There's nothing like having siblings who are several years older and in their teens. You admire them for being so mature and so big. When you wanted to hang out with them, though, maybe they told you to buzz off.
If you work for a firm intent on bringing a PMA device to market, FDA's insistence on a 1,000-patient post-approval study (PAS) for the Sapien transcatheter valve might have given you a bad case of deja vu because a small firm might not be able to get investors on board, even if it could finance something as costly as the Partner trial to start with.
The folks at FDA might not be fond of reading something like that, and I understand why up to a point. It's not as if anyone at the agency's Center for Devices and Radiological Health has a collection of badly mangled voodoo dolls representing modestly financed device makers. Not as far as I know.
All the same, small device makers are surely growing weary of growing wary. After all, the agency has yanked a 510(k) without legal justification – the Menaflex – and now has asked Edwards Lifesciences (Irvine, California) to conduct what looks an awful lot like a second pivotal study for the Sapien.
This PAS is sure to carry a hefty price tag. It is, after all, a hypothesis-driven study with extensive follow-up requirements. This study is also interesting because it'll take five years to complete, by which time the Sapien is nearly guaranteed to be yesterday's news, and Edwards already has a successor, the Sapien XT, in the works. So what's in it for Edwards?
The answer? FDA's Bram Zuckerman, MD, chief of cardiovascular devices at FDA, said this jumbo PAS is "one component of an eventual strategic plan" from which "everyone will benefit."
That sounds pretty good if you're Medtronic (Fridley, Minnesota) with its CoreValve trial, but who could blame Edwards for resenting having to do all the heavy lifting? Yes, Edwards has a market cap of $10 billion, but Medtronic's is about four times that number.
But what makes the whole thing even more odd is that this trial has specific endpoints that could force the device back to panel (assuming Edwards hasn't completely abandoned the Sapien by then). Zuckerman said as much at the hearing, adding that an alternative to a second hearing is that CDRH could "make an internal decision" if the agency doesn't like the returns.
“Internal decision.” Sounds chummy, doesn't it?
Look, I understand the problem at FDA: The agency is underfunded and gets hung out to dry in the newspapers and on Capitol Hill every time someone sneezes and no one says "gesundheit." All the same, Zuckerman's complaint about the "DES trauma" sounds a little overwrought.
After all, total stent thrombosis was about equal between drug-coated stents and their bare-metal counterparts despite the hysteria of 2006 in Barcelona, and the numbers for restenosis were still outstanding. Sorry if some docs went bonkers with DES, but physician behavior is not in FDA's portfolio, however much the agency wishes otherwise.
So how is a PAS of between 750 and 1,000 not overkill? And how on earth can a small firm afford to finance new device through trials for more than $100 million – and then do another study that will probably cost at least another $10 million – to take up a set of questions the sponsor reasonably assumed were fairly well answered in the first?
Message to FDA: The message you're sending to small device makers is: A) stick with the 510(k) thing and suffer the changes to that program gladly; or B) just get the bleep out of the U.S. altogether.
In other words, buzz off.