Really? What is this conclusion based on? Numerous cases of Canadians
dropping dead from bad drugs?

I wonder if the FDA is so deserving of our trust?

http://health.discovery.com/news/reu/20010521/fda.html

Lancet: FDA far too cozy with drug industry

By Richard Woodman

May 18, 2001 ‹ LONDON (Reuters Health) - Patients taking a controversial
new drug for irritable bowel syndrome may have died because the US Food
and Drug Administration (FDA) has become a "servant of [the drug]
industry," the editor of The Lancet medical journal claimed in the May
19th issue.

In a devastating editorial, Richard Horton said that although
GlaxoSmithKline (GSK) voluntarily withdrew Lotronex (alosetron) from the
US market last November after the deaths of five patients, senior FDA
officials were now seeking to reintroduce it.

"This story reveals not only dangerous failings in a single drug's
approval and review process but also the extent to which the FDA, its
Center for Drug Evaluation and Research (CDER) in particular, has become
the servant of industry," he said.

The two-page editorial, entitled "Lotronex and the FDA: a fatal erosion of
integrity," accuses the FDA of receiving hundreds of millions of dollars
funding from industry.

It claims the views of FDA scientists who raised safety questions about
the drug were dismissed by FDA officials and that the scientists were
excluded from further discussion about the drug's future.

And it alleges that negotiations between the FDA and GSK on the drug's
future involved a "two-track process, one official and transparent, one
unofficial and covert."

Lotronex was licensed by the FDA in February 2000 but was never approved
by the European Medicines Evaluation Agency.

The company withdrew the product in the US on November 28 after 49 cases
of ischaemic colitis and 21 of severe constipation, including instances of
obstructed and ruptured bowel. In addition to five deaths, 34 patients had
required admission to hospital and 10 needed surgery.

The Lancet says that as early as July, it was known that seven patients
had developed serious complications. The clinical data confirmed
"substantial and potentially life-threatening risks" but instead of
withdrawing Lotronex the FDA issued a medication guide. "This decision was
to prove fatal."

The editorial says FDA scientists knew that the medication guide advising
patients to stop taking Lotronex if they felt "increasing abdominal
discomfort" was impractical since abdominal pain is also a cardinal
symptom of an irritable bowel.

FDA scientists argued that it was unreasonable to expect either patients
or their physicians to judge pain as an early warning of possibly fatal
ischaemic colitis. This view was dismissed by FDA officials.

"The scientists who raised these issues felt intimidated by senior
colleagues and were excluded from further discussions about Lotronex's
future."

The journal says that in a memorandum dated November 16, FDA scientists
said, "Early warning of the dire side effects of this drug is clearly not
feasible" and added a "risk management plan cannot be successful."

However, this conclusion was blurred by the time of the key November 28th
meeting between GSK and FDA officials. Rather than reject the company's
risk management proposal and withdraw Lotronex, the FDA offered several
conciliatory options including voluntarily withdrawal pending further
discussion.

The editorial claims "many within the FDA's leadership now want to bring
Lotronex back. An advisory committee meeting set up to do so is being
planned for June or July."

In April, GSK chief executive Jean-Pierre Garnier said he believed the
odds were low that Lotronex would be relaunched because of the difficulty
of predicting which patients might be at risk of severe side effects. But
industry analysts who have met R&D head Tachi Yamada more recently told
Reuters the company now appeared to be more optimistic about a Lotronex
relaunch.

GSK spokesman Martin Sutton told Reuters, "We regard the editorial as
misleading. There have been discussions between FDA and GlaxoSmithKline
officials. These meetings have all been conducted according to usual
regulatory and industry practices. Both the FDA and ourselves are trying
to find a resolution that will benefit and protect patients."

He added that the timing of any advisory committee meetings was a matter
for the FDA.

An FDA spokesperson said the agency is still formulating its response to
the editorial.

Horton told Reuters Health he became interested in Lotronex because The
Lancet published some of the trial data that led to the FDA approving the
drug. "As the year went on, we noticed that there were increasing reports
of adverse events.

