New York Times Feature Article on Vioxx

[Guest guest]

[The New York Times Feature Article on Vioxx follows after two posts

from Mercola about it]

 

Vioxx - - The Beginning of the End for Conventional Medicine

http://www.mercola.com/blog/2004/nov/14/vioxx____the_beginning_of_the_end_for_co\

nventional_medicine

 

You can read my post below for the enormous economic consequences Merck

will suffer in the near future. Their stock went down by $30 billion and

they stand to lose another $20 billion or more in law suits.

 

Does Merck Deserve to Lose $50 Billion Dollars?

 

You better believe they do.

 

If you don't believe it, then I strongly encourage you to read the

single best review of this topic that I have seen to date. It is likely

the NY Times is the best newspaper in the country and they did an

incredible piece of journalism in their Magazine section this morning. A

full seven page detailed reconstruction of Merck's handling of Vioxx,

based on interviews and internal company documents.

 

The NY Times articles details how in 2000 Merck executives rejected

pursuing a study focused on Vioxx's cardiovascular risks as their

marketers feared it could send the wrong signal about the company's

confidence in Vioxx. Despicable behavior.

 

Please also remember that FIVE years ago I posted warnings about Vioxx,

BEFORE it was even on the market . I don't know how much more of a

warning I could have posted. Five years ago I knew this drug was a

prescription for disaster and I specifically recall conversations with

Merck drug reps who laughed at me when I showed them the study published

in the Proceedings of the National Academy of Sciences. I'll bet they

aren't laughing now.

 

But folks, believe me this is merely the tip of the ice berg. The entire

conventional system is posed to fall. You simply can not pull the wool

over the public eyes for that much longer. People are craving the truth.

They want authentic real solutions to their health challenges that don't

cost them an arm and a leg. That is one of the main primary intentions

of this site. And as result of providing consumers with this information

and education the paradigm will shift.

 

I am highly confident it will happen in my lifetime and seeing Merck

fall is a strong indication that we are winning.

 

====================================================

 

Drug Company's Greed Coming Around to Bite Them

http://www.mercola.com/blog/2004/nov/14/drug_companys_greed__coming_around_to_bi\

te_them

 

Merck faces not only Congressional and Justice Department

investigations, but also potentially thousands of personal-injury

lawsuits that could tie the company up in litigation for years to

resolve as a result of how it dealt with Vioxx. So how bad might this

get for once-mighty Merck? While it's impossible to say precisely what

the Vioxx debacle will cost the drugmaker, analysts' estimates range

from a few billion dollars to nearly $20 billion. For now, Wall Street

and some plaintiffs' lawyers agree that the Vioxx fallout is unlikely to

lead to a Merck bankruptcy.

 

Merck's legal bill is likely to be considerable. The potential liability

based on the fact that 20 million Americans had taken Vioxx is huge.

Roughly 0.25% of those who took the drug had serious cardiovascular

problems. That means some 50,000 people may have suffered consequences.

Assuming that the size of average awards or settlements will range from

$100,000 to $300,000, and factoring in other variables such as the

likely success rate in court and added in other legal costs -- including

settling suits where Vioxx users didn't suffer a major cardiovascular event.

 

The total hit can range from$4 billion to as high as $18 billion. But

even that $18 billion figure may prove conservative; if criminal

wrongdoing surfaces, in a worst-case scenario the cost could go even

higher. This is exactly what is needed to level the playing field folks.

These multinational drug companies are finally getting their just

desserts. They have profited far too long from the public by offering

them expensive options that cause serious side effects and in no way

shape or form address the cause of the problem. I predict that this is

the beginning of the end for the drug companies and we will see more of

them crippled by their avarice for profits at the expense of human

suffering.

 

==========================================================

November 14, 2004

DANGEROUS DATA

Despite Warnings, Drug Giant Took Long Path to Vioxx Recall

By THE NEW YORK TIMES

http://www.nytimes.com/2004/11/14/business/14merck.html?th

 

This article was reported and written by Alex Berenson, Gardiner Harris,

Barry Meier and Andrew Pollack.

 

In May 2000, executives at Merck, the pharmaceutical giant under siege

for its handling of the multibillion-dollar drug Vioxx, made a fateful

decision.

