Califf has plenty of unfinished business at FDA

 Robert Califf, President Biden’s new pick to lead the Food and Drug Administration, doesn’t have much to show for his first tenure at the agency.

His grand plans for modernizing the way drug makers and the FDA collect patient data were shelved in 2017 after he left the agency’s top spot. His efforts to ban flavored tobacco products were foiled by the Obama White House. Even his push to finally fix the FDA’s hiring woes still hasn’t been fully implemented.

Now Califf, who Biden formally tapped on Friday to retake the FDA’s top job, will have another shot at delivering on those promises.

“Rob has a unique opportunity to have a more transformational impact that wasn’t possible at the tail end of an administration,” said Mark McClellan, a former FDA commissioner. Califf didn’t achieve everything he wanted to during his first stint at the agency, McClellan added.

It’s unclear if it was his short tenure or something else that kept Califf from delivering on all of his pledges to transform the country’s regulation of food and drugs — he was in the role for just 10 months. But former FDA officials and allies of Califf who spoke with STAT about his first stint at the agency were clear: He has plenty of unfinished business that he’ll want to tackle as soon as he’s confirmed.

Since he left the FDA in 2017, Califf has led clinical policy and strategy at Verily, the life sciences arm of Google parent company Alphabet, where he’s focused on guiding the organization’s efforts to modernize data collection and clinical trials, an endeavor he could continue at the FDA if he is confirmed. But he is best known for creating the world’s largest academic clinical research center, the Duke Clinical Research Institute. As the leader of that institute for a decade, Califf made a name for himself as a vocal advocate for transforming the way drug makers and academic researchers conduct clinical trials.

Amy Abernethy, a former FDA official who now works with Califf at Verily, described him as “one of the grandfathers of clinical trials in America and worldwide” and “a rockstar, grand poobah physician” who not only has advanced how medicine thinks about clinical research, but has put those ideas into practice.

“He really is able to be visionary and maestro at the same time,” Abernethy added.

Below STAT walks through some of Califf’s most notable pieces of unfinished business and how he might tackle those issues this time around. Califf declined an interview request.

Transforming the medical system’s use of data

It’s no secret that Califf is on a lifelong pursuit to transform the way drug makers, doctors, and the FDA use data.

In his 2015 confirmation hearing, he proclaimed the pursuit “my real professional love.” In a 2016 editorial with NIH Director Francis Collins and other top Obama administration officials, he laid out a plan to create a “learning health system” “that takes full advantage of digital data to help us make informed choices.”

Califf had some success implementing his plans at the FDA. He launched an initiative dubbed IMEDS in 2017, which allowed drug makers to mine patient safety data to identify potential red flags with their drugs.

But most of his ideas fizzled.

One of his first initiatives as FDA commissioner was creating a data clearinghouse called the National Medical Evidence Generation Collaborative, which, he thought, could help with everything from recruiting patients for clinical trials to detecting epidemics. Califf and a top deputy released a report outlining their vision for the collaborative, including various ideas on how to structure the organization and fund it but the idea never progressed past a concept paper.

Whether Califf decides to revive the collaborative remains to be seen, but it’s clear he hasn’t abandoned his overarching goal since leaving FDA.

Califf has spent the last several years holding two jobs focused on this exact pursuit: He has led a group at Duke University whose stated goal is to “free the data to enable actionable insights and measurements that will guide implementation efforts across health systems,” and he’s leading a team at Verily with a similar goal: “Making information work better so that healthcare works better.”

Covid-19 also seems to only have strengthened his resolve: Califf has co-authored articles claiming that the pandemic has “laid bare [that] our clinical trials ecosystem is inefficient and siloed and fails at critical moments.”

Fixing the FDA’s broken hiring system

Califf repeatedly told lawmakers and the press in 2016 that the only task more important to him than improving data was fixing the FDA’s broken hiring and HR systems.

Califf promised to work on a “corporate recruiting campaign” to lure top doctors and scientists to work at the FDA, and during his tenure as commissioner, he supported a bill known as the 21st Century Cures Act that gave the FDA the power to pay higher salaries more comparable to those paid in the drug industry and academia.

