The Voice in the Ear -- Burt's Blog
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November 2005 Archives:
29» Déjà Lu
26» My Night With MAUDE
25» Blog Returns with New Features


November 29, 2005

Déjà Lu
I apologize for the continuing French references, but it's just that the French have a word for it -- and today's is a cousin of Déjà Vu (already seen); it's Déjà Lu (already read).

I am referring to today's press release from Boston Scientific or more correctly their PR firm, Hill & Knowlton. It is headlined: "TAXUS™ Stent Demonstrates Excellent Efficacy and Safety in Independent 'STENT' Registry". It is subtitled: "Trends Favour Boston Scientific's TAXUS Stent Over J&J's Cypher in Interim 9-Month Data From Largest Independent DES Registry in US". Following on the heels of this weekend's Taxus-touting Wall Street Journal article, it looks like Boston's stent is suddenly gaining a lot of positive momentum.

Except that today's press release is old news, literally a reprint of their October 25 release with two small changes, both time-date references which would reveal that the study had been presented (and touted) over a month ago at the TCT meeting. And it follows an interesting article in yesterday's Charlotte (North Carolina) Observer about the same study; it is titled "Drug-coated stents equally effective" and quotes hometown Sanger Clinic cardiologist Charles Simonton MD who actually ran the study. He states:

"These two stents are performing almost identically.... There's no reason why an interventional cardiologist ought to pick one over the other based on the way patients are turning out."

Sigh! Who to believe....

(It's also a case of Déjà Écrit. "already written", because I discussed this disparity in perceptions of the STENT registry study data last month.)

But cardiologists already know about all this stuff -- and by going to meetings like TCT, ACC, AHA and others, they are getting very detailed info about the differences and similarities and outcomes about these two drug-eluting stents, as well as other therapies. So the audience for these "Stent War" vollies is not the medical community. Here's a hint: the press release appears on the Yahoo! Finance boards.

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November 26, 2005

My Night With MAUDE
Ok. It's a movie reference and in this 1969 French film, "Ma nuit chez Maud", the characters sit around and talk and talk and make references to Pascal, the famous mathematician/philosopher. They're talking about love; I'll be talking about money -- and the uses of math in the pursuit thereof. And our lead character is MAUDE: the Manufacturer and User Facility Device Experience database compiled by the U.S. FDA.

In today's Wall Street Journal, staff reporter Sylvia Pagan Westphal writes of a new study commissioned by Boston Scientific -- it claims superiority of its Taxus stent over the competing Cypher from Cordis/J&J. In the article Boston COO Paul LaViolette states that his company hired the Missouri-based CRO (Contract Research Organization) Certus International to analyze the FDA's "adverse report" database from January 2003 to June 2005. (I am assuming that would be the MAUDE device database -- there is also the Adverse Event Reporting System or AERS, but that's for drugs -- the article didn't specify which database was used.) They came up with data showing the Cypher stent experienced many more adverse events with regard to restenosis (reclosure) and thrombosis (clotting). Here's a quick view of the results that Certus certified:

Patients Who Experienced Adverse Events
from Jan 2003 - June 2005 (source: FDA)

    
TAXUS
CYPHER
Restenosis
110
580
Thrombosis
331
589

Wow!!! The Cypher had five times more restenosis and almost twice the thrombosis rate. Unbelievable!! Guess that puts all those clinical trials to shame.

Unbelievable is the correct word, however. There are so many things wrong with this data that it's hard to know where to begin. Various Cordis officials complained in the WSJ that Boston Scientific included a longer time period for the Cypher than for the Taxus (Taxus went on sale in March 2004 -- the midpoint of the data set). Cordis also said the data included Japan, where the Taxus is not yet approved for sale.

But dudes! You're all caught up in the details. Look at the big picture. In the article Boston Scientific defends its sampling method by stating that during the 30-month-period both companies sold a similar number of stents, about 1.6 million each, so it's "even Stephen".

But in that very claim lies the flaw! Every clinical trial shows and every cardiologist knows that the restenosis rate in all drug-eluting stents is low -- somewhere around 5%. So do the math! (And it's only 7th grade level math at that.) Stay with me here: 3.2 million stents sold, maybe 2 stents per patient, that's 1.6 million patients, 5% of all patients would mean there should be 80,000 patients who experienced restenosis, not 690. That makes the FDA data off by a factor of over 11,000 percent! Do we have any way of determining which stent closed up in the 79,000 patients who are not in the MAUDE data? Not really. Is the MAUDE data a valid statistical sample? The FDA doesn't think so (read on).

Ditto with thrombosis. The lowest rates are somewhere in the 0.5-1.0% range (and that's in clinical trials -- Antonio Colombo's group in Milan has shown that real-world stent thrombosis rates are at least double or triple that). So even at the very conservative 0.5%, there should have been 8,000 patients with stent thrombosis, not 920.

The MAUDE database is accessible to the public (after all, you paid for it). Search it yourself. The MAUDE data is voluntary -- lots of adverse events don't get reported for a number of reasons (and that's a subject for another blog entry, perhaps a book).

What's the point of MAUDE then? Well, first off, it's better than nothing. Secondly, it's quite instructive to read the stories of device failures or problems, something all interventionalists should do -- there's a wealth of information there about difficulties you might encounter and ways to avoid or rectify them. Thirdly, if there is something wrong with a device, one would hope the reports might spotlight a manufacturing defect (Boston Scientific should know -- in 2004 reports of balloon withdrawal problems got them to investigate and pinpoint a laser weld problem, which was quickly fixed.)

My point is that while the FDA database of adverse events may be useful for some things, it is not a comprehensive registry or a randomized trial, and it is certainly not a suitable well of data to use as fuel for the marketing spin machine. In fact the FDA states right on the MAUDE home page :

MAUDE data is not intended to be used either to evaluate rates of adverse events or to compare adverse event occurrence rates across devices.

Could it be clearer? For once the U.S. Government actually writes in English.

Last month I reported that Boston Scientific told Angioplasty.Org it had formed a new internal "data messaging" unit to fight back against the J&J propaganda that hurt Taxus sales since last spring's ACC -- Cordis had used results from the REALITY trial to insinuate a safety issue into the "Stent Wars" when in fact the numbers did not support such a conclusion. But one would like to hope that the minds at Boston Scientific, a company that has brought truly innovative and life-saving technologies to the public, could and should do better than spending their time and money trying to coax wildly inappropriate data out of MAUDE.

Ah mon cheri, maybe, with the Liberté on the horizon, they're just feeling French....

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November 25, 2005

Blog Returns with New Features
The past month has been extra busy, with conferences (American Heart, VEITHSymposium, Advanced Coronary and Endovascular Demonstrations, etc.) and between attendance, reports and ongoing fundraising duties, not to mention Thanksgiving(!) I've violated the first commandment of blogging -- "Thou Shalt Keep Current". So I'll try to make up for it over the next month.

For loyal fans, I've instituted a subscribe feature, which will email you when the blog is updated, and an RSS Feed, for those of you who keep current that way.

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