 

The company's top research and marketing executives met that month to

consider whether to develop a study to directly test a disturbing

possibility: that Vioxx, a painkiller, might pose a heart risk. Two

months earlier, results from a clinical trial conducted for other

reasons had suggested such concerns.

 

But the executives rejected pursuing a study focused on Vioxx's

cardiovascular risks. According to company documents, the scientists

wondered if such a study, which might require as many as 50,000

patients, was even possible. Merck's marketers, meanwhile, apparently

feared it could send the wrong signal about the company's confidence in

Vioxx, which already faced fierce competition from a rival drug, Celebrex.

 

" At present, there is no compelling marketing need for such a study, "

said a slide prepared for the meeting. " Data would not be available

during the critical period. The implied message is not favorable. "

 

Merck decided not to conduct a study solely to determine whether Vioxx

might cause heart attacks and strokes - the type of study that outside

scientists would repeatedly call for as clinical evidence continued to

show cardiovascular risks from the drug. Instead, Merck officials

decided to monitor clinical trials, already under way or planned, that

were to test Vioxx for other uses, to see if any additional signs of

cardiovascular problems emerged.

 

It was a recurring theme for the company over the next few years - that

Vioxx was safe unless proved otherwise. As recently as Friday, in

newspaper advertisements, Merck has argued that it took " prompt and

decisive action'' as soon as it knew that Vioxx was dangerous.

 

But a detailed reconstruction of Merck's handling of Vioxx, based on

interviews and internal company documents, suggests that actions the

company took - and did not take - soon after the drug's safety was

questioned may have affected the health of potentially thousands of

patients, as well as the company's financial health and reputation.

 

The review also raises broader questions about an entire class of

relatively new painkillers, called COX-2 inhibitors; about how drugs are

tested; and about how aggressively the federal Food and Drug

Administration monitors the safety of medications once they are in the

marketplace.

 

The decisions about how to test Vioxx were made in a hothouse

environment in which researchers fiercely debated how the question

should be pursued, and some even now question whether the drug needed to

be withdrawn. It also took place amid a fierce battle between Vioxx and

Celebrex in which federal regulators said marketing claims ran ahead of

the science.

 

Today Merck faces not only Congressional and Justice Department

investigations, but also potentially thousands of personal-injury

lawsuits that could tie the company up in litigation for years and

possibly cost it billions to resolve.

 

In late September, more than four years after that May 2000 meeting,

Merck announced that it was pulling the drug off the market because a

long-term clinical trial showed that some patients, after taking the

drug for 18 months, developed serious cardiovascular problems. The data

that ultimately persuaded the company to withdraw the drug indicated 15

cases of heart attack, stroke or blood clots per thousand people each

year over three years, compared with 7.5 such events per thousand

patients taking a placebo.

 

But the company never directly tested the theory that it used to explain

the worrisome results of the clinical trial in 2000. Merck was

criticized for what some charged was playing down the drug's possible

heart risks; in one case, it received a warning letter from the Food and

Drug Administration for minimizing " potentially serious cardiovascular

findings.'' And when outside researchers found evidence indicating Vioxx

might pose dangers, Merck dismissed their data.

 

In 2001, Dr. Deepak L. Bhatt, a cardiologist at the Cleveland Clinic,

proposed to Merck a study of Vioxx in patients with severe chest pain.

Merck declined, saying the patients proposed for the study did not

reflect typical Vioxx users. In Dr. Bhatt's view, the company feared

what it might find if it directly examined the dangers of Vioxx, one of

Merck's biggest products, with sales last year of $2.5 billion.

 

" They should have done a trial like this, " Dr. Bhatt said. " If they

internally thought this drug was safe in patients with heart disease,

there was no reason not to do it. "

 

Merck executives said last week that the company acted responsibly,

voluntarily withdrawing Vioxx as soon as it had clear evidence the drug

was harmful. And they said that even if they had conducted the type of

study they discussed internally and rejected in 2000, the company might

not have detected Vioxx's risks any sooner.

