October 15, 2015 (Vol. 35, No. 18)

A Data-Driven Professional, Dr. Califf Could Be the Next
FDA Commissioner

Robert M. Califf, M.D., recently shared how his daughter gave birth to his third grandchild after a complicated pregnancy: “I was reminded about 15 times about how little evidence we have for most of what we do in medicine.”

Dr. Califf, deputy FDA commissioner for medical products and tobacco, shifted from family to agency in discussing evidence outlined in his July 29 presentation to the agency’s Science Board: “When the evidence is in, you can have arguments, but they’re a whole different type of argument than the argument you have when no one knows the right answer. But somebody has to make a decision. We have so many of those right now, it’s really a shame. Business is moving way ahead of medicine in this regard, and we’ve got to catch up.”

Nearly two months later, Dr. Califf is poised to lead that catchup effort and other FDA initiatives following nomination by President Obama for FDA commissioner, a nomination the U.S. Senate is expected to confirm. Dr. Califf joined FDA after 33 years with Duke University School of Medicine and the Duke University Medical Center, most notably vice chancellor of clinical and translational research and, in 2006, founder of the Duke University Clinical Research Institute. At Duke, Dr. Califf led several key  clinical trials, including the pivotal ROCKET AF study that led to FDA approval of Jansen Pharmaceuticals’ Xarelto® (rivaroxaban) in 2011. With more than 1,200 publications in peer-reviewed journals to his credit, he has been recognized by the Institute for Scientific Information as one of the 10 most-cited medical authors.

“He has clinical trial experience, a deep understanding of the scientific standards industry is held to, and a healthy appreciation for innovation,” Nancy Bradish Myers, J.D., president of Catalyst Healthcare Consulting, a strategic policy and regulatory affairs advisory firm, told GEN. “He has a strong network of high level academics, industry experts, and patients with whom he can consult and bounce ideas off of.”

“Looking forward, the FDA is going to need a leader who recognizes that novel cutting-edge technologies are advancing so rapidly that they will likely challenge some of the core tenets of FDA regulation in place today,” said Myers, a former FDA official. “He seems to be a person who truly appreciates that innovation will challenge the status quo, while at the same time he’ll remain the data-driven professional who is grounded in the reality that the FDA’s mission is to protect and promote the public health.”

Dr. Califf approaches the FDA helm at a time when drug and device developers, healthcare providers, and patients struggle to incorporate genomic data into clinical decision making. In July, FDA confirmed it was partnering with Google to better identify adverse events of drugs using company technology. The FDA’s work with Google, Dr. Califf said, showed him the importance of improving curation and comparison of data.

“Their dependent variable is ad revenue over time. Our dependent variable is how long you live or how you feel. But the principles are all the same, and A/B comparisons, pragmatic randomized trials, is now a standard part of the first semester of business school,” Dr. Califf said. “It’s data, data, data.”

Other FDA priorities Dr. Califf said his office was working on, as articulated to the Science Board and elsewhere:

  • Clinical research—The FDA will work to streamline trials, promote patient engagement, join the NIH and other agencies to develop common data standards, and foster more collaboration: “We will continue working with other agencies and the healthcare community, including members of patient groups, academia, and industry,” he said July 16 on the FDA Voice blog.
  • Human phenotyping—The agency will join in efforts to characterize disease and disease risk via more and better use of genomics, biomarkers, as well as measures of environment, social interaction, preferences, and data from wearable devices.
  • Laws and regulation—The FDA is preparing a sixth phase of user fee negotiations with developers, and faces additional legislation—from the 21st Century Cures Act, which the Senate will likely consider this fall, to the Orphan Product Extensions Now Accelerating Cures and Treatments Act (OPEN ACT), a Senate bill that encourages drug developers to repurpose previously-approved drugs for rare diseases.
  • Precision medicine—FDA will carry out its share of President Obama’s initiative by developing a new approach to evaluating next-generation sequencing tests, and developing an “information commons” where developers would furnish data demonstrating their tests’ characteristics.
  • Staffing—Agency officials are working on plans to address staff retention as well as hiring. The agency’s Office of Medical Products and Tobacco, he said, had “well over 1,000 open jobs with funding in place.”

The current clinical research system, Dr. Califf said, was “well-intentioned but flawed. It’s too slow, too expensive, not reliable, doesn’t answer questions that matter to most patients, and is unattractive to clinicians and administrators that need to work in it. Otherwise, it’s a great system.”

With Dr. Califf, noted Myers, the FDA will have leadership that will be constructive and creative in its approach to regulation: “He is going to have to challenge his team to think in new ways when it comes to precision medicine, next-gen sequencing technologies, platform technologies, and gene therapy. The agency needs to be prepared for them.”

Kim Allan Williams, Sr., M.D., president of the American College of Cardiology (ACC), praised Dr. Califf in a statement as “an acclaimed leader in the cardiovascular community who has been recognized by his colleagues throughout his career. He has made important contributions to the field of cardiovascular medicine which gives him a perspective valuable to the FDA’s work, which impacts the health of many people.”

In an interview published May 26 in the ACC’s membership magazine, Dr. Califf said his clinical trial work as a cardiologist resulted in numerous interactions with FDA, providing what he called an excellent foundation for his role as deputy commissioner. “From my perspective as a researcher, working to answer scientific questions through clinical research is a fun, interesting, and immensely rewarding experience,” Dr. Califf told Cardiology. “But at the same time, I believe that many aspects of the current clinical research enterprise are suboptimal from both process and outcome perspectives.”

Robert M. Califf, M.D., hopes to be the next FDA Commissioner. As a deputy FDA commissioner, he has emphasized evidence- based medicine and improving clinical research.

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