FDA
Feeling The Heat
By Evelyn Pringle
19 January, 2007
Countercurrents.org
Over
the past year, the Bush administration's FDA has been the focus of non-stop
investigations and with the Democrats in control of Congress, a long
overdue overhaul of the agency is in the cards.
The Government Accountability
Office has identified serious problems within the FDA. In an April 21,
2006, report, the GAO found the FDA's performance "disorganized,"
"bureaucratic," and undermined by infighting between drug
evaluation administrators whose allegiance is with the pharmaceutical
industry, and the Office of Drug Safety.
According to the GAO, the
drug safety office is under-funded, lacks independence and lacks decision-making
responsibility. It also criticized the way FDA scientists were prevented
from speaking at advisory committee meetings on drugs they were studying.
Investigators point to a
major conflict within the Office of New Drugs because it is not only
responsible for approving a drug in the first place, it is also responsible
for taking regulatory action related to the safety of drugs once they
are on the market.
The GAO report said that
day-to-day oversight of safety issues is still hampered by poor information,
lack of legal authority to order drug company studies, and bickering
between the powerful FDA bureau that reviews drugs for approval and
a smaller safety office.
To improve postmarketing
safety, the GAO recommends that Congress expand the FDA’s authority
to require drug companies to conduct studies when additional data is
needed.
Another report was released
on June 26, 2006, titled, “Prescription for Harm: The Decline
in FDA Enforcement Activity,” after an investigation was commissioned
by the House Committee on Government Reform to evaluate the FDA's enforcement
activities related to the pharmaceutical industry under the Bush administration.
When requesting the investigation,
Rep. Waxman, wrote to the committee Chairman specifically asking for
“attention to cases where career investigators believed official
action to protect the public health was warranted but could not proceed.”
For the investigation, in
addition to reviewing the FDA documents, the investigators obtained
information from current and former FDA officials and independent experts.
The experts consulted included
Dr. Jerry Avorn, Professor of Medicine at Harvard Medical School; Dr.
Michael Wilkes, Vice Dean of Medical Education at the University of
California at Davis School of Medicine; and Sammie Young, former Director
of Compliance at FDA’s Bureau of Biologics and a 29-year veteran
of the agency.
As to methods available for
enforcement, when a serious violation of FDA standards is found during
an inspection, the FDA has the statutory authority to seize or recall
products, impose civil fines, or initiate criminal action.
However, most often the FDA
will send the manufacturer either a “warning letter” or
a “notice of violation,” which is also called an “untitled
letter.” A warning letter notifies a company of violations, requires
a written response, and warns that failure to correct the violations
can lead to additional enforcement action.
Under FDA procedures, the
agency must evaluate the response to a warning letter to determine whether
the violations have been corrected. If the firm’s response is
inadequate, the agency must take other enforcement action “as
necessary to achieve correction."
An untitled letter is less
serious and informs a company of the violations but does not require
a written response or warn that enforcement action may follow if violations
are not corrected. An untitled letter also does not require an FDA follow-up.
The Prescription for Harm
investigation found that there has been a sharp decline in FDA enforcement
actions against pharmaceutical companies since December 2001. After
reviewing the records, in a May 25, 2006, letter, Dr. Avorn told the
Reform Committee, "In all of FDA's once-proud recent history, I
cannot recall a time of greater concern about its work on the part of
doctors, patients, and policy researchers."
"In overview,"
he said, "there appears to have been a sharp drop-off in the number
of warning letters FDA has issued in recent years, from an average well
over 1,000 for the period 1992 - 2001 to an average of only about 700
for the years 2002 - 2004."
"It is unlikely,"
Dr Avorn advised, "that the behavior of the regulated industries
improved so much during these years to account for a reduction of 300
warning letters per year."
Another expert consulted
for the investigation, Dr. Wilkes, stated in a June 10, 2006, letter
to Rep. Waxman:
"Today the snake oil
salesman need not travel in horse and cart nor even in automobiles —
they use the internet and the mail to make the same outrageous claims
with products that contain sometimes dangerous ingredients and often
inert useless ingredients.
