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https://www.statnews.com/2018/01/30/pharmaceutical-industry-fake-news-tobacco/

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Accusations of “fake news” are all the rage now, with people often throwing around the term when they read an article that tells them something they don’t want to hear. But an entire industry called“product defense,” created years ago by the tobacco industry, uses falsehoods and misdirection to protect companies from bad media and regulatory scrutiny. The pharmaceutical industry is no stranger to these tactics.

Document archives have revealed how tobacco companies helped create and hone product defense strategies. In my years as a reporter and during a stint as an investigator for the U.S. Senate, I’ve seen them deployed by a range of industries.

I fell into this world back in 2005, while working as an editor for the news section of Environmental Science & Technology, the top journal in the field of environmental science. After spending weeks digging through the tobacco archive, I wrote a story about Steven J. Milloy, a columnist for FoxNews.com who ran a website called JunkScience.comand headed a shady organization called The Advancement of Sound Science Coalition (TASSC). In a 1993 letter, the public relations firm APCO explained how it launched TASSC “to expand and assist Philip Morris in its efforts with issues in targeted states in 1994.”

While I never learned if Milloy had direct ties to pharmaceutical companies, he had published a book called “Silencing Science” that argued regulatory agencies like the Food and Drug Administration had “eliminated science from public policy.”Milloy was also one of the early defenders of Vioxx, arguing that a study that caused the drug to be withdrawn for increasing the risk of heart attacks was a “tremendous overreaction.”

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https://en.wikipedia.org/wiki/Rofecoxib

Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.^[1]

On September 30, 2004, Merck withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, resulting in between 88,000 and 140,000 cases of serious heart disease.^[2] Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx.^[3] Merck reserved $970 million to pay for its Vioxx-related legal expenses through 2007, and has set aside $4.85bn for legal claims from US citizens.

Rofecoxib was available on prescription in both tablet-form and as an oral suspension. It was available by injection for hospital use.

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https://www.alternet.org/2020/02/the-art-of-scientific-deception-former-assistant-secretary-of-labor-explains-how-corporations-use-mercenary-science-to-whitewash-harmful-products-and-drugs/

no lnx

The art of scientific deception: Former Assistant Secretary of Labor explains how corporations use ‘mercenary science’ to whitewash harmful products

Written by Keith A. Spencer / Salon February 2, 2020

One curious difference between humans and corporations is our capacity to harm others and emerge unscathed. If you or I were to poison someone on camera in broad daylight, we would be given a trial and sent to prison in a hurry. But if you or I were a corporation, we could hire consulting firms to produce research papers that claim that the poisoning didn’t happen, and/or question the existence of the poison, or claim that said concoction actually does good rather than harm. If that failed, we could then gum up the legal and political system with lobbyists and lawyers for decades.

In public discourse about our supposed post-truth society, most op-eds fixate on the way that social media can create separate reality bubbles. Few focus on what David Michaels, Obama’s Assistant Secretary of Labor for the Occupational Safety and Health Administration (OSHA), calls “mercenary science” — science-for-hire, contracted out by chemical and pharmaceutical companies to prove that their harmful products aren’t harmful by giving them the quantitative imprimatur of STEM knowledge. The idea that science and truth could diverge is profoundly troubling for our entire civilization.

While the vast majority of scientists, both employed publicly and privately, are honest and do their work as part of a larger quest for truth, there are a few notable exceptions. Specifically, a few mercenary science consulting firms have been very effective at helping corporations continue selling harmful chemicals and drugs long after they should have stopped.

Michaels, who has a new book on the topic titled “The Triumph of Doubt: Dark Money and the Science of Deception,” has been studying this problem for years, in part by virtue of his 8-year tenure at OSHA.  Now a public health professor at George Washington University, Michaels’ book pulls back the curtain on the way that dark money and for-profit science is quite literally killing Americans.

I spoke with Michaels over the phone about the problem of corporate science and his insider’s view; as usual, this interview has been condensed and edited for clarity.

Salon: To start, what is “mercenary science”? How do you define this?

David Michaels: Mercenary science means [when scientists] produce studies that aren’t designed to better understand the world, or they help make the world a better place — which is why most scientists are in the business of science – but to defend products and to defend corporations. And often to influence regulation or to slow the compensation of victims.

This is the Enron-ization of science. It’s created a fiction in order to promote an actual game, fiction around science. And it is quite mercenary. In fact, this phrase is not one that I invented, but actually is used by these consulting companies whose business model is to provide some using reports and testimonies to corporations, so they can continue to market dangerous products or activities without being hindered by regulation or by compensating the people they’ve hurt.

What would you say is the most shocking, real-life example of something like this — of mercenary science becoming embedded in mainstream discourse?

I think the most famous [example] is in the tobacco industry… who didn’t invent it, but who certainly gained the most from it — and in climate change. There’s actually some overlap between some of the same mercenary scientists in both examples.

But as I write [in my book], this is now become standard operating procedure for virtually every industry, and in many cases, it’s the same so-called scientists who are involved in doing it.  Nowadays, the instinct of corporate leaders — CEOs and executives —when there’s an allegation that their product could be causing harm is to say, “How can we show that it isn’t causing harm?” Not, “how can we determine whether or not we cause harm,” and then figure out what to do about it.

Other examples [include] opioids, and essentially how a few pharmaceutical companies misrepresented the studies to make it look like these opioids were not addictive. We have a death toll of tens of thousands a year as a result of that.

So do you think the people who are actually doing this kind of mercenary science, do they —

How they sleep at night?

Yes — and, how do they find these people? My parents were scientists and I hung out around a lot of scientists, and in my experience pretty much all of them were driven by the quest for truth, not money.

I mean, go look back at the 1994 tobacco hearings with Henry Waxman. You had well-educated corporate executives put their right hands in the air, swear that they did not believe that nicotine was addictive. I opened [my book] with a quote from Upton Sinclair, “It’s difficult to get a man to understand something when his salary depends upon him not understanding it.”

It’s very clear that your financial relationship with products, with corporations influences how you think about them. The example I like to give, and this isVioxx. You may remember Vioxx — it was a pain killer, a prescription drug invented by scientists at Merck to be used for arthritis and other sorts of pain, especially for people who couldn’t take aspirin. They, to test effectiveness they did a randomized clinical trial comparing it to Naprosyn, also known as Aleve. And they found it was effective, it was approved by the FDA, it went on the market, immediately became a very widely used, and successful and profitable drug.

Shortly after it came out, scientists independent of Merck looked at the results and found that the patients who were given Vioxx had more than twice the cardiovascular incident rate — including heart attacks  —  of the people who took comparable drugs like Naproxen (Aleve).

Instead of saying, “well, this is a significant problem,” scientists who were associated with Merck — and these wereacademic scientists at major academic medical centers— looked at these data, and they said, “No, Vioxx doesn’t increase risk of heart attack and stroke. It prevents it.”

And it’s true, you could look at it that way, but we don’t have a drug that prevents 60% percent of heart attacks — if we did, we’d put it in the water supply. We quickly learned the truth though, because at the same time, Merck started a randomized clinical trial to see if Vioxx prevented colon polyps, and we have no prevention for colon polyps — so [they did] a randomized, double-blind placebo trial, and that trial had to be stopped early because Vioxx was killing people. It more than doubled the risk of cardiovascular events.

In the few short years since Vioxx was on the market, FDA scientists estimated it cost somewhere between 88,000 and 120,000 heart attacks.

Here were very well-known cardiologists who were blinded for the truth by their financial relationship with Merck. And they were scientists who were not even in the business of product defense. So I think what happens is if your business model, if your financial relationships can influence how you look at science, it does.

What that tells me is we desperately need good science, and we desperately need accurate interpretation of scientific results, but they have to be done independently of the corporations that make these products or we won’t have honest results.

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http://www.theglobeandmail.com/life/vioxx-took-deadly-toll-study/article1113848/

2005

Vioxx, the blockbuster arthritis and pain medication pulled off the market last September, could have killed more than 40,000 people in the United States, according to an FDA scientist who has said his employer silenced his earlier warnings about the drug's safety.

David Graham, associate director of science for the U.S. Food and Drug Administration's Office of Drug Safety and lead author of a study published on-line by The Lancet yesterday, found that Vioxx raised a person's risk of coronary heart disease by 34 per cent,compared with other anti-inflammatory drugs, including Celebrex, its onetime rival in the class of drugs known as cox-2 inhibitors.

(Celebrex has also been linked to heart attacks at high doses).

Dr. Graham and colleagues estimate that during the five years Vioxx was sold in the United States, it caused between 88,000 and 140,000 excess cases of serious heart disease. Based on national statistics of heart disease and deaths, the researchers estimate that close to half of those cases, or 44 per cent, would have resulted in fatalities. This means anywhere from 39,000 to 61,000 deaths in the United States could be linked to Vioxx.

"It's a huge number," saidDr. Graham, now widely known as a whistle-blower scientist.avandia?

"In the future, when trials show that a new treatment confers a greater risk of a serious adverse effect than a standard treatment, we must be much more careful about allowing its unrestrained use."

Dr. Graham said in an interview yesterday that it was fair to extrapolate the U.S. numbers to Canada. According to IMS Health, a private company that tracks prescription-drug sales, pharmacies in Canada dispensed more than 15 million prescriptions for Vioxx after it hit the market in 1999.

"The population of Canada is about an eighth, or ninth, in terms of the size. And the level of use, or exposure to, Vioxx in Canada was the same, if not greater, than in the U.S.," Dr. Graham said.

Such an extrapolation would suggest Vioxx could be associated with as many as 4,000 to 7,000 deaths in Canada.

But Muhammad Mamdani, a senior scientist with the Institute for Clinical Evaluative Sciences in Toronto who has studied Vioxx and other cox-2 inhibitor drugs in its class, cautioned that those numbers "seem a bit more like back-of-the envelope calculations."

"Do I believe those numbers? Not really," he said. "They could be higher or they could be lower. It's dangerous to extrapolate a number from the data."

Certain factors might skew the information, Dr. Mamdani said. For example, he noted most of the heart problems uncovered were linked to patients taking Vioxx at doses higher than 25 milligrams a day.

As well, he said, people taking Vioxx in the study may have been at higher risk of coronary disease: "People who use traditional NSAIDS [non-steroidal anti-inflammatory drugs such as ibuprofen]are typically healthier."

He said if Vioxx had such a dramatic effect on heart attack rates, researchers here would have detected a spike. Instead, he said, none was apparent.

Still, Dr. Mamdani added: "I think David Graham's work should be commended. It shows in a reasonably convincing manner that there's a problem there."

No one from Health Canada would comment on Dr. Graham's study. But spokeswoman Jirina Vlk said Health Canada officials are combing through "volumes" of safety information to assess the cardiovascular and other problems Vioxx caused here before Merck & Co. pulled its drug off markets worldwide on Sept. 30.

That move followed evidence that Vioxx doubled the risk of heart attacks and strokes in a clinical trial studying whether the drug could prevent colon cancer. Other studies have suggested that the drug, which blocks an enzyme linked to pain and swelling, contributes to blood clotting and hypertension. But the cancer study was not the first to point to the heart risks of taking Vioxx.

Dr. Graham decided to lead a Vioxx study after a large trial intended to highlight the gastrointestinal safety of the drug instead suggested it carried five times the risk of heart problems compared with naproxen, an older anti-inflammatory and pain-killing medication.

At the time,Merckofficials suggested naproxen actually protected the heart, which made it appear as though Vioxx was having a damaging effect. Dr. Graham decided to investigate further.

He and colleagues analyzed data from 1.4 million people between the ages of 18 and 84 in California who were treated between January of 1999 and December of 2001 with one of the new cox-2 drugs and those taking the older NSAIDS.

Not only did they find that naproxen did not protect against serious heart disease, they uncovered the risk that Vioxx posed.

But Dr. Graham said that his supervisors at the FDA discouraged him from presenting his findings to a drug-safety meeting last summer. As well, he said, "They tried to block it from being published."

"I was threatened with severe consequences if I went forward. I took that to mean I would be fired," said Dr. Graham, who testified at a U.S. Senate committee hearing last fall that he felt the FDA fumbled its duties on the Vioxx file.

FDA officials deny Dr. Graham's allegations and say they feel Dr. Graham's study required further review before it could be submitted.

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http://www.nytimes.com/**2004**/11/14/business/despite-warnings-drug-giant-took-long-path-to-vioxx-recall.html?_r=0

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.

==

Timeline: The Rise and Fall of Vioxx : NPR

www.npr.org/templates/story/story.php?storyId=5470430

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1. https://www.google.com/search?q=related:www.npr.org/templates/story/story.php%3FstoryId%3D5470430+vioxx+pbs+npr&tbo=1&sa=X&ved=0ahUKEwj_k6-DncbNAhUD5GMKHbwuDPkQHwghMAA

NPR:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{Nov 10, 2007 -Shortly before the FDA approved :{Vioxx:(style="font-weight:bold"):}: in 1999, drug maker Merck launched a study it hoped would prove that :{Vioxx:(style="font-weight:bold"):}: was superior to older painkillers, because it caused fewer gastrointestinal problems. ... November 1998: Merck asks the Food and Drug Administration (FDA) for approval of ...:(style="word-wrap:break-word"):}:

Vioxx: The Downfall of a Drug : NPR

www.npr.org/series/5033105/vioxx-the-downfall-of-a-drug

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1. https://www.google.com/search?q=related:www.npr.org/series/5033105/vioxx-the-downfall-of-a-drug+vioxx+pbs+npr&tbo=1&sa=X&ved=0ahUKEwj_k6-DncbNAhUD5GMKHbwuDPkQHwgoMAE

NPR:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{Merck removed one of the world's best-selling painkillers from the market in 2004 after a study showed :{Vioxx:(style="font-weight:bold"):}: caused an increased risk of serious cardiovascul:(style="word-wrap:break-word"):}:

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:{R:(style="word-wrap:break-word"):}:ofecoxib - Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/**Rofecoxib**

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1. https://webcache.googleusercontent.com/search?q=cache:uMvTX6hXkgsJ:https://en.wikipedia.org/wiki/Rofecoxib+&cd=12&hl=en&ct=clnk&gl=us
2. https://www.google.com/search?q=related:https://en.wikipedia.org/wiki/Rofecoxib+vioxx+pbs+npr&tbo=1&sa=X&ved=0ahUKEwj_k6-DncbNAhUD5GMKHbwuDPkQHwhVMAs

Wikipedia:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{:{Rofecoxib:(style="font-weight:bold"):}: /ˌrɒfᵻˈkɒksɪb/ is a nonsteroidal anti-inflammatory drug (NSAID) that has now ..... :{PBS:(style="font-weight:bold"):}: NewsHour. .... :{National Public Radio:(style="font-weight:bold"):}: 2004 Q&A on the case, following withdrawal announcement · Court TV's full coverage of the :{Vioxx:(style="font-weight:bold"):}: civil ...:(style="word-wrap:break-word"):}:

Transcript | The Other Drug War | FRONTLINE | PBS

www.pbs.org/wgbh/pages/frontline/shows/other/etc/script.html

:{:(style="border-color:#006621;;border-style:solid;border-width:5px 4px 0px !important;width:0px;height:0px;margin-left:3px;top:7.5px;margin-top:-4px;position:absolute;left:0px"):}:

1. http://webcache.googleusercontent.com/search?q=cache:an0kV7_EzmwJ:www.pbs.org/wgbh/pages/frontline/shows/other/etc/script.html+&cd=13&hl=en&ct=clnk&gl=us
2. https://www.google.com/search?q=related:www.pbs.org/wgbh/pages/frontline/shows/other/etc/script.html+vioxx+pbs+npr&tbo=1&sa=X&ved=0ahUKEwj_k6-DncbNAhUD5GMKHbwuDPkQHwhcMAw

PBS:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{Nov 13, 2003 -They're after Lipitor, :{Vioxx:(style="font-weight:bold"):}: and Fosamax, the prescription drugs they ...... JULIE ROVNER, :{NPR:(style="font-weight:bold"):}:: Both the House and Senate actually passed ...:(style="word-wrap:break-word"):}:

Supplements and Safety | FRONTLINE | PBS

www.pbs.org/wgbh/frontline/film/supplements-and-safety/

:{:(style="border-color:#006621;;border-style:solid;border-width:5px 4px 0px !important;width:0px;height:0px;margin-left:3px;top:7.5px;margin-top:-4px;position:absolute;left:0px"):}:

1. http://webcache.googleusercontent.com/search?q=cache:2SsDHINrqYsJ:www.pbs.org/wgbh/frontline/film/supplements-and-safety/+&cd=14&hl=en&ct=clnk&gl=us
2. https://www.google.com/search?q=related:www.pbs.org/wgbh/frontline/film/supplements-and-safety/+vioxx+pbs+npr&tbo=1&sa=X&ved=0ahUKEwj_k6-DncbNAhUD5GMKHbwuDPkQHwhkMA0

PBS:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{For shame :{PBS:(style="font-weight:bold"):}:. .... Same here, and glad to see someone else bring up :{Vioxx:(style="font-weight:bold"):}:. .... of thousands died from :{Vioxx:(style="font-weight:bold"):}: or other drugs before being stopped by the FDA?:(style="word-wrap:break-word"):}:

Flirting with Disaster: Why Accidents are Rarely Accidental

https://books.google.com/books?isbn=1402753039

Marc S. Gerstein, ‎Michael Ellsberg, ‎Daniel Ellsberg - 2008 - ‎Social Science

November 12, 2002, www.pbs.org/wgbh/nova/volcano/chouet.html. Prakash, Snigdha. “Documents Suggest Merck Tried to Censor Vioxx Critics.” NPR: All ...