Five years later, the FDA is still facing many of the same hiring woes. A 2020 report commissioned by the FDA found major flaws in the agency’s recruitment and hiring process. The agency’s HR systems are so bad, the report said, that they prevented the consultant charged with writing the report, Booz Allen Hamilton, from fully reviewing them.

“Stakeholders overwhelmingly consider the hiring process to be inefficient and ineffective,” it states.

A separate May 2020 report from the Government Accountability Office also found that the FDA had yet to use the new hiring powers from the Cures law.

There’s some signs that the FDA’s long-standing hiring woes are improving. Patrizia Cavazzoni, the director of the FDA’s Center for Drug Evaluation and Research, recently said that her center “has entirely pivoted to using that authority for all eligible positions.”

Getting tougher on tobacco

Califf might not get the credit, but he was actually one of the FDA officials at the center of the agency’s early efforts to regulate e-cigarette companies.

Califf served as the deputy FDA commissioner charged with overseeing tobacco products when the FDA was finalizing the fundamental e-cigarette regulations, and when he stepped up to commissioner, he was also charged with implementing that regulation and defending it in court.

But Califf’s efforts weren’t without missteps. Under his watch, the White House stepped in to overrule the FDA and strike out a provision of a vaping rule that would have banned the flavored products that eventually gave rise to the youth vaping epidemic. Califf told the New York Times in 2019 that he had no idea how the provision was deleted.

Now, Califf, if confirmed, will get a second shot at reshaping the e-cigarette industry: The FDA is currently in the process of reviewing marketing applications for several major e-cigarette makers, including Juul, and is locked in several legal battles that will decide whether smaller vape shops can stay in business.

In recent months, Califf has urged the Biden administration to get tough on tobacco companies.

“Tobacco use is becoming one of the most important markers of disparities in our economy and our health care system,” Califf said during a March panel discussion hosted by STAT. “I hope that this administration will have the courage to fight what will be tough battles.”

He has also laid out a sweeping plan for regulating tobacco products that, if implemented, would constitute the most aggressive plan for tackling tobacco use to date. Califf’s plan, which he detailed in a 2019 blog for the Association of American Medical Colleges, includes lowering the level of nicotine in cigarettes to non-addictive levels, banning all over-the-counter vape products, and mandating that any future e-cigarettes only be sold with a prescription as a way to quit smoking.

It’s unclear, however, whether he would push such a plan if confirmed, especially since the FDA has already given one vape company the green light to sell their products over the counter.

Finally starting from scratch on opioids

Califf didn’t even wait to be confirmed as FDA commissioner before unveiling a sweeping overhaul of how the agency reviews opioid drugs.

The plan, which Califf released while he was technically still serving as deputy FDA commissioner, included promises to reexamine the way FDA judges the benefits and risks of opioid drugs, to convene expert advisory panels any time the FDA considered approving certain new opioids, and to require opioid makers include new warnings on their drugs.

Califf did deliver a number of the reforms shortly after being confirmed. Most notably, the FDA announced in March that it was requiring all immediate-release opioids to include new warnings on their label.

But there are still major tasks Califf started in 2016 that aren’t complete.

Califf’s 2016 plan mandated that opioid makers submit new data testing whether opioids were safe to use long-term. Califf promised the order would “result in the most comprehensive data ever collected in the field of pain medicine and treatments for opioid use disorder.”

Much of those data still aren’t available. Opioid makers agreed to conduct 11 studies testing everything from the effectiveness of existing tests that spot addiction in patients to the risks of addiction for chronic pain patients treated with opioids, but only eight of the 11 studies have been completed, according to ClinicalTrials.gov.

Califf lamented the lack of good data on long-term opioid use in a March panel hosted by STAT.

Biden’s FDA commissioner, Califf insisted, should “demand that the evidence be generated.”

https://www.statnews.com/2021/11/12/biden-nominates-califf-to-helm-fda-an-agency-where-he-has-plenty-of-unfinished-business/