Lyme Disease - Now the SCUMBAGS are after Merck!!

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Now the SCUMBAGS are after Merck!!

Greatcod

2004-11-04, 2:08 am

Lord God, deliver us from the those ignorant people who attack our
healthcare industry--now they are after Merck, which employs PhD
biologists and Lawyers
and even some Yale grads, charging, can you believe it, that Merck
suppressed
information that Vioxx was killing people (death-now that's real pain
relief).
They got their emails and everything. Please Man and Mann, leave us
and go help Merck. I think, and hope, we can carry on without you for
a while.

Greatcod

2004-11-04, 11:08 am

Here is today's NYT article on the rapid FDA response to Vioxx
toxicity.
Our little world is upside down.

November 4, 2004
Drug-Safety Reviewer Says F.D.A. Delayed Vioxx Study
By GARDINER HARRIS

n a series of testy e-mail exchanges with his bosses, a federal
drug-safety reviewer contends that an effort to publish his study
demonstrating the dangers of Vioxx was delayed and demeaned by top
officials at the Food and Drug Administration.

The e-mail and meeting notes also show that Dr. David Graham, an
official in the F.D.A.'s Office of Drug Safety, is seeking to launch a
study of the safety of Bextra and Mobic, two arthritis pills that are
similar to Vioxx. Merck withdrew Vioxx in September after finding that
it caused an increase in the risk of heart attacks.

The proposed study of Bextra and Mobic would use data from the
California Medicaid program, according to a note written Oct. 29 by
Dr. Graham about a meeting held between Dr. Graham and his boss, Dr.
Paul Seligman, director of the Office of Drug Safety.

The exchanges are part of a stream of e-mail suggesting a tense
environment in the F.D.A. office. In one note, Dr. Graham reports that
the atmosphere has gotten so bad that Dr. Seligman has said he was
going to resign.

In the note from the meeting of Oct. 29, Dr. Graham wrote that Dr.
Seligman said to him: "This only confirms what I suspected, that the
staff don't trust me. You can't lead if the staff don't trust you.
That's why I have a letter of resignation I am handing in next
Tuesday.''

Dr. Seligman could not be reached for comment.

In e-mail dated Oct. 25, 2004, Dr. Graham said one of his bosses, Dr.
Anne Trontell, referred to his Vioxx study's conclusions "as nothing
more than a scientific rumor."

Dr. Graham defended his study and chided Drs. Trontell and Seligman
for taking weeks to decide whether they would approve the study's
publication in the Lancet, a leading medical journal. Dr. Trontell is
the office's deputy director. Dr. Graham's study concluded that Vioxx,
also known as rofecoxib, had a dangerous effect on the heart. The
study has been submitted to the Lancet for peer review and possible
publication. Meanwhile, the F.D.A. posted a version of the study on
its Web site on Tuesday, after certain parts of the study were first
published in The Wall Street Journal.

"For all the center claims in its operating principles that respect
for others is a core value, my experience with rofecoxib was just the
opposite from management, once the results from this study and their
potential implications came to light in August," Dr. Graham wrote in
e-mail dated Oct. 26.

The e-mail and notes, which were made available to The New York Times,
come in the midst of a Congressional inquiry into whether the agency
has been slow to respond to findings that antidepressants may cause
children to become suicidal and that Vioxx may be harmful to the heart
in some cases. Senator Charles E. Grassley, Republican of Iowa, who is
chairman of the Senate Finance Committee, has criticized the agency
for failing to respond more quickly to these findings and for
suppressing the findings of its own drug safety reviewers that
concluded that the drugs were risky.

In the case of antidepressants, Dr. Andrew Mosholder, another reviewer
at the Office of Drug Safety, concluded last fall that depressed
children should not be prescribed most antidepressants because they
have failed to show any benefit against depression and may cause some
to become suicidal.