935 Lies: The Future of Truth and the Decline of America's Moral ...

https://books.google.com/books?isbn=1610391179

Charles Lewis - 2014 - ‎Social Science

... 2012, at http://www.pbs.org/tradesecrets/docs/pdf/BOB_20010215_162533.pdf. ... “Timeline: The Rise and Fall of Vioxx,” National Public Radio, November 10, ...

==

Under Elizabeth J. Cabraser's leadership, Lieff Cabraser has become one of the country's largest law firms serving clients seeking redress for financial and consumer fraud, anti-competitive practices, harmful drugs and products, and illegal employment practices. For over three decades, Elizabeth has made sure that our firm remains dedicated to its core values.

Possessing unparalleled expertise in complex civil litigation, Elizabeth has served as court-appointed lead, co-lead, or class counsel in scores of federal multi-district and state coordinated proceedings. These cases include multi-state tobacco, the *Exxon Valdez* disaster,Breast Implants, Fen-Phen (Diet Drugs), Vioxx, Toyota sudden acceleration, numerous securities/investment fraud cases, and Holocaust litigation. Today, Elizabeth serves in court-appointed leadership positions in several of the nation's highest profile civil cases: the BP Gulf Oil Spill, GM ignition switch defect, and Takata defective airbag litigation.

A Pillar of the Plaintiffs' Bar

Elizabeth has been repeatedly recognized as one of the foremost litigators in our nation, including being selected an unprecedented four times as one of the 100 Most Influential Lawyers in America by the National Law Journal, which has called her "a pillar of the plaintiffs' bar." In 2015, the National Law Journal named her as one of the 75 outstanding women lawyers in America. She has been named repeatedly to the Lawdragon 500, The Top 100 California Lawyers, and as a SuperLawyer in multiple fields.

The Daily Journal has described Elizabeth as

"a commanding attorney and a role model for other

:{:{litigators, especially fellow female lawyers."}:

Law360 noted in a profile of Elizabeth that

"Her reputation among defense attorneys is that

:{:{of a formidable opponent who comes to cases}:

thoroughly prepared and can win a Judge's ear.

Commitment to Advancing the Legal Profession and Society

Elizabeth serves on the Executive Committee of the Council of the American Law Institute (ALI) and is an advisor to several ALI projects, including Aggregate Litigation, the Restatement Third, Torts: Liability for Economic Harm. Since 2011, she has served on the Federal Civil Rules Advisory Committee.

Elizabeth has written and spoken extensively on substantive legal issues as well as ones related to the advancement of women in the profession, including last year for Trial magazine, published by the American Association for Justice, a commentary entitled "Where are all the women in the courtroom?"   

In 2010, the American Bar Association Commission on Women in the Profession honored Elizabeth with its Margaret Brent Women Lawyers of Achievement Award. The award recognizes the accomplishments of women lawyers who have excelled in their field and have paved the way to success for other women lawyers. It is regarded by many as the highest honor in the legal profession for women lawyers.

Elizabeth is also a fellow of the American Academy of Arts and Sciences. Many of our nation’s most accomplished leaders from academia, the social sciences, the study and practice of law, business, public affairs, the humanities, and the arts are members of the Academy.

==

low end killed 30K americans, accounted for ripple in death rate stats:

The year after the scandal unfolded, Merck's long-time CEO resigned and was replaced by one of his top lieutenants. But heretained the $50 million in financial compensation he had received over the previous five years.Neither he nor any other Merck executives was charged with corporate malfeasance.

Senior FDA officials apologised for their lack of effective oversight and promised to do better in the future. The Vioxx scandal began to sink into the vast marsh of semi-forgotten international pharmaceutical scandals.

Then in 2005, as he now remembers it, Ron Unz "was reading my morning newspapers, as I always do, and noticed tiny items about an unprecedented drop in the American death rate. Hmm I said, I wonder if that might have anything to do with all those other stories about that deadly drug recently taken off the market and all the resulting lawsuits."

The year after Vioxx was pulled from the market, the New York Times and other media outlets were running minor news items, usually down-column, noting thatAmerican death rates had undergone a striking and completely unexpected decline. These were what Unz, a dedicated news browser, was reading.

Typical was the headline on a short article that ran in the 19 April 2005 edition of USA Today: 'USA Records Largest Drop in Annual Deaths in at Least 60 Years.' During that one year,American deaths fell by 50,000 despite the growth in both the size and the age of the nation's population. Government health experts were quoted as being greatly "surprised" and "scratching [their] heads" over this strange anomaly, which was led by a sharp drop in fatal heart attacks.

For his Chinese melamine/Vioxx comparison, Unz went back to those 2005 stories. Quick scrutiny of the most recent 15 years worth of national mortality data provided on the US Government's Centers for Disease Control and Prevention website offered Unz some useful clues.

"We find the largest rise in American mortality rates occurred in 1999, the year Vioxx was introduced, while the largest drop occurred in 2004, the year it was withdrawn," says Unz. "Vioxx was almost entirely marketed to the elderly, and these substantial changes in the national death-rate were completely concentrated within the 65-plus population.

Ron Keeva Unz(born September 20, 1961) is a formerbusinessmanand political activist, best known for an unsuccessful race in 1994 for thegovernorshipofCalifornia, and for sponsoring propositions promoting structuredEnglishimmersion education. He waspublisherofThe American Conservativefrom March 2007 to August 2013.

unz original:The impact of these shifts was not small. After a decade of remaining roughly constant, the overall American death rate began a substantial decline in 2004, soon falling by approximately 5 percent, despite the continued aging of the population. This drop corresponds to roughly 100,000 fewer deaths per year. The age-adjusted decline in death rates was considerably greater.

Patterns of cause and effect cannot easily be proven. But if we hypothesize a direct connection between the recall of a class of very popular drugs proven to cause fatal heart attacks and other deadly illnesses with an immediate drop in the national rate of fatal heart attacks and other deadly illnesses, then the statistical implications are quite serious. Perhaps 500,000 or more premature American deaths may have resulted from Vioxx, a figure substantially larger than the 3,468 deaths of named individuals acknowledged by Merck during the settlement of its lawsuit. And almost no one among our political or media elites seems to know or care about this possibility. A recent Wall Street Journal column even called for relaxing FDA restrictions aimed at avoiding “rare adverse events,” which had been imposed after the discovery of “unanticipated side effects of high-profile drugs like Vioxx.”

http://readersupportednews.org/opinion2/272-39/11399-when-half-a-million-americans-died-and-nobody-noticed

==

http://www.sourcewatch.org/index.php/Vioxx

Vioxxis a subsection of the main SourceWatch articleMerck.

Contents

[hide]

• 1Marketing
• 2Recall
• 3Doctored science and lawsuits
• 4Merck promotional campaign
• 5Censoring spokes doctor-turned-critic
• 6Another attempt to rehabilitate Merck's image
• 7References

Marketing

Vioxx is the brand name forMerck's anti-inflammatory drug and pain medication, initially marketed as an alternative to analgesics that aggravate stomach ulcers. Merck's marketing of Vioxx was unusually aggressive. In January 2001,O'Dwyers PR Dailyreported that Merck had paid Bruce Jenner and the former Olympic skater Dorothy Hamill for media interviews they gave discussing Vioxx.^[1]A November 2001 study by theNational Institute for Health Care Management Research and Educational Foundationfound that Merck spent $160 million to advertise Vioxx in 2000 alone; more thanAnheuser-Buschspent that year promoting Budweiser beer.^[2]

Recall

Concerns about Vioxx's safety reached the FDA as early as 2000, but the FDA failed to act, in part due to:

• • "laboratories and network of independent drug safety experts in favor of hiring more people to approve drugs. ...the agency (is) increasingly reliant on and bound by drug company money."^[3]

It was not until 2004 that strong, publicly available research tied Vioxx (a COX-2 inhibitor), to a significant increase in heart attacks among users. The drug was pulled off the shelves that fall.^[4]Following the Vioxx recall, many faulted Merck's over-the-top**direct-to-consumer advertising**. According to**Public Citizen**'s Health Research Group director, "Advertising and promotions played a major role in making people think Vioxx was safer and more effective than it is." According to formerFood and Drug Administration(FDA) associate commissionerWayne Pines:

• • "If we see product liability emanating from Merck's decision... (It will) encourage drug companies to disclose the maximum amount of a drug's risks in their advertising."^[5]

TheNew York Timescited Vioxx and other COX-2 drugs as "perhaps the clearest instance yet of how the confluence of medicine and marketing can turn hope into hype - and how difficult it is for the Food and Drug Administration to monitor the safety of drugs after they have been approved for the market."^[6]

Merck responded to the Vioxx recall by launching a**public relations**campaign to salvage its image and portray its pulling the drug in as positive a light as possible.^[7]The campaign included three full page ads in seven prominent newspapers; several television appearances and testimony before Congress by the company's CEO. However, leaked emails and other internal documents indicated that the company knew about the side effects long before the drug was withdrawn. According to Merck's media relations director, "the mantra has been openness, integrity and transparency."^[8]

Doctored science and lawsuits

After Merck withdrew Vioxx, evidence surfaced that the company had withheld early evidence of its dangers.In December 2005, the editors of the prestigious:{New England Journal of Medicine:(style="background-color:#fff200"):}:issued a rare "Expression of Concern" regarding a 2000 Merck report on Vioxx in which "Merck scientists failed to report three nonfatal heart attacks among the Vioxx users. The total number of heart attacks among the drug users was 20 ... not the 17 reported." Merck argued that the heart attacks occurred after the study cut-off date, but the editors maintained that they should have submitted an update, as "the three heart attacks occurred shortly after the study's end." According to the editors, Merck:

• • "withheld more relevant data about strokes and other heart problems linked to the drug, producing inaccuracies and deletions that 'call into question the integrity of the data'."

• • "Experts disagreed on how medically significant the three heart attacks were, but agreed that the decision not to include the cases could bolster claims in thousands of lawsuits against Merck and that the company was deliberately withholding data about the drug's health risks," reported the**Los Angeles Times**. "The accusations by the prestigious New England Journal of Medicine could hurt Merck's ability to defend itself in the 6,500 lawsuits blaming Vioxx for heart attacks, strokes and deaths. Analysts have estimated that the cases could eventually cost the company $50 billion."^[9]

In November 2007, it was reported that Merck had agreed to pay $4.85 billion to settle 27,000 lawsuits in death and injury claims from victims and their relatives. The settlement came after nearly 20 Vioxx civil trials over two years. Merck lost the first civil suit, paying $253 million, but won most of the rest. According to Alex Berenson of the New York Times in November of 2007:

• • "The settlement will help put Vioxx behind Merck, as well as sharply reduce its Vioxx-related legal defense fees, which are now running at more than $600 million annually. The deal becomes binding only if 85 percent of all plaintiffs agree to drop their cases and take the deal. ... Based on the fact that the 27,000 suits cover about 47,000 sets of plaintiffs, the average plaintiff will receive just over $100,000 before legal fees and expenses. ... While eye-popping, the settlement payment represents less than one year's profits for the company."^[10]

In April 2008, theJournal of the American Medical Association(JAMA) published two studies analyzing Merck documents that had surfaced during Vioxx litigation. Collectively, they concluded that Merk had violated scientific publishing ethics byghostwritingdozens of academic articles and minimized the impact of patient deaths in its analyses of clinical trials.

According to one study, medical papers on Vioxx were often prepared by ghostwriters and subsequently attributed academic investigators who often did not disclose financial support. Another study concluded that Merck did not provide to the FDA, nor make public the evidence that Vioxx was linked to increased risk of death.^[11]Five of the six authors of the two JAMA studies had served as paid consultants to plaintiffs' lawyers in Vioxx lawsuits. A Merck researcher called the findings "false and misleading."^[11]

In August of 2008, an analysis of Merck's internal documents were published in theAnnals of Internal Medicine. They concluded that Merck carried out a clinical study of Vioxx in 1999, primarily to support their marketing campaign before launching the drug. According to Merck, the study was done "to test side effects of the painkiller Vioxx."

The 1999 "ADVANTAGE" study compared Vioxx to the widely-used painkiller (Naproxen), in order "to accelerate uptake and advocacy for Vioxx," according to the Merck documents disclosed during litigation.^[12]According to another document, (a nomination of the 1999 study for a marketing award), the study was, "designed and executed in the spirit of Merck marketing principles." According to theWall Street Journal, carrying out clinical studies for marketing purposes:

• • "would raise ethical and scientific questions, from whether study participants were unknowingly -- and needlessly; put in harm's way, to whether a company's research is reliable."

Again, the authors of the Merck document analyses were paid consultants in Vioxx lawsuits against Merck.^[13]Merck responded to the analysis in an open letter, claiming that the analysis "contains numerous inaccuracies." For example, the analysis concluded that the 1999 Vioxx "ADVANTAGE" clinical trial was designed by one of Merck's marketing units. However, Merck maintained that the trial was "designed, conducted, analysed, interpreted and published by the scientific department of Merck’s U.S. Human Health organization." Merck also stressed that there were legitimate, scientific reasons for conductin the trial; such as assessing the "gastrointestinal tolerability of VIOXX compared to naproxen."^[14]

In April 2009, an Australian class action revealed tactics used by Merck to intimidate or discredit doctors or researchers who were critical of Vioxx. According to an internal email, "We may need to seek them out and destroy them where they live".^[15]Merck staff produced a list of people who they wished to "neutralize" or "discredit".

Merck promotional campaign

In June 2005, the ad agencyOgilvy & Mather Worldwidelaunched the first promotional campaign ever for Merck- a $20 million, 6-month campaign with the slogan:

• • "Merck. Where patients come first."

The campaign was planned before the company was forced to withdrawVioxxand evidence came to light that Merck not only ignored evidence that Vioxx caused heart complications, but also heavily marketed the drug.The major goal of the promotional campaign was "to build emotional ties between Merck and consumers". One television commercial shows children reacting in charming confusion to requests to define "measles," "mumps" and "chicken pox":

• • "Most kids today don't have a clue about diseases adults remember, thanks to Merck's scientists." The female announcer adds, "We've invested billions to research heart disease and asthma. Now we're trying to make Alzheimer's, diabetes and cancer history too."

Over 40% of the ads in the campaign are devoted to information about "access programs"; or efforts to provide consumers with prescription drugs either free or at reduced prices. According to Michael Guarini, managing director for Ogilvy & Mather's health care practice:

• • "We want the public to understand a little more who Merck is and raise the awareness of Merck, but we also want to communicate useful information. While the Vioxx scandal had tarnished Merck and public opinion of drug companies in general was low, it's always good to engage in dialogue, to make sure the public has true, balanced, accurate information."^[16]

Censoring spokes doctor-turned-critic

In June 2005, U.S.National Public Radio's Snigdha Prakash reported:

• • "New documents obtained by NPR suggest that even as Merck was making Vioxx into a bestseller, the company was putting pressure on independent doctors. The company's apparent aim: to keep them from discussing evidence of Vioxx's potential safety problems. The documents show that Merck exerted pressure not only on individual doctors, but also on several of the nation's top medical schools."

Merck's campaigned torecruit physician Gurkirpal Singh ofStanford Universityas a Vioxx spokesperson "because he was a senior researcher on a seminal study of arthritis patients." Starting in 1998, Singh became a Vioxx booster and was paid $2,500 per speaking engagement by Merck. However, in 2000, a study suggesting heart problems among Vioxx users worried Dr. Singh and he requested the data. According to Dr. Singh in an interview with NPR:

• • "I wanted to know how many heart attacks, how many strokes, how many deaths were occurring in each one of the groups, and what were these actual number of patients at risk, and how many ended up having an event."

Merck originally promised to share the information with Dr. Singh, but never did. When Dr. Singh began including his concerns in his public presentations on Vioxx, Merck began closely tracking his activities. According to NPR, almost a dozen Merck executives were involved in tracking Dr. Singh. According to an October 4, 2000 email sent by a senior, regional executive who had supervised his scientific handlers:

• • "I have in excess of 80 e-mails pertaining to interactions with Dr. Singh from March 1999 to present. The following is my best recollection of what has happened. Because of the sensitive nature of the following, I strongly encourage you not to share with anyone unless they clearly have a need to know."

As Singh's public criticisms of Vioxx continued (he was by this time, promoting Vioxx's rival, Celebrex, while being paid byPfizer),^[17]Merck began calling his superiors at the university. According to Stanford medical professor James Fries:

• • "(I) received a call from a medical director at Merck, stating that someone on my staff had been making wild and irresponsible public statements about the cardiovascular side effects of Vioxx." According to Dr. Fries, the representative "hinted there would be repercussions for Fries and Stanford if Singh's statements didn't stop. He was left with the sense that Merck's financial support to Stanford was at risk."^[18]

Another attempt to rehabilitate Merck's image

According to the PR firmAPCO Worldwidein May of 2006:

• • "APCO Worldwide is supporting Merck's PR efforts for the controversial arthritis drug Vioxx, which was found to increase heart attack risk in patients."^[19]

APCO was founded byArnold & Porter, one of Washington D.C.'s largest law firms, also well known as atobacco industrylaw firm. According to theWall Street Journal:, the PR boost came as Merck

• • "acknowledged that it misidentified a statistical method used in the study that led it to pull Vioxx from the market."^[20]

The admission calls into question Merck's claim that patients were only at risk if they took Vioxx for 18 months or longer. According to doctors who oversaw the study, risks associated with Vioxx were evident as soon as four months into taking the drug. As of May of 2006, there were over 11,000 Vioxx related lawsuits filed against Merck. The company retainedBurson-Marstellerfor a $20 million "image campaign," after withdrawing Vioxx in 2004.^[21]

See alsoAustralian class action against Merck over Vioxx safety risks.

