With millions of people around the world looking to the U.S. Food and Drug Administration (FDA) for reassurance that the COVID vaccines their governments are either recommending or mandating are safe, the question of who heads the FDA has never been so pertinent.
Janet Woodcock has headed the agency for the last eight months as acting commissioner; under federal law, a permanent head has to be appointed by mid-November. According to multiple sources, former FDA commissioner Robert Califf is the favored candidate, though President Biden has made no comment confirming or denying expectations.
Opinion is divided on Califf’s suitability for the key role. On one side of the debate are those who welcome the idea of having an experienced hand at the wheel, especially with big decisions looming on various COVID-related issues. On the other side are those who point to decisions made by Califf during his first tenure in the position, and, perhaps more critically, to his known ties to the pharmaceutical industry.
Robert Califf first served as FDA commissioner between February, 2016, and January, 2017. Although his appointment was confirmed overwhelmingly in an 89-4 vote, several lawmakers raised objections even back then to his ties to pharma companies, via the Duke Clinical Research Institute which he founded in 1996.
During the years prior to his tenure at the FDA, Califf was a paid consultant for a long list of pharma companies, including Merck Sharp & Dohme, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, and Eli Lilly, sometimes being paid as much as $87,500 (by Johnson & Johnson, in 2012) for his services. He continues to provide paid consulting services for several companies including Merck and Novartis, and is on the medical advisory boards of at least two pharma companies.
More recently, Califf has been serving as head of clinical policy and strategy for Google’s Verily and Google Health. Verily describes itself as a research company, one that is “forging deep collaborations across the entire healthcare ecosystem, from academic research institutions to life sciences companies to hospitals and health systems.”
“It would obviously improve Verily’s prospects on the markets if everyone knows they have a friend in charge of the agency approving their products,” said Jeff Hauser, head of the Revolving Door Project, part of the Center for Economic and Policy Research. Given that Verily is “working relentlessly to identify and develop the next wave of healthcare innovation” (in its own words), the FDA’s role in approving its products is likely to be key in assuring (or impeding) its future success, both in professional and in economic terms.
With such a potential conflict of interest, the question is whether there is anything in Califf’s past to suggest that the conflict would raise practical problems. According to Dr. Vinay Prasad, Califf made “one decision of monumental importance” during his first tenure as FDA commissioner that should ring warning bells for President Biden when considering whether to appoint him to serve a second term.
The case he cites was the question regarding whether to approve a drug called Eteplirsen (produced by Sarepta) to treat Duchenne muscular dystrophy. Prasad notes that, “The evidence supporting the drug was of very poor quality. We did not have a randomized controlled trial showing kids who get this drug lived longer or lived better,” and this was even noted in the package insert itself.
With this in mind, the FDA’s drug advisory committee voted against approving Eteplirsen, as did the FDA’s reviewers. However, Janet Woodcock (the current acting FDA commissioner, who was then director of the Center for Drug Evaluation and Research) expressed her opinion in favor of approval, pending additional research * — otherwise known as accelerated approval — and Califf deferred to her.
Precisely what was going on in Woodcock’s mind as she pushed for Eteplirsen’s approval is impossible to know, but according to Luciana Borio, the FDA’s acting chief scientist at the time of the controversy, what motivated Woodcock was the fear that Sarepta would collapse if its drug was rejected.
While that is entirely likely, the opposite was also true, as events confirmed — following the drug’s approval, “The effect on Sarepta’s fortunes was immediate,” the Los Angeles Times writes. “The day the decision was announced, the company’s share price soared…”
Dr. Prasad cites the decision to approve Eteplirsen as “not just a bad decision” but also one that provided “the intellectual precedent needed for further erosion of FDA standards.” Indeed, this was not the last time that the FDA would grant approval for drugs that failed to prove their efficacy.
Responding to the likelihood that Califf is to be appointed to head the FDA again, Dr. Michael Carome, director of Public Citizen’s Health Research Group, released a statement noting Califf’s “long history of extensive financial ties to Big Pharma.”
“The country desperately needs an FDA leader who will reverse the decades-long trend in which the agency’s relationship with the pharmaceutical and medical-device industries has grown dangerously cozier – resulting in regulatory capture of the agency by industry,” he wrote. “Biden must nominate an individual who has been dedicated to advancing public health – one who unquestionably will place the public interest ahead of the interests of FDA-regulated industries.”
Others, however, see the “public interest” and the role of the FDA very differently from Carome. According to Dr. Jeffrey Drazen, editor-in-chief of The New England Journal of Medicine, “The country needs a strong and experienced leader who can keep the FDA focused on its mission,” adding that he hoped Califf would be confirmed “as quickly as possible.”
If the role of the FDA is to expedite the approval of medications, based on the independent assessment of the commissioner, whose opinion is apparently to be trusted even if it contradicts that of the members of his advisory board, then Drazen’s words are understandable.
And so, if Califf’s words in 2014 are to be interpreted as a statement of his vision for the FDA, what he will be doing, if appointed FDA commissioner next month, is ensuring that the government is not permitted to interfere with his powers so as not to serve as a “barrier” to innovation.
And if that innovation just happens to be to the benefit of Verily, where Califf is policy head, then the consumer must make the presumption of coincidence and reassure himself that the honorable stamp of FDA approval remains the gold standard of safety and efficacy, whatever the price to be paid.
*As late as 2020, Sarepta still had not conducted any post-approval clinical trials regarding the efficacy or safety of Eteplirsen (following the approval granted in 2016). The author was unable to ascertain whether or not trials were conducted in 2021.