"Then as I got more intrigued about what was happening, it opened up into
an issue of how science is dealt with by the FDA and how, because of
industry funding, it has fatally compromised its independence.

"The scientists within the FDA who analyze and interpret adverse drug
reactions have been largely ignored after the drug was approved and
marketed. That is where there has been a terrible failure in evaluating
the safety of this drug.

"The FDA is not only compromised because it receives so much funding from
industry but because it comes under incredible Congressional pressure to
be favourable to industry. That has led to deaths."

Horton pointed out that irritable bowel syndrome may be extremely
unpleasant but is not life-threatening. To approve a drug that can lead to
ruptured bowel and death was at odds with the normal balance between risk
and benefit, he said.

"This is a drug whose application was approved for full unrestricted
marketing within 7 months. That is insufficient to gather safety data.
Pushing through an application so quickly is irresponsible."

Horton said that GlaxoSmithKline "has failed to gather sufficient evidence
to justify the safety of this product." He added that the company had
applied pressure through private communication to senior FDA officials.
"Instead of an accountable review process, one has a covert, unofficial
process."

This is not Horton's first attack on the drug industry. In recent
editorials he has criticised the "tightening grip of big pharma" over what
researchers can publish in medical journals.

His latest editorial demands that:

*  Lotronex should be reclassified as an investigational new drug, thus
limiting its use to experimental settings only.
*  Covert private communications between FDA officials and industry must stop.
*  Drug approvals and safety reviews should take place through accountable
procedures.
*  Greater weight should be given to the epidemiologic advice provided to
advisory committees.
*  There should be an independent congressional audit of the FDA's drug
approval processes.
*  Oversight of the pharmaceutical industry should be removed from CDER's
control because safety cannot be overseen by a centre that received
industry funding.
*  FDA should welcome, not censure, differences of opinion within the
organisation.
*  The FDA's new commissioner should be an epidemiologically trained
physician experienced in conducting clinical trials and independent of
industry.

SOURCE: The Lancet 2001;357:1544-1545.

** NOTICE: In accordance with Title 17 U.S.C. Section 107, this material
is distributed without profit to those who have expressed a prior interest
in receiving the included information for research and educational
purposes. **
_____
Scientific American Feb. 2003

February 2003 issue
Bad Medicine
Why data from drug companies may be hard to swallow
By Gunjan Sinha

    Getting drugs on the market means playing games. So says Peter Lurie of
Public Citizen, an interest group founded by Ralph Nader and based in
Washington, D.C. Of course, it's the agency's mission to be leery. But lately
pharmaceutical companies are giving groups like Lurie's more to be leery
about. Drug firms now wield a great deal of control over their research,
Lurie charges, and they are frequently manipulating their data or withholding
unfavorable results entirely.
One of Public Citizen's latest battles is over a drug for irritable bowel
syndrome (IBS). Three years ago the Food and Drug Administration approved
Lotronex (alosetron hydrochloride), the first agent to treat the disorder
specifically. As published in the Lancet, clinical trials in women revealed
that 41 percent taking the drug felt some relief, as did 29 percent taking a
placebo...................

    "Some scientists argue that the FDA has become so chummy with the drug
industry partly because of the Prescription Drug User Fee Act, passed in
1992.  The act requires firms to pay the FDA almost $5000,000 in total fees
for each approved drug.  Such fees account for almost half the agency's cost
of reviewing drugs......."
____________________________
http://www.fda.gov/oc/pdufa/

In 1992, Congress passed the Prescription Drug User Fee Act (PDUFA). PDUFA
authorized FDA to collect fees from companies that produce certain human drug
and biological products. Any time a company wants the FDA to approve a new
drug or biologic prior to marketing, it must submit an application along with
a fee to support the review process. In addition, companies pay annual fees
for each manufacturing establishment and for each prescription drug product
marketed. Previously, taxpayers alone paid for product reviews through
budgets provided by Congress. In the new program, industry provides the
funding in exchange for FDA agreement to meet drug-review performance goals,
which emphasize timeliness.