References

1. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑"Drug companies pushing celebrity message",O'Dwyers PR Daily, January 8, 2001
2. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑What Happens When Drug Dealers Advertise?, PR Watch, (Advertising Age, November 21, 2001)
3. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑FDA, Heal Thyself, PR Watch, (Source: New York Times, December 6, 2004)
4. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Vioxx (rofecoxib) Information Center, Merck, accessed December 2009
5. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Drug Ads Just Got Harder to Swallow, PR Watch,Wall Street Journal, October 2004)
6. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Pushing Pills for Profit, PR Watch,New York Times, December 2004
7. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Merck Public Relations, Yahoo Finance, November 2004
8. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Merck Toots Its Own Horn, PR Watch,Associated Press, November 22, 200)
9. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Thomas H. Maugh II, Lisa GirionJournal Slams Vioxx Study: Questions about 3 heart attacks not included in data analysis could hurt Merck's legal defense,Los Angeles Times, December 9, 2005
10. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Alex Berenson, "Merck Agrees to Settle Vioxx Suits for $4.85 Billion,"New York Times, November 9, 2007.
11. ↑^Jump ^up ^to:11.011.1^Ron Winslow, Avery Johnson "Merck's Publishing Ethics Are Questioned by Studies," Wall Street Journal (sub req'd), April 16, 2008
12. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Kevin P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; Harlan M. Krumholz, MD, SMThe ADVANTAGE Seeding Trial: A Review of Internal Documents, Annals of Internal Medicine, vol. 149 no. 4 251-258, August 19, 2008
13. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Ron Winslow, Jacob Goldstein, "Report Says Merck Vioxx Study Aimed at Marketing," Wall Street Journal, August 19, 2008.
14. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Merck hits out at controversial paper,PM Live, August 27, 2008
15. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Milanda Rout "Vioxx maker Merck and Co drew up doctor hit list",The Australian, April 1, 2009
16. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Stuart Elliott, "A Drug Maker's Ads, Hold the Disclaimer," New York Times, June 2, 2005.
17. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Snigdha Prakash "Part 1: Documents Suggest Merck Tried to Censor Vioxx Critics",All Things Considered,National Public Radio, June 9, 2005.
18. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑Snigdha Prakash "Part 2: Did Merck Try to Censor Vioxx Critics?",All Things Considered, NPR, June 9, 2005.
19. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑"APCO Tackles Litigation PR For Merck, Vioxx",O'Dwyer's PR Daily, May 31, 2006
20. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑John Carreyrou, Ron Winslow, Heather Won Tesoriero, "Merck Admits Error in Vioxx Study", Wall Street Journal, May 31, 2006; Page D7.
21. :{Jump up:(style="top:-99999px;clip:rect(1px 1px 1px 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:↑"APCO Tackles Litigation PR For Merck, Vioxx",O'Dwyer's PR Daily, May 31, 2006

 ==

wiki

Rofecoxib /:{ˌ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{r:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{ɒ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{f:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{ɨ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{ˈ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{k:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{ɒ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{k:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{s:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{ɪ:(style="border-bottom-width:1px;border-bottom-style:dotted"):}::{b:(style="border-bottom-width:1px;border-bottom-style:dotted"):}:/ is a nonsteroidal anti-inflammatory drug (NSAID) that has now been withdrawn over safety concerns. It was marketed by Merck & Co. to treat osteoarthritis, acute pain conditions, and dysmenorrhoea. Rofecoxib was approved by the Food and Drug Administration (FDA) on May 20, 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx.

Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.^[1]

On September 30, 2004, Merck withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, resulting in between 88,000 and 140,000 cases of serious heart disease.^[2] Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx.^[3] Merck reserved $970 million to pay for its Vioxx-related legal expenses through 2007, and have set aside $4.85bn for legal claims from US citizens.

Rofecoxib was available on prescription in both tablet-form and as an oral suspension. It was available by injection for hospital use.

Contents

 [hide]

• 1 Mode of action
  • 1.1 Pharmacokinetics
  • 1.2 Fabricated efficacy studies
• 2 Adverse drug reactions
  • 2.1 Adverse cardiovascular events
    • 2.1.1 VIGOR study and publishing controversy
    • 2.1.2 Alzheimer's studies
    • 2.1.3 APPROVe study
    • 2.1.4 Other studies
    • 2.1.5 Other COX-2 inhibitors
    • 2.1.6 Other NSAIDs
• 3 Withdrawal
• 4 Litigation
• 5 Other effects
• 6 See also
• 7 Footnotes
• 8 References
• 9 External links

 ...

Fabricated efficacy studies

On March 11, 2009,Scott S. Reuben, former chief of acute pain at Baystate Medical Center, Springfield, Mass., revealed that data for 21 studies he had authored for the efficacy of the drug (along with others such ascelecoxib) had been fabricated in order to augment the analgesic effects of the drugs. There is no evidence that Reuben colluded with Merck in falsifying his data. Reuben was also a former paid spokesperson for the drug company Pfizer (which owns the intellectual property rights for marketing celecoxib in the United States). The retracted studies were not submitted to either the FDA or the European Union's regulatory agencies prior to the drug's approval. Drug manufacturerMerckhad no comment on the disclosure.^[10]

§Adverse drug reactions

See also: Non-steroidal anti-inflammatory drug

Prostaglandin is a large family of lipids. Prostaglandin I2/PGI2/prostacyclin is just one member of it. Prostaglandins other than PGI2 (such as PGE2) also play important roles in vascular tone regulation. Prostacyclin/thromboxane are produced by both COX-1 and COX-2, and rofecoxib suppresses just COX-2 enzyme, so there is no reason to believe that prostacyclin levels are significantly reduced by the drug. And there is no reason to believe that only the balance between quantities of prostacyclin and thromboxane is the determinant factor for vascular tone.^[11]Indeed Merck has stated that there was no effect on prostacyclin production in blood vessels in animal testing.^[12]Other researchers have speculated that the cardiotoxicity may be associated withmaleic anhydridemetabolites formed when rofecoxib becomes ionized under physiological conditions. (Reddy & Corey, 2005)Aside from the reduced incidence of gastric ulceration, rofecoxib exhibits a similar adverse effect profile to other NSAIDs.

§Adverse cardiovascular events

§VIGOR study and publishing controversy

The VIGOR (Vioxx GI Outcomes Research) study, conducted by Bombardier, et al., which compared the efficacy and adverse effect profiles of rofecoxib and naproxen, had indicated a significant 4-fold increased risk of acute myocardial infarction (heart attack) in rofecoxib patients when compared with naproxen patients (0.4% vs 0.1%, RR 0.25) over the 12 month span of the study. The elevated risk began during the second month on rofecoxib. There was no significant difference in the mortality from cardiovascular events between the two groups, nor was there any significant difference in the rate of myocardial infarction between the rofecoxib and naproxen treatment groups in patients without high cardiovascular risk. The difference in overall risk was by the patients at higher risk of heart attack, i.e. those meeting the criteria for low-dose aspirin prophylaxis of secondary cardiovascular events (previous myocardial infarction, angina, cerebrovascular accident, transient ischemic attack, or coronary artery bypass).

Merck's scientists interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect.^[13] Some commentators have noted that naproxen would have to be three times as effective as aspirin to account for all of the difference,^[14] and some outside scientists warned Merck that this claim was implausible before VIGOR was published.^[15] No evidence has since emerged for such a large cardioprotective effect of naproxen, although a number of studies have found protective effects similar in size to those of aspirin.^[16][17] Though Dr. Topol's 2004 paper criticized Merck's naproxen hypothesis, he himself co-authored a 2001 JAMA article stating "because of the evidence for an antiplatelet effect of naproxen, it is difficult to assess whether the difference in cardiovascular event rates in VIGOR was due to a benefit from naproxen or to a prothrombotic effect from rofecoxib." (Mukherjee, Nissen and Topol, 2001.)

The results of the VIGOR study were submitted to the United States Food and Drug Administration (FDA) in February 2001. In September 2001, the FDA sent a warning letter to the CEO of Merck, stating, "Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)."^[18] This led to the introduction, in April 2002, of warnings on Vioxx labeling concerning the increased risk of cardiovascular events (heart attack and stroke).

Months after the preliminary version of VIGOR was published in the New England Journal of Medicine, the journal editors learned that certain data reported to the FDA were not included in the NEJM article. Several years later, when they were shown a Merck memo during the depositions for the first federal Vioxx trial, they realized that these data had been available to the authors months before publication. The editors wrote an editorial accusing the authors of deliberately withholding the data.^[19] They released the editorial to the media on December 8, 2005, before giving the authors a chance to respond. NEJM editor Gregory Curfman explained that the quick release was due to the imminent presentation of his deposition testimony, which he feared would be misinterpreted in the media. He had earlier denied any relationship between the timing of the editorial and the trial. Although his testimony was not actually used in the December trial, Curfman had testified well before the publication of the editorial.^[20]

The editors charged that "more than four months before the article was published, at least two of its authors were aware of critical data on an array of adverse cardiovascular events that were not included in the VIGOR article." These additional data included three additional heart attacks, and raised the relative risk of Vioxx from 4.25-fold to 5-fold. All the additional heart attacks occurred in the group at low risk of heart attack (the "aspirin not indicated" group) and the editors noted that the omission "resulted in the misleading conclusion that there was a difference in the risk of myocardial infarction between the aspirin indicated and aspirin not indicated groups." The relative risk for myocardial infarctions among the aspirin not indicated patients increased from 2.25 to 3 (although it remained statitistically insignificant). The editors also noted a statistically significant (2-fold) increase in risk for serious thromboembolic events for this group, an outcome that Merck had not reported in the NEJM, though it had disclosed that information publicly in March 2000, eight months before publication.^[21]

The authors of the study, including the non-Merck authors, responded by claiming that the three additional heart attacks had occurred after the prespecified cutoff date for data collection and thus were appropriately not included. (Utilizing the prespecified cutoff date also meant that an additional stroke in the naproxen population was not reported.) Furthermore, they said that the additional data did not qualitatively change any of the conclusions of the study, and the results of the full analyses were disclosed to the FDA and reflected on the Vioxx warning label. They further noted that all of the data in the "omitted" table were printed in the text of the article. The authors stood by the original article.^[22]

NEJM stood by its editorial, noting that the cutoff date was never mentioned in the article, nor did the authors report that the cutoff for cardiovascular adverse events was before that for gastrointestinal adverse events. The different cutoffs increased the reported benefits of Vioxx (reduced stomach problems) relative to the risks (increased heart attacks).^[21]

Some scientists have accused the NEJM editorial board of making unfounded accusations.^[23][24]Others have applauded the editorial. Renowned research cardiologistEric Topol,^[25]a prominent Merck critic, accused Merck of "manipulation of data" and said "I think now the scientific misconduct trial is really fully backed up".^[26]Phil Fontanarosa, executive editor of the prestigiousJournal of the American Medical Association, welcomed the editorial, saying "this is another in the long list of recent examples that have generated real concerns about trust and confidence in industry-sponsored studies".^[27]

On May 15, 2006, the Wall Street Journal reported that a late night email, written by an outside public relations specialist and sent to Journal staffers hours before the Expression of Concern was released, predicted that "the rebuke would divert attention to Merck and induce the media to ignore the New England Journal of Medicine '​s own role in aiding Vioxx sales."^[28]

"Internal emails show the New England Journal's expression of concern was timed to divert attention from a deposition in which Executive Editor Gregory Curfman made potentially damaging admissions about the journal's handling of the Vioxx study.In the deposition, part of the Vioxx litigation, Dr. Curfman acknowledged that lax editing might have helped the authors make misleading claims in the article." The Journal stated that NEJM '​s "ambiguous" language misled reporters into incorrectly believing that Merck had deleted data regarding the three additional heart attacks, rather than a blank table that contained no statistical information; "the New England Journal says it didn't attempt to have these mistakes corrected."^[28]...

^...^

Withdrawal

Due to the findings of its own APPROVe study, Merck publicly announced its voluntary withdrawal of the drug from the market worldwide on September 30, 2004.^[36]

In addition to its own studies, on September 23, 2004 Merck apparently received information about new research by the FDA that supported previous findings of increased risk of heart attack among rofecoxib users (Grassley, 2004). FDA analysts estimated that Vioxx caused between 88,000 and 139,000 heart attacks, 30 to 40 percent of which were probably fatal, in the five years the drug was on the market.^[37]

On November 5, the medical journal The Lancet published a meta-analysis of the available studies on the safety of rofecoxib (Jüni et al., 2004). The authors concluded that, owing to the knowncardiovascularrisk, rofecoxib should have been withdrawn several years earlier.The Lancetpublished an editorial which condemned both Merck and the FDA for the continued availability of rofecoxib from 2000 until the recall.^[38]Merck responded by issuing a rebuttal of the Jüniet al.meta-analysis that noted that Jüni omitted several studies that showed no increased cardiovascular risk. (Merck & Co., 2004).

In 2005, advisory panels in both the U.S. and Canada encouraged the return of rofecoxib to the market,stating that rofecoxib's benefits outweighed the risks for some patients. The FDA advisory panel voted 17-15 to allow the drug to return to the market despite being found to increase heart risk. The vote in Canada was 12-1, and the Canadian panel noted that the cardiovascular risks from rofecoxib seemed to be no worse than those from ibuprofen—though the panel recommended that further study was needed for all NSAIDs to fully understand their risk profiles. Notwithstanding these recommendations, Merck has not returned rofecoxib to the market.^[39]

In 2005, Merck retained Debevoise & Plimpton 

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CB4QFjAA&url=http%3A%2F%2Fwww.sourcewatch.org%2Findex.php%2FDebevoise_%2526_Plimpton&ei=3HEIVfXrMIKfggTGwYNo&usg=AFQjCNHko32q9GaEZmkvSNfBdqY-lfamOg&sig2=fhXGHMklseb_sqv_0CvtsQ&bvm=bv.88198703,d.eXY

LLP to investigate Vioxx study results and communications conducted by Merck. Through the report, it was found that Merck's senior management acted in good faith, and that the confusion over the clinical safety of Vioxx was due to the sales team's overzealous behavior. The report that was filed gave a timeline of the events surrounding Vioxx and showed that Merck intended to operate honestly throughout the process. Any mistakes that were made regarding the mishandling of clinical trial results and withholding of information was the result of oversight, not malicious behavior. The Martin Report did conclude that the Merck's marketing team exaggerated the safety of Vioxx and replaced truthful information with sales tactics.[citation ^needed]^ The report was published in February 2006, and Merck was satisfied with the findings of the report and promised to consider the recommendations contained in the Martin Report.

§Litigation

See also: Elsevier § Sponsored journals

As of March 2006, there had been over 10,000 cases and 190 class actions filed against Merck[citation ^needed]^ over adverse cardiovascular events associated with rofecoxib and the adequacy of Merck's warnings. The first wrongful death trial, Rogers v. Merck, was scheduled in Alabama in the spring of 2005, but was postponed after Merck argued that the plaintiff had falsified evidence of rofecoxib use.^[40]

On August 19, 2005, a jury in Texas voted 10-2 to hold Merck liable for the death of Robert Ernst, a 59-year-old man who allegedly died of a rofecoxib-induced heart attack. The plaintiffs' lead attorney was Mark Lanier. Merck argued that the death was due to cardiac arrhythmia, which had not been shown to be associated with rofecoxib use. The jury awarded Carol Ernst, widow of Robert Ernst, $253.4 million in damages. This award will almost certainly be capped at no more than US$26.1 million because of punitive damages limits under Texas law.^[41] As of March 2006, the plaintiff had yet to ask the court to enter a judgment on the verdict; Merck has stated that it will appeal.

On November 3, 2005, Merck won the second case Humeston v. Merck, a personal injury case, in Atlantic City, New Jersey. The plaintiff experienced a mild myocardial infarction and claimed that rofecoxib was responsible, after having taken it for two months. Merck argued that there was no evidence that rofecoxib was the cause of Humeston's injury and that there is no scientific evidence linking rofecoxib to cardiac events with short durations of use. The jury ruled that Merck had adequately warned doctors and patients of the drug's risk.^[42]

The first federal trial on rofecoxib, Plunkett v. Merck, began on November 29, 2005 in Houston. The trial ended in a hung jury and a mistrial was declared on December 12, 2005. According to the Wall Street Journal, the jury hung by an eight to one majority, favoring the defense. Upon retrial in February 2006 in New Orleans, where the Vioxx multidistrict litigation (MDL) is based, a jury found Merck not liable, even though the plaintiffs had the NEJM editor testify as to his objections to the VIGOR study.

On January 30, 2006, a New Jersey state court dismissed a case brought by Edgar Lee Boyd, who blamed Vioxx for gastrointestinal bleeding that he experienced after taking the drug. The judge said that Boyd failed to prove the drug caused his stomach pain and internal bleeding.

In January 2006, Garza v. Merck began trial in Rio Grande City, Texas. The plaintiff, a 71-year-old smoker with heart disease, had a fatal heart attack three weeks after finishing a one-week sample of rofecoxib. On April 21, 2006 the jury awarded the plaintiff $7 million compensatory and $25 million punitive. The Texas state court of appeals in San Antonio later rules Garza's fatal heart attack probably resulted from pre-existing health conditions unrelated to his taking of Vioxx, thus reversing the $32 million jury award.^[43]

On April 5, 2006, the jury held Merck liable for the heart attack of 77-year-old John McDarby, and awarded Mr McDarby $4.5 million in compensatory damages based on Merck's failure to properly warn of Vioxx safety risks. After a hearing on April 11, 2006, the jury also awarded Mr McDarby an additional $9 million in punitive damages. The same jury found Merck not liable for the heart attack of 60-year-old Thomas Cona, a second plaintiff in the trial, but was liable for fraud in the sale of the drug to Cona.