Top agency officials refused to allow Dr. Mosholder to testify about
his findings at a public meeting in February because they disagreed
with his conclusions. A second study conducted by researchers at
Columbia university confirmed Dr. Mosholder's conclusions in August,
and the agency has since decided to place a "black-box" warning on the
labels of antidepressants warning of the suicide risk.

In his notes on an Oct. 29 meeting with Dr. Seligman, Dr. Graham
writes that he, Dr. Mosholder and others in the Office of Drug Safety
feel that "the review and clearance process had been turned into a
battleground, full of contention and intimidation because our
managers, the people who fill out our performance evaluations, had
created a system where it was taking a great risk to stand firm in our
scientific beliefs."

Indeed, according to the meeting note written by Dr. Graham, Dr.
Mosholder recently asked to have his name removed from a textbook
chapter on risk management "because under the current climate, he's
afraid to do anything that will set him up for retaliation or adverse
disciplinary action.''

The e-mail responses from Drs. Seligman and Trontell are mostly brief
requests from seemingly harried bosses asking for more time to review
Dr. Graham's manuscript.

Top agency officials have said they have no convincing evidence that
either Bextra or its cousin Celebrex is unsafe, but independent
researchers have speculated that the entire class of medicines known
as Cox-2 inhibitors may be harmful to the heart. Bextra, Celebrex and
Vioxx are all Cox-2 inhibitors. The F.D.A. will hold an advisory panel
meeting in January to discuss these concerns.

Mobic is made by Boehringer Ingelheim Pharma. They could not be
reached. Officials at F.D.A. and Pfizer did not immediately have
comment.

Steve Galson, director of F.D.A.'s Center for Drug Evalution and
Research, said the back-and-forth between Dr. Graham and his bosses is
part of a scientific peer review that "is a totally normal process
that takes place all over the government dozens of times a day.''

He said he would consider Dr. Graham's request to perform studies on
the safety of Bextra and Mobic, but he said other studies are under
way into the safety of Bextra that might provide better evidence.

Andrew McCormick, a spokesman for Pfizer, said he could not comment on
e-mail that he had not seen.

Dr. David Campen, Dr. Graham's co-author on the Vioxx study and a top
medical director at Kaiser Permanente, which provided data for the
Vioxx study, supported Dr. Graham's view of events, including the
proposal for a new study.

"This has been a real challenge for us with respect to the support we
have received from F.D.A.,'' Dr. Campen said. "There were a number of
e-mails that were generated within F.D.A. that were really an effort
to delay publication of our study."

Greatcod

2004-11-09, 4:06 am

Here is the WSJ article on Merck. It offers insight into the
interactions
of business, science and medicine: increasingly, its how the game is
played. The question is whether this sort of thing has impacted the
diagnosis and treatment of Lyme.

..
When Merck & Co. pulled its big-selling painkiller Vioxx off the
market in September, Chief Executive Raymond Gilmartin said the
company was "really putting patient safety first." He said the study
findings prompting the withdrawal, which tied Vioxx to heart-attack
and stroke risk, were "unexpected."

But internal Merck e-mails and marketing materials as well as
interviews with outside scientists show that the company fought
forcefully for years to keep safety concerns from destroying the
drug's commercial prospects.

Merck's first worry, in the mid-to-late 1990s, was that its drug would
show greater heart risk than cheaper painkillers that were harsh on
the stomach but were believed to reduce the risk of heart attacks.
Several company officials discussed in e-mails how to design a study
that would minimize the unflattering comparison, even while admitting
to themselves that it would be difficult to conceal.

By 2000, one e-mail suggests Merck recognized that Vioxx didn't merely
lack the protective features of old painkillers but that something
about the drug itself was linked to an increased heart risk. On March
9, 2000, the company's powerful research chief, Edward Scolnick,
e-mailed colleagues that the cardiovascular events "are clearly there"
and called it a "shame." He compared Vioxx to other drugs with known
side effects and wrote, "there is always a hazard." But the company's
public statements after Dr. Scolnick's e-mail continued to reject the
link between Vioxx and increased intrinsic risk.