PDUFA's original intent was to provide FDA with additional revenue so it
could hire more reviewers and support staff and upgrade its information
technology to speed up the application review process for human drug and
biological products without compromising review quality. The revenues are
provided by a set of three fees, with one-third of the total annual revenue
coming from each of the following fees:

Application fees for the submission of certain human drug or biological
application (in fiscal year (FY) 2001, $309,647 per application with clinical
data, and $154,823 per application without clinical data or per supplemental
application with clinical data);
Annual establishment fees paid for each establishment that manufactures
prescription drugs or biologicals (in FY 2001, $145,989 per establishment);
and
Annual product fees assessed on certain prescription drug and biological
products (in FY 2001, $21,892 per product).
In the aggregate these fees are expected to generate $135 million this fiscal
year, and increase to about $162 million in FY 2002, the last year of PDUFA
II. No separate fees are charged for investigational new drug applications.
However, since the review of investigational new drug applications is
included in the definition of the process for the review of human drug
applications, as defined in PDUFA, FDA uses some of the application,
establishment, and product fees collected for the review of investigational
new drug applications.

In consultation with industry and the Congress, FDA agreed to meet a set of
review PDUFA I goals that became more stringent each year if FDA also
received sufficient fee resources to enable goal achievement. These goals
applied to the review of original new human drug and biological applications,
resubmissions of original applications, and supplements to approved
applications. FDA met every PDUFA I performance goal and, to date, has met
all but one PDUFA II performance goal. Industry also insisted on a statutory
provision that fees could only be collected and spent each year if a large,
inflation-adjusted portion of drug review costs would continue to be funded
from appropriations rather than fees, so that the fees were funding
additional drug review resources rather than replacing appropriations.

Under PDUFA II, the review goals continue to shorten. By 2002, the PDUFA II
goals call for FDA to review and act on 90 percent of:

Standard new drug and biological product applications and efficacy
supplements within 10 months;
Priority new drug and biological product applications and efficacy
supplements (i.e., for products providing significant therapeutic gains)
within 6 months;
Manufacturing supplements within 6 months, and those requiring prior approval
within 4 months;
Class 1 resubmissions within 2 months, and Class 2 resubmissions within 6
months.
In addition, PDUFA II added a new set of procedural goals intended to improve
FDA's responsiveness to, and communication with, industry sponsors during the
early years of drug development. These goals specify timeframes for
activities such as scheduling meetings and responding to various sponsor
requests. While PDUFA's original intent was to speed up the review process,
PDUFA II's intent is to speed up the entire drug development process.

PDUFA has had a dramatic and undeniable impact on the drug review process.
Total resources for drug review activities have increased from $120 million
in 1992, before PDUFA was enacted, to an estimated $325 million in FY 2002,
about half of which will come from fees paid by industry. These resources
allowed FDA to increase its drug and biological review staff by almost 60%
between 1993 and 1997, adding about 660 staff-years to the program by 1997.
By the end of PDUFA II in 2002, FDA expects to have added another 313
staff-years of effort to this program. These additional staff, and resources
to support them, have enabled FDA to respond more rapidly to new drug and
biologic applications without compromising review quality.

While it is important to note that PDUFA's goals specify decision times, not
approval times, both decision and approval times have decreased dramatically.
Total approval time, the time from the initial submission of a marketing
application to the issuance of an approval letter, has dropped from a
pre-PDUFA median of 23 months to 12 months. Total approval time for priority
applications, those for products providing significant therapeutic gains, has
dropped from a median of over 12 months in the early PDUFA years to 6 months.
In addition, because FDA has put greater effort into communicating what it
expects applicants to submit, a higher percentage of applications are being
approved. Before PDUFA, only about 60 percent of the applications submitted
were ultimately approved. Now, about 80 percent are approved. For the
consumer, this has meant more products available more quickly.

The agency has also encountered some challenges with PDUFA. Assuring that
enough appropriated funds are spent on the process for the review of human
drug applications to meet requirements of PDUFA, and at the same time
spending our resources in a way that best protects the health and safety of
the American people is becoming increasingly difficult. Each year, the amount
that FDA must spend from appropriations on the drug review process is
increased by an inflation factor. Yet since 1992 FDA has not received
increased appropriations to cover the costs of the across-the-board pay
increases that must be given to all employees.