In March 2010, an Australian class-action lawsuit against Merck ruled that Vioxx doubled the risk of heart attacks, and that Merck had breached the Trade Practices Act by selling a drug which was unfit for sale.^[44]

In 2010, the national US case against Vioxx and Merck was resolved with a $4.85 billion settlement.^[45] After the settlement, the lawyers for the case disputed the $315 million awarded in legal fees.^[45][46] Ultimately, the judge determined how the fees would be awarded to the plaintiff’s attorneys.^[47] The judge additionally ordered the plaintiff lawyers to cap their fees at 32% of the settlement amount.^[48]

The above dispute over lawyer fees has caused scholars and observers to consider tort reform throughout the country. Articles on the subject include The Vioxx Litigation: A Critical Look at Trial Tactics, the Tort System, and the Roles of Lawyers in Mass Tort Litigation ^[49]^ and 10 Years of Tort Reform in Texas Bring Fewer Suits, Lower Payouts.^[50]

In November 2011, Merck announced a civil settlement with the US Attorney's Office for the District of Massachusetts, and individually with 43 US states and the District of Columbia, to resolve civil claims relating to Vioxx.^[51] Under the terms of the settlement, Merck agreed to pay two-thirds of a previously recorded $950 million reserve charge in exchange for release from civil liability. Litigation with seven additional states remains outstanding. Under separate criminal proceedings, Merck plead guilty to a federal misdemeanor charge relating to the marketing of the drug across state lines, incurring a fine of $321.6 million.^[52]

Vytorin

Merck and Schering-Plough, which co-marketed the cholesterol drug Vytorin, went intodamage-controlmode taking out newspaper ads, reportedAdvertising Agein January 2008. The pharmaceutical companies'public relationscampaign followed their reluctant publication of a study which revealed that neither drug in present in Vytorin reduced fatty plaque build-up in arteries.The study was completed in 2006, but Merck and Schering did not release it for 21 months, allegedly due to "complexity of the data and their own scientific concerns."

The drug companies' newspaper ads, which ran in theNew York Timesand USA Today, referred to the damning study as "a single study that has generated a lot of confusion." They stressed that the drugs "have been proven to lower LDL (bad) cholesterol." However, the study showed was that Vytorin was not "any better than generic Zocor in reducing the buildup of fatty plaque." Members of Congress called for an investigation into why the "massiveadvertisement campaignfor Vytorin was allowed to continue," after the study was belatedly made public. Class-action lawsuits were file, alleging that Merck and Schering-Plough "misrepresented and withheld significant information" from theFood and Drug Administration(FDA) and the public.^[9]In July 2008, a major European study of over 1,800 patients and researchers at 173 hospitals and other sites found that Vytorin:

• • "was no better than placebo at lowering the risk of major cardiovascular events -- including heart attack, stroke, heart surgery and death -- in patients with aortic stenosis." Vytorin "did cut cholesterol levels about 60 percent," but that effect was previously known and is also seen when Zocor (one of two drugs that comprise Vytorin) is taken alone. The European study also observed an increase in cancer cases and deaths among patients taking Vytorin, but researchers said this was not likely due to the drug.^[10]

Mercury levels and Thimerosol vaccines

The Truth is Out There - Interview with Dr. Leonard Horowitz - Maureen Kelleher Productions & Mystique Films - 2008

In early 2005, theLos Angeles Timesobtained a memo from Merck revealing that, prior to the first public disclosure, seniorexecutives were concerned about mercury levels in vaccinations containing a widely used sterilizing agent. The March of 1991 memo revealed concerns about 6-month-old children getting a mercury dose as much as 87 times higher than guidelines for the maximum daily consumption of mercury from fish. According to Dr. Maurice R. Hilleman in a memo to the president of Merck's vaccine division:

• • "When viewed in this way, the mercury load appears rather large."

The memo was prepared as U.S. health authorities aggressively expanded their immunization schedule by adding five new shots for children in their first six months. Many of these shots, as well as some previously included on the schedule, contained thimerosal, an anti-bacterial compound that is nearly 50% ethyl mercury, a neurotoxin. In 1999, federal health officials disclosed that many infants were being exposed to dangerously high mercury levels, following a review by theFood and Drug Administration(FDA). However, the memo revealed that Merck was aware of the concern much earlier.

As of February of 2005, over 4,200 claims have been filed in a special federal tribunal, theVaccine Injury Compensation Program, by parents asserting that their children suffered autism or other neurodevelopmental disorders from mercury poisoning. Thimerosal has been largely removed from pediatric vaccines as a "precautionary measure."^[11]

Gardasil

TROY BAK 921

see wlf and fda

see avandia gottlieb cmpi

see vioxx

ggl doc endgame:

LEGAL FOUNDATIONS

PACIFIC LEGAL1973

memo --> The Alliance document reported that the California Chamber of Commerce picked up onPowelland proposed what became in 1973 the Pacific Legal Foundation, the first of eight regional litigation centers.

[ Cases argued up the judicial ladder by radical litigators have often reached the Supreme Court. They tried unsuccessfully to roll back the Miranda rights of prisoners placed under arrest, and to limit the right of states to enforce certain environmental protections.]

[The Pacific Legal Foundation (PLF) was formed in California in 1973 to counter public-interest law firms and represent the interests of business and private property holders againstenvironmental regulations.PLF’s prospectus quoted the Powell memo at length. (Kim Phillips-Fein, “Invisible Hands,” p. 162).

When asked for his opinion of the “most critical” area of public interest law, PLF’s then-executive legal director replied, “environmental law,” citing the firm’s support for the use of DDT, the construction of a dam and reservoir project, the use of herbicides in national forests and the use of public grazing lands without environmental impact review. The early cases established a clear pattern for PLF and its followers at the Mountain States Legal Foundation and other regionally named corporate defenders.

Environmental cases would be a priority and the foundations’ positions in such cases would invariably be those of their business benefactors, including Monsanto, Weyerhaeuser, Gulf Oil, ARCO, Ford and other companies (Houck, "With Charity for All," pp. 1461-1462). The work of these groups also supported the Wise Use movement; radical property rights activists and corporate front groups that attacked environmental laws and regulations on behalf of landowners, ranchers and the oil industry (Helvarg, The War Against the Greens).]

{Soon the California Chamber of Commerce would propose what would become in 1973 the Pacific Legal Foundation, a nonprofit set up in Sacramento, California, from seed money raised by J. Simon Fluor of the Fluor Corporation [MIC]. And in 1975, the National Legal Center for the Public Interest (NLCPI) was formed "to assist in the establishment of independent regional litigation foundations dedicated to a balanced view of the role of law in achieving economic and social progress."}

WASHINGTON LEGAL FOUNDATION

CIR Vioxx 38 - 60K dead;  Tozzi: CRE went after hayes; ~EPA GHG;  Starr Olsen  TORT --> defund the left (class action?)  RICO? Popeo Samp CoC

D'Aubusson

Merck called half dozen medical schools to get them to stop talking about harm of Vioxx, including Stanford; dossier on Singh

TROYVIOXX:DQA, Graham, Bork

FDA regs 22% of economy;

Troy does tobacco and pharma at Wiley, then FDA (1st political vs civil service appointee; // to RR put pro-corp ppl to run regulatory agencies, but maybe they actually knew something about the industry; B43 staffed with corp PR hacks, eg Cooney CEQ Connaughton, not to mention Timberwolf, beef boy etc).  Troy not only helps industry worm in, but then lays foundation for them to continue to undermine regs after he’s left; goes back to CTT and legal foundations CIR WLF, w/ Graham [Lamar Smith builds on this DQA → IQA to gut EPA regs and stack science advisory boards, cut NOAA and NSF budget, and get “quality” research vs new incarnation of Junk science?]

[But the Bush administration made the chief counsel a political appointee for the first time since the 1980s, easing out civil-servant Porter and empowering Troy...Appointed in August, 2001, Troy had vast authority. With no FDA commissioner until November 2002, Troy reigned for more than a year as top administrator in an agency that regulates 22 percent of the U.S. economy.

"He sent a signal to companies that if you want to deal with the FDA on a number of issues, he's the man to see," said a senior FDA official.

In three years, Troy has held 129 meetings with lobbyists and others with issues before the FDA.

Mark McClellan, commissioner from October 2002 to March 2004, held 30 such meetings, FDA records show.

From 1998 to 2001, Troy's predecessor, Margaret Porter, held one meeting.]

{August 2001: Bush Appoints Daniel E. Troy as the FDA’s chief counsel

President Bush appoints Daniel E. Troy as the FDA’s chief counsel. [FINANCIAL TIMES, 8/14/2001] Before taking the position, Troy was a partner at the law firm Wiley Rein & Fielding, where he sued the FDA several times on behalf of drug companies, including pharmaceutical giant Pfizer. He has repeatedly argued that the agency has only limited authority to regulate drug companies. Troy is mostly known for his involvement in the landmark Supreme Court case that ruled the FDA does not have the authority to regulate tobacco. [BOSTON GLOBE, 12/22/2002; DENVER POST, 5/23/2004] }

Troy "was a symbol of what is rotten at the FDA: the pharmaceutical industry's influence has ensured that business interests take precedence over public safety.

[In a dramatic legal novelty, the FDA has intervened for manufacturers in lawsuits, urging courts to dismiss damages claims against them. FDA briefs have helped the world's two largest drug companies win product-liability cases.

The FDA says courts are not equipped to judge a product's safety. On regulation, officials say their position reflects court rulings that warn about restricting commercial speech. Allowing inconclusive health claims on food labels such as walnuts gives consumers more information, the agency says...A Queens-born Columbia Law School standout, Troy, 44, came to the FDA primed for activism: Clerk for conservative icon Robert Bork;partner at blue-chip Wiley, Rein & Fielding[acta anna neal?]; scholar at the pro-business American Enterprise Institute; litigant for the anti-regulatory Washington Legal Foundation.

Representing a tobacco company against the FDA in the late 1990s, Troy helped win a landmark Supreme Court ruling blocking the agency's attempt to regulate tobacco products.

Litigating for the legal foundation, which drug-company foundations help fund, Troy challenged the FDA's restrictions on promoting drugs for uses the FDA has not approved.

The policy, Troy wrote in 1999, reflects "an overzealous FDA."

Appointed in August, 2001, Troy had vast authority. With no FDA commissioner until November 2002, Troy reigned for more than a year as top administrator in an agency that regulates 22 percent of the U.S. economy.

"He sent a signal to companies that if you want to deal with the FDA on a number of issues, he's the man to see," said a senior FDA official.

In three years, Troy has held 129 meetings with lobbyists and others with issues before the FDA.

Mark McClellan, commissioner from October 2002 to March 2004, held 30 such meetings, FDA records show.

From 1998 to 2001, Troy's predecessor, Margaret Porter, held one meeting..'] th frank

"WLFis to the first amendment what the NRA is to the second amendment. That is, every argument by WLF begins and ends with the first amendment as it applies to a special interest group -- i.e., businesses like the pharmaceutical industry. "

{ Expanding corporate influence over the U.S. educational system was one of the crucial themes of Powell's memo to the U.S. Chamber of Commerce. Corporate power in society gained longevity from influencing the opinions of educated young adults about to enter the workforce and helped reshape institutions of higher learning to prioritize commercial interests.}

https://www.scoop.co.nz/stories/HL0708/S00239/fda-henchmen-protect-avandia-profits.htm

no lnx

...Evelyn Pringle

The FDA's latest campaign to protect the profits of a drug company over the safety of Americans is unprecedented, and the organizers include a gang of current and former FDA officials largely credited with turning the nation's regulatory beagle into a lapdog for Big Pharma under the Bush Administration.

FDA spokesman Douglas Arbesfeld, apparently the industry's new inside guy, kicked off the campaign by sending an e-mail to journalists which was intended to discredit Dr Steven Nissen and the Cleveland Clinic. Dr Nissen's study appeared online on May 21, 2007, in the New England Journal of Medicine and warned that GlaxoSmithKline's diabetes drug Avandia increased the risk of heart attacks by 43% and death from cardiovascular events by possibly 64%.

The talking points for the media appear to have been formulated and agreed upon ahead of time between Arbesfeld and others (see below) because more than one story from ostensibly different sources later appeared in the media and on the internet referring toDr Nissen with such names as "St Steven", "Patron Saint of Drug Safety" and "Saint Steven the Pure."

In his email to journalists, Mr Arbesfeld pasted portions of an article which appeared on the Heartwire website, containing umpteen critical comments about Dr Nissen and the Avandia study, as well as comments made by an anonymous blogger on the internet who said that business at the Cleveland Clinic is run similar to a Mafia TV series. The full bog states:

"Wake up pharmaceutical companies, this is a call from Dr. Nissen, if you don't hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company."

"The Cleveland Clinic was one of the most respected names in medicine, now they are positioning themselves as candidates to take over for a new series on HBO to replace the Soprano's — the Clinico's 'next week who should we wack ......' — Bata bing bata boon. Comment by Brian A - May 22, 2007."

However, it could just as easily be inferred that Mr Arbesfeld authored the slanderous blog and supplied it to Heartwirewith the intention of quoting it later from a “reputable” web site. For its part, Heartwire has since removed what it says are "unsubstantiated remarks about Dr Nissen and the Cleveland Clinic," and states: "In retrospect we regret that we published those sentences, as they do not meet the highest standards of journalistic or scientific integrity or credibility."

The smear campaign has federal lawmakers up in arms. At a June 6, 2007 hearing before the House Oversight and Government Reform Committee, in response to questions about Mr Arbesfeld sending the e-mail under his official title of FDA spokesman, FDA Commissioner Andrew von Eschenbach told the lawmakers, "It was an inappropriate and unfortunate act on the part of an individual which has been addressed through disciplinary procedures."

Dr Nissen is none too happy about the stunt either. "I'm a pretty tough guy," he told ABC News on May 30, 2007, "but I'll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is -- it's an outrage."

As for his part, Mr Arbesfeld told the Boston Globe that the email reflected his own personal views and not the FDA's. Any assertion that the email reflected his own personal views is not quite credible considering that his previous employment was always promoting the views of the industry.

A few articles in the media mentioned thatMr Arbesfeld worked for Johnson & Johnson, but his employment with public relations firm Manning Selvage & Lee was not noted. On December 16, 1999, the Healthcare Marketing & Communications Council reported that Mr Arbesfeld had joined Manning as Senior Vice President in New York.

On January 5, 2001, the firm issued a press release to announce the promotion of Mr Arbesfeld and others and referred to Manning as "one of the largest healthcare practices worldwide and has a broad array of clients including Allergan, Amgen, Eli Lilly and Company, Genentech, Hoffmann La-Roche, Kaiser Permanente, Novartis, Pharmacia and Procter & Gamble."

In reading the press release, Mr Arbesfeld's expertise with using the Internet is apparently a bi-product of his work for Manning. "In this role," it said, "Arbesfeld will help healthcare clients maximize internet-relations in the marketing and communications mix, and will expand the Practice's strategic e-product offerings."

On August 5, 2002, Arbesfeld identified himself in a Reuters article as representing none other than Glaxo,along with six other drug giants including Bristol-Myers, Aventis, J&J, AstraZeneca, Abbott Labs and Novartis, in a campaign to promote the "Together Rx" prescription drug card program for senior citizens. In 2005, the Reporters Handbook listed him as the contact person for J&J subsidiaries, Janssen Pharmaceutica, Ortho-McNeil Pharmaceutical and Ortho Biotech Products.

Less than a week after Mr Arbesfeld's hatchet job on Dr Nissen, ex-FDA Deputy Commissioner Dr Scott Gottlieb planted an editorial in the May 29, 2007, Wall Street Journal entitled, "Journalist Malpractice," accusing the New England Medical Journal of intentionally publishing the Nissen study to make the FDA look impotent. "The publication was timed," he wrote, "to get ahead of the Food and Drug Administration's more careful evaluation of the same issues."

"The journal seemed bent on beating the FDA to the punch," Dr Gottlieb claimed.

"The goal?" he said, "Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals."

The only problem with the Nissen-NEJM conspiracy theory is that the issue under investigation in Congress right now is why the FDA did not warn the public about Avandia heart risks six months before the Nissen study was ever published.

In the end, when it comes to "Journalistic Malpractice," the larger question would seem to be how was it that so many industry shills were able to get the major media outlets and medical journals to immediately publish commentaries and editorials attacking the NEJM and the Nissen research with headlines splashing all over the internet.

In his editorial, Dr Gottlieb notes that there are "questions" whether Avandia is associated with heart risks, but says they are "so far unsupported by more rigorous, randomized studies and extensive review by the FDA and other authorities around the world."

"When it comes to the issue du jour, drug safety," he wrote, "no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval."

Assuming this is true, the problem is that the industry insiders running the FDA refuse to act on the advice of the agency's top scientists with first hand access to the underlying data. In a July 26, 2007 speech on the Senate floor, Senator Charles Grassley (R-Iowa), of the Senate Finance Committee, said that, in the case of Avandia, "Not only did the FDA disregard the concerns and recommendations from the office responsible for post-marketing surveillance, but I have found that it also attempted to suppress scientific dissent."

In the past two months, he told his fellow senators, "I've had to write to the FDA regarding the suppression of dissent from not one but two FDA officials involved in the review of Avandia."

The Heartwire website conveniently echoed Dr Gottlieb's sentiments by featuring portions of a May 23, 2007, unsigned editorial from the medical journal The Lancet, which claimed that the verdict on Avandia should await the results of a Glaxo sponsored trial called RECORD, not due out until 2009.

"Taken together," the editorial said of Dr Nissen's findings, "these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone's safety."

"But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase 3 trial designed specifically to study cardiovascular outcomes," it said.

"Until the results of RECORD are in," the Lancet noted, "it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses."

The problem with waiting two years for the results of the RECORD trial is that FDA scientist Dr David Graham reviewed the results of this study thus far and told an FDA advisory panel that the study design is so flawed that the results should not be considered in any risk benefit analysis of Avandia now, or in 2009.