As academic researchers increasingly raised questions about Vioxx's
heart safety, the company struck back hard. It even sued one Spanish
pharmacologist, trying unsuccessfully to force a correction of an
article he wrote. In another case, it warned that a Stanford
University researcher would "flame out" unless he stopped giving
"anti-Merck" lectures, according to a letter of complaint written to
Merck by a Stanford professor. A company training document listed
potential tough questions about Vioxx and said in capital letters,
"DODGE!"

The revelations shed new light on the interplay between marketing and
science at Merck as bad news piled up about a blockbuster drug used by
some 20 million Americans. Amid growing danger signs, Merck fought a
rearguard action for 4 1/2 years, clinging to a hope that somehow
Vioxx's safety could be confirmed -- even though its research chief
had already privately acknowledged its risks.

Some of the internal documents may also prove damaging to Merck in
court, where it faces lawsuits by the families of those who suffered
heart attacks after taking the drug. Such lawsuits had begun before
Vioxx's withdrawal, and since the announcement the number of potential
plaintiffs has multiplied.

Merck said in a news release Friday that it "acted responsibly and
appropriately as it developed and marketed Vioxx." It added, "When
questions arose about the safety of Vioxx, Merck took steps to
investigate and address these issues." The study that ultimately led
Vioxx to be withdrawn was sponsored by Merck itself, the company has
noted.

Ted Mayer, a lawyer representing Merck, said the internal e-mails and
marketing materials were "taken out of context" and "do not accurately
represent the conduct of Merck and its employees." People with access
to a selection of internal documents that tend to reflect poorly on
Merck permitted The Wall Street Journal to review them, but Merck
didn't provide other documents to furnish context, citing ongoing
litigation.

Merck declined to discuss in detail the internal documents or make
their authors available for comment, citing ongoing litigation. The
Friday news release said "the business practices of Merck may well be
misrepresented in any reporting" because of the selective release of
documents.

Mr. Mayer also said Merck "is committed to open and vigorous
scientific debate" and "never has had a policy of retaliating against
scientists" but "has a right to defend its medicines against false
claims."

Older painkillers such as aspirin and Aleve, known generically as
naproxen, block two enzymes -- Cox-1 and Cox-2 -- that are involved in
inflammation and pain. Blocking Cox-1 can damage the stomach and
intestines but it also may prevent blood clots. Vioxx and another
drug, Pfizer Inc.'s Celebrex, were designed to block only Cox-2.

From early on, companies developing Cox-2 inhibitors faced a dilemma.
The drugs seemed to offer clear benefits to arthritis and other pain
sufferers who couldn't stand the stomach damage of aspirin, naproxen
or ibuprofen. But that was a relatively small market. The real bonanza
lay with the general mass of pain patients.

In the late 1990s Merck was facing the loss of patent protection on
several top drugs and needed a big hit. However, it would be difficult
to penetrate the mass market if doctors and patients believed that by
choosing Vioxx, they were forgoing a potential heart benefit.

A Nov. 21, 1996, memo by a Merck official shows the company wrestling
with this issue. It wanted to conduct a trial to prove Vioxx was
gentler on the stomach than older painkillers. But to show the
difference most clearly, the Vioxx patients couldn't take any aspirin.
In such a trial, "there is a substantial chance that significantly
higher rates" of cardiovascular problems would be seen in the Vioxx
group, the memo said.

A similar view was expressed in a Feb. 25, 1997, e-mail by a Merck
official, Briggs Morrison. He argued that unless patients in the Vioxx
group also got aspirin, "you will get more thrombotic events" -- that
is, blood clots -- "and kill [the] drug."