 

" Merck wasn't dragging its feet,'' said Kenneth C. Frazier, the

company's general counsel. " It's pretty hard for me to imagine that you

could have done this more quickly than we did. " The F.D.A., which Merck

consulted, also agreed that designing a trial to specifically assess

Vioxx's cardiovascular risks would have been difficult and, unless

constructed to provide benefits to patients, would have been unethical

as well.

 

But the F.D.A. itself is now under scrutiny for its handling of Vioxx.

Congressional investigators are looking at whether the agency, which is

charged with protecting Americans from dangerous medicines, was too lax

in its monitoring of the mounting evidence against Merck's drug.

Internal memos show disagreement within the F.D.A. over a study by one

of its own scientists, Dr. David Graham, that estimated Vioxx had been

associated with more than 27,000 heart attacks or deaths linked to

cardiac problems.

 

So far, no clinical evidence has linked the next best-selling version,

Celebrex, to cardiovascular risks. But its maker, Pfizer, has

acknowledged that its other COX-2 drug, Bextra, has been shown to pose

risks to patients after heart surgery. Scientists outside the company

say there is evidence that Bextra's problems may affect wider groups of

patients.

 

But Merck is the company drawing fire. Senator Charles E. Grassley, the

Republican chairman of the Senate Finance Committee, has summoned

Merck's chief executive, Raymond V. Gilmartin, to testify this week as

part of the committee's investigation of the matter. The Justice

Department recently started a criminal investigation of the company, and

the Securities and Exchange Commission has begun an informal inquiry.

 

Some people associated with lawsuits against Merck, and company

officials, provided internal Merck documents to The New York Times. The

Wall Street Journal previously disclosed some of those records.

 

Controversy had shrouded Vioxx almost since its introduction in 1999.

The drug was among the first of the COX-2 inhibitors, which were

developed to reduce pain and inflammation without the risk of ulcers and

other gastrointestinal side effects posed by aspirin and other

over-the-counter medications. Thousands of Americans die every year from

internal bleeding caused by the older drugs.

 

But when studies on Vioxx and Celebrex became available in 1998 and

1999, many doctors were disappointed. Neither drug alleviated pain any

better than the older medicines. And the drugs cost close to $3 a pill;

over-the-counter pain relievers, in contrast, cost pennies a dose.

 

Analysts say, however, that the success of Vioxx was critical to Merck.

The patents on several popular Merck drugs expired in 2000 and 2001,

opening them to generic competition. Merck badly needed Vioxx to replace

those lost sales, said Michael Krensavage, a drug industry analyst at

the investment bank Raymond James & Associates. " Vioxx was Merck's

savior, it's as simple as that. "

 

The Critics: Outside Scientists Sounded an Alarm

 

The data that first alerted Merck to the heart risks with Vioxx arrived

in March 2000, derived from a study of 8,100 rheumatoid arthritis

patients begun in January 1999. In the study, called Vigor, patients

were treated with either Vioxx or naproxen, an older pain reliever.

While Vioxx reduced the risk of internal bleeding, it also appeared to

raise the incidence of heart problems. Five times as many patients

taking Vioxx had heart attacks as those taking naproxen.

 

Merck disclosed the Vigor data almost immediately and said it believed

the difference resulted not from problems with Vioxx but from naproxen's

strong protective effect on the heart. Many scientists outside the

company found that theory implausible, and a rush to examine Vioxx, as

well as Celebrex, began.

 

In 2001, the first major study critical of the drugs appeared in The

Journal of the American Medical Association. The report, written by Dr.

Eric J. Topol and cardiologists at Cleveland Clinic, reanalyzed data

from several clinical trials of Vioxx and Celebrex. It reported that

both drugs appeared to increase the risk of heart attack and stroke, but

that the danger from Vioxx appeared higher.

 

Dr. Topol, the chairman of the clinic's department of cardiovascular

medicine, immediately called for trials to specifically determine

whether the drugs increased cardiovascular risk. Both Merck and Pfizer

rebuffed that request, and said the Cleveland Clinic report was flawed

because it failed, among other things, to include data from other studies.

 

Dr. Topol became a harsh critic of both drugs, but his ire focused on

Vioxx and Merck. Even before his 2001 report appeared, he said in a

recent interview, company scientists came to Cleveland to try to

persuade him not to publish it; Merck officials deny doing so.

