New York Times
February 18, 2005

F.D.A. Panel Says Pain Relievers Should Remain on Market
By GARDINER HARRIS

WASHINGTON, Feb. 18 - A federal drug advisory panel unanimously agreed
today that the huge-selling painkillers Celebrex, Bextra and Vioxx
cause worrisome heart problems, but its members voted to recommend that
all three nonetheless be available to patients, accompanied by strong
warnings of the risks.

The panel only narrowly supported the continued marketing of Pfizer's
Bextra or the return of Merck's Vioxx, voting 17-13 on Bextra and 17-15
on Vioxx. The panel was much more comfortable supporting the continued
marketing of Celebrex, favoring the Pfizer painkiller 31-1. The Food
and Drug Administration, which has the final word on the regulation of
pharmaceuticals, is not obliged to accept the panel's recommendations.

Shares of Merck, which took Vioxx off the market late last year, closed
up $3.76, or 13 percent, at $32.61, while Pfizer gained $1.74, or 6.9
percent, at $26.80. Before the hearings, traders feared that the panel
might recommend banning all the drugs, which would have been a severe
blow to their makers.

Most panelists said that the F.D.A. should place stern warnings on the
drugs' labels, ban consumer advertising for the drugs unless they were
balanced by ads shaped by the F.D.A. or an independent group, and
require that drug makers provide patients with a letter or medication
guide outlining the drugs' risks.

"We could have direct-to-consumer advertising and have well-known
people including a skater skating about a rink and then dropping dead,"
the panel's chairman, Dr. Alastair Wood, said.

Despite the recommendation to make the drugs available to patients, the
panel's votes were wounding to Pfizer, which had insisted in its
presentation to the committee that there was little evidence that
either Celebrex or Bextra caused heart problems. The committee greeted
many of Pfizer's claims with deep skepticism.

Several panel members said that patients should be urged to first try
taking naproxen, sold as Aleve, before taking Celebrex, Bextra or
Vioxx. Studies have shown that naproxen does not hurt the heart and may
even provide some protection against heart attacks, although naproxen
may cause more ulcers than the other drugs.

In each case, the panel's members considered varying data indicating
the health risks posed by each medication, but in the end agreed by
varying margins that the potential benefits of the pain-killing drugs
outweighed the dangers they posed for cardiovascular problems.

But there was debate over how restricted the drugs' use should be. Some
committee members suggested that all Cox-2 drugs should be "last
resorts," while others disagreed or quibbled over what "last resort"
meant.

The differing margins in support of the three drugs were in part
related to the varying amounts of research available on each. While a
majority of the panel narrowly agreed that Bextra, a newer Pfizer pain
reliever than Celebrex, should remain on the market, members also
acknowledged that less data was available about Bextra's safety.

The panel's recommendations came during the last of three days of
hearings at which panel members said they believed that all the Cox-2
drugs - which include Vioxx as well as Bextra and Celebrex - carried
heart risks.

In December, the F.D.A. said in a statement that data showed higher
cardiovascular risks for patients taking 400 milligrams or 800
milligrams a day of Celebrex, and it advised physicians who continued
to prescribe Celebrex to choose "the lowest effective dose of
Celebrex." The company says that Celebrex is available in 100- and 200-
milligram capsules, as well as 400 milligrams.

The panel's assessment of the Cox-2 drugs today came just a day after a
top research official at Merck, which makes Vioxx, suggested to the
federal drug advisory panel that the company might soon decide to
resume selling its painkiller in the United States.

The Merck official, Dr. Peter Kim, said that if the panel decided that
Celebrex and Bextra, drugs similar to Vioxx, also hurt the heart, "then
that would be important to us to take that into consideration with
regard to Vioxx."

Dr. Alastair Wood, the chairman of the advisory panel reviewing drugs
in a class known as Cox-2, asked Dr. Kim what he meant. "Are you saying
that if we think that the cardiovascular risk is a class effect, then
you would consider putting Vioxx back on the market?" Dr. Wood asked.

Dr. Kim did not answer directly, but said: "The science has progressed.
There are unique benefits to Vioxx."