In response, Alise Reicin, now a Merck vice president for clinical
research, said in an e-mail that the company was in a "no-win
situation." Giving study subjects both Vioxx and aspirin, she wrote,
could increase the "relative risk," apparently referring to
gastrointestinal problems. But, she added, "the possibility of
increased CV [cardiovascular] events is of great concern." From the
context, it seems Dr. Reicin meant "increased" relative to older
drugs.

She added in parentheses: "I just can't wait to be the one to present
those results to senior management!" She proposed that people with
high risk of cardiovascular problems be kept out of the study so the
difference in the rate of cardiovascular problems between the Vioxx
patients and the others "would not be evident."

It's not clear what happened to the proposed trial discussed in the
1996-97 documents. But in early 1999, Merck started an 8,000-person
trial named Vigor -- for the Vioxx Gastrointestinal Outcomes Research
study -- to prove the drug's gastrointestinal safety benefits. The
trial compared people taking a high dose of Vioxx with those taking
naproxen. It excluded patients who were at high risk of heart
problems. No patients were allowed to take aspirin.

In March 2000, the results of Vigor came in. They showed that Vioxx
patients suffered fewer stomach problems than the naproxen group, but
significantly more blood-clot-related problems -- precisely the sort
of result anticipated in the 1996-97 internal documents. The heart-
attack rate in the Vioxx group appeared to be four times as high as
the naproxen group. (Later analysis would show it to be five times as
high.)

The difference was so wide that Dr. Scolnick, the Merck research
chief, appeared to recognize it couldn't come solely from naproxen's
protective effect but must involve some sort of risk inherent in
Vioxx. In a March 9, 2000, e-mail with the subject line "Vigor," Dr.
Scolnick said the results showed that the cardiovascular events "are
clearly there." In an apparent acknowledgment that Vioxx's own
mechanism was at least partially at fault for the heart data, he
wrote: "it is a shame but it is a low incidence and it is mechanism
based as we worried it was."

Dr. Scolnick wrote that he wanted other data available before the
results were presented publicly, so "it is clear to the world that
this" was an effect of the entire Cox-2 class, not just Vioxx. The
research chief, by then nearing retirement after 15 years in his post,
then recalled some of his greatest hits that also had side effects but
were big sellers. In Vioxx, he wrote, "We have a great drug and like
angioedema with vasotec and seizures with primaxin and myopathy with
mevacor there is always a hazard. The class will do well and so will
we." Dr. Scolnick didn't respond to phone messages seeking comment.

But in a news release that month, Merck offered no hint of Dr.
Scolnick's suggestion that there was a "mechanism-based" problem with
Vioxx or a "hazard" that went beyond Vioxx's failure to offer the
protective benefits of other painkillers. Merck said the Vigor trial
results were "consistent with" naproxen's favorable effects, implying
that this could explain why Vioxx didn't do as well.

The next month Merck issued another news release headlined, "Merck
confirms favorable cardiovascular safety profile of Vioxx." While
acknowledging the Vigor results, it said other trials and data had
shown "NO DIFFERENCE in the incidence of cardiovascular events"
between Vioxx and a placebo or between Vioxx and older painkillers.

Mr. Mayer, the lawyer representing Merck, says such statements
accurately reflected the state of scientific knowledge at the time.
"The known antiplatelet properties of naproxen strongly suggested that
a property of naproxen was responsible for the differential rates in
the Vigor trial," he says. Mr. Mayer declined to comment on Dr.
Scolnick's e-mail.

In November 2000, the Vigor results were published in the New England
Journal of Medicine. The article, written by academics who received
consulting contracts or research grants from Merck and by Merck
employees, discussed Vioxx's benefits for the stomach and heart-
attack rates. But it didn't include information that, in retrospect,
was important. Among patients who weren't already at high risk for
heart attacks, it said, Vioxx didn't show a significant rise in heart
attacks. That implied it was all right for people with healthy hearts
-- say, a jogger in his 30s with joint pain -- to take Vioxx. But the
article didn't provide detailed information about other serious
cardiovascular complications such as strokes or blood clots.

