At the FDA Rob Califf Will Champion Clinical Trials

Everyone wants to know what Rob Califf is going to do at the FDA. His critics say he’s going to hand the car keys over to industry and allow them to drive the agenda. Or, as one reporter tweeted:

Hey, is that the sound of the FDA approving things faster? Must be because the Senate is confirming Robert Califf as new FDA chief.

On the other hand, his supporters think he’ll improve the approval process, perhaps removing some unnecessary hoops through which industry is forced to jump but also adding rigor where necessary. (After all the drama of the past few weeks you can bet new opioid applications are going to be scrutinized very carefully under Califf.)  The big hope is that Califf, with his extensive insider knowledge, won’t be easily surprised or fooled by industry tricks.

I’ve been watching Robert Califf for 30 years, since he was a junior faculty member at Duke. I have no idea what he’ll actually do as FDA commissioner. But I’m pretty sure that he won’t abandon the one consistent theme and obsession of his entire career: clinical trials. He didn’t build the Duke Clinical Research Institute just to siphon money from industry, as some have argued. Instead he built an infrastructure to perform more and better clinical trials. I can’t imagine Califf commitment to clinical trials will now somehow be diminished.

So what does that suggest about what he’ll do at the FDA?

Randomized clinical trials (RCTs)will remain the cornerstone of drug approval. He will look askance at any attempt to short circuit the requirement for RCTs. If anything he may try to raise the bar for drug categories that have shaky support from clinical trials. Don’t expect him to rock the boat right away and raise the bar for cancer drugs and others that are politically sensitive. He’s politically savvy and he’ll wait his time before tackling something really controversial. But a few small incremental changes might give a hint of what may come if he settles in for the long haul in the next administration.

Califf is also acutely aware of the limitations and burdens of the current system, which sometimes seems to be collapsing under its own weight. RCTs have become enormously expensive and often don’t even provide much useful information by the time they’re done. Califf knows this first hand. After all, he was the PI of IMPROVE-IT, one of the longest lasting, controversial, and deeply frustrating trials in the history of cardiovascular medicine. There’s been a lot of quiet discussion in the last few years about using technology to improve and speed up clinical trials. I wouldn’t be surprised to see Califf support initiatives that will encourage the development of randomized registry trials, for instance.

At the European Society of Cardiology meeting last year Califf responded to critics of the FDA requirement that the makers of diet and diabetes drugs have to perform cardiovascular outcomes trials. He said that the FDA has taken the position that “we need to understand the long term risk of these drugs that people may need to take for a lifetime.” It’s unlikely Califf will change his mind about this.

I’ll bet that Califf will seek to tighten the requirements for approving devices. He’s been a consistent critic of interventional cardiology, at one point describing interventional cardiologists as “knuckle dragging.” The main problem is that device trials are rarely as rigorous as drug trials. There are some good reasons why this is so, but Califf isn’t likely to simply accept an inherently weak system. He’ll try to strengthen it.

While he was still at Duke, Califf gave a talk at the American College of Cardiology meeting in 2014 in which he analyzed one of the most important device trials in recent years. The SYMPLICITY HTN-3 trial, which failed spectacularly, put an end to early hopes that renal denervation was the next big thing in blood pressure treatment.

His slides, which he shared with me at the time, illustrate Califf’s devotion to evidence-based medicine (EBM), and why it’s unlikely anyone will be able to pull a fast one on him. He knows all the tricks. Here’s his slide showing all the poor excuses used as alternatives to EBM:

Screen Shot 2016-02-24 at 6.48.30 PM

At the end of this talk Califf said, “Efforts to bring medicine up to modern evidentiary standards must continue.” His slide illustrates Califf’s commitment to increasing, not decreasing, the evidence basis for medical practice:

Screen Shot 2016-02-24 at 6.52.32 PMI’d be surprised if Califf wouldn’t see his main role at the FDA to help bring about this effort to improve the evidence base of medicine.

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  1. Brilliant piece. I could not agree more. He’s a great pick.

  2. FDA should champion value based medicine, not just evidence based medicine. Evidence generated by statistical manipulations should not be the basis for EBM in clinical practice.

    No drug or device should be approved solely on the basis of the results of single clinical trials.

    Fast track approval process should be reserved for life saving products, not for any new me too products, especially based on non-inferiority results from clinical trials.

    Results of flawed, frivolous, falsified, if not fraudulent clinical trials should be detected and analyzed appropriately by FDA before it becomes evidence and science!

    Are we getting money’s worth in health care outcomes after spending 18% of our GDP? FDA has a significant role to play in health care expenditures.

    With the great power of the US FDA comes great responsibility. Business as usual should not be the business any more!

    Hope the new commissioner with impeccable credentials will be able to make the essential changes in the FDA to help improve the health of our citizens and wealth of our country.

    • Larry Husten says

      Agree. Important points worth restating. But one caveat: as far as I understand the FDA is forbidden from considering cost or economics in its decisions. By law it is only allowed to consider the science and the medicine. Of course this does not prevent them from detecting “flawed, frivolous, if not fraudulent clinical trials.”

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