Originally Published MDDI January 2005
Drip by drip, CDRH has been getting more aggressive about making device companies do postmarket studies. After Vioxx, expect that trickle to turn into a flood.
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When it comes to linical studies, the device industry is used to doing the minimum required for market approval, and little, if any, more.
That is changing, and firms must adapt.
The withdrawal of Merck's drug Vioxx from the market after postmarket studies showed it put patients at greater risk for heart attack and stroke, and allegations that the company may have suppressed that evidence, can only accelerate CDRH's desire for more clinical work from device companies. Expect CDRH to ramp up its demands for more and larger premarket studies, and to require more firms to conduct post-market studies as a condition of approval.
Why would a controversy over a drug affect the device regulatory landscape? There are several reasons.
First, with the advent of combination products, the drug and device worlds are converging. Figuring out whether a device is safe and effective takes a relatively short time. Doing so for a drug-device or biologic-device combination takes much longer. After the Vioxx incident, CDRH could very well require a higher burden of proof for combination products. Given the culture at FDA, that demand could creep across to standard devices as well.
Second, bad news for any part of FDA is bad for the whole agency. In 1989, when a few FDA reviewers were found to have taken payoffs from generic-drug companies, the fallout hit all agency review teams, not just those in the drug center. As a result, CDRH reviewers fell under intense scrutiny and became more cautious in their reviews. There's no reason to think it can't happen again.
And last, the lessons learned from the Vioxx incident correspond to some CDRH initiatives already in play. Since taking office, CDRH director Daniel Schultz has made it a priority to improve postmarket studies. The Vioxx incident should give momentum to his plans for requiring more device postmarketing studies and for making firms design and track them better.
At the Cleveland Clinic Medical Innovation Summit in October, executives seemed aware of this new landscape.
Michael A. Mussallem, chairman and CEO of Edwards Lifesciences, noted that because FDA reviewers are "charged with the health and safety of the U.S. public, they get punished for making a mistake. They rarely get rewarded for opening the door [to a new technology]. Therefore, if we punish them because of a Vioxx, they are likely to turn more cautious when the next innovation is developed."
Boston Scientific chairman and CEO James R. Tobin chronicled the extensive premarket and postmarket studies done for its drug-eluting stent, Taxus. These experiences, he said, might soon become commonplace for device makers.
"Device companies do just enough trials to get their products approved. But we didn't stop there," he said. "We went from the 'lay-up lesions' [studied in premarket trials] to [postmarket studies] with more of the tough clinical situations you see in the real world. We can understand how our product performs in real-world situations, as opposed to in carefully designed pivotal trials."
So, device companies can expect to have their premarket studies questioned more vigorously. Some may have to resort to more-expensive tactics such as larger patient populations and outcomes research to prove their case to the agency.
They can also expect more postmarket studies to be required. And as Melissa Walker, a vice president of Stereotaxis Inc., noted, they may see greater scrutiny of post-approval issues such as device tracking, complaint handling, and customer feedback. "This means you need a postmarket risk assessment plan," she said at the Regulatory Affairs Professionals Society annual conference in October. "You need to decide on how you will handle, recognize, and act upon issues. A good analysis is never done as long as the product is on the market."
The days when a device company did not need to verify safety and efficacy after FDA approval are fast dwindling. The Vioxx incident will only speed that process.
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