In fact, Dr Graham says the RECORD study is so useless that it is probably unethical to allow it to continue because no possible benefit can be achieved by allowing it to go on and that Avandia should be pulled off the market now because thousands of patients are being injured each month by using the drug.

At the end of his editorial, Dr Gottlieb lists himself as a physician and a resident fellow at the American Enterprise Institute, as well as former Deputy Commissioner of the FDA from 2005 to 2007. However, back on August 24, 2005, the Seattle Times provided a much better picture of his background and highlighted the oddity of the FDA hiring him in the first place in light of his solid alliance with the industry. "Only a month ago," the article states, "Dr Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors."

At the time, the Times noted, "Now Gottlieb holds the No. 2 job at the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted."

"Now, as one of three deputy commissioners," the article said, "Gottlieb will help oversee such major policies as the FDA's fast-track approval process for drug and biotech products, a priority for many Wall Street funds and the pharmaceutical industry."

The Times also noted that a half-dozen current and former FDA officials said they did not know of anyone else from Wall Street ever moving directly into such a high-level job at the agency.

A couple months later, the November 12, 2005, Boston Globe reported that Dr Gottlieb could not participate in formulating the nation's defense plan against the avian flu due to conflicts of interest. He "was recused from key parts of the planning effort because his past consulting work forManning Selvage & Leeinvolved companies whose products would be used to combat a flu pandemic," it said. Yes, the very sameManning Selvage & Leeat which Arbesfeld held the Senior Vice President position. Does anyone smell a rat (or several)?

The article pointed out that Dr Gottlieb's former clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the parent company of the nation's sole flu vaccine maker.

According to the Globe,Manning paid Gottlieb a $12,500 monthly retainerfor nine months for projects that included eight companies, and he was also paid $9,000 for private consulting work for VanGen Inc, a firm that won a $878-million contract to supply the US government with 75 million doses of anthrax vaccine.

Dr Nissen and Dr Gottlieb's disputes are not new. In fact, on August 2, 2006, they participated in a debate on the topic: "Government Science Panels: Fair and Balanced?" sponsored by the Center for Science in the Public Interest, and reported on byRussell Mokhiber and Robert Weissman in Common Dreams.

Likewise, lawmakers have mentioned in their communications with the FDA that they found it "troubling" that Mr Arbesfeld might be trying to settle old scores with Dr Nissen because they were on opposite sides regarding the approval of the heart failure drug Natrecor.

Much to his credit, Dr Nissen openly communicated his objections to the industry's infiltration of the FDA. While sitting right next to Dr Gottlieb, he candidly described the conflicts of interest, which he stated were "evident at the highest levels of the FDA."

"For years," he said of FDA leadership, "we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies."

"Then the administration appointed Andrew von Eschenbach as interim commissioner creating another conflict," he said. "In his role as director of the National Cancer Institute, von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict," he noted.

"But even worse," Dr Nissen stated, "the administration appointed Scott Gottlieb as deputy commissioner."

"He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter," Dr Nissen told the audience.

Dr Gottlieb's response to Dr Nissen's comments was, in essence, that he would not dignify the comments with a response.

Firms with which Dr Gottlieb was involved prior to his gig at the FDA, according to the Globe, also include the Inamed Corp, one of two companies that were seeking to return silicone gel implants to the market and on November 17, 2006, the FDA announced that it would lift restrictions on the sale of the implants.

When Dr Gottlieb left the FDA, he headed right back to greener pastures with the drug giant Novartis. The press release to announce his hiring read: "Bench International Places Eminent Regulatory Advisor Scott Gottlieb, M.D., as Senior Counsel to Novartis."

"Under an exclusive consulting agreement," the release stated, "Scott Gottlieb, M.D., will provide advisory services to Novartis on matters of global regulatory policy and strategy."

Two more members of FDA’s alumni, Peter Pitts and Robert Goldberg took another swipe at Dr. Nissen in a June 6, 2007 commentary in the Washington Times, using the same talking points as the anonymous blogger, likewise referring to Dr. Nissen as a “self-appointed and media-anointed Patron Saint of Drug Safety” and “Saint Steven the Pure.”

For much of the childish commentary, they poke fun at Dr Nissen because he acknowledged in the NEJM that he consults for many drug companies but said he "requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction."

At the end of the commentary, Mr Pitts says he is a former FDA associate commissioner, and both men list their affiliation with the Center for Medicine in the Public Interest; but as usual, that listing really does not give credit where credit is due.

On its web site, the Center describes itself as "a non-partisan, non-profit educational charity," and Mr Pitts is indeed listed as President, but his bio also says he is the Senior Vice President for Global Health Affairs at none other than Manning, Selvege & Lee.

The Manning firm apparently fills two important roles. It's a breeding ground for industry moles preparing to enter "public service" and serves as an employment hub for industry shills once they finish their on average 2- to 3-year stint inside the Bush Administration.

In his CMPI bio, Mr Pitts describes his duties as the FDA's Associate Commissioner from 2002 to 2004 as serving as the agency's "Chief Messaging Officer."

On June 7, 2007, Mr Pitts had this to say in defense of fellow hit-man Mr Arbesfeld on the Pharmalot web site: "I know Doug Arbesfeld and he is a guy devoted to advancing the public health."

According to Mr Pitts, in sending the derogatory e-mail about Dr Nissen to journalists, Mr Arbesfeld was just standing up for the FDA and that people should know about the sacrifice he made by accepting a job in government.

"He is also a guy," Mr Pitts says, "who took a pretty significant pay cut to put in some time in public service."

Some would no doubt argue that it's difficult to imagine that Mr Arbesfeld will end up in the poor house as a result of serving as the top industry mole inside the FDA.

Mr Pitts' sidekick, Mr Goldberg, is indeed listed as the vice president of CMPI, but Mr Goldberg's bio also says he used to be Director of the Manhattan Institute's Center for Medical Progress and Chairman of its 21st Century FDA Task Force.

In fact, a review of the CMPI web site turned up a whole nest of ex-moles who served the industry in one capacity or another in the Bush Administration's FDA. For instance,Daniel Troy, the former FDA Chief Counsel, also known as the "Godfather of Preemption," sits on this "charity's" Advisory Board.

Troy’s bio points out that he "played a principal role in FDA’s generally successful assertion of preemption in selected product liability cases."

This "assertion of preemption" says that, as long as the FDA has approved a drug and its label, private citizens in state courts cannot sue the drug company for failing to warn about a product's serious health risks, even in cases where it can be shown that the company concealed studies that revealed the risk from the public and the FDA.

Now that he's switched back to private practice, Mr Troy's CMPI bio says he currently specializes in constitutional and appellate litigation, as well as strategic counseling with "particular focus" on what else - clients regulated by the FDA.

The Advisory Board also includes, Tomas Philipson, whose bio says he served as the Senior Economic Advisor to the commissioner of FDA during 2003 and 2004 and as the Senior Economic Advisor to the administrator of the Centers for Medicare and Medicaid Services in 2004 and 2005.

That would mean that Mr Philipson served Mark McClellan, and they are now apparently joined at the hip because, as part of a program called "Patient-Centric and Prospective Medicine," CMPI says it has created the Patient-Centric Health Forum and that Mr McClellan, "former Medicare administrator and FDA commissioner, will chair the group."

So, it would appear that anyone looking for the retirement home for industry hit men who served in the Bush Administration's FDA can find it right in the middle of cyberspace on the CMPI web site.

Persons seeking legal advice regarding Avandia can contact Baum, Hedlund, Aristei, Goldman & Menzies Law Firm at: (800) 827-0087; http://www.baumhedlundlaw.com/

http://www.avandia-heart-lawyers.com/.

*************

Evelyn Pringle

evelyn-pringle@sbcglobal.net

(Evelyn Pringle is a columnist for OpEd News and an investigative journalist focused on exposing corruption in government and corporate America)

(This article is part of the Avandia Update series sponsored by the Baum Hedlund law firm)

What Message is GSK Sending the FDA With Its Appointment of Daniel Troy as General Counsel?

July 23, 2008

Could it be, “GSK to DDMAC: Drop Dead?” Possibly.

As outlined on Pharmalot (hereandhere) and by John Mack (hereandhere), Troy is hostile to the idea that drug advertising should be heavily regulated. In fact, Troy joined the conservative legal think tank Washington Legal Foundation in June 2005, right beforeWLF launched its “DDMAC Watch” campaign. (DDMAC stands for Division of Drug Marketing, Advertising & Communications.)

The campaign essentially challenges every warning letter that the FDA sends out. (FDA warning letters ask drug companies to change or halt advertising which the FDA believes is misleading.) The position of the WLF is that FDA has extremely limited authority to control drug advertising, which should be First Amendment protected speech.

Further, WLF believes that the current regs banning off-label promotion should also be thrown out, to allow drug companies to distribute scientific literature for unapproved uses. The FDA is currently reviewing that regulation.

The WLF, for whom Troy is a legal policy advisor, has been chipping away at the FDA’s power to control drug advertising for years. In addition to its DDMAC Watch, the WLF files amicus briefs in cases where off-label allegations are made.The WLF has even defended drug execs who have blinded their patients by arguing that the off-label law is unconstitutional.

The move by GSK to appoint Troy is a fascinating one, because it again raises the question of how aggressively drug companies want to challenge FDA’s authority to regulate what they do. (At one time, Pfizer also employed a WLF sympathizer.)

GSK’s answer seems to be, more aggressive than ever.

==

http://www.motherjones.com/politics/2008/03/daniel-troys-poison-pill

When it comes to notorious Bush political appointees, Daniel Troy's name doesn't usually make the top-10 list, overshadowed as he is by more high profile cronies such as FEMA's Michael Brown. But for three years in the president's first term, Troy served as the chief counsel to the Food and Drug Administration (FDA), where he quietly advanced a legal revolution that is playing out in earnest in the U.S. Supreme Court this year. This revolution has the potential to affect the health and safety of the nation's citizens for years to come, all whilemaking Troy a rich man. In fact, his career is an illustration of how the Bush administration's revolving door has allowed industry lawyers to radically reshape regulatory agencies to benefit the big businesses they once represented and then profit from those changes when they return to the private sector.

Back in 2001, when the president tapped Troy for the FDA, Bush made history for turning the general counsel's job into a political appointment,when most of the previous occupants of the position had been civil servants. The appointment was a sign that the president intended to impose a political agenda on the agency. A former clerk to Robert Bork, Troy was a die-hard conservative who had spent most of his career suing the FDA on behalf of drug and tobacco companies over regulations those industries didn't care for. Before going to the FDA, he had worked at the D.C. powerhouse law firm of Wiley, Rein & Fielding, where he represented a number of pharmaceutical companies, including Pfizer, which paid the firm more than $350,000 for Troy's services the year he was appointed to the FDA. A year after the ban on working on matters involving former clients had passed, Troy quickly got to work helping out the drug companies who used to pay his fees.

Under Troy's leadership, the FDA started showing up in state courts, offering briefs in civil cases on the side of drug companies being sued by people who'd been injured by dangerous prescription drugs and other medical devices. In an unprecedented move, agency lawyers argued that because those products had been approved by the FDA, such lawsuits were "preempted"by federal law and should be dismissed.

Troy's FDA was promoting the idea that tort lawsuits in state court interfere with federal regulatory authority by letting judges and juries second-guess decisions over drug labeling and approval made by the experts in federal agencies.The drug companies were arguing, with the agency's help, that FDA approval for a product should be the gold standard and that if companies meet that standard, they shouldn't be subjected to the rules of 50 different states trying to impose their own health and safety standards through lawsuits.

Promoting preemption is a radical new policy for the FDA, which has long believed that, far from interfering with its mission, state tort lawsuits actually enhanced public safety by providing a financial incentive for companies to comply with federal regulations. Troy's predecessor, Margaret Porter, a career official, wrote in 1997 that the agency had a long-standing policy against preemption, because "even the most thorough regulation of a product such as a critical medical device may fail to identify potential problems presented by the product.... Preemption of all such [tort liability] claims would result in the loss of a significant layer of consumer protection."

The Bush administration has embraced preemption largely because it allows the White House to use its regulatory power to achieve what big businesses haven't been able to do through legislation, which is immunize themselves from lawsuits over defective products. In recent years, federal agencies, dominated by industry insiders, have written preemption language into safety regulations, from rules issued by the Consumer Products Safety Commission governing mattress flammability to those introduced by the National Highway Traffic Safety Administration on seat-belt placement and automobile-roof strength. In fact, while the NHTSA was run by a former lawyer for DaimlerChrysler, it issued a roof-strength regulation that was so weak the only possible explanation for its issuance was that it was designed to help auto manufacturers head off lawsuits.Even the EPA has gotten into the act, once filing a brief on behalf of Dow chemicalsupporting its preemption defense in a case before the Supreme Court in 2005.

But no federal agency has pursued a preemption agenda as aggressively as the FDA did when Troy worked there. In 2003, he appeared at a conference of defense lawyers and in-house legal counsels from drug companies and publicly invited them to contact his office if they had a case the FDA could help them out with. "We can't afford to get involved in every case," he said, according to an affidavit written by someone who was there. "We have to pick our shots…so make it sound like a Hollywood pitch."

During Troy's tenure, between August 2001 and November 2004, the FDA participated in several private lawsuits, including one involving Pfizer, and argued that state courts and juries were illegally usurping federal regulatory power by trying to impose safety standards on drugs or medical devices approved by the FDA. The results of Troy's intervention in the state court suits were mixed, but, to be sure, the FDA's position bolstered the drug companies' position.

Troy's work at the FDA didn't go unnoticed. In 2004, after he attracted some negative publicity for coming to the aid of his former client Pfizer in a lawsuit, Rep. Maurice Hinchey (D-N.Y.) attempted to defund his office. In November of that year, Troy retreated to private practice, where he continues to counsel companies regulated by the FDA. But before he left, he ensured that the preemption doctrine was firmly enshrined at the FDA in regulatory language covering drug labeling.

The "preemption preamble," as it's known, states that this rule preempts all state tort lawsuits against manufacturers who make drugs approved by the FDA. The regulation allows drug companies to invoke the FDA's approval to beat back lawsuits without actually having to get the agency to enter the case. This is a hedge against future Democratic presidents who might want to institute a change of course. The preamble was inserted into the regulation without any public input. Since then, lawyers have repeatedly invoked it when defending companies against personal-injury lawsuits.

The courts have not swallowed Troy's work whole hog. Several courts have rejected the preemption argument outright, and as a result the Supreme Court, which has not been especially sympathetic to injured plaintiffs, recently decided to clear up the confusion. Its most significant ruling arrived in late February in Riegel v. Medtronic. The case was filed by the family of Charles Riegel, who was injured when a balloon catheter burst during an angioplasty. He later died, and his wife sued the manufacturer, alleging that the catheter was defective.

The court ruled for the manufacturer in an 8-1 decision, siding with Troy, who filed an amicus brief on behalf of the medical-device industry arguing that because the device had received premarket approval from the FDA, private lawsuits in state court were preempted. The decision effectively wipes out pending litigation over everything from faulty pacemakers to defective insulin pumps. But the decision is a huge boon to Medtronic, a company whose conduct in the marketplace has hardly been stellar. Not only has it been accused of bribing surgeons to use its products, but the FDA has recalled a host of the company's products. Now, people who have been injured by some of Medtronic's products will have no way of forcing the company to pick up the tab.

Last week, the Supreme Court heard arguments in a second preemption case, Kent v. Warner-Lambert, which was filed by Michigan residents injured by the recalled diabetes drug Rezulin. Michigan bans lawsuits against drug and medical-device manufacturers for products approved by the FDA, but it has an exemption allowing suits to proceed if the manufacturer won approval of a product by engaging in fraud. Troy's firm represents Warner-Lambert in the case. On behalf of the government, the U.S. solicitor general argued that even conning the FDA into approving a product wasn’t a good enough reason to allow a suit proceed. On Monday, the court upheld a Second Circuit court decision permitting the case to move forward.

But the decision was hardly a reason for plaintiffs and consumer advocates to rejoice. The only reason the defendants didn't prevail was because Chief Justice John Roberts owns stock in Warner-Lambert's parent company, Pfizer, and had to recuse himself.In all likelihood, he would have voted with the other conservatives in favor of the manufacturer. The 4-4 decision doesn't bode well for the plaintiffs in another coming drug case that the justices decided to take up, much to the surprise of veteran court watchers. The plaintiff inWyeth v. Levineis a musician who won a multimillion-dollar jury verdict after her arm was amputated due to an improperly administered drug. The drug company, Wyeth, is arguing that the verdict should be overturned because the FDA's 2006 preemption preamble on drug labeling bans such lawsuits. If Wyeth wins, essentially all private, state-court lawsuits over dangerous drugs and medical devices will be wiped out—and a window into the workings of the companies poorly regulated by the FDA will be boarded up.

Indeed, the underlying assumption behind preemption is that federal regulatory agencies actually do a good job of protecting the public, when there is a host of evidence suggesting that's not the case. In fact, it's been the very private lawsuits that big companies want to eliminate that have often led to major efforts to strengthen the nation's health and safety net.

If the Supreme Court follows Troy's lead, it won't just be pharmaceutical and medical-device lawsuits that are affected. A ruling for the drug company in Levine could also limit lawsuits over everything from toxic chemical exposure to tainted beef—a pretty grim scenario for the average consumer. And there’s reason to believe the court will do just that.

During the oral arguments in the Kent case last week, Justice Stephen Breyer, one of the high court's most liberal justices, showed little sympathy for the plaintiffs or confidence in juries. "Who would you rather have make this decision as to whether this drug is, on balance, going to save people or, on balance, going to hurt people?" he asked. "An expert agency, on the one hand, or 12 people pulled randomly for a jury role who see before them only the people whom the drug hurt and don't see those who need the drug to cure them?"