 

A year later, in October 2002, a study by Dr. Wayne Ray, an

epidemiologist at Vanderbilt University, found that Medicaid patients in

Tennessee who were taking high doses of Vioxx - greater than the

recommended long-term dosage of 25 milligrams daily - had significantly

more heart attacks and strokes than similar patients who were not taking

high doses.

 

In an interview, Dr. Ray said that he had become concerned about Vioxx's

safety as soon as the Vigor data became public. The Tennessee study

confirmed his doubts, he said.

 

" A heart attack in exchange for an ulcer is a poor treatment, " said Dr.

Ray, who is now consulting with lawyers suing Merck.

 

But Merck said at the time, and still maintains, that the study from Dr.

Ray and others like it did not shake its confidence in Vioxx's safety.

Dr. Ray had examined patient records to look for a correlation between

patients taking Vioxx and having heart problems, in what scientists call

an epidemiological study. But such studies are considered less reliable

than clinical trials, which medical researchers consider the gold

standard of tests. In clinical trials, scientists enroll patients,

carefully control their drug intake and monitor their reactions so that

a drug's risks and benefits can be determined.

 

The quandary facing Merck and others in the Vioxx controversy was how to

design a trial that could quickly identify any risks posed by the drug

while also conferring some kind of benefit to the patients involved.

 

Dr. Rory Collins, an epidemiologist at Oxford University, said that

examining patient records alone was useful only to find very large

differences in risk, like those caused by cigarette smoking. While Dr.

Ray's study showed a link between Vioxx and heart attacks, other studies

did not, said Dr. Collins, who has conducted studies financed by Merck.

 

But other researchers were also finding worrisome signs. In 2002,

Elucida Research, a small laboratory in Massachusetts, examined the way

that Vioxx and other anti-inflammatory drugs interacted with lipids, or

fatty compounds found in blood. That laboratory study found that Vioxx

damaged the lipids in a way that made them more susceptible to clotting,

said R. Preston Mason, the lead investigator on the study.

 

Meanwhile, more epidemiological studies backed Dr. Ray's findings. In an

April 2004 study in the journal Circulation, researchers from Harvard

Medical School found that Vioxx raised the risk of heart attacks

relative to Celebrex; two months later, several of the same researchers

reported in another journal that Vioxx increased the risk of hypertension.

 

Then, in August 2004, an epidemiological study by an F.D.A. researcher,

based on data from 1.4 million patients in the Kaiser Permanente health

care system, also showed a heightened cardiovascular risk for Vioxx.

 

The Company: An Indirect Road to Assessing Risk

 

For Merck, the Vioxx episode has been bitter.

 

Company executives and researchers say that from the moment they were

told in March 2000 about the preliminary results from the Vigor trials,

they sought every possible explanation for the signs of increased

cardiovascular risk. And, they say, they were open to the possibility

that Vioxx was at fault.

 

" We were stunned, " by the finding, said Dr. Alise S. Reicin, the Merck

researcher who ran the Vigor study. " It's fair to say that we were all

concerned. "

 

She and other Merck officials said in interviews last week that nothing

in any previous tests of Vioxx, including those submitted by the company

in November 1998 to win its regulatory approval, suggested the drug

posed a danger of increased heart attacks or stroke. Within days of

learning the Vigor results, Dr. Reicin said that she, along with

colleagues and academic consultants retained by Merck, were chasing the

question of why the rate of heart problems was so high.

 

One possibility was that it was the result of chance. Another was that

the problems were caused by Vioxx. And the third was that naproxen

provided heart protection and had skewed the results. Merck researchers

looked for data from other studies, aware that studies of two other

little-used painkillers in the same class as naproxen had shown

cardioprotective effects.

 

In the spring of 2000, Merck researchers also reviewed safety data from

a continuing study in which Vioxx was being used in patients with

Alzheimer's disease to test a theory that the painkiller might slow the

disease's progress. Dr. Reicin said that there was no evidence in that

study, which had started in 1998, that Vioxx posed a risk.

 

Merck researchers soon concluded that naproxen was cardioprotective.

Some academic researchers, including some who consulted for Merck, also

supported this theory.

