Device Makers Profit by Promoting
Biliary Stents for Dangerous Unapproved Uses
|May 16, 2007. By
Washington DC: There is a major
controversy brewing over the off-label sale of biliary stents for unapproved
uses. On March 12, 2007, the FDA held a meeting in Washington with the
makers of the bile stents to remind them about the restrictions on their
promotion of these devices for unapproved uses.
For the record, the FDA approved use for
the majority of bile stents
is for the temporary relief of bile-duct obstruction in cancer patients
who are expected to live less than 6 months. For this reason alone,
critics say, these devices should not be implanted in the arteries
of patients with a normal life expectancy.
"Biliary stents are metal or plastic flexible tubes used to prop open
the bile duct in patients with obstructions related to pancreatic cancer,"
according to the March 16, 2007 Pioneer Press. "The treatment helps
drain the biliary tract and keep the bile duct open, thereby relieving
On its web site, the FDA stated that the March meeting was the result
of an investigation "prompted by the promotion of metal biliary stents
for vascular indications."
Representatives from between 10 and 20 stent makers attended the meeting,
including officials from Medtronic, Ev3, and Boston Scientific, according
to the Pioneer Press.
When a new device is approved, the FDA also approves the labeling which
lists the indications for which the product may be used. Although doctors
are allowed to implant a device in patients for indications not listed
on the label, the maker of the device is banned by law from asking surgeons
to use the product for uses not approved by the FDA.
At the March meeting, the FDA warned that some company web sites had
crossed a "very fine line" in using language that could be considered
to promote or encourage the use of biliary stents in vascular procedures.
FDA spokesperson, Karen Riley stated in the Pioneer Press, "FDA has
become aware that metal biliary stents are being promoted and used to
open arteries in the vascular system -- something they have not been
tested to do, or approved for by the agency."
Ms Riley also added that the FDA "is concerned about the increasing
reports of adverse events in patients who received biliary stents off-label
for vascular therapy."
Specifically, the FDA has found the use of biliary stents for the
treatment of femoral artery disease has led to an increase in adverse
According to Kenneth Cavanaugh, Jr PhD, a Regulatory Review Scientist
with the FDA, in the September, 2006 Endovascular Today: "A recent
search of the FDA's publicly available Manufacturer and User Facility
Device Experience (MAUDE) database for medical
device adverse event reporting suggests that
virtually all of the renal stenting
procedures currently conducted in the US are performed using stents
not indicated for use in the renal vasculature, most commonly including
The off-label use
of devices for RAS, he says, "can subject the patient to unknown risks
because the safety and effectiveness of the devices, when used to treat
renal artery stenosis, have not been adequately evaluated."
"Potential procedural adverse events that can result from such use,
"Dr Cavanaugh warns, "are vascular trauma, such as dissections and perforations,
and embolization of air bubbles from the delivery system or particulates
from the lesion."
Longer-term adverse effects, he notes, "may include stent fracture,
additional particulate embolization, and restenosis."
According to experts, to gain approval for a class 3 implantable stent
for use in arteries within the vascular system, a company is required
to go through a Pre-Market Approval that requires extensive documentation
of engineering and clinical testing and the process is costly and lengthy.
On the other hand, the approval process for non-vascular devices such
as biliary stents is far less demanding. Documentation and required
testing are much simpler and the device maker normally only needs to
show that the stent is substantially equivalent to a similar device
that is already on the market in the US.
However, true to form, the FDA has known about the rampant off-label
sales of bile stents for years and this is another example of how the
nation's regulatory watchdog has failed to protect consumers from the
profit driven pharmaceutical industry.
According to Dorothy Abel, in the March 2003
Endovascular Today, in early 2003
the FDA sent a letter to bile stent makers "to remind them of their
obligation to ensure that their devices are appropriately labeled for
the way they are actually being used."
"In other words," she wrote, "they have been told to obtain the necessary
approvals for the specific vascular indications."
"In addition," Ms Abel said, "the marketing clearance letter from the
FDA for nonvascular stents now specifically states that these devices
are not approved for use in the vascular system."
"The level of regulatory oversight for a device," she explains, "depends
on several factors, including the potential risks associated with the
device and how well the device, its testing, and its anticipated performance
Biliary stents she notes, "are intended to provide palliative treatment
for patients with malignancies who have a life expectancy of approximately
Given the terminal status of such patients, any long-term risks are
not ordinarily a matter of concern, she says, "making the less-stringent
regulatory oversight reasonable."
Agency enforcement records show that the FDA had knowledge of the continued
off-label use 3 years ago as evidenced by the May 7, 2004, announcement
by Cordis Endovascular, a J&J subsidiary, for a nationwide Class I recall
of the firm's revised instructions for use of a biliary stent contained
in its medical device notification dated March 29, 2004, because they
were not approved by the FDA.
A Class I recall is the most serious recall, indicating that there is
a reasonable probability that use of a product will cause serious adverse
health consequences. The press release went on to list the serious adverse
events that had occurred with the off-label use of the devices, stating
the company is "aware of nine patient injuries due to air embolism,
including seizure and coma, as well as seven incidents of device malfunction
in connection with the use of this system outside of its approved indication."
Cordis also noted that it had sent a follow-up notification to customers
on May 4, 2004, describing these severe adverse events and advising
them to limit the use of the device to the FDA-cleared uses only.
And yet four years later in March 2007, the Wall Street Journal estimates
that US bile duct stent makers sell about 90% of their devices to catheterization
labs for use in arteries.
In addition to all the risks associated with the use of these devices
for unapproved uses, their widespread off-label use
is effecting the ability of bile stent makers who are seeking FDA approval
to treat vascular indications to enroll patients in the required studies
needed to gain approval because the off-label use is so common that
many patients and doctors believe the devices are allowed to be used
for other indications.
However, the profit-driven sales of devices for
unapproved uses may be nearing the end because law enforcement agencies
are warning that off-label marketing will continue to be a focus of
anti-fraud enforcement efforts over the next two years, with
more aggressive prosecution
companies in particular, according to speakers at an American Bar Association
health law conference February 22, 2007.
James Sheehan, of the US Attorney's Office for the Eastern District
of Pennsylvania, told the audience that changing promotional practices
of device makers will be more "problematic" because the industry has
a different structure. Compared with very large pharmaceutical companies,
he said, many device makers are typically much smaller, making it harder
to communicate rules across the industry.
Also, he said, while there are perhaps a million doctors who can write
prescriptions for drugs, only a relatively few number of people decide
which particular devices will be used in a hospital, and
often these doctors are involved
in designing the device in the first place.
a marketing perspective, it's very hard to do unilateral disarmament,"
Mr Sheehan said of device companies. "If your competitors are closely
involved with physicians, it's very hard to hold back and still have
As with most cases of off-label uses, experts say that most patients
are unaware when a surgeon decides to use a bile stent for an off-label
use and thus, if an adverse
event occurs patients are also unaware that the cause might be the bile
to be sure, the hospital and surgeons are not going to own up to the
mistake after the fact, unless they find themselves blocked into a corner
where they absolutely have no choice. They are also not going to warn
other medical providers not to us the bile stents because it would require
them to disclose their own culpability for what happened to the patient.
This in turn is a win-win situation
for device makers because it allows them to avoid any liability for
the injuries directly caused by the illegal marketing of the biliary
stents for dangerous unapproved uses while the off-label profits continue
to roll in.
With all the secrecy agreements in place as far as what goes on in the
operating room, calculating
an accurate estimate of exactly how many patients may have been injured
or killed due to the off-label use of these devices is not possible.