John Abramson, a family doctor and clinical instructor at Harvard
Medical School, scrutinized detailed data on the Vigor trial provided
by Merck to the FDA and posted on the FDA Web site. In a book
published this summer, "Overdosed America: The Broken Promise of
American Medicine," he concluded that even those without a history of
heart trouble doubled their risk of developing a cardiovascular
problem by taking Vioxx instead of naproxen.

Gregory Curfman, executive editor of the New England Journal, says the
journal "didn't have all the details that the FDA had later on." Given
the available data, he says editors "spent a great deal of time trying
to make sure that these unexpected cardiovascular side effects were
fairly and accurately represented" in the article.

By 2001, the Vigor data had clearly caused the debate to shift. The
main question was no longer whether Vioxx lacked the benefits of older
painkillers and if so whether that was significant. Now the issue was
squarely Vioxx itself: Was the drug intrinsically risky?

In February 2001, the FDA presented its analysis of the Vigor data to
an agency advisory committee. It showed that the number of people who
had a digestive problem while taking naproxen was about double the
figure for Vioxx takers -- but that difference was almost exactly the
same as the additional number of Vioxx users who suffered a
cardiovascular problem such as a stroke.

FDA officials wanted to highlight the cardiovascular risk prominently
on Vioxx's label. Merck resisted, complaining that the agency was
putting more weight on the negative findings than on the positive
gastrointestinal aspects. In the end, the two sides compromised. The
new Vioxx label, which went into effect in April 2002, listed the good
news about fewer upset stomachs first. Then it added two tables with
the bad news about more heart attacks and strokes.

The agency, meanwhile, had become increasingly concerned about Merck's
marketing of the drug to doctors. It complained in a Sept. 17, 2001,
warning letter about a Merck-sponsored presentation by a doctor in
June 2000. The doctor had said the Vigor trial showed that naproxen
was "a wonderful drug" for reducing the risk of heart problems -- not
that there was anything wrong with Vioxx. Such statements, the FDA
said, "minimized the potentially serious cardiovascular findings" of
Vigor.

A Merck internal marketing document reviewed by The Wall Street
Journal, addressed to "all field personnel with responsibility for
Vioxx," provided an "obstacle handling guide." If a doctor said he was
worried that Vioxx might raise the risk of a heart attack, he was to
be told that the drug "would not be expected to demonstrate
reductions" in heart attacks or other cardiovascular problems and that
it was "not a substitute for aspirin." This wasn't a direct answer.

One training document is titled "Dodge Ball Vioxx" and consists of 16
pages. Each of the first 12 pages lists one "obstacle," apparently
representing statements that might be made by a doctor. Among them
are, "I am concerned about the cardiovascular effects of Vioxx" and
"The competition has been in my office telling me that the incidence
of heart attacks is greater with Vioxx than Celebrex." The final four
pages each contain a single word in capital letters: "DODGE!"

Mr. Mayer, Merck's lawyer, declined to discuss the document
specifically but said sales representatives were trained to discuss
Vioxx in a manner "consistent with FDA-approved labeling" and "were
not trained to avoid physicians' questions."

Merck also went on the offensive against academic researchers who
began to question Vioxx's safety. Gurkirpal Singh of Stanford
University, a prominent Cox-2 expert who was giving lectures sponsored
by Merck and other companies, says he pressed Merck repeatedly for
more cardiovascular safety data. When Merck refused, Dr. Singh added a
slide to his presentations that showed a man -- representing the
missing data -- hiding under a blanket. "This was the first time they
didn't answer my questions," he says. "With Vigor, suddenly it was a
clampdown."