 

One of them, Dr. Marvin A. Konstam, the chief of cardiology at the New

England Medical Center in Boston, said his review of the data suggested

Vioxx was safe.

 

" Based on these data, there was nothing that suggested to me that there

was an increase in cardiovascular events with Vioxx, " said Dr. Konstam

in a recent interview.

 

But Merck never ran a clinical trial seeking to scientifically establish

the heart-protecting properties of naproxen or to quantify how powerful

an effect might be. In recent interviews, company officials said they

did not believe there was a reason to conduct such tests because the

critical issue was not proving naproxen's benefits but determining if

Vioxx posed a risk.

 

Meanwhile, company scientists began to discuss the possibility of

designing a trial to directly examine the drug's cardiovascular risks,

Merck documents show.

 

At a meeting in May 2000, a top policy-making group met to discuss ways

to defend Vioxx against competing drug makers' accusations that it posed

risks. Among the issues they considered was whether to finance the

development of a cardiovascular risk study, meeting documents show.

 

The documents show that Merck's researchers were not in agreement about

how, or even whether, a trial could be performed. The documents also

make clear that marketing executives were opposed to it.

 

Mr. Frazier, Merck's top lawyer, acknowledged that the decision to forgo

the cardiovascular study was made at the meeting, but said that the

decision was not driven by marketing concerns. He added that even if

such a study had been undertaken, it would have taken years to produce

results and would not necessarily have provided faster answers.

 

Merck executives opted to take a different road. In early 2000, the

company had started a clinical trial to determine whether Vioxx could

prevent the recurrence of colon polyps. Merck decided to intensely

monitor the cardiovascular condition of patients in that test, known as

the Approve trial, as well as subsequent studies. Dr. Reicin said last

week that she and others at Merck felt devastated when they learned this

past September about the findings from the colon polyp trial. But she

said she believed that running the trials as the company did was the

best way to learn whether the drug had a problem or not.

 

" We did our best to think of the most comprehensive study we could have

done, " she said. " I'm sorry that I didn't know four years ago what I

know now, but the data didn't lead us there four years ago. "

 

The Regulator: Balancing Ethics Against Suspicions

 

The F.D.A., already under fire for its recent handling of pediatric

antidepressants, faces a new round of questions from Congress this week

over why it allowed Vioxx to be sold for so long while evidence mounted

against it.

 

For years, drug reviewers at the F.D.A. had raised the possibility that

Vioxx might be a danger to the heart, but without being able to answer

the question, or even agreeing on the best way to get an answer.

 

Even before Vioxx's approval, an F.D.A. drug reviewer had written that

Vioxx could conceivably hurt the heart. Studies of the drug at that

point, however, showed nothing more than a suggestion of a risk.

 

That suggestion became more powerful when Merck presented the

preliminary results of the Vigor study to the F.D.A. in March 2000. In

that study, those taking Vioxx were clearly at greater risk than those

taking naproxen; Merck officials argued that the difference was a result

of naproxen's cardioprotective properties.

 

" We just didn't buy that, " said Dr. Sandra Kweder, deputy director of

the F.D.A.'s office of new drugs. Still, data in mid-2000 from other

clinical trials did not show a heart risk. Flummoxed, the agency hired a

cardiologist to take a careful look at the studies, and it summoned a

panel of independent experts to discuss the data publicly.

 

The panel met in February 2001, and while several members expressed

concerns about the heart risks, none suggested that the drug be

withdrawn. Doctors on the panel who treated ulcers argued that Vioxx's

protective effects far outweighed its possible harm to the heart;

cardiologists argued that the drug's possible harm to the heart was a

real problem. All agreed that more studies should be done.

 

The agency consulted with Merck and discussed the idea of a study

designed solely to answer questions about the heart risks. As Merck

officials had done in May 2000, the agency concluded that such a trial

was difficult to envision. Giving placebos and Vioxx to groups of

at-risk patients solely for the purpose of comparing side effects would

be unethical, Dr. Kweder said.

 

Besides, Merck already had begun placebo-controlled trials assessing

Vioxx's benefits against colon polyps, she said.