In a statement before today's voting, Merck said, "If the advisory
committee and the F.D.A. conclude that the benefits of this class
outweigh the risks in some patient populations, then we would have to
consider the implications of these new data given the unique benefits
Vioxx offers."

Dr. Paul Seligman, a top F.D.A. official, said before the panel's
action today that it was too early to determine how the agency would
respond if Merck sought to resume Vioxx sales.

The Merck statement was a remarkable disclosure in an already landmark
hearing. Panel members have been sifting through studies trying to
weigh the risks and benefits of Vioxx, Celebrex and Bextra. None of the
drugs cure pain any better than older medicines. They were developed
with the hope that they would cause fewer ulcers than older medicines,
but Merck withdrew Vioxx in September after a study showed that the
drug doubled the risks of heart attack and stroke.

Since then, more studies have shown similar risks for Celebrex and
Bextra. The agency called the committee together to tell it what to do.
According to much of the testimony, the committee will probably suggest
that the drugs stay on the market, with tough warnings about the risks
of taking them.

"I don't think any one of us is saying that these drugs should be taken
off the market but that they should be used at the lowest safest dose,"
said Dr. Gary Hoffman of the Cleveland Clinic.

Dr. Michael Domanski of the National Institutes of Health agreed,
saying, "It's pretty clear that there is an excess risk confirmed by
some or all of these drugs."

The problem, many committee members said, is that patients who are at
high risk of developing ulcers are often the same ones who are at risk
of heart attacks.

"Finding the sweet spot for these drugs becomes a little bit harder,"
said Dr. Steven Nissen, a panel member from the Cleveland Clinic.
"Older people are at greater risk for gastrointestinal bleeding, and I
can assure you that they are greater risk for coronary disease."

Trying to find the right balance between the risks and benefits is the
committee's task today. Dr. Wood said that had the advisory panel known
about the cardiac risks years ago, it would probably not have voted to
approve the drug. But he said something had to be done.

"The number of events that these drugs are going to cause are going to
be vastly in excess of anything we've seen before," he said, "so we
have to do something."

Several panel members also expressed frustration that the F.D.A. did
not have the legal authority to force drug makers to test approved
medicines when concerns were presented about their safety.

"I would like to see Congress empower F.D.A. to mandate these kind of
trials as these situations occur," said Dr. John Cush, a rheumatologist
from Dallas.

Among the most widely anticipated presentations was that of Dr. David
Graham, a drug-safety officer for the agency who has sometimes feuded
with top agency officials. Dr. Graham suggested that taking high doses
of Cox-2 drugs hurt the heart even more than smoking, diabetes or high
blood pressure.

He said the Cox-2 drugs did not seem to have clear benefits to outweigh
those risks. The drugs are supposed to cause fewer ulcers than older
pain pills, although evidence for that effect has been mixed. Dr.
Graham said that 40 percent of those who suffer heart attacks die,
compared with 5 percent who suffer serious ulcers. But Dr. Graham also
condemned Indocin and Mobic, both popular painkillers.

A study of California Medicaid patients found that Indocin, known
generically as endomethacin, nearly doubled the risks of heart attacks
in patients, Dr. Graham said.

For Mobic, the risks of heart attack and stroke rose 37 percent, Dr.
Graham's study showed. Mobic is manufactured by Boehringer Ingelheim.
In the wake of Vioxx's withdrawal and news that Celebrex and Bextra may
hurt the heart, sales of Mobic have risen sharply. Dr. Graham suggested
that the move toward Mobic was a problem. Several panel members
expressed skepticism because the findings were derived from
observational studies, which are not completely trustworthy.

Dr. Christopher Grubb, a captain in the Army Medical Corps, said
soldiers in the 82nd Airborne were required to carry a Cox-2 drug in
the event of a battlefield injury. Dr . Grubb said the drugs had
allowed many soldiers who otherwise would have been sidelined by pain
to be deployed overseas.

The drugs, he said, "are essential for our global war on terrorism."
The comment prompted loud laughter in the meeting.

----------------------------------------

Ten on US drug panel had industry ties, group says
25 Feb 2005

WASHINGTON, Feb 25 (Reuters) - Ten of the 32 U.S. advisers who
supported future sales of pain relievers Celebrex, Bextra and Vioxx
have consulted in recent years for the drug makers, according to a
consumer group analysis of medical journals and other records.