Merck canceled several presentations by Dr. Singh that it had been
scheduled to sponsor, and it didn't stop there. In October 2000, a
Merck official, Louis Sherwood, called James Fries, a Stanford
University Medical School professor, to complain that Dr. Singh's
lectures were "irresponsibly anti-Merck and specifically anti-Vioxx,"
as Dr. Fries described the call in a January 2001 letter to Mr.
Gilmartin, the Merck chief executive. The Merck official "suggested
that if this continued, Dr. Singh would 'flame out' and there would be
consequences for myself and for Stanford," Dr. Fries wrote.

Dr. Fries struck back. "There is a line that you can't go across. . .
.. It had gone over that line," he says. He wrote to the Merck chief
that researchers at several other top medical schools complained about
"a consistent pattern of intimidation of investigators by Merck" on
Vioxx.

Mr. Gilmartin responded that Merck had a "deep and abiding commitment
to the highest ethical standards in all our dealings with physicians
and other healthcare providers." Dr. Fries and other researchers
mentioned in the letter say the company did try to repair relations
subsequently. Dr. Singh, now an adjunct clinical professor at
Stanford, says he stopped using the blanket slide after Merck gave him
more data.

Lee Simon, a rheumatologist at Beth Israel Deaconess Medical Center in
Boston, says he publicly mentioned data showing Vioxx might be
associated with a risk of high blood pressure and swelling. While Dr.
Simon was closely involved with research on the rival Cox-2 drug
Celebrex, he had worked with Merck in another area. Merck's Dr.
Sherwood called Dr. Simon and one of his superiors at the hospital to
complain that Dr. Simon's lectures were slanted against Vioxx.

"I was shocked that there was a phone call made like that," Dr. Simon
says. "The company was attempting to suppress a discussion about this
data."

M. Thomas Stillman, a professor at the university of Minnesota, also
discussed the data on high blood pressure and swelling in his lectures
-- and also got a call from Dr. Sherwood. "We had a very direct
conversation that I wouldn't call friendly," Dr. Stillman says. "It
had a tone to me of, 'You better be careful of what you're saying.' .
.. . I thought that was inappropriate." He had given Merck-sponsored
lectures but that ended after the disagreement, he says.

In August 2001, researchers at the Cleveland Clinic published an
analysis in the Journal of the American Medical Association that once
again raised concerns about Vioxx's cardiovascular risks. Before it
came out, Merck's Dr. Reicin and other officials met with the authors,
arguing that "they didn't think there was a problem with the drug,"
says Steven Nissen, one of the Cleveland Clinic researchers. The
company also asked the journal to run a Merck rebuttal but it refused,
people with knowledge of the matter said at the time.

One of Merck's most aggressive moves came against Joan-Ramon Laporte
of the Catalan Institute of Pharmacology in Barcelona, Spain. In the
summer of 2002, a publication of the institute edited by Dr. Laporte
repeated criticisms of Merck's handling of Vioxx that had been
published in the British journal Lancet. Soon after, Dr. Laporte says,
Merck officials sent him a "rectification" to publish, but he
responded that there would be no correction. After Merck officials
approached him twice more, the company filed suit in a Spanish court
against Dr. Laporte and the institute, taking advantage of a Spanish
law that allows plaintiffs to demand a public correction of inaccurate
published information.

In January of this year, a judge ruled that Dr. Laporte's publication
accurately reflected the medical debate about the cardiovascular
safety of Vioxx, and ordered Merck to pay court costs.

This March, Dr. Laporte was a featured speaker at an annual update on
the pharmaceutical world for about 1,000 Spanish family physicians.
Merck had helped pay for the meeting for the previous eight years. It
contacted the organizer, Ramon Morera i Castell, and told him that the
company "preferred" if Dr. Laporte stayed off the program this year,
says Dr. Morera. After Dr. Morera rejected the request, Merck withdrew
its financing -- about $140,000. Though there wasn't any specific
threat, "the message was clear," says Dr. Morera.