The arguments showed how successful Troy and other preemption advocates have been in changing the focus on the legal debate, from providing recourse to those injured by faulty products to protecting the companies that make them. They have launched a legal revolution that is as profound as the consumer protection movement Ralph Nader touched off in the 1960s and '70s, only the beneficiaries are the big corporations that want to escape the last remaining check on their work: private lawsuits. The Supreme Court's decision in Riegel and its move to take up the other preemption cases suggests that the revolution is indeed having a transformative effect.

==

fedsoc expert

Troy joined GSK as Senior Vice President & General Counsel in September 2008. Reporting to Andrew Witty, he is based in Franklin Plaza, Philadelphia PA, and is a member of the Corporate Executive Team.

Previously a Partner at the Washington law firm Sidley Austin LLP, where he represented mainly pharmaceutical companies and trade associations on matters related to the US Food and Drug Administration (FDA) and government regulations, Dan was formerly Chief Counsel for the FDA, where he served as a primary liaison to the White House and the US Department of Health and Human Services (HHS).

While leading an office of attorneys who reviewed and approved all major regulations and guidances, Dan oversaw the legislative implications of many of the most important issues facing the pharmaceutical industry today, including the reform of the Hatch-Waxman Act and subsequent legislative ratification. His office also approved and managed all agency litigation, and Dan established procedures for the FDA legal team to follow in preparing and then litigating high-profile cases.

==

• #### :{General Counsel:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

GlaxoSmithKline

Present

• #### :{Partner:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

Sidley Austin LLP

2005 – 2008 (3 years)

• #### :{Chief Counsel:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

Food and Drug Administration

2001 – 2004 (3 years)

• #### :{Partner:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

Wiley, Rein & Fielding

1990 – 2001 (11 years)

• #### :{Partner:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

Wiley Rein LLP

1990 – 2001 (11 years)

Education

• #### :{Columbia Law School:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

JD

1980 – 1983

• #####

:{Cornell University:(style="margin:0px;padding:0px;border:0px;font-style:inherit;font-variant:inherit;font-weight:inherit;font-stretch:inherit;vertical-align:baseline"):}:

BS -- ILR, Industrial and Labor Relations

1978 – 1980

==

interv w. amana b fedsoc bk: everyone who was a lawyer in B2 was fedsoc p 154

==

An Address by the Honorable Daniel Troy - The Federalist Society

www.fed-soc.org/.../an-address-by-the-honorable-danie...

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1. http://webcache.googleusercontent.com/search?q=cache:aOLIVq0PKngJ:www.fed-soc.org/publications/detail/an-address-by-the-honorable-daniel-troy+&cd=1&hl=en&ct=clnk&gl=us

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:{Oct 1, 2002 -MR. TROY: Thank you very much. It is always a pleasure to get outside the beltway. You know what Justice O'Connor said about Washington, ...:(style="overflow-wrap:break-word"):}:

Hon. Daniel E. Troy : Experts : The Federalist Society

www.fed-soc.org/experts/detail/daniel-e-troy

:{:(style="border-color:#006621;;border-style:solid;width:0px;height:0px;margin-left:3px;top:7.5px;margin-top:-4px;position:absolute;left:0px;border-width:5px 4px 0px !important"):}:

1. http://webcache.googleusercontent.com/search?q=cache:He6smzzHke0J:www.fed-soc.org/experts/detail/daniel-e-troy+&cd=2&hl=en&ct=clnk&gl=us
2. https://www.google.com/search?biw=1029&bih=719&q=related:www.fed-soc.org/experts/detail/daniel-e-troy+daniel+troy+federalist+society&tbo=1&sa=X&ved=0ahUKEwi16LGvosbNAhUO5GMKHSm-CjUQHwgnMAE

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:{Dan Troy joined GSK as Senior Vice President & General Counsel in September 2008. Reporting to Andrew Witty, he is based in Franklin Plaza, Philadelphia ...:(style="overflow-wrap:break-word"):}:

Taking Commercial Speech Seriously - The Federalist Society

www.fed-soc.org/.../taking-commercial-speech-seriousl...

:{:(style="border-color:#006621;;border-style:solid;width:0px;height:0px;margin-left:3px;top:7.5px;margin-top:-4px;position:absolute;left:0px;border-width:5px 4px 0px !important"):}:

1. http://webcache.googleusercontent.com/search?q=cache:HvxLumWLbT0J:www.fed-soc.org/publications/detail/taking-commercial-speech-seriously+&cd=3&hl=en&ct=clnk&gl=us
2. https://www.google.com/search?biw=1029&bih=719&q=related:www.fed-soc.org/publications/detail/taking-commercial-speech-seriously+daniel+troy+federalist+society&tbo=1&sa=X&ved=0ahUKEwi16LGvosbNAhUO5GMKHSm-CjUQHwguMAI

Federalist Society:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{Taking Commercial Speech Seriously. Free Speech & Election Law Practice Group Newsletter - Volume 2, Issue 1, Spring 1998. By Daniel E. Troy May 01, 1998.:(style="overflow-wrap:break-word"):}:

Daniel Troy Legacy: Public Virtually Defenseless against Unsafe ...

ahrp.org/daniel-troy-legacy-public-virtually-defenseless-against-unsafe-d...

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1. http://webcache.googleusercontent.com/search?q=cache:5aRsHNFLIdUJ:ahrp.org/daniel-troy-legacy-public-virtually-defenseless-against-unsafe-drugs/+&cd=4&hl=en&ct=clnk&gl=us

:{Dikinson's FDA Webview reports (below) that Daniel Troy hand-picked ... use of forums provided by the ultra-conservative/libertarian Federalist Society and his ...:(style="overflow-wrap:break-word"):}:

Ideas with Consequences: The Federalist Society and the Conservative ...

https://books.google.com/books?isbn=0199385521

Amanda Hollis-Brusky - 2015 - ‎Political Science

The Federalist Society and the Conservative Counterrevolution Amanda Hollis- ... For example, as Federalist Society member Daniel Troy described it to me, ...

Talk:Federalist Society - Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Talk%3A**Federalist**_**Society**

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1. https://webcache.googleusercontent.com/search?q=cache:gx8BBwkQ7zEJ:https://en.wikipedia.org/wiki/Talk%253AFederalist_Society+&cd=6&hl=en&ct=clnk&gl=us

Wikipedia:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{misplaced comments[edit]. This reads like an ad for the Federalist Society, with the POV that its ..... with roles in the Bush administration have written for Federalist Society publications, notably Daniel Troy, James Ho and Shannen W. Coffin.:(style="overflow-wrap:break-word"):}:

:{[PDF]:(style="font-weight:bold;cursor:auto;margin:0px 3px 0px 0px;float:left"):}:The Federalist Society for Law and Public Policy presents AGENCY ...

https://www.chapman.edu/.../CLR-11-cass-merrill-sh...

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1. https://webcache.googleusercontent.com/search?q=cache:tnumaImLWl8J:https://www.chapman.edu/law/_files/publications/CLR-11-cass-merrill-sharkey-troy-oscannlain.pdf+&cd=7&hl=en&ct=clnk&gl=us

Chapman University:{:(style="border-width:4px 4px 0px;border-style:solid;width:0px;height:0px;top:8.5px;position:absolute;margin-left:6px;margin-top:-3px;border-color:#aaaaaa;"):}:

:{Apr 17, 2008 -Professor Catherine M. Sharkey, New York University School of Law. Hon. Daniel E. Troy, Sidley Austin and Former Chief Counsel, United.:(style="overflow-wrap:break-word"):}:

Daniel Troy - Bush Administration's Preemption Gang - Part II

https://www.lawyersandsettlements.com/.../bush-preemption-troy-10030....

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1. https://webcache.googleusercontent.com/search?q=cache:Q-icm5PYAvIJ:https://www.lawyersandsettlements.com/articles/drugs-medical/bush-preemption-troy-10030.html+&cd=8&hl=en&ct=clnk&gl=us

:{Feb 26, 2008 -Washington, DC In the fall of 2004, Daniel Troy left the FDA armed with ... Journal of The Federalist Society Practice Groups and presented an ...:(style="overflow-wrap:break-word;font-weight:normal"):}:

###

==

This insulting garbage is brought to us courtesy of theWashington Legal Foundation, which, as notedhereby SourceWatch, was established in 1977 by Chairman and General CounselDaniel J. Popeoto "fight activist lawyers, regulators, and intrusive government agencies at the federal and state levels, in the courts and regulatory agencies across the country."

This 1998interviewwith Popeo noted that the WLF, at that time, had received about $3 million in contributions from about 500 companies, though the SourceWatch article notes that, between 1985 and 2003, the group has received about $7 million in funding on top of that.

Though Popeo, in the 1998 story, apparently did not like being associated with any coalition or funding source, SourceWatch states that the WLF “sought and obtained funding from Philip Morris and the now defunct Tobacco Institute.” As a result, the WLF has also repeatedly sued government agencies that oversee public health functions, like the Food and Drug Administration and the Environmental Protection Agency, who they sued over workplace smoking policies (decrying what it calls the “junk science” of “anti-tobacco zealots”).

The WLF went after the FDA because of what the group thought was delays in allowing drugs and medical devices to market, and to show the revolving door that exists between the WLF and Bushco,this postnotes that Daniel E. Troy effectively landed on the WLF board after leavingBushco’s FDA, doing his very best to hurt the agency from doing its job to ensure the safety of products under its purview (such as, in particular, Vioxx…as John Mack says, the WLF is to the First Amendment what the NRA is to the Second Amendment, with Troy as the Mike-Brown-FEMA equivalent)....http://liberaldoomsayer.blogspot.com/2007/08/monkeying-around-with-wlf.html

Daniel Troy Legacy: Public Virtually Defenseless against Unsafe Drugs

Thu, 18 Nov 2004

The Associated Press reports that at a Congressional hearing today, Dr. David Graham a drug safety expert at the FDA told the Senate Finance Committee that the public is "virtually defenseless" if another medication such as Vioxx proves unsafe after it has won Food and Drug Administration approval.

"I would argue that the FDA as currently configured is incapable of protecting America against another Vioxx." Dr. Graham warned that the arthritis drug had been linked to an increased risk of heart attack and stroke. He also testified that there were at least five other drugs on the market that warrant scrutiny: the acne drug Accutane, the weight loss drug Meridia, the anti-cholesterol drugCrestor, the pain reliever Bextra, and the asthma drug Serevent.

Dr. Sandra Kweder of FDA's office of new drugs, did not agree with Graham's assessment of the risk posed by the five drugs. She said "there is no magic formula" to determine which drugs most raise the most serious safety concerns.

If the FDA would at least monitor MedWatch--its own database of adverse drug event reports - we would not have to wait for a "magic formula."

Dikinson's FDA Webview reports (below) that Daniel Troy hand-picked Gerald F. Masoudi as his successor as Chief Counsel. Thus, Troy's legacy may not be over. Dickinson and Newsday (excerpt below) provide insight into how the FDA became the permissive lap dog of the food, drug, and cosmetics industry when Troy, a political appointee with long standing ties to industry, ran the agency and methodically downgraded public safety issues.

There are many speculations about what prompted Daniel Troy toresign:[asst too] perhaps theprospect of having to testify under oathbefore congressional committees may have influenced his resignation which was announced on Nov 16, effective Nov 28.

There has been growing public criticism of FDA's failure to protect the public from hazardous drugs and the agency's continued failure to monitor drug safety, coupled with the inordinate influence of industry in setting policy. Troy's active intervention on behalf of drug manufacturers in lawsuits filed by individuals who had been harmed by drugs or devices--whose adverse effects were concealed--was a radical departure from FDA policy. Troy's legal argument rested on the infallibility of "FDA's scientific judgment" about safety.

One of the legal briefs submitted by Daniel Troy denied the need for a suicide warning on the drug label. However, FDA's judgments have been shown to be unscientific--inasmuch as crucial safety evidence from clinical trials had been concealed. Industry selectively reported clinical trial results, hiding the adverse findings. When challenged publicly with evidence from antidepressant pediatric trials, the FDA was forced to re-analyze the complete data. Only then did the FDA reach a scientifically valid judgment: Black Box warnings were issued (Oct 15, 2004), acknowledging a causal relation between antidepressants and increased suicide risk.

The basis for Troy's claims rested on scientifically faulty FDA-judgments that had relied on partial - therefore unscientific - information. This demonstrates that entrusting health / safety issues to a single agency is bad public policy. It invites manipulation by powerful stakeholders, undermining rational, science-based health / safety determinations. Neither the FDA nor any of us mortals is infallible; we all prone to errors in judgment.

Contact: Vera Hassner Sharav 

212-595-8974

FDA Webview Reports /Review/Update/DTC Marketer)

FDAers Think Troy Weakened Them, Worry About Masoudi

11/17/2004

As chief counsel Daniel E. Troy's impending departure from FDA is being noisily applauded by external critics, it is also being welcomed, quietly, by many program managers inside the agency who say that he has weakened them in meeting new regulatory and scientific public health challenges. And they worry about his apparent successor, raw newcomer Gerald F. Masoudi, who is an unknown factor but who they see as having been hand-picked by Troy.

For example, a high official told us 11/17, in sharply narrowing FDA's traditional broad interpretations of statutory authority, Troy removed many previously effective tools for dealing with complex new issues not addressed in the Food, Drug and Cosmetic Act, such as biotechnology, gene transplants, dietary supplements, health claims for foods and others.

"Of course, Dan would say 'Well, you have tried to interpret the statute in a broad way in the past, and now you've started losing in court,'" this official said. Such court losses - e.g., on the agency's  tobacco rule, and a string of First Amendment cases - were seen by Troy as being likely to continue so long as the agency persisted in exercising its traditional broad statutory interpretations, so he set about trimming the agency's sails.

Instead of helping his "client" (FDA management) attain its goals, Troy routinely advised that it lacked statutory authority to reach those goals, this official said. "In writing regulations, we have attempted to put in requirements that might not have been explicitly in the statute, but that we would traditionally have used, be it records authority, or requirements for certain sorts of reporting by a firm. He would say, 'Well, no, you don't have that authority, I'm going to scale that back.'"

One example of this wasTroy's rejection of a CVM plan toregulate genetic transfers in food-producing animalsunder the new animal drug regulations. CVM protested that the 1938 FD&C Act could not have anticipated gene transfer technology, and that Congress has not been able to deal effectively with this issue,so creative regulation is the only way."You're putting a compound in a fish or a cow to cause it to grow differently - the scientists think that's essentially the same as putting a drug in the animal," a senior CVM official said. Troy refused to budge.

In a lengthening stream of such narrowing decisions, Troy managed to restrict FDA's ability to use its statutes creatively, and this in turn deterred mid-level managers from advocating new approaches to emerging scientific issues, leaving the agency looking - and feeling - weak. There is a philosophical basis for this result that many see in Bush Administration policies: reduce the power of government to "interfere" in the free working of the marketplace.

Troy's past use of forums provided by the ultra-conservative/libertarian Federalist Society and his actions since as chief counsel present a sharp contradiction between FDA's traditional modus operandi and that society's dictum: "The courts must declare the sense of the law; and if they should be disposed to exercise WILL instead of JUDGMENT, the consequences would be the substitution of their pleasure for that of the legislative body." In other words, if FDA did not get from Congress what it needs, it should not try litigation, or regulatory initiatives that might lead to litigation.

There are two ways FDAers look at this posture: (1) Troy was trying to protect the agency from losing any cases in court, and (2) Troy was trying to prevent it from winning any cases in courts that could, in Federalist parlance, legislate from the bench.

Troy's resignation has thrust his apparent choice of successor onto center stage. As expected, HHS general counsel Alex Azar named Masoudi acting chief counsel "until a permanent replacement is appointed," according to an 11/16 statement by acting commissioner Lester Crawford. Informed sources speculated that Masoudi could be that appointee. A 1993 graduate of the University of Chicago Law School, he joined FDA as deputy associate general counsel/deputy chief counsel earlier this month, anddid not respond to requests for his biography and an interview.

However, an Internet search revealed that he authored in 1993, University of Chicago Law Review article, Kosher Food Regulation and the Religion Clause of the First Amendment, which has since become very widely referenced on various legal Web sites and by other scholars.

At Kirkland & Ellis, whose Web site no longer mentions him, he was one of four attorneys who in 1999 sued three cable Internet companies for client GTE in Western Pennsylvania federal court alleging Sherman Antitrust Act violations in the bundling of high-speed cable data transport services. In 2001, he represented the H.J. Heinz Co. in defending against a Federal Trade Commission suit that sought to block a proposed merger between Heinz and Beech-Nut Foods.

One of Masoudi's most recent cases at Kirkland & Ellis involved a rate-regulation case this year before the Louisiana Public Service Commission in which he represented Arkansas Electric Energy Consumers, Inc.

Meanwhile, outside critics of Troy have raised their rhetoric against him. In a public e-mail to acting commissioner Lester Crawford 11/17, Alliance for Human Research Protection director Vera Hassner Sharav charged that Troy "was a symbol of what is rotten at the FDA: the pharmaceutical industry's influence has ensured that business interests take precedence over public safety.

"Industry-influenced advisory committees," she continued, "have led to the approval of lethal drugs that were widely marketed until the death toll became publicly known. Troy actively intervened on behalf of pharmaceutical companies in civil cases brought by individuals who sought justice in the court. Let us hope that other senior FDA officials who have similarly disregarded their role as public servants and have shielded drug manufacturers who concealed the hazardous effects of their products, resulting in preventable deaths, will resign as well.

"The FDA has been derailed from its mission, which is to ensure that the public is protected from unsafe and ineffective drugs, and that physicians and the public rare provided scientifically accurate information.