Last week, a Food and Drug Administration (FDA) advisory panel said
Merck & Co Inc.'s withdrawn arthritis drug Vioxx was safe enough to
rejoin Pfizer's Celebrex and Bextra on the U.S. market after
concluding all three medicines posed some heart risk.

Ten panelists were paid consultants for Pfizer or Merck, according to
the consumer group Center for Science in the Public Interest (CSPI).

If those 10 panelists had not voted, the committee would have rejected
future sales of Bextra and Vioxx. The Celebrex vote would not have
changed because all but one member supported keeping that drug on the
market.

"By failing to at least disclose those conflicts before the meeting,
the (FDA) has undermined the credibility of the committee's advice,"
said Merrill Goozner, director of CSPI's integrity in science program.

The FDA screens panelists' consulting arrangements and stock holdings
before deciding if they can participate in a committee meeting.
Panelists who considered the pain drugs were reviewed "according to
the same strict ethics guidelines FDA applies to all its advisory
committees," said Sheila Dearybury Walcoff, FDA associate commissioner
for external relations.

The analysis sparked more congressional concerns over the FDA and its
policing of drug safety.

"Unfortunately, the votes ... are now, justly or unjustly, tainted,"
said Iowa Republican Sen. Charles Grassley, chairman of the Senate
Finance Committee. Massachusetts Democrat Sen. Edward Kennedy called
on the agency to make its panel selection process more open.

The CSPI analysis, first reported by the New York Times, cited
references from financial disclosures in medical journals and in
public databases such as www.guideline.gov.

Celebrex, Bextra and Vioxx, known as COX-2 inhibitors, were designed
to ease pain like older, nonprescription drugs while being easier on
the stomach but studies have recently shown links to cardiovascular
risks.

Each of the 10 advisers with industry ties voted to keep Bextra on the
market. Nine of them voted to let Vioxx be sold again. Merck withdrew
Vioxx last September after a study linked the pain reliever to heart
attacks and strokes.

If those 10 members had not cast their votes, the committee would have
voted 13-7 to recommend that Bextra be withdrawn and 14-8 that Vioxx
should not return to the market.

kron <kron@no.sp.net> wrote:
This is not unusual. Disclosure is an issue, but it's otherwise
pretty tough to find the expertise, since big pharma funds most of the
drug studies, and many of the best docs have some tie to the industry.

"kron" <kron@no.sp.net> wrote in message
news:nchv11h8q17imfslncf67v20snio5s9lqv@4ax.com...
It's hard not to find leaders in the field who have not participated in
industry sponsored trials. That's the sort of expertise you want on AC
panels.

On Sat, 26 Feb 2005 16:09:05 -0500, "nobody special"
<nospam@4methankz.com> wrote:

The public trust in the FDA is at an all-time low. The perception that
they're rubber stamps for the drug industry is being strengthened
every day.

San Francisco Chronicle
February 27, 2005

The side effects of drug promotion
Aggressive ads for painkillers left more patients exposed to risks
- Bernadette Tansey, Chronicle Staff Writer

The painkillers Vioxx, Celebrex and Bextra may go down in history as a
classic example of the danger posed by aggressive industry promotion of
prescription drugs to both patients and doctors.

When Vioxx and Celebrex hit the market in the late 1990s, they were
touted as a breakthrough class of arthritis drugs that would help avoid
ulcers and other digestive ailments linked to medicines such as
aspirin.

With their debut coinciding with a surge in advertising aimed directly
at consumers, they and Bextra, which was approved in 2001, quickly
became one of the most heavily promoted drug classes.

In 2003, their manufacturers spent more than $1.5 billion to promote
the drugs through television spots, print ads and pitches to doctors.
By 2003, sales topped $5.3 billion, according to IMS Health, a
pharmaceutical information and consulting company.

But now that the drugs have been linked to an increased risk of heart
attacks and strokes, critics say millions of people were needlessly
exposed to those dangers as intense advertising helped make the
painkillers some of the most widely prescribed medicines in the United
States.

