Will he stay or will he go? Crunch time approaches for FDA's Califf

A litmus test of President-elect Donald Trump's plans for the FDA will come when the agency's commissioner, Dr. Robert Califf, hands in his resignation letter in the coming weeks.

It is standard procedure for the head of the FDA to offer to resign after a change in administration, and the new president may or may not accept. How Trump responds to Califf's letter could be an indicator of his plans for the FDA, having pledged reforms after winning the election to put a "greater focus on the need of patients for new and innovative medical products."

The commissioner's uncertain position comes at a particularly difficult time for the agency. The 21st Century Cures Act—passed by the House of Representatives this week—has proved particularly controversial amid claims that it will introduce a lessening in FDA standards. And the agency is already under fire on that score, following its controversial approval of Sarepta's Duchenne muscular dystrophy medicine Exondys 51 (eteplirsen) against the advice of its own advisory committee.

Since taking up the role in February, Califf has won plaudits in some quarters for taking the FDA in a more patient-centric direction, but also criticism from others, including Democratic presidential candidate Bernie Sanders, for being too close to the pharma industry, a legacy of years spent as a practicing cardiologist and prominent clinical investigator.

Nevertheless, several senior cardiologists at the American Heart Association (AHA) expressed their support for Califf, according to a Reuters report, and he also recently received a ringing endorsement from the chair of the BIO trade group, CEO of Acorda Therapeutics Ron Cohen.

History would suggest they may be disappointed, however. In fact there is only one previous example when the incumbent commissioner has held onto his job after a change in president: David Kessler stayed at the helm when Bill Clinton took over from George H.W. Bush in 1993.

Right now, Trump's decision is tough to predict. Many recent changes at the FDA sit well with his pro-business stance, including the introduction of swifter reviews for drugs that tackle unmet medical needs. But throughout his campaign he vowed to eliminate and repeal regulations he deemed were burdensome for American businesses and taxpayers.

On the table? Aside from the threat of shaking up Obamacare and potentially allowing Medicare to negotiate drug pricing, Trump has mentioned making it easier to import medicines made outside the U.S., reducing restrictions on promoting drugs for off-label uses and lowering the bar for getting access to new medicines.

As with many of Trump's campaign pledges, all those plans remain speculative. On the issue of altering the threshold for safety and efficacy data to allow patients to access drugs, Califf's stance may be at odds with the president-elect. 

The FDA commissioner has been a proponent of the FDA accepting different forms of evidence such as real-world data when reviewing drugs. However, he has been increasingly critical of late on the quality of data it works with. In a speech to the Food and Drug Law Institute (FDLI) earlier this year he said that the agency often "lacks vital evidence needed to support definitive regulatory determinations."

Dr. Patrick O'Gara of Brigham & Women's Hospital in Boston, a former director of the American College of Cardiology, is among those who fear Trump's aversion to regulation could destabilize the FDA and Califf's position.

He told Reuters that Califf is "terrific for the job" as he has a "really broad overview of regulatory affairs as well as these issues about safety that affect patient care."