"Whereas Troy intervened on behalf of pharmaceutical companies claiming that the FDA's authority pre-empted all others in matters of drug safety - even when they concealed lethal drug effects - New York State Attorney General, Eliot Spitzer, brought action against GlaxoSmithKline, charging the company with fraudulent marketing of Paxil (seroxat). That action undermined Troy's pre-emption authority argument - and ultimately undermined his standing.

"In light of the skyrocketing expenditures for prescription drugs - U.S. consumers spent $216 billion on prescription drugs last year, up 11.5% in a year (according to IMS Health) -Dr. Lester Crawford's claim that Daniel Troy's 'reforms' saved consumers $35 billion, is not credible." Meanwhile,Rep. Maurice Hinchey (D-NY), who has had several policy run-ins with Troy, said 11/16 the resignation announcement (see earlier story) "is a rare bright spot in what has been a dark period for FDA."According to Hinchey, Troy worked tirelessly to weaken FDA's ability to face challenges such as the withdrawal of Vioxx and the flu vaccine shortage. "Under Troy's direction," he said, "the agency has argued in court that manufacturers, some of whom he represented in private practice, should not be held responsible if their products injure customers. He wasted precious taxpayer dollars on other personal ideological pursuits as well. Instead of working to strengthen FDA's mandated role as a guardian of public health, Troy has made it the agency's mission to protect corporate profits." Hinchey called on Crawford to "return FDA to its appropriate mission... by removing politics from the chief counsel's office and appointing a career civil servant" as Troy's replacement.

[fedsoc bs bio

Gerald Masoudi is a partner in the firm’s Washington, DC office and co-chair of the Food and Drug practice group. 

Before joining Covington in 2009, Mr. Masoudi served as Chief Counsel of the Food and Drug Administration.  In that capacity he was responsible for supervising FDA’s involvement in civil and criminal litigation and investigations; providing legal review of warning letters, guidances and regulations; and providing advice to the FDA commissioner and senior leadership on matters relating to the products regulated by FDA.  Before joining the FDA, Mr. Masoudi served as Deputy Assistant Attorney General for international, policy and appellate matters in the Antitrust Division at the Department of Justice.  He also served as Principal Deputy Chief Counsel for the FDA in 2004 and 2005.  Before entering government service, Mr. Masoudi had a decade of experience in private practice in the areas of antitrust, telecommunications, patent law and energy.

Education 

• The University of Chicago Law School, J.D., 1993
• Amherst College, B.A., 1990]

http://www.newsday.com/news/politics/ny-usfda114002814oct11,0,5464956,print.story

NEWSDAY

ERASING THE RULES Industry has some friends on the inside

Bush-appointed administrators at the FDA have consistently sided with the interests of business

BY THOMAS FRANK

October 11, 2004

Two years ago, California walnut growers conceived the perfect promotion: put labels on packages saying walnut consumption reduces the risk of heart disease.

There was one problem.

The Food and Drug Administration demanded substantial evidence to allow such claims, and it found that studies the growers touted were "of poor to moderate quality" or "not directly relevant."

Even three outside experts the FDA hired said a link between walnuts and heart disease was "uncertain."

But then the agency relaxed its standards. And on March 9, it reached an unprecedented decision: Labels could claim that walnuts "may" reduce heart-disease risk while noting that research was "not conclusive."

The eased standards were long sought by the food industry, which found key allies in the Bush administration FDA. Top appointees who once advocated for FDA-regulated industries have heeded industry lobbying in ways that medical groups and consumer advocates say jeopardize public health.

After food-industry groups complained, a top appointee killed a measure to discourage consuming a cholesterol-raising fat. Plans to eliminate misleading sunscreen labels have been tabled following cosmetics-industry complaints. A post-Sept. 11 plan to help contain food contamination is nearly a year late as food-processing groups have objected.

Letters directing drug companies to stop false or misleading ads are reduced and delayed under new policy that some critics say increases the public's exposure to misinformation.

In a dramatic legal novelty, the FDA has intervened for manufacturers in lawsuits, urging courts to dismiss damages claims against them. FDA briefs have helped the world's two largest drug companies win product-liability cases.

The FDA says courts are not equipped to judge a product's safety. On regulation, officials say their position reflects court rulings that warn about restricting commercial speech. Allowing inconclusive health claims on food labels such as walnuts gives consumers more information, the agency says.

"Naturally, our approach to enforcement may evolve as we adapt to new FDA legal authorities or evolving science and technology," the FDA said in a recent statement. "But the goal of judicious enforcement of the law, to fulfill our mission of promoting and protecting the public health, remains constant."

The walnut industry is already profiting from the new labels that will start next year. Walnut processing giantDiamond of Californiasays publicity about them hashelped lift sales 30 percent over last year.

But the American Medical Association said consumers may be duped. The walnut claims "have a reasonable chance of being erroneous," it said. "An educated consumer will not know whether to believe or not to believe the claim."

Rep. Henry Waxman (D-Calif.) wrote the 1991 law requiring "substantial scientific evidence" for health claims."Congress didn't want food manufacturers to make claims without substantiation," he said. "The clear language of the statute is just being ignored."

The influence behind many FDA decisions is chief counsel Daniel Troy, who was a sharp critic of the agency before President George W. Bush put him in charge of its legal affairs.

A Queens-born Columbia Law School standout, Troy, 44, came to the FDA primed for activism: Clerk for conservative icon Robert Bork; partner at blue-chip Wiley, Rein & Fielding; scholar at the pro-businessAmerican Enterprise Institute; litigant for the anti-regulatory Washington Legal Foundation.

Representing a tobacco company against the FDA in the late 1990s, Troy helped win a landmark Supreme Court ruling blocking the agency's attempt to regulate tobacco products.

Litigating for the legal foundation, which drug-company foundations help fund, Troy challenged the FDA's restrictions on promoting drugs for uses the FDA has not approved.

The policy, Troy wrote in 1999, reflects "an overzealous FDA."

Appointed in August, 2001, Troy had vast authority. With no FDA commissioner until November 2002, Troy reigned for more than a year as top administrator in anagency that regulates 22 percent of the U.S. economy.

"He sent a signal to companies that if you want to deal with the FDA on a number of issues, he's the man to see," said a senior FDA official.

In three years, Troy has held 129 meetings with lobbyists and others with issues before the FDA.

Mark McClellan, commissioner from October 2002 to March 2004, held 30 such meetings, FDA records show.

From 1998 to 2001, Troy's predecessor, Margaret Porter, held one meeting.

"She did not directly interact with industry," said Jane Henney, FDA commissioner in 1999 and 2000. "She felt those interactions were done by the staff, and [lobbyists] should make their case to them."

But the Bush administration made the chief counsel a political appointee for the first time since the 1980s, easing out civil-servant Porter and empowering Troy.

At the end of a meeting with cosmetics-industry officials two months into his job, Troy decided to delay indefinitely sunscreen regulations the industry opposed.

"We asked them to put it off. They've done what we asked," said Tom Donegan, general counsel of the Cosmetic, Toiletry and Fragrance Association.

Donegan's group opposed a proposed ban on sun-protection factors higher than 30, which the FDA found provided "extremely small" amounts of extra protection. Donegan told Troy the ban raised free-speech issues.

"He's very receptive," Donegan said.

The regulations, developed after 21 years of study and debate, also would have banned from sunscreen labels starting in 2003 terms such as "sunblock" and "waterproof," which it determined were "misleading" and "unsupported." Their use remains common.

Food-industry officials got Troy's help after a National Academy of Sciences study requested by the FDA recommended "trans fat consumption be as low as possible" because it raised cholesterol. The FDA wanted that statement on food labels starting in 2006.

Industry officials who met Troy said the label may violate the First Amendment and could lead consumers and food processors to substitute similarly harmful saturated fat for trans fat.

Xxxcut xxx

 2004, Newsday, Inc.

Daniel E. Troy was a participant or observer in the following events:

August 2001: Bush Appoints Daniel E. Troy as the FDA’s chief counsel

President Bush appoints Daniel E. Troy as the FDA’s chief counsel. [FINANCIAL TIMES, 8/14/2001] Before taking the position, Troy was a partner at the law firmWiley Rein & Fielding, where he sued the FDA several times on behalf of drug companies, including pharmaceutical giant Pfizer. He has repeatedly argued that the agency has only limited authority to regulate drug companies. Troy is mostly known for his involvement in the landmark Supreme Court case that ruled the FDA does not have the authority to regulate tobacco. [BOSTON GLOBE, 12/22/2002; DENVER POST, 5/23/2004] 

As chief counsel, Troy will help the FDA commissioner, a post that is currently vacant, to draft policy and enforcement provisions. The commissioner’s post will remain vacant until October 2002. So far, Bush has considered two people for the position—Michael Astrue, senior vice-president at Transkaryotic Therapies, a British biotech company, and Eve Slater, Merck’s senior vice-president. In both cases the Senate made it clear that their nominations would be rejected because of their involvement in FDA-regulated industries. [FINANCIAL TIMES, 8/14/2001]

Entity Tags: Daniel E. Troy, George W. Bush

Timeline Tags: US Health Care

October 2001: FDA Chief Counsel Orders Pre-Screening of All Enforcement Letters Sent to Drug Companies

The US Department of Health and Human Services implements a new policy requiring that all enforcement letters to drug companies potentially engaged in false advertising be pre-screened by FDA Chief Counsel Daniel E. Troy. Prior to the policy change, the FDA’s drug-marketing division and district offices were free to determine when an enforcement letter was warranted. After the policy change, the number of enforcement letters sent annually drops by two-thirds.BOSTON GLOBE, 10/19/2002; [BOSTON GLOBE, 12/22/2002; DENVER POST, 5/23/2004] In October 2002, the General Accounting Office (GAO) finds that the FDA is taking so long to review the letters that “misleading advertisements may have completed their broadcast life cycle before FDA issued the letters.” [BOSTON GLOBE, 12/22/2002]Fifteen months later, another report by the GAO finds that the review process is still slow, with the average approval time being six months. [BOSTON GLOBE, 1/30/2004]

Entity Tags: Daniel E. Troy, US Department of Health and Human Services

Timeline Tags: US Health Care

October 19, 2001: FDA Considers Drug Industry’s Argument that Regulation of Ads is a Violation of Companies’ Free Speech Rights

The Boston Globe reports that the FDA is considering the validity of the pharmaceutical industry’s argument that the agency’s regulation of drug advertisements violates manufacturers’ “free speech” rights. The inquiry is being led by FDA Chief Counsel Daniel E. Troy, who represented drug companies before being appointed to the FDA position in August 2001 (see August 2001). [BOSTON GLOBE, 10/19/2002]

Entity Tags: Daniel E. Troy

Timeline Tags: US Health Care

July 2002-September 3, 2002: FDA Chief Counsel Intervenes in Lawsuit on Behalf of Drug Company

Pfizer attorney Malcolm Wheeler calls FDA chief counsel Daniel E. Troy requesting that the agency intervene in a lawsuit filed against the company. The lawsuit alleges that Zoloft, an antidepressant drug manufactured by Pfizer, caused Victor Motus of California to kill himself on November 12, 1998. It also says that the drug company should have warned physicians that Zoloft might cause suicidal thoughts in some people. On September 3, the FDA files a brief stating that the agency’s scientists have found no evidence that antidepressants cause suicidal thoughts. Furthermore, the FDA argues, if Pfizer had warned doctors of such a link, it would have been a violation of the law because all warnings must first be vetted by the FDA. According to Troy, the agency has “absolute control over the label.” This position, notes one of the plaintiff attorneys in the Pfizer case, contradicts arguments that Troy made when he was practicing in the private sector. Before he had argued that the agency’s rulings were arbitrary and capricious. [BOSTON GLOBE, 12/22/2002]

Entity Tags: Daniel E. Troy, Pfizer, Malcolm Wheeler

Timeline Tags: US Health Care

August 2003: FDA Sides with Drug Company in False Advertising Lawsuit

FDA chief counsel Daniel E. Troy intervenes in a lawsuit against Glaxo SmithKline, the manufacturer of the drug Paxil. The FDA says it disagrees with the judge’s temporary order that the phrase “not habit-forming” be removed from the company’s advertisements promoting Paxil. The plaintiffs in the case alleged that the phrase is misleading because they experienced withdrawal symptoms after they stopped taking the drug. The judge agreed saying, “It is difficult to imagine that the FDA would object to the removal of the reference that ‘Paxil is not habit-forming.’” But Troy does object. The FDA, taking the side of Glaxo SmithKline, says the product is not habit-forming and contend that the symptoms experienced by patients were not withdrawal symptoms, but rather symptoms of “discontinuation syndrome.” According to Troy, the FDA has absolute authority on the content of drug labels. Following the FDA’s intervention, the judge lifts her temporary order. [BOSTON GLOBE, 12/22/2002]

Entity Tags: Daniel E. Troy, Glaxo SmithKline

Timeline Tags: US Health Care

February 18, 2005: Panel Votes to Allow Bextra and Vioxx to Stay on Market; Final Vote Possibly Affected by Industry Ties

An expert panel convened by the US Food and Drug Administration unanimously agrees that Celebrex, Bextra, and Vioxx “significantly increase the risk of cardiovascular events” such as heart attacks. However the panel does not believe that the risk is so great that these drugs should be banned from the market. (Vioxx was withdrawn from the market voluntarily by its manufacturer in September (see September 30, 2004).) The sales of these drugs should be permitted to continue, but only under strict conditions, the panel says. It also recommends a prohibition on direct marketing to consumers, a patient’s guide for the drug, and a black box warning—the most severe possible—detailing the drug’s cardiovascular side effects. [CNN, 2/18/2005; WASHINGTON TIMES, 2/19/2005] 

After the vote, the New York Times reveals that 10 of the panel’s 32 members had at one time been paid-consultants to the makers of the drugs in question. In analyzing the votes, the Times discovers that neither Bextra nor Vioxx would have survived the vote if the scientists with connections to the company had not voted. For both Bextra and Vioxx, the industry-connected panelists voted 9 to 1 in favor, while the experts with no ties voted 14 to 8 and 17 to 15 to ban Bextra and Vioxx, respectively. The Times notes in its article that “these votes were deeply important” for the makers of those drugs. After the votes, the shares of Merck and Pfizer increase substantially. In e-mails to the Times, eight of the panelists, responding to questions from the newspaper, say their votes were not influenced by their ties to the companies. Two of the panelists do not respond. One of the panel members, Dr. John Farrar, who has received research support from Pfizer, says, “I think FDA would have a hard time finding people who are good at what they do who never spoke to a pharmaceutical company.” But another panel member, Dr. Curt Furberg, who has no ties, says he was “uncomfortable with the Pfizer-friendly undertone” at the meeting and he felt the industry ties might have contributed to that tone. Furberg adds that it has never been proven that Celebrex, Bextra, or Vioxx offer better pain relief than ibuprofen or more than a dozen other over-the-counter drugs. Daniel E. Troy, the FDA’s former chief counsel and a longtime advocate of drug-maker interests, plays down the importance of the ties, saying that any suggestion that experts’ votes were influenced by industry connections “buys into an overly conspiratorial view of the world.” [NEW YORK TIMES, 2/25/2005]

Entity Tags: Daniel E. Troy, John Farrar, Curt Furberg, US Food and Drug Administration

Timeline Tags: US Health Care

http://www.cooperativeresearch.org/entity.jsp?entity=daniel_e._troy_1

Statement of Dr. Lester M. Crawford, Acting Commissioner of Food and Drugs on the Resignation of Daniel E. Troy

Acting FDA Commissioner Dr. Lester M. Crawford today issued the following statement on the departure of Chief Counsel Dan Troy: It is with mixed emotions that I announce the resignation of Daniel E. Troy, Associate General Counsel/Chief Counsel of the Food & Drug Division of the Department's Office of the General Counsel. Dan has been FDA's senior legal advisor since his appointment in August 2001.  His resignation is effective November 28.

Since August 2001, Dan has served the Agency with tireless dedication. Shortly after Dan's arrival, he faced a major challenge, assisting the Agency in addressing the myriad public health dimensions of the terrorist attacks of September 11, 2001. Thereafter, he provided excellent legal support to the Agency as we responded to the anthrax attacks and reoriented the Agency to its new counterterrorism responsibilities.

 Under the leadership of the Department's General Counsel Alex Azar, Dan's legal acumen has equally benefited FDA's programs aimed at carrying out the Agency's traditional public health mission, including the notable accomplishment of the major package of reforms to the Hatch Waxman amendments to the Federal Food, Drug and Cosmetic Act, which are estimated to save drug consumers $35 billion over ten years

 In my estimation, Dan's principal legacy is having instilled in the Agency a deep and abiding respect for the rule of law. Dan embraced the responsibility, as befits an agency's top lawyer, of helping FDA achieve our public health mission with respect for the powers Congress has -- and has not -- given us.

Dan is joined in his resignation by his special assistant, Coleen Klasmeier. Coleen joined the agency in June 2002.  

General Counsel Alex Azar has named Jerry Masoudi, the current Deputy Associate General Counsel of the Food and Drug Division, as Acting Associate General Counsel/Chief Counsel of the Food and Drug Division of the Office of the General Counsel until a permanent replacement is appointed.

Throughout Dan's tenure, he has given of himself and his time with utmost generosity and good humor. I am deeply sorry to lose his wise counsel and steadfast support. I thank Dan for his hard work and wish him and his family all the best.

hmmn

When Half a Million Americans Died and Nobody Noticed

By Alexander Cockburn, The Week

12 May 12

Was the US drug Vioxx responsible for far more deaths than has been acknowledged so far?

RE American lives cheaper than those of the Chinese? It's a question raised by Ron Unz, publisher ofThe American Conservative, who has produced a compelling comparison between the way the Chinese dealt with one of their drug scandals - melamine in baby formula - and how the US handled the Vioxx aspirin-substitute disaster.