Studies show that many patients took the expensive new drugs
unnecessarily, because they were never at risk for ulcers or other
digestive problems.

Now, as the FDA considers recommendations from an advisory panel that
it ban consumer advertising of the drugs, many health experts say the
case has delivered a harsh lesson -- that the FDA needs to change the
way drugmakers launch their new products.

Former FDA commissioner David Kessler said the rapid adoption of new
drugs -- fueled by heavy promotional campaigns -- is an inherent threat
to the public.

"The way it used to be, if a drug got approval, its use would increase
gradually over time," said Kessler, who is dean of the UCSF School of
Medicine. Thus, when unexpected side effects surfaced, he said,
relatively few people had been exposed to the risk.

In recent years, though, new medicines explode into widespread use
before they build up a safety track record, said Kessler, who prevented
the widespread use of drug commercials on television when he was FDA
commissioner. "Many more people are going to be exposed. That's the
nightmare."

Free speech battle looms

As the FDA prepares to decide how Celebrex and the other drugs, which
together are known as COX-2 inhibitors, can be marketed, some people
doubt the agency has the authority to limit consumer advertising if the
pharmaceutical industry takes it to court.

While critics say overpromotion sends poorly informed patients
clamoring to their doctors for medicines whose benefits are exaggerated
and risks are obscured, drug companies argue adamantly that patients
gain important information from advertising.

On Feb. 18, a federal safety panel advised the FDA to ban consumer
advertising of the COX-2 drugs. In general, the FDA frequently adopts
the recommendations of its advisory panels. But at the panel hearing,
the agency's director of the Office of New Drugs, Dr. John Jenkins,
said the agency lacks the power to impose the ban.

When asked to elaborate on Jenkins' comment, the FDA gave no direct
answer.

"The tools we have to regulate prescription drug promotion include
untitled letters, warning letters, consent decrees, and referrals for
criminal prosecution," according to a statement provided by the FDA
press office.

FDA can wield power

But former FDA officials, including Kessler, say the agency clearly has
the power it needs.

"I think there is no doubt that the agency could, on its own, tighten
up direct-to-consumer advertising and impose requirements on that
advertising to make sure that the promotion is in the public interest,"
he said.

Kessler's former deputy commissioner, Mary Pendergast, said the agency
can ask for voluntary advertising restrictions and can also seek court
orders telling drugmakers to curb consumer ads when such promotion
could threaten public health.

"They're not helpless," said Pendergast, now a private consultant in
Washington, D.C. "In my opinion they can bring an injunction,
especially if there have been past shame-on-you warnings" about
promotional campaigns.

History of complaints

Celebrex, Vioxx and Bextra promotions have all drawn such FDA warnings,
according to a review of agency records. Celebrex promotions to
consumers and doctors were the subject of eight separate complaints
between 1997 and 2005, spanning a period when the drug changed hands
among three different companies.

Among the accusations: Doctors were being encouraged to give as much as
double the maximum dose on Celebrex's FDA-approved label -- a
disquieting charge in light of evidence now indicating that
cardiovascular risks emerge when the drug is given at those higher
doses.

Although Bextra's manufacturer, Pfizer Inc., denies promoting the drug
directly to consumers, the FDA sent the company a letter in January
faulting a TV infomercial and direct mail brochures sent to patients
for misrepresenting or completely omitting information about serious
risks.

In 2001, the FDA faulted a Vioxx campaign denying that the drug boosted
heart attack risks, in spite of troubling evidence that had already
surfaced by then that the risk could be four or five times greater.

Neither Vioxx manufacturer Merck & Co. nor Pfizer Inc., which makes
Celebrex and Bextra, would say whether they will agree voluntarily to
forego direct-to-consumer ads permanently if the FDA requests it, or
would mount a legal battle if the FDA sought a court injunction. Pfizer
honored the FDA's request for a suspension of consumer ads for Celebrex
after Merck's voluntary withdrawal of Vioxx from the market last year
raised concerns that the whole COX-2 group increased heart risks.

Both drugmakers said they are focusing first on negotiations with the
FDA over possible changes to the drug labels that could incorporate
strong safety warnings also advocated by the advisory panel.

