress in 2016, put the focus on real-world data—which embraces everything from electronic health records (EHRs) and product/disease registries to health-monitoring devices and claims/billing activities—in healthcare decision-making, and directed the FDA to develop an implementation plan. “[Commissioner Gottlieb] is very much pushing for real-world evidence, which can dramatically reduce surprises and the cost of trials, and speed them up,” Califf says. “I give him a lot of credit for taking this seriously.”
Mehran, too, welcomes the direction Gottlieb has embarked on, viewing it as progress toward “a more pragmatic, simpler approach.” She envisions clinical trials moving “at the same pace as innovation and change in practice” and leveraging vast troves of patient data as well as programming tools that feed EHR data into a clinical database that is then used to understand the outcomes of patients undergoing treatment. “That has to be the way we are going to do large-scale clinical trials,” she insists. “When I see big pharma walking away from cardiovascular and toward oncology because the trials there involve fewer patients, quicker outcomes and earlier approvals from the FDA, I get very worried about the future of innovation in the cardiovascular space,” she explains.
As he moves to reset the processes around the development of drugs and digital devices, Gottlieb’s communications savvy—honed over years of traveling in Washington health policy circles—promises to serve him. As commissioner, he has been a frequent tweeter and blogger and speaks regularly at conferences. Few issues appear to be off limits to him. In issuing new guidelines to speed the introduction of gene and cell therapies with the potential to address unmet medical needs, for example, Gottlieb also announced a crack-down on rogue clinics offering dangerous or unproven versions of the treatments. “If you’re overly worried about who you’re attacking, you’ll never accomplish much in this job,” Califf says. “Scott has shown the courage to speak out—and that has clearly put him on top.”