"And the Food and Drug
Administration seems unable and unwilling to step in to protect the
American public."
The Report cites examples
of serious problems that were ignored, including a GlaxoSmithKline plant
in Puerto Rico, where the FDA's field inspectors found several violations
between 2002 and 2004, and even recommended that the facility be closed.
Yet it was not until 2005, that the FDA censured Glaxo, and even then
it did not impose a fine, shut down the plant, or order a recall of
the products it was unable to seize.
In some cases, the Report
states, FDA headquarters rejected the recommendations of field inspectors
despite findings that violations led to multiple deaths or serious injuries.
Internal agency documents obtained during the investigation reveal that
in at least 138 cases over the last 5 years, the FDA failed to take
actions recommended by field inspectors.
The problems identified by
inspectors in these cases included 110 where drug labeling and new drug
application requirements were violated; 99 cases where manufacturing
standards were violated; and 2 cases where firms failed to report adverse
drug events. And over 40% of the files, the report said, involved multiple
types of violations.
In nearly half of the cases,
the FDA took no enforcement action against the firm and in the remaining
cases, it took action that was weaker than recommended by the field
inspectors.
Most interesting is the fact
that during the Congressional investigation, the FDA provided no records
from the Office of Chief Counsel, even though a previous investigation
had attributed a sudden decline in enforcement actions to the issuance
of a change in FDA policy by then Chief Counsel, Mr Daniel Troy, in
September 2001, that required all warning letters and untitled letters
to be approved by his office before being issued.
According to the revised
procedures, the Chief Counsel is required to “state in writing
the reason for nonconcurrence” whenever it objects to an enforcement
action. Yet when the FDA was asked to explain why there were no records
from Mr. Troy's office, FDA staff claimed that the Office of the Chief
Counsel does not maintain copies of its decisions or recommendations,
or even a record of which files it has reviewed.
The FDA was slammed again
when the Institute of Medicine released a September 22, 2006, report
that said that the nation’s drug safety system is impaired by
“serious resource constraints that weaken the quality and quantity
of the science that is brought to bear on drug safety; an organizational
culture in [FDA] that is not optimally functional; and unclear and insufficient
regulatory authorities particularly with respect to enforcement."
The report listed the agency's
lack of stable leadership in recent years, and the detrimental effect
on personnel; the failure to provide the agency with the necessary authority
to regulate post-marketing assessments and enforce compliance; the undue
influence caused by the agency's dependence on user fees; and the impact
of stacking advisory committees with members that have clear conflicts
of interest.
A recent session of the Senate
Committee on Health, Education, Labor, and Pensions, gave the Democrats
the first opportunity to show how they intend to deal with the major
problems at the FDA, so aptly identified by investigations over the
past year.
A November 17, 2006, hearing
was held to push forward Senate Bill 3807, the "Enhancing Drug
Safe and Innovation Act of 2006," previously introduced by outgoing
chairman, Senator Michael Enzi (R-WY), and incoming chairman, Senator
Edward Kennedy (D-MA), who began working on the bill shortly after the
Vioxx disaster.
At the hearing, critics called
for stricter conflict of interest rules for advisory panels. Merrill
Goozner, Director of Integrity in Science Center for Science in the
Public Interest, testified about the conflicts of interest involving
the expert panel that reviewed the COX-2 inhibitors, and how the panel
decided that Vioxx was safe enough to stay on the market, even though
its maker, Merck, had already removed it from the market.
Mr. Goozner told the Senators
that ten of the 32 scientists on the committee had financial ties to
the drugs' makers. "Had their votes been eliminated," he said,
"two of the drugs in the class would have been voted down by the
panel."
The president of Consumers
Union, Jim Guest, testified that improvements are needed to prevent
future disasters like Vioxx and called for a rule requiring that at
least 90% of the members who decide whether a drug should be approved
be free of conflicts of interest.
Dr. Steven Nissen, of the
Cleveland Clinic, who has served on advisory panels, testified to "a
crisis in public confidence in the FDA following an unprecedented series
of revelations about drug and device safety" and called the Senate
reform bill a "major step forward."