"The label defines everything we can say about any medication, and
until that process is completed, we're not thinking about our
direct-to-consumer advertising," said Pfizer spokeswoman Susan Bro.

Consumer pitch unfolds

The era of direct-to-consumer advertising, augmenting traditional
campaigns aimed at doctors, began in the 1980s when manufacturers of
two products ventured into the arena. At that point, the FDA requested
a voluntary moratorium on the ads while it reviewed their possible
impact on public health.

After a couple of years, the FDA withdrew the request. But for a long
period, the agency limited the use of TV ads by requiring the short
spots to include information on possible health risks. It was a rule
Kessler refused to eliminate. But once he left, drugmakers were allowed
to refer TV viewers to other sources like Web sites for the risk
information. That rule change in 1997 opened the floodgates to the
pervasive drug commercials seen today.

The first FDA complaint about misleading promotion of a COX-2
painkiller was sent the same year.

In 1997, more than a year before Celebrex received marketing approval,
the FDA accused its maker at the time, G.D. Searle, of touting it over
the Internet as "a breakthrough in arthritis therapy," and suggesting
that it caused no gastrointestinal bleeding.

That was certainly the hope held out for the COX-2 drugs as they were
being developed. Doctors needed a solution to a serious dilemma
discovered in the mid-1990s by researchers like Dr. James Fries, a
Stanford rheumatology expert. Arthritis patients needed relief from
chronic pain, but the drugs they used could cause stomach bleeding and
other gastrointestinal problems serious enough to land patients in the
hospital -- and sometimes cause deaths.

Misleading claims

But in fact, Searle was not able to get that claim of gastrointestinal
safety included in the Celebrex label when the drug was approved for
marketing. Yet Celebrex manufacturers, from Searle to its successors
Pharmacia and finally Pfizer, were each reprimanded by the FDA for
stating or implying in promotional campaigns that the drug was better
than traditional painkillers because it posed no gastrointestinal
risks.

In Bextra's case, the direct mail piece that Pfizer was warned about in
January said "your stomach stays protected," even though the drug label
lists gastrointestinal damage as a risk.

The Pfizer spokeswoman, Bro, acknowledges that the Celebrex label still
includes gastrointestinal side effects as a risk for the drug, but she
said recent studies show that Celebrex is gentler than other
painkillers.

Fries said both Pfizer and Merck are still getting away with a
"marketing ploy" by positioning their drugs as gentler on the
gastrointestinal tract than other painkillers. Although Vioxx trial
data show somewhat lower gastrointestinal impact than some of the
older, cheaper painkillers, it is no better than several others, Fries
said.

The case of the COX-2 drugs has turned Fries, who once supported
direct-to-consumer advertising, into an opponent.

"We should empower the consumer, but they should be empowered against
getting brainwashed," he said.

Closer COX-2 drug scrutiny

The scientific controversy over the COX-2 drugs is by no means over.
More studies are planned, and some FDA safety advisers have raised the
point that little is known about the possible cardiovascular risks of
some of the other painkillers used as alternatives.

The FDA safety panel, after hearing testimony that some patients might
do better on the COX-2s than other drugs, recommended keeping them on
the market. But the majority advocated so-called "black box warnings"
of the heart and stroke risks for all three drugs.

If the FDA accepts that recommendation, its decision would probably
inhibit the manufacturers from using one type of consumer ad. Under
long-standing FDA policy, drugs with such warnings can't be promoted
with "reminder ads," which simply mention the name of the drug without
identifying its uses.

Other pitches aimed at consumers would be permitted, though, unless the
FDA takes additional action as advocated by the panel. Such ads would
have to detail the drug's risks.

If the FDA does attempt to block consumer advertising for the drugs
permanently, it could be headed for a showdown with Pfizer.

Pfizer and free speech

Pfizer, the world's largest drug company, has been one of the most
tenacious industry proponents of the position that many FDA rules
restricting drug promotion violate the free speech rights of
manufacturers. That First Amendment argument has made significant
headway in a number of court cases, Pendergast acknowledged.

But she said the FDA could still win a case for promotional limits if
it marshals evidence that public health could be at risk.