No one knows for sure why Vioxx might be tied to heart attacks and
strokes. Some scientists point to a class effect of the Cox-2
inhibitors, but several studies suggest that Pfizer's Celebrex doesn't
share Vioxx's risks. Pfizer says Celebrex might actually protect the
heart.

Throughout 2002 and 2003, critics of Vioxx had one problem: The
principal evidence against the drug came from a single source, the
Vigor study. Conducting a new prospective trial, in which patients
would be given Vioxx or a placebo and followed to see what happened,
would be expensive for academic researchers to conduct on their own.

Several groups did conduct "retrospective" analyses, trawling through
large databases of patient records for hints as to whether Vioxx was
risky. Such studies are prone to confounding factors but can add to a
body of evidence.

Merck itself sponsored one retrospective analysis by researchers at
Harvard. It found Vioxx was "associated with an elevated relative
risk" of heart attacks compared to use of Pfizer's Celebrex or no
similar painkiller. Merck asked the researchers to delete or tone down
the part of the statement about the no-painkiller group, but they
refused, according to Daniel Solomon, a Harvard professor who was the
lead author. "We made a decision that we should let the science rule
the day," he says. Just before the paper was to be published in May
2004 in Circulation, the journal of the American Heart Association,
Merck removed the name of an employee who had worked on the study from
the paper's list of authors.

On Aug. 25, data presented at a medical conference by a researcher
from the FDA's own drug-safety office showed that higher doses of
Vioxx correlated with a tripled risk of a heart attack or sudden
cardiac death compared to people who weren't taking any similar drug.

The evidence was now piling up, yet Merck stuck to the line it had
kept since March 2000. A news release said Merck "strongly disagreed"
with the FDA study's conclusion, noting that it was a retrospective
analysis. The top of the release read: "Merck stands behind the
efficacy, overall safety and cardiovascular safety of Vioxx."

The next month, company officials were informed that a safety
monitoring board wanted to stop an ongoing study of Vioxx's ability to
prevent colon polyps because people on the drug were having more heart
attacks and strokes. The numbers were small. Among patients taking
Vioxx for more than 18 months, there were 15 heart attacks or strokes
for every 1,000 patients compared with 7.5 per 1,000 who were on
placebo. For patients who took the drug 18 months or less, there was
no increased risk, according to Merck.

This was a prospective study comparing Vioxx to a placebo. Merck's
previous defenses -- criticizing retrospective studies or attributing
results to the benefits of a pill used for comparison -- collapsed,
and it withdrew the drug. Its stock price fell 27% and now stands
about where it was in early 1996.

---

Warning Signs

-- February 1997: Internal Merck e-mail warns that a proposed trial
may
show Vioxx patients having more blood clots than those taking another
medication and "kill [the] drug.

-- May 1999: FDA approves Vioxx for arthritis and other types of pain.

-- March 2000: Vigor trial results available inside Merck. They
eventually
show Vioxx group has five times the rate of heart attacks as naproxen
group.

-- March 9, 2000: Merck research chief says in internal e-mail that
cardiovascular problems "are clearly there" in Vigor trial and appear
to be
"mechanism based."

-- April 2000: Merck press release says Vigor trial results are
"consistent
with" clot-preventing effects of naproxen.

-- October 2000: Merck official threatens that a Stanford researcher
will
"flame out" if he continues "anti-Vioxx" lectures.

-- September 2001: FDA sends Merck a warning letter, accusing it of
misleading public about Vioxx's cardiovascular safety.

-- April 2002: FDA approves a label change for Vioxx, showing data
about
potential heart risk.

-- September 2004: Merck announces worldwide withdrawal of Vioxx.

Source: WSJ Research
---
Trial Results

A Merck trial compared people taking a high dose of Vioxx with those
taking naproxen.

VIOXX NAPROXEN

Total number in trial 4,047 4,029
Cardiovascular adverse events 101 46
Digestive system adverse events 48 97

Source: FDA analysis of Vigor trial data

Greatcod

2004-11-16, 4:30 pm