The Chinese scandal surfaced in 2008, shortly before the Beijing Olympics. Crooked dairymen diluted their milk products, then added a plastic chemical compound called melamine to raise the apparent protein content back to normal levels. Nearly 300,000 babies across China suffered urinary problems, with many hundreds requiring lengthy hospitalisation for kidney stones. Six died.

Long prison sentences were handed down and a couple of the guiltiest culprits were tried and executed for their role. Throughout these events, American media coverage was extensive, with appropriate sneering about the Chinese leadership's indifference to human life.

Four years earlier, in September 2004, Merck, one of America's largest pharmaceutical companies, issued a sudden recall of Vioxx, its anti-pain medication widely used to treat arthritis-related ailments.

The recall came just days after Merck discovered that a top medical journal was about to publish a study by an FDA (Food and Drug Administration) investigator indicating that the drug in question greatly increased the risk of fatal heart attacks and strokes and had probably been responsible for at least55,000 American deaths during the five years it had been on the market.

It soon turned out Merck had known of potential lethal side effects even before launching Vioxx in 1999, but had brushed all such disturbing tests under the rug.

With a TV ad budget averaging a hundred million dollars per year, Vioxx swiftly became one of Merck's bestsellers, generating over $2 billion in yearly revenue. Twenty-five million Americans were eventually prescribed Vioxx as an aspirin-substitute thought to produce fewer complications.

There was a fair amount of news coverage after the recall, but pretty slim considering the alleged 55,000 death toll. A class-action lawsuit dragged its way through the courts for years, eventually being settled for $4.85 billion in 2007.

When the scandal first broke, Merck's stock price collapsed, and many believed that the company could not possibly survive, especially after evidence of a deliberate corporate conspiracy surfaced. Instead, Merck's stock price eventually reached new heights in 2008 and today it is just 15 per cent below where it stood before the disaster.

The year after the scandal unfolded, Merck's long-time CEO resigned and was replaced by one of his top lieutenants. But heretained the $50 million in financial compensation he had received over the previous five years.Neither he nor any other Merck executives was charged with corporate malfeasance.

Senior FDA officials apologised for their lack of effective oversight and promised to do better in the future. The Vioxx scandal began to sink into the vast marsh of semi-forgotten international pharmaceutical scandals.

Then in 2005, as he now remembers it, Ron Unz "was reading my morning newspapers, as I always do, and noticed tiny items about an unprecedented drop in the American death rate. Hmm I said, I wonder if that might have anything to do with all those other stories about that deadly drug recently taken off the market and all the resulting lawsuits."

The year after Vioxx was pulled from the market, the New York Times and other media outlets were running minor news items, usually down-column, noting that American death rates had undergone a striking and completely unexpected decline. These were what Unz, a dedicated news browser, was reading.

Typical was the headline on a short article that ran in the 19 April 2005 edition of USA Today: 'USA Records Largest Drop in Annual Deaths in at Least 60 Years.' During that one year, American deaths fell by 50,000 despite the growth in both the size and the age of the nation's population. Government health experts were quoted as being greatly "surprised" and "scratching [their] heads" over this strange anomaly, which was led by a sharp drop in fatal heart attacks.

For his Chinese melamine/Vioxx comparison, Unz went back to those 2005 stories. Quick scrutiny of the most recent 15 years worth of national mortality data provided on the US Government's Centers for Disease Control and Prevention website offered Unz some useful clues.

"We find the largest rise in American mortality rates occurred in 1999, the year Vioxx was introduced, while the largest drop occurred in 2004, the year it was withdrawn," says Unz. "Vioxx was almost entirely marketed to the elderly, and these substantial changes in the national death-rate were completely concentrated within the 65-plus population.

"The FDA studies had proven that use of Vioxx led to deaths from cardiovascular diseases such as heart attacks and strokes, and these were exactly the factors driving the changes in national mortality rates."

The impact of these shifts, Unz points out, was not small. After a decade of remaining roughly constant, the overall American death rate began a substantial decline in 2004, soon falling by approximately five per cent, despite the continued ageing of the population. This drop corresponds to roughly 100,000 fewer deaths per year. The age-adjusted decline in death rates was considerably greater.

"Patterns of cause and effect cannot easily be proven," Unz continues. "But if we hypothesise a direct connection between the recall of a class of very popular drugs proven to cause fatal heart attacks and other deadly illnesses with an immediate drop in the national rate of fatal heart attacks and other deadly illnesses, then the statistical implications are quite serious."

Unz makes the point that the users of Vioxx were almost all elderly, and it was not possible to determine whether a particular victim's heart attack had been caused by Vioxx or other factors. But he concludes: "Perhaps 500,000 or more premature American deaths may have resulted from Vioxx [my italics], a figure substantially larger than the 3,468 deaths of named individuals acknowledged by Merck during the settlement of its lawsuit. And almost no one among our political or media elites seems to know or care about this possibility."

I remarked to Unz that it seemed truly incredible that a greater than expected death rate of this dimension should scarcely have caused a ripple.

"I'm just as astonished," he said. "From 2004 onwards, huge numbers of America's toughest trial lawyers were suing Merck for billions based on Vioxx casualties - didn't they notice the dramatic drop in the national death rate?

"The inescapable conclusion is that in today's world and in the opinion of our own media, American lives are quite cheap, unlike those in China.

"Besides," says Unz laughing, "it shows the stupidity of our political leaders that they didn't seize upon this great opportunity. They should have just renamed Vioxx the 'Save Social Security Drug,' and distributed it free in very large doses to everyone, starting on their 65th birthday. Maybe they should have even made it mandatory, three times per day. At sufficiently large levels of national consumption, Vioxx could have almost singlehandedly eliminated all our serious budget deficit problems. 'Vioxx - The Miracle Anti-Deficit Drug'."

pharma mkt blog john mack

Tuesday, June 28, 2005

WLF Watches FDA Watching Drug Ads

The Washington Legal Foundation (WLF), a conservativewatchdoggroup funded by businesses (including drug companies), last week launched the "FDA/DDMAC Watch" program to "scrutinize" FDA advertising regulations. DDMAC is the FDA's Division of Drug Marketing, Advertising, and Communications, which oversees drug ads.DDMAC Watch's first action challenged an FDA warning letter regarding a TV ad for Eli Lilly & Co.'s adult ADD therapy, Strattera (see "Watchdog Group Blasts FDA").

According to the WLF, theFDA is acting “"outside its legal authority"” when its writes such letters, and shows "“disregard for the First Amendmentby alleging that materials are misleading with no evidence of how consumers understand them." ” (See theWLF Letter to DDMAC).

In short, the Washington Legal Foundation claims, the FDA "“invented" much of its power to police drug advertising. ("Watchdog Group Blasts FDA").

:{WLF is to the first amendment what the NRA is to the second amendment. That is, every argument by WLF begins and ends with the first amendment as it applies to a special interest group -- i.e., businesses like the pharmaceutical industry.

The House(s) That Troy Built}:

:{What's really interesting, however, are the ties that bind WLF, FDA, and the Pharma industry.

One of the main ties is Daniel E. Troy, former chief counsel to the FDA who joined WLF's board of directors just 4 days before the DDMAC Watch letter.According to the WLF Web site, Troy was "the first appointee to the Food and Drug Administration made by President George W. Bush."}:

"Troy managed to restrict FDA's ability to use its statutes creatively, and this in turn deterred mid-level managers from advocating new approaches to emerging scientific issues, leaving the agency looking - and feeling - weak." (See "FDAers Think Troy Weakened Them, Worry About Masoudi").

Before his stint at the FDA, Troy repeatedly sued the FDA. He argued that the FDA had only limited ability to regulate drug companies. Troy filed those suits through --- you guessed it -- the WLF! He also did legal work for Pfizer. Oh well, just another case of "What goes around, comes around."

What About Those Warning Letters?

The WLF criticism of the Strattera warning letter, which I will get to in a moment, comes at a time when the FDA is sharply increasing the number of warning letters sent to pharmaceutical companies.

The FDA issues two types of letters: untitled letters or Notices of Violation and warning letters. Thewarning letter goes to the CEO and essentially says "we think you have really screwed up and in a way that we think is important to the public health and we expect you to put out some kind of additional information to correct the misinformation you sent."(I quote here John Kamp, Executive Director, Coalition for Healthcare Communication. Kamp was speaking at a CME conference in Princeton, NJ.)

An untitled letter is sent to the head of marketing and says "we think you have a problem, let's sit down and work something out."This type of letter is much less serious and effective than a warning letter.In fact, I've heard it said thatuntitled letters are considered rites of passage by pharma product managers, who frame them and hang them on their office walls. That's what I've heard some people say.

According to the Philadelphia Inquirer ("Deluge of drug ads has FDA struggling to stop the hype"):

In January 2002, the Office of theFDA Chief Legal Counsel, Daniel Troy, began reviewing the evidence behind all proposed enforcement letters with an eye toward scuttling any that might not hold up in court. Claude Allen, the deputy secretary of the Health and Human Services Department, the FDA's parent agency, ordered the change in policy.

Troy effectively hobbled the issuance of warning letters by the FDA.

An October 2002 study by the General Accounting Office, the investigative arm of Congress, said that, before Troy's reviews began, FDA notices went out within days after a problem ad was spotted. Under the new policy, clearing the letters took 13 to 78 days, the report said. "Some regulatory letters may not be issued until after the advertising campaign has run its course," the GAO found. (Phila Inquirer)

:{While the number of total enforcement letters sent by the FDA has hovered around 23-25 in the last three years, the number of warning letters increased dramatically in 2004 (before Troy left the FDA but during the VIOXX debacle). In that year the FDA issued 12 warning letters compared to 5 in 2003 and 1 in 2002. 2005 promises to be a record year -- already nine warning letters have been issued.

The FDA may be getting the impression that the drug industry is not listening. According to Kamp, "DDMAC is saying the same things over and over again [in warning letters], but the industry is just not getting it. FDA is turning up the heat. How much higher, might I add, does it have to get before we start paying attention?"

If the WLF represents the pharma industry -- and with Troy involved it's hard to dispute that it does -- then the industry is paying attention, but responding by criticizing the FDA. There has been some more positive response as well. Recent DTC policy changes by J&J and BMS come to mind (see "DTC Straight Talk" and "New DTC Principles Emerging").

So What's the Beef With the Strattera TV Ad?}:

:{The FDA had asked Lilly on June 14 to pull its Strattera TV ad on the grounds that the flashy graphics made the warnings on side effects too difficult for consumers to comprehend (see warning letter and "Watchdog Group Blasts FDA").

WLF had this to say:}:

"DDMAC cites no evidence demonstrating that consumers cannot process the information presented in the advertisement. In fact, the TV advertisement conveys its message regarding attention deficit disorder so many times that it is incomprehensible that consumers would miss it. The sole source of authority for DDMAC's allegations against Lilly is the individual judgment of the DDMAC reviewer who signed the letter."

:{I don't recall seeing the ad myself, but the FDA presented promotional material, submitted by Lilly, which included screen shots from the ad. It looks distracting to me. I don't think you have to do a scientific study to tell whether or not an ad is effectively presenting labeling information. To suggest that "evidence" be produced is merely a ploy to delay the process so the ad can run it's course.

The problem is that the review by the FDA happens after the ad is already produced and running. It would be better, as proposed by BMS, that DTC ads be submitted to the FDA for approval BEFORE they run (see "New DTC Principles Emerging").

Guidance Needed

There is at least one point made by the WLF that I can agree with. It has to do witrh guidance from the FDA regarding TV DTC ads for Rx drugs:}:

"DDMAC should start providing concrete guidance to industry to help them fulfill this objective and stop playing 'gotcha' with drug companies," said WLF Chief Counsel Richard Samp.

Maybe Samp has a point. While the FDA has issued guidance regarding print DTC ads (see "Future of Drug Print Ads"), it hasn't done the same for TV DTC ads. Perhaps that will come sooner than Samp would like.

===

npr 2004

Pharmaceutical giant Merck & Co. is pulling its arthritis drug Vioxx from the market after a study confirmed earlier concerns that it raises the risk of heart problems, including heart attacks and stroke. Vioxx is currently used by 2 million people worldwide and has been used by more than 84 million people around the world, according to Merck, [GRAF]

chart above shows the total number of prescriptions written for Vioxx, Celebrex and Bextra, the three drugs in the class of compounds known as Cox-2 inhibitors. These are mainly used for arthritis and other types of pain. Prescriptions for the largest selling drugs, Celebrex and Vioxx, began to fall off in 2001 after reports of a possible link between Vioxx and heart disease. Studies have so far indicated that only Vioxx poses a risk of heart problems. The Food and Drug Administration will examine the other two drugs to see if there is any cause for concern....The drug was approved by the FDA in May 1999 for the relief of osteoarthritis and menstrual pain, and later for treatment of the signs and symptoms of rheumatoid arthritis. At that time, studies didn't show any significant risk of heart disease related to Vioxx. But data from a study started by Merck last year showed a doubling in the rate of cardiovascular problems, when compared with placebo. The problems appeared only after patients had been taking Vioxx for 18 months or more.

The FDA advises that patients who are currently taking Vioxx should contact physicians to discuss alternative treatments.

NPR Health Editor Joe Neel answers questions about today's withdrawal of Vioxx from the market.

Q: How dangerous is Vioxx?

A: The company that voluntarily withdrew Vioxx from the market, Merck, found that there was an elevated risk of heart problems for people taking a standard dose of Vioxx (25 mg per day). Technically, the risk of heart problems relative to people taking a placebo 1.9, which can be interpreted as a doubling of the risk. But a person's risk of a heart attack or stroke is relatively low. Double the risk is still means the chance of a cardiovascular event is still "small," according to the Food and Drug Administration.

Q: Why haven't we heard about this risk before?

A: There have been a few reports since 2000 suggesting that there may be heart problems associated with Vioxx. Merck and the Food and Drug Administration have been monitoring the situation. Today's surprise announcement comes from a study Merck was doing for a totally different reason. It was looking at 2,600 patients to see if Vioxx prevented such problems as colon polyps. The findings of an increased risk for heart problems were discovered by scientists monitoring safety in the study.

Q: What kinds of heart problems?

A: There was an increase in heart attacks and strokes for people taking 25 mg of Vioxx a day for 18 months or more. The study did NOT find problems in people who had taken Vioxx for a shorter period of time.

Q: What should I do if I'm taking Vioxx?

A: The Food and Drug Admininstration issued a Public Health Advisory to inform patients of Merck's action and to advise patients taking Vioxx to consult with a physician about alternative medications. (See the Web Resources on this page) These alternative medications might include drugs that are similar to Vioxx, like Celebrex or Bextra.

Q: Are Celebrex and Bextra safe?

A: Because Celebrex and Bextra are closely related to Vioxx, the FDA says it will now investigate whether these drugs cause the same problems as Vioxx. There's no evidence that that's the case right now. Other alternatives include older nonsteroidal anti-inflammatory drugs and aspirin. Some of these drugs have been associated with gastrointestinal, liver and kidney problems when used over the long term.

Q: Will the increased risk of heart problems go away when I stop taking Vioxx?

A: The FDA and Merck say that they don't know the answer to that. Merck will continue to follow patients in the study to see if there are any problems after they stop taking Vioxx.

Q: I remember my doctor saying that Vioxx was much better than the other drugs I was taking for arthritis and pain - better than high-dose aspirin or naproxen or ibuprofen.

A: Your doctor was acting on the best evidence at the time. Vioxx was the second member of a class of drugs called Cox-2 inhibitors. (The first was Celebrex; the other is Bextra.) These drugs were considered a major advance in the treatment of osteoarthritis and rheumatoid arthritis because they did not cause stomach or intestinal problems like ulcers and bleeding. In fact, it appeared that the drugs might even protect people from digestive problems. That's why Merck was doing the study that led to today's withdrawal of Vioxx.

Q: How soon should I stop taking Vioxx?

A: Again, the FDA advises that you consult a physician. Merck is asking pharmacies to stop selling all dosages and formulations of Vioxx immediately, including the 12.5 mg and 50 mg doses.

Q: What if I have leftover medications? Vioxx isn't cheap.

A: You're right. One Web site I checked (drugstore.com) listed a 30-day supply of the 25-mg dose for $81.99.

Merck will reimburse patients for unused Vioxx. Patients seeking a refund should return any unused Vioxx tablets and oral suspension via regular U.S. mail to the following address:

ATTN: NNC Dept., Merck Order Fulfillment Center, 1645 Satellite Blvd., Duluth, GA 30097

Patients must include the following information when returning any unused Vioxx tablets and oral suspension:

1. Name, address and phone number

2. Unused product in its original pharmacy packaging

3. Pharmacy receipt corresponding to returned product

Merck says that patients will receive a full refund of the price paid as reflected on their pharmacy receipt, plus the cost of shipping via regular U.S. mail.

Q: Why didn't the FDA act faster?

The studies required by the FDA for approving a drug don't usually run as long as the study Merck was doing on colon polyps. So an effect of a drug that doesn't show up until 18 months after you've started taking it wouldn't have been noticed in the studies the FDA requires for approval.

Q: Why didn't Merck act faster?

Today's voluntary withdrawal of Vioxx from the market is an unusual move for a drug company. In many cases, companies wait for an order to recall a drug from the FDA, even after serious side effects are found. And a recall is not always the first response to reports of serious side effects. Though each case is different, the usual scenario is for the FDA and the manufacturer to agree on a warning label listing the risks. That's what happened when the first reports of heart problems were connected to Vioxx. In extreme cases, the FDA has tried to restrict sales of some prescription drugs to certain people. In this case, Merck acted voluntarily after seeing preliminary results of a large study it was doing. It notified the FDA, but there was no intervention by the government.

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