"You don't have a First Amendment right to lie, to say false and
misleading things," she said.

--------------------------------------------------------------------------------

"kron" <kron@nosp.net> wrote in message
news:c1t121pdi4n3u31j1p4gacv0gppclq6hpc@4ax.com...
Perceptions are frequently wrong, particularly when based on poor
information.

"nobody special" <nospam@4methankz.com> wrote in message
news6Gdndi0ivlitr_fRVn-hQ@comcast.com...
The hoopla over COX 2 inhibitors has been way overblown (bextra, celebrex,
vioxx).

We had a patient who recently came to the hospital comatose and passed away.
Cause of death? Water intoxication.

WATER INTOXICATION. It drove her sodium so low it killed her.

We had a 19 year in fulminant heptatic failure from tylenol toxicity.
Suicide? Nope, just a really bad headache for which he took tylenol like
candy. He got a liver transplant and survived - but barely.

Can something like Vioxx kill you? Yep. But so can just about anything you
put in your body.

Isn't the larger question whether the phenomenon of direct-to-consumer
advertising (along with other factors) doesn't lead to the prescription of
high-profit drugs that are in the marketing spotlight, in preference to
other agents that might be better, but make somebody less money? In this
area, the under-use of meloxicam in North America, and the virtual
abandonment of Disalcid (salsalate), which for some patients is a perfect
and ultra-safe choice, are prime examples.

DM

On Fri, 25 Feb 2005, Steve wrote:

I've followed the subject since Vioxx was volontarily withdrawn.

Like those depression-pills that the 15-year old claimed were
responsible for the killing of his grandparents...The FDA says yep, il
may do some harm but the overall benefit to society is greater than
that incremental danger.

Users need to question themselves and stay sensible to what is really
going on inside their bodies. They also need to question themselves
and alternative medicine experts.

Many Natural medicines have successfully helped the Orient cope with
Arthritis for thousands of years... And they still do. It's not a cost
issue, it's an effectiveness reasoning mixed with customs.

My mother was getting crippled by Rhuematoid Arthritis and
Fibromalgya. After 10 or 20 years of crying in pain, she discovered
the power of antler (like the Orientals were into since 2000 years --
so they say).

Soon after, they bought a small elk farm as a pre-retirement hobby. By
telling friends about it, their demand for antler (all locally sold)
grew and today, well, they don't have a retirement -- they raise
almost 200 Elk.

The point here is not to sell antler to you, dear reader. I just want
to underline that yes, as some "modern" medication may have harsh side
effects, Antler-one of the many natural solutions, has positive side
effects such as increased stamina, to state only one.

Look over the web, there must be 50 sites selling this stuff. If you
would like more guidance, I'll respond to any email sent to me.
dave.beaupre@gmail.com

Good luck,

Dave


"Skeptic" <bcs002b@yahoo.com> wrote in message news:<YeuUd.71090$4q6.3649@attbi_s01>...

"Dave" <dave.beaupre@gmail.com> wrote in message
news:f12d8cfb.0503030536.79eb553b@posting.google.c om...
Have not seen this one for quite awhile. It is laughable,,,, the power of
antler,,, LOLOL

Reported for advertising.

While I can't comment on antler (quite interesting at the very least), I can
comment on medications. Sure, some have side effects, as you allude to.
What doesn't? Should the FDA have approved Vioxx? Yep. In fact, one my
biggest complaints with the FDA is their reluctance to approve good
medications that are essentially common practice in other countries,
especially Europe. But I digress. Vioxx was approved for use at safe
dosages. Advil will kill you if you take too much of it.

The anti-depressant saga is a totally different beast. Here we can NOT say
X led to Y which resulted in Z. Those are opinions. People's speculations.
Possibly nothing more than some lawyer's defense strategy and completely
fabricated - only the lawyer, the killer, and their maker will know.

Vioxx led to the deaths of the people in question, without a doubt. The
Celexa - or whatever SSRI it was - probably did not kill the user and in all
likelihood, had absolutely nothing to do with the death of the innocent
people that were slaughtered.

"Dave" <dave.beaupre@gmail.com> wrote in message
news:f12d8cfb.0503030536.79eb553b@posting.google.c om...