FDA’s Gottlieb preparing to lower the bar to approval

Medicolegal

By Larry Husten

4 Oct 2017

The new FDA commissioner Scott Gottlieb is quietly and persistently revamping the FDA to make it easier for drug and device companies to get their products on the market.

The news, which is being welcomed by industry, also almost certainly means that more people will be exposed to weak, ineffective, or dangerous products.

Gottlieb’s entire career has centered on loosening regulatory restrictions to enable industry to thrive.

At the core of his philosophy is the view that with fewer restrictions the force of unbridled capitalism will unleash a torrent of industry innovation. In this view negative consequences, should they occur, will be quickly addressed by an efficient marketplace.

Others, however, believe that Gottlieb at the FDA is a case of the fox guarding the henhouse.

As Gottlieb has settled into his job it is now starting to become clear how he is planning to advance his agenda.

In a recent speech at the MedTech Conference, the annual meeting of the medical device industry, Gottlieb set forth the basic principles underlying this effort.

The conference was a particularly appropriate venue since, as he explained, “some of the most creative, and forward-leaning advances in regulatory policy involve what we’re doing on the device side of FDA’s house.”

The more liberal standards for device approval will now serve as the model for the rest of the FDA. The relaxed policies for approving devices “are going viral at FDA,” said Gottlieb.

A key part of his strategy is to shift the regulatory burden from preapproval to postapproval, from randomized controlled trials to real world evidence.

In fact, said Gottlieb, “since early 2015 alone, we’ve approved or cleared more than 8 new medical devices and expanded the use of more than 6 technologies based on evidence derived from real world evidence….

In these cases, we’re using robust evidence that was generated in less time and at a lower cost than in the past, in some cases saving one to two years of development time. Increasingly, medical device makers are also meeting their post-market study requirements by leveraging real world data sources.”

The Device Model

But is the device model as good as Gottlieb claims? I’ve written in the past about the slippery slope of cardiac devices, in which expensive devices with little or no benefit have entered the market, putting patients at risk.

Sanjay Kaul (Cedars-Sinai) said the large number of approvals is itself concerning. “It appears to me, judging from the number of devices approved in the past 2 years, the FDA has not seen a device it didn’t like!”

An important recent example is the FDA approval of Absorb, Abbott’s bioabsorbable stent, which was approved, as Kaul observes, “based on marginal, not robust, evidence.” He notes that “at the time of approval there was already evidence that outcomes at longer follow up were uniformly going in the wrong direction.”

Currently, the device still has FDA approval, though recent data has been so frightening that Abbott is no longer marketing the device.

This illustrates how difficult it is for the FDA to rescind approval, and the dangers of shifting the burden of proof from pre-approval randomized controlled trials to post-approval studies. There is no reason to think that the Absorb case is in any way unusual or unlikely to be repeated.

It is important to recognize that the shift to real world evidence necessarily means that there will be a lower bar to approval, making it easier for companies to get their foot in the door.

To make it worse, there is no guarantee whatsoever that the real world followup will be sufficient, since it is impossible for real world evidence to provide the same rigorous evaluation as a randomized controlled trial.

On a related note, as I recently wrote about, the FDA has consistently failed to demand that companies live up to their post-marketing requirements.

Gottlieb neglected to address this problem in his MedTech talk. (To be fair, this trend began before Gottlieb’s arrival at the FDA. However, so far he has shown no inclination to fix this problem.)

Gottlieb explained in his talk that quicker approvals will allow “patients to gain faster access to life-saving devices when it’s appropriate to accept greater uncertainty premarket and resolve those issues in the post-market setting.” But, we need to ask, in the face of that uncertainty how can we really know a drug or device is life-saving if it hasn’t been tested?

Think, for instance, of all the drugs and devices that went down the tubes only after being tested in large randomized controlled trials, despite the widespread belief by all the experts in the certainty of the benefits.

In Gottlieb’s alternative universe anti-arrhythmic drugs, hormone-replacement therapy, renal denervation, CETP inhibitors, and the Absorb stent, to name only a few examples, might now be thriving products.

In the end there is no substitute for randomized controlled trials. Another important and related point: even if a therapy really is “life-saving,” we still don’t know how to use the therapy correctly unless we do the proper trials .

Key questions about timing and dosage and the appropriate patient population can’t be answered by observational data. A life-saving device in one person may be a killer in another.

Inevitably, greater reliance on real world evidence means that patients will become unwitting participants in ongoing experiments, and there may well be no end or conclusion to some of these experiments.

Gottlieb also spoke about incorporating “patient preference information to support regulatory decisions, including product approval.” On its face this sounds reasonable.

After all, who could be against incorporating the patient perspective into FDA decisions?

But this also would be an invitation to industry to redouble its efforts to underwrite grass roots organizations and manipulate them to conform to its agenda, a phenomenon known as “astroturfing.”

The sad truth is that most patient advocacy groups— or at least the large, visible, well-funded ones— have now been captured by industry.

Taking this view to an extreme, I imagine Gottlieb or his successors just might consider dissolving the various FDA advisory committees and turning over the advisory process to the patients who participate in the open-microphone portion of the hearing.

This article has been republished from Larry’s blog CardioBrief as part of a licensing agreement between Everyday Health and the limbic.  

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