If the cascade of news reports are true, President Biden is finally about to name his choice to lead the Food and Drug Administraion: Dr. Robert Califf, a cardiologist and clinical trialist who spent most of his career at Duke University, led the FDA under President Obama from February 2016 to January 2017, and who is currently head of clinical policy and strategy at Verily, Google’s health subsidiary.
Given the essential work the FDA does — it oversees industries that account for 20 cents of every dollar spent by Americans — it deserves an extraordinary leader. And I believe Califf to be exactly that.
Full disclosure: I know Rob Califf and have worked with him on research projects since 2018. He did not ask me to write this essay, and doesn’t know I am doing it.
I can still picture first meeting him. Califf had returned to Duke after leading the FDA and launched a data science center there. As an ambitious fellow in cardiology hoping to make a strong impression, I put together a research proposal to use machine learning to predict adverse events from medical devices. Califf wasn’t impressed. When he asked how the approach might improve on previous less-flashy analytic techniques, I didn’t have a compelling answer. Even though my idea was rejected, I came away with a greater appreciation for Califf.
Since then, he and I have collaborated on several research papers, editorials and op-eds. While some co-authors are happy to sign off with minimal input, Califf’s attention to little details is his hallmark. He often pushes analysts to dive deeper in the data. Califf is particularly passionate about disparities in health outcomes, and much of the work I have done with him has focused on identifying rising mortality rates in rural America.
I think that Califf’s greatest contribution to medical science pertains to his work on the highest standard of medical evidence — the randomized controlled trial — which is the foundation for much of what the FDA reviews. He helped found the Duke Clinical Research Institute, which is today the world’s largest academic research organization, and mentored countless men and women who are now leading medicine and science across the country.
Califf’s critics point to his ties to the drug and device industry as blemishes on his resume. Similar concerns were raised when he was confirmed 89-to-4 by the U.S. Senate in 2016. It is true that much of Califf’s research has been funded by the drug industry, but I and leaders in academia such as Eric Topol and Harlan Krumholz believe that his work has been fair and never skewed unfairly in favor of corporate interests.
As Vivian Lee, a former dean and CEO of the University of Utah Health system who worked with Califf in her role as president of health platforms at Verily, told me, “He has depth of experience in the role. He has the respect of the key leaders at FDA,” adding, “In my experience Rob has always acted with the highest integrity.”
Amy Abernethy, who has known Califf since 1991 when she was a medical student and who, until recently, was the FDA’s principal deputy commissioner, sees his experience at the intersection of academia and industry as a strength. “He has learned how to figure out how to advance all sides of the ecosystem, ask really hard questions of each other and demand the best outcome for patients,” she told me. “FDA is a science-based public health agency and you need someone who understands the science and cares deeply about public health. What is remarkable is that he is exactly that.”
At the Duke Clinical Research Institute, he developed a partnership with industry which was more balanced and independent than other research organizations, a partnership that has helped both academics and their industry collaborators. Califf fought for the right to perform independent analyses of results. Furthermore, while some in the pharmaceutical industry had previously tried to suppress negative trial results — and still try to do so — Califf has been a strong proponent of publishing negative trials. In an endorsement of his candidacy from when he was nominated to lead the FDA in 2016, Jeffrey Drazen, then editor-in-chief of the New England Journal of Medicine, cited that of the seven industry-funded trials Califf had been a part of since 2005, four did not favor the intervention and one had a mixed result.
Another example was an industry-funded trial which showed that giving the hormone erythropoietin, which helps the body make red blood cells, to patients with anemia was actually harmful. In Califf’s words, not publishing the results of a negative trial is akin to a company telling patients: “We did an experiment on you, but we didn’t like the result, so we didn’t publish the results in a form that would really inform the many doctors who might put patients at risk in the future.”
Far from becoming a de facto spokesperson for the biopharma industry’s interests, Califf’s focus has been on protecting patients and the scientific method. He has publicly criticized charities set up by doctors that served as fronts for pharma interests. And the industry has often turned to him as a fair umpire. After the heart failure drug nesiritide (Natrecor) made headlines given concern about side effects and sales plummeted, Johnson & Johnson mulled pulling the drug rather than invest more in it with an expensive trial. Yet Califf convinced it to perform a 7,000-patient multinational trial, the largest heart failure study at that time, which revealed that while the drug was not harmful, it didn’t benefit patients either. “Unless we do these kinds of large clinical trials we are engaged in a comedy of errors,” he told the New York Times.
Don’t get me wrong: I’m not an FDA cheerleader. In a 2018 essay I wrote for the New York Times, I lamented the lax standards used to approve potentially dangerous and ineffective medical devices. Given the intractable connections between the drug and device industry and medicine, many of my colleagues responded harshly to my call for the need for a more stringent bar for regulatory approval of medical devices. I received death threats on Twitter and had job offers rescinded. More recently, I pointed out in a First Opinion how the FDA had been partly complicit in igniting the opioid epidemic.
High-profile failures have continued to mount at the FDA. Many have criticized its response to the Covid-19 pandemic as being too anemic and timid in the face of a raging pandemic. On the other hand, others have lambasted the agency for being too aggressive in pushing for the approval of Aduhelm, a controversial Alzheimer’s drug, based on flimsy and indirect evidence.
These failures all but doomed the candidacy of Janet Woodcock, who the Biden administration kept on as an interim commissioner, but whose prior track record with opioids torpedoed her candidacy.
The FDA deserves to have a strong, ethical, and independent leader, and whoever that is faces difficult challenges: The FDA needs to be more transparent, needs to elevate the evidentiary standard required for novel drugs and devices, needs to swiftly adapt to challenges raised by the pandemic, needs to learn stark lessons from the opioid epidemic, needs to corral the cushy relationship between the agency and the industry it regulates, and needs more resources and be elevated to the status of an independent agency.
Rob Califf is just the leader the FDA needs at this historic juncture. “He cares about America. He really does,” Abernethy told me. “He has a ton of unfinished business.”
Haider Warraich is a physician and researcher at the VA Boston Healthcare System and Brigham and Women’s Hospital, an assistant professor of medicine at Harvard Medical School, and author of the forthcoming book, “The Song of our Scars: The Untold Story of Pain” (Basic Books, April 2022). The views expressed here are his alone and do not necessarily represent those of his employers.
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