From The Editor | September 23, 2015

Should A Clinical Mastermind Run The FDA?

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader


We all know that a primary driver of the high cost of drug development is clinical trials. The process is not only costly, but lengthy and difficult. And even once you complete the four phases and submit your data to the FDA, there is no guarantee the drug will be approved. All this might make you wonder: Could the drug development process be made easier if we had a clinical researcher at the helm of the FDA?

You may not need to wonder much longer. If President Obama has his way, we may soon find out. In January FDA Commissioner Margaret Hamburg appointed Dr. Robert M. Califf, a cardiologist and recognized leader in clinical research and medical economics, to be FDA Deputy Commissioner for Medical Products and Tobacco. On September 15th, the President Obama tapped Califf to be the next Commissioner of the FDA. Prior to his appointment in January, Califf was the Vice Chancellor for Clinical and Translational Research at Duke University.

Needless to say, this announcement should create excitement with many in the clinical arena. But Califf does have some detractors. According to a recent article in The New York Times, Califf has deeper ties to the pharmaceutical industry than any commissioners in recent history. As a result, some public health advocates question whether his background might lead him to be overly supportive of the companies he is tasked to supervise.

The article quotes Daniel Carpenter, a Harvard political science professor, who refers to Califf as “the ultimate industry insider.” Michael Carome, a health research professional at consumer advocacy group Public Citizen, believes speaking and consulting fees Califf has received from pharma companies, along with other funds received through research grants, might “…color his views when it comes to making regulatory decisions.” Califf’s supporters note his extensive clinical trial experience will be a major asset to the position.

Despite his detractors, it is unlikely that Califf’s appointment will be stymied. According to the Times article, Califf is a registered democrat, but when his name has been mentioned for the commissioner post in the past, he has been more popular with republicans than democrats. With the nomination coming from a democrat president, and republicans in control of the senate, the risk of a confirmation fight seems to be minimal.  

That still does not lessen the importance of his appointment. It could be especially significant now that congress is in the middle of a significant overhaul of drug approvals via the 21st Century Cures initiative that could have a major impact on the agency and the approval process. But are the concerns legitimate?

In determining his mindset, one thing we do have to fall back on is a presentation that Califf made in May 2014 to a group of bio researchers, lawyers, and industry experts in Durham, NC. Although the presentation primarily centered on improving innovation via a transformation in how we perform research, he did touch on the role played by regulators.

Transforming Clinical Trials

In the slide show, titled Disrupting Clinical Research: Transforming A System, Califf notes the drug development and clinical trial systems are “in crisis.” He notes three challenges having a detrimental impact on the industry: expiring patents, the growth of generics, and drug recalls. Two opportunities are the new health care act which has the potential to provide health insurance and prescription drug coverage to 32 million people, and a doubling of the 65 and over population between 2010 and 2030.

Noting the number of new drugs approved by the FDA per billion inflation-adjusted US dollars spent on research has halved about every nine years since 1950, Califf concludes the clinical research system is “well-intentioned but flawed.” He further cites the system being too slow, too expensive, and unreliable. This is hardly a surprise to anyone reading this article. But more importantly, he concludes, “We are not generating the evidence we need to support the healthcare decisions that patients and their doctors have to make every day.”

After presenting on the strategy of CTTI (the Clinical Trials Transformation Initiative), its goals, member organizations, and projects, Califf notes a transformed clinical trial system via CTTI could be more efficient, timely, and patient centered. He then gives a nod to PCORnet (the National Patient-Centered Clinical Research Network), which also hopes to improve clinical research via a large and national patient-centered network supporting more efficient clinical trials.

Few would argue that any of these ideas are controversial for an incoming FDA commissioner. Where Califf runs afoul of some in the industry is his references to regulation. Califf notes disruptive innovation is good for markets, creating new performance trajectories and speeding the pace of technological progress. He even goes so far as to cite Joseph Schumpeter’s take on creative destruction (“…new does not grow out of the old but appears alongside of it and eliminates it competitively…”)

It’s his second to last slide, however, that has drawn the most ire. In it, Califf posits that regulation can serve as a barrier to disruptive innovation. I understand some questioning his slant, but is that a dig at the FDA or simply an acknowledgement of reality that exists in pharma? No one is advocating that the FDA be eliminated, or even that its mission be stymied in any way. But true disruptive innovation, which involves looking at challenges in new and novel ways, can certainly be curtailed by regulation, especially an industry as highly conservative and regulated as pharma.

Califf certainly has the blessing of Hamburg, who in January noted, “Dr. Califf’s deep knowledge and experience in the areas of medicine and clinical research will enable the agency to capitalize on, and improve upon, the significant advances we’ve made in medical product development and regulation over the last few years.”

Still, some will be leery. Carpenter notes it is too early to determine how Califf would lead. “We won’t know until we see how he behaves,” he says. Or, to paraphrase Nancy Pelosi, we need to appoint him so we can see how he will regulate.