 

But the F.D.A. did require Merck to add to Vioxx's label a warning that

patients with a history of heart disease should use the drug with caution.

 

And the agency underwrote a study at Kaiser Permanente, the giant health

maintenance organization, to see if patients given Vioxxhad a higher

incidence of heart-related problems.

 

Meanwhile, the marketing battle between Vioxx and Celebrex grew heated.

The F.D.A. scolded both drugs' makers for exaggerated claims about their

drugs. In September 2001, the agency sent Merck a warning letter stating

that Merck's promotional campaign for Vioxx " minimizes the potentially

serious cardiovascular findings " in Vigor. The agency required Merck to

send letters to physicians across the country " to correct false or

misleading impressions and information. "

 

This past August, the results of the Kaiser Permanente study came in

and, according to Dr. Graham, who works in the F.D.A.'s office of drug

safety, they were damning. Dr. Graham eventually concluded that high

doses of Vioxx increased the risk of heart disease 3.7 times.

 

Dr. Graham contends that his bosses delayed his efforts to have the

study published and, in a series of testy e-mail messages, demeaned his

conclusions. A message from one superior called his findings " nothing

more than a scientific rumor. "

 

Dr. Kweder pointed out that Dr. Graham was unable to tell which patients

had taken aspirin and whether patients given Vioxx were already at a

higher risk of heart disease before the study started. In the end, she

said, Dr. Graham's study did little more than to suggest that Vioxx

might harm the heart.

 

" That's nothing new, " Dr. Kweder said. " We knew that from Vigor. "

 

A month later, when Merck informed the agency that the company would

withdraw Vioxx, based on the polyp study, Dr. Kweder said agency

officials were stunned.

 

Some experts still contend that Vioxx could be helpful for those at

great risk of ulcer who do not have weak hearts. Asked if the agency

would have required the drug's withdrawal if Merck had come to a

different decision, Dr. Kweder said the agency would have had to examine

the polyp study closely " and determine where the benefit might outweigh

the risk. "

 

" We haven't done that,'' she said. " We wish we had had the opportunity

to do that. "

 

Some critics say the episode highlights a more systemic problem - that

the F.D.A., having approved a drug for the market, does not adequately

monitor it afterward for safety problems.

 

But Dr. Kweder said she had no regrets about the handling of Vioxx. " The

case of Vioxx,'' she said, " is one where the agency left no stone unturned. "

 

The Plaintiffs: Coming Soon, a Flood of Litigation

 

Jamie Gregg, a 32-year-old construction worker from Katy, Tex., and

father of three boys, had just reported for a job at Houston's Hobby

Airport last May 28 when he collapsed, apparently from a heart attack.

 

He was rushed to the hospital, where a medical team saved his life. But

his brain had been deprived of oxygen for so long that Mr. Gregg is now

in a nursing home in Lufkin, Tex., fed through a tube, unable to move

more than his head or to utter more than a few syllables.

 

" We really don't know what he's thinking in his head, " said his wife,

Lisa Gregg, who said she was not sure if her husband even recognized his

family.

 

Mr. Gregg, who had undergone a series of back surgeries, had been taking

a high dosage of Vioxx, 50 milligrams a day, for four years to treat

back pain. So the day after Mrs. Gregg heard that Vioxx was being

withdrawn from the market, she walked into the offices of Goforth Lewis

Sanford, a law firm in Houston. That firm, along with W. Mark Lanier, a

prominent Houston plaintiffs' lawyer, are now preparing a lawsuit

against Merck.

 

" This has got to be the reason " for her husband's problem, she said.

" And if it is the reason, they've got to pay. There's people's lives

that have been ruined by this, and I'm one of them. "

 

Stories like the Greggs' underscore the very human nature of Merck's

business problems. So far, 375 personal-injury lawsuits, representing

1,000 plaintiff groups, have been filed against Merck, according to the

company's third-quarter filing with securities regulators. Some of the

suits predate Vioxx's withdrawal. But with people like the Greggs just

awakening to the issue, attorneys expect the number to grow markedly.

 

" From the scope of how many people are affected, it's as big as anything

that ever occurred with a pharmaceutical, " said Justin G. Witkin, a

personal injury lawyer in Gulf Breeze, Fla.