The result is that our workforce and real resources for most programs other
than PDUFA have contracted each year since 1992 while we struggle to assure
that enough funds are spent on the drug review process to meet this PDUFA
requirement. Several consecutive years of operating in this way have made it
difficult to continue to further reduce staffing levels in FDA programs other
than drug review. We are increasingly concerned that spending enough
appropriations on the drug review process to meet the statutory conditions
makes FDA less able to manage the resources available in a way that best
protects the public health and merits public confidence. Just one example of
an area we have not been able to fund adequately is responding to reports of
adverse events related to the use of prescription drugs.

** NOTICE: In accordance with Title 17 U.S.C. Section 107, this material
is distributed without profit to those who have expressed a prior interest
in receiving the included information for research and educational
purposes. **

_________
5-17-2001

"It is an impossible conflict for safety issues to be overseen by a center that
receives funding from industry to review and approve new drugs," Horton said.
....."

Medical journal slams FDA as "servant of industry"

By Pat Reaney

LONDON (Reuters) - The U.S. Food and Drug Administration, guarding the health
of 274 million Americans, is compromised by funding from the drugs industry and
pressure from Congress, the editor of a top British medical journal said
Friday.

Richard Horton of The Lancet accused the world's most powerful drug watchdog,
which regulates products worth over $1 trillion, of endangering the lives of
people in its handling of GlaxoSmithKline Plc's controversial bowel drug
Lotronex and being a servant of the pharmaceutical industry.

The FDA approved Lotronex in February 2000, but the company voluntarily
withdrew it from the market nine months later after the deaths of five patients
who had been taking it.

Senior FDA officials are now trying to reintroduce it, Horton said.

"This story reveals not only dangerous failings in a single drug's approval and
review process but also the extent to which the FDA, its Center for Drug
Evaluation and Research (CDER) in particular, has become a servant of the
industry," he wrote in an editorial in the British journal.

According to Horton, serious side effects from Lotronex were evident during the
pre-approval process and shortly afterward, but the FDA kept the product on the
market.

"The decision was to prove fatal," Horton said.

In response to Horton's accusations, the FDA told Reuters that it had been
holding discussions with GlaxoSmithKline about issues surrounding Lotronex.

"If Lotronex was to be introduced in any manner, FDA safety concerns would have
to be adequately addressed," said Victor Raczkowski, the deputy director Office
of Drug Evaluation III which oversees the department that reviewed Lotronex.

"MISREPRESENTATION" OF FDA

He said the editorial was a misrepresentation of the FDA and how it works and
he denied that the review process was secretive or that opinions had been
suppressed.

"The FDA is a large scientific organization. We have many people who have
worked in the review. We expect and encourage them to be frank about their
scientific opinion," Raczkowski said.

The Lancet said scientists within the FDA who raised concerns about the drug's
safety were sidelined and excluded from future discussions. An independent
review of research found serious flaws, but calls for more studies were
ignored.

"That is where there has been a terrible failure in evaluating the safety of
this drug," Horton told Reuters.

"The FDA is not only compromised because it receives so much funding from
industry, but because it comes under incredible Congressional pressure to be
favorable to industry. That has led to deaths," he added.

The agency monitors the safety, labeling, import, transport, storage and sale
of food ingredients, drugs, cosmetics and surgical supplies.

GlaxoSmithKline confirmed the company was in discussions with the FDA but it
refused to discuss the timing of any decision.

"We are in discussions with the FDA over Lotronex," a spokesman said. "Both the
FDA and ourselves are trying to find a resolution that will benefit and protect
patients."

Lotronex was developed to treat irritable bowel syndrome which can cause
disabling bouts of constipation, diarrhea, abdominal pain and bloating.

But soon after its launch, reports of side effects such as severe constipation
and ischemic colitis, a restriction of blood flow to the colon, began to
surface.

"It is an impossible conflict for safety issues to be overseen by a center that
receives funding from industry to review and approve new drugs," Horton said.

17:48 05-17-01
____________________