November 2005
Archives:
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.
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....
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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