 

Another plaintiffs' lawyer amassing Vioxx clients is Andy D. Birchfield

Jr., of Montgomery, Ala., who noted that fen-phen, the diet drug

combination linked to heart valve problems, was used by six million

people. " You've got 20 million Americans who took Vioxx, " he said.

Wyeth, which manufactured two drugs, either of which was combined with a

third to make the fen-phen combination, has set aside $16.6 billion to

cover its liability.

 

Some of the first Vioxx cases are expected to go to trial next year.

Lawyers and courts are still trying to sort out whether to consolidate

the lawsuits and in which courts to try them.

 

Last Tuesday, about 300 personal-injury lawyers gathered in a ballroom

at the Ritz-Carlton Huntington Hotel & Spa in Pasadena, Calif., for a

combination strategy session and pep rally on Vioxx claims.

 

But the plaintiffs' lawyers face a big obstacle in convincing juries

that a person's heart attack or stroke was caused by Vioxx, because many

people suffer such attacks for many reasons.

 

Merck has not discussed its defense strategy in detail. But besides

arguing that it took the drug off the market as soon as it had solid

evidence of Vioxx's dangers, it is also likely to argue in many cases

that a person's problems could have other causes. Mr. Gregg, for

instance, smoked half a pack of cigarettes a day, his wife said. And

since April 2002, the Vioxx label recommended that the 50-milligram dose

Mr. Gregg used not be taken for extended periods.

 

Thomas B. Moore, a Los Angeles lawyer who represents pharmaceutical

companies in such matters, although not Merck in this case, predicted

that even the estimate by Dr. Graham of the F.D.A. that the drug caused

more than 27,000 deaths and heart attacks would not help plaintiffs win

cases. " The problem is that David Graham can't name one of them, " Mr.

Moore said. " He can't name one of those 27,000. "

 

He said Merck did not appear to have hidden any data, but instead

disagreed about the interpretation, and had withdrawn the drug

voluntarily. " Voluntary withdrawals do much better with jurors than a

withdrawal by the F.D.A, " he said.

 

The Future: Merck's Costs Still Lie Ahead

 

As if trial lawyers, federal prosecutors and congressional committees

were not challenges enough, Merck has had little success introducing new

drugs since Vioxx. The company's laboratories, once among the most

productive in the pharmaceutical industry, have suffered a long string

of failures and the company's new drug pipeline is nearly bare.

 

Merck's stock has fallen 40 percent since it announced the Vioxx recall

in September, lowering its market value by about $50 billion. Merck

shares closed Friday at $26.45, up 30 cents.

 

Merck will not disclose its strategy for resolving the Vioxx-related

suits. But analysts who have studied the issue say that Merck may follow

the route taken by Bayer, which faced thousands of suits claiming injury

from its cholesterol drug Baycol, which was linked to a serious muscle

disorder.

 

Bayer tried to settle most of the stronger suits, while pushing for

trials in cases where it felt plaintiffs had overreached and the company

had a tactical advantage. Bayer won a crucial case in Texas last year,

and its stock has nearly tripled since March 2003, when concerns about

its legal liability peaked.

 

Still, Merck's legal liability could top $10 billion, according to two

studies by Wall Street analysts. Merrill Lynch estimated that the

company's legal liability would be $4 billion to $18 billion, depending

on the number of people who suffered heart attacks while taking Vioxx

and how much the company pays to resolve each claim. But that estimate

did not include potential punitive damages, Merrill noted.

 

In an estimate last month, since withdrawn, Sanford C. Bernstein &

Company estimated that the company could spend $12 billion. But Richard

Evans, the Bernstein analyst, said he withdrew the estimate because the

company faced so many uncertainties that an accurate calculation was

impossible. He said, though, that he did not think the company faced a

serious risk of bankruptcy.

 

Merck is expected to have $20 billion in sales and $6 billion in profits

next year, not counting its Vioxx costs, giving it the financial

flexibility to settle thousands of suits. And its legal liabilities and

relatively weak prospects for new drugs could actually provide a

protective effect, by making Merck an unpromising takeover candidate for

other big drug companies.

 

For now, Merck appears likely to limp along independently, analysts say.