"I served on a 2001
Advisory Panel that recommended a warning label for Vioxx," he
told the Senators, "but it took 14 months before the FDA could
secure agreement from the company to accept a weakly written warning."
Dr. Nissen also said improvements
"in the Advisory Committee process will help to ensure that FDA
consultants are less likely to be influenced by financial conflicts
of interest."
In 2005, a law was passed
that required panel members to make full disclosure of all financial
ties to Big Pharma. However, after reviewing the disclosure forms submitted,
the FDA is still permitted to grant waivers that allow experts to sit
on panels even if they have financial ties to a drug company.
On April 21, 2006, the Boston
Globe discussed the practical effects of the law since it was enacted
and quoted FDA critics as saying "the new transparency has changed
little, and scientists who have conflicts of interest can still guide
FDA decision making."
In less than 6 months, the
Globe determined, close to 100 waivers had been granted.
Congressman Hinchey is the
author of an amendment to the spending bill that funds the FDA, which
would ban waivers. "Plain and simple," he says, "if a
doctor or scientist has a personal, financial stake in a drug they should
not be allowed to sit on an FDA advisory panel and determine whether
that drug is safe."
In response to the FDA's
renewed push to maintain its ability to grant waivers, on July 24, 2006,
Rep Hinchey released a statement stating, "The FDA continues to
demonstrate a lack of commitment to ensuring that all of its advisory
panels are filled with members who have no conflicts of interest with
the drug or device being reviewed."
"Saying that there are
not enough potential advisory panel members available without conflicts,
as the FDA argues, is an empty claim," he said.
Most disturbing, he said
is that the FDA denies only 1% of the waivers requested. "When
the FDA is handing out waivers 99 percent of the time," he states,
"it is a clear sign that the system is broken."
No doubt in attempt subdue
the hornet's brought on by the investigations into the approval of Ketek
based on fraudulent studies, in late July 2006, the FDA announced a
series of changes it plans to make in the methods used to evaluate clinical
trials.
One would require a company
to notify the FDA immediately if it believes a researcher has committed
fraud during a clinical trial. As it is now, drugs companies are trusted
to remove unreliable data and are not required to report any fraudulent
activity to the FDA until they actually submit the new drug application.
The agency also says it plans
to clarify which adverse events must be reported to the review boards
that monitor the studies and standardize the forms used to collect information
and revise the rules on how patients may qualify to participate in clinical
trials.
The new FDA commissioner
was confirmed on December 7, 2006, but critics say the agency is incapable
of change under the Bush regime. Rep. Hinchey released a statement stating:
"Unfortunately, the Senate's confirmation of Dr. Andrew von Eschenbach
represents anything but a fresh start for one of the most troubled agencies
in the federal government."
"I have not seen anything
substantive from Dr. von Eschenbach," he stated, "to make
me believe that the mismanagement, misplaced priorities, and ineptitude
of the agency's leadership will change during his tenure."
"Among many other things,"
he said, "Dr. von Eschenbach has presided over the FDA as it issued
a new rule that prevents Americans from filing lawsuits against drug
companies if they or a loved one become seriously ill or die as the
result of a particular drug."
"And in just the last
few days," Rep. Hinchey reported, "the FDA has approved numerous
waivers for panelists on its advisory boards who have financial conflicts
of interest with drugs and devices they are reviewing."
Houston attorney, Robert
Kwok, makes the point that "fortunately, there are just two years
left in this administration, so Dr von Eschenbach's term may be short."
"But he can still do
a lot of damage in that time," he warns, "to the rights of
Americans, their health, and their privacy."
Families seeking legal advice
for infants born with birth defects to mothers who were prescribed Celexa
during pregnancy can contact Robert Kwok & Associates, LLP at (713)
773-3380; http://www.kwoklaw.com/about.php
[email protected]
(Evelyn Pringle is a columnist
for OpEd News and an investigative journalist focused on exposing corruption
in government and corporate America)
(This article is written
as part of a series on pharmaceutical litigation and is sponsored by
Robert Kwok & Associated, LLP)
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