Merck has no Plan to pay Vioxx Victims

Evelyn Pringle April 30, 2007

In 2006, Merck spent $500 million, including $175 million in the fourth quarter, in legal defense costs worldwide related to Vioxx litigation, according to SEC filings.

In addition, after reviewing actual costs and estimating future costs, the company says it has recorded a charge of $75 million to increase the reserve for future defense costs related to Vioxx to $858 million as of December 31, 2006.

However, although the legal team obviously plans to get paid well, there is no indication that Merck plans to pay any money to people injured by Vioxx because, according to the filing, Merck has not established any reserves for potential liability related to Vioxx.

Judging by the win-lose scorecard for Vioxx, it appears that juries are ignoring Merck’s culpability in placing a lethal drug on the market with full knowledge that people would be injured and killed and that 100s of thousands of Americans were in fact injured and killed.

People who may have forgotten how much damage was done while Merck was raking in billions of dollars off Vioxx should go back and read the transcript of a November 19, 2004 hearing before the Senate Finance Committee, where Dr David Graham, a career scientist at the FDA who has no dog in this hunt, stated, “Vioxx has been a disaster.”

“This is unparalleled in the history of the United States,” he testified.

To give a clearer picture of the Vioxx disaster, he described the harm in relationship to the number of Americans who took the drug and experienced heart attacks and strokes. Based on an estimated range of 88,000 to 139,000 people, Dr Graham said, “Of these, 30 to 40 percent probably died.”

He also offered a hypothetical scenario to help members of the committee recognize the magnitude of injuries and deaths caused by Vioxx, stating:

“Now, imagine that we were talking about jetliners. If there were an average of 150 to 200 people on an aircraft, this range of 88,000 to 139,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky. This translates to two to four aircraft every week — week in, week out — for the past five years.”

Dr Graham testified that research indicated that Vioxx caused up to 160,000 heart attacks and strokes and was responsible for an additional 27,785 deaths from heart ailments from 1999 to 2003.

Years later, nothing has changed as far as Merck getting honest about the known dangers associated with Vioxx. A study in the September 2006 Journal of American Medical Association found that heart problems could develop in Vioxx users much sooner than the 18 months that Merck claimed and, in fact, could develop in one month.

Still another study in the same JAMA issue found Vioxx to be associated with an increased risk in erratic heartbeats, or arrhythmia, and renal events including swelling of the hands and feet, high blood pressure and kidney dysfunction.

According to the company’s SEC filings, as of March 31, 2007, Merck had been served, or was aware that it had been named as a defendant, in approximately 27,250 lawsuits, which include about 45,700 plaintiff groups alleging personal injuries and approximately 266 putative class actions alleging personal injuries and/or economic loss.

Of these cases, approximately 8,400, representing about 23,450 plaintiff groups, are slated to be in the federal MDL and approximately 16,550 lawsuits representing about 16,550 plaintiff groups in a coordinated proceeding in New Jersey Superior Court.

In addition, the filing notes, approximately 13,700 claimants had entered into Tolling Agreements with Merck, which halt the running of statutes of limitations for claimants who seek to toll claims alleging injuries resulting from a thrombotic cardiovascular event that results in a myocardial infarction or ischemic stroke.

The filing also reports that individual and putative class actions have been filed in state and federal courts alleging personal injury and/or economic loss. A number of these actions, it says, are coordinated in a separate proceeding in an MDL in the US District Court for the Eastern District of Louisiana, and in coordinated proceedings in state courts in New Jersey, California and Texas; and in the counties of Philadelphia, Pennsylvania, Washoe County, Nevada and Clark County, Nevada.

Legal experts agree that the greatest threat to Merck comes from class-action lawsuits seeking recovery under consumer fraud statutes with claims that Merck failed to disclose damaging information to the public and, as a result, received a higher price for Vioxx than it would have if the information had been disclosed.

Legal experts say the most worrisome is a class-action filed in October 2003, now pending before the New Jersey Supreme Court. In the case of International Union of Operating Engineers Local 68 Welfare Fund vs Merck, New Jersey State Superior Court Judge Carol Higbee held that New Jersey’s consumer fraud statute applies to all Vioxx sales in the US and granted class-action status to third-party payors nationwide in July 2005.

Most purchases for Vioxx were made by health plans run by insurance companies and health maintenance organizations, and the Union case could include millions of Vioxx users. Considering that an estimated 20 million consumers used Vioxx in the US since it came on the market in 1999, legal experts says, Merck could get hit with a judgment worth billions of dollars if it loses this one case.

The plans say they lost significant amounts of money after being persuaded by Merck’s marketing efforts to add Vioxx to their formularies, or the lists of drugs for which they agree to reimburse members. The Union alleges that Merck’s marketing and advertising of the drug was fraudulent and misrepresented the safety and efficacy of the drug.

Third-party payors in this case can recover the actual payments made for Vioxx, and they are entitled to treble damages, as well as attorney fees, under New Jersey consumer fraud laws. For instance, if there were 10 million Vioxx users who each bought $1,000 worth of the drug through the benefit plans at the going price at the time of $72 for a 30-day supply, a judgment could conceivably reach $10 billion, in addition to attorney fees.

Unlike personal injury cases, attorneys for the Union do not have to prove that anyone was injured, all they have to show is that the third-party payors were influenced to purchase Vioxx by Merck’s deceptive marketing and promotion of the drug.

In allowing the lawsuit to go forward, Judge Higbee drew no distinction between a company defrauding a person or a third-party payor. “This Court,” she wrote, “sees no reason why the duty to be honest about the safety and usefulness of a drug when marketing it as a product for sale should not extend to the third-party payors who actually pay for the purchase of drugs for members.”

Merck appealed Judge Higbee’s class certification, and in a unanimous decision in March 2006, the New Jersey appellate court affirmed the certification. From there, Merck appealed the appellate ruling to the New Jersey Supreme Court.

On March 19, 2007, a five-judge panel heard arguments, and the Union’s lead attorney, Christopher Seeger, told the court that, because Merck concealed the risks of Vioxx from the health care plans, the drug was chosen over about 30 other cheaper products.

Mr Seeger said, New Jersey consumer fraud statutes should govern the case because all of the decisions about what information was disclosed about Vioxx and how the drug should be promoted and advertised to the public were made at Merck’s New Jersey headquarters.

“It’s perfect for a class action,” Mr Seeger said. “If we really want to deter bad conduct, as is alleged in this case, the way to do it is to protect every purchaser of the product.”

Legal analysts say a ruling by the high court is not expected for several months.

Another class-action got the go-ahead in Canada on November 9, 2006, when Quebec Superior Court Judge Andre Denis authorized a lawsuit by Quebec residents who suffered “damages caused by the use of the medication,” between October 1999 and September 2004, according to the November 11, 2006 Moose Jaw Times Herald.

Dimitri Lascaris, an attorney for plaintiffs in Quebec and Ontario, said there have been more than 20 requests for class-action Vioxx lawsuits filed in Canada but this is the first case that has received clearance to proceed.

Big Pharma’s Battle Over Direct to Consumer Advertising

Evelyn Pringle November 21, 2006

Big Pharma has Americans running to the doctor demanding the latest advertised drug to treat the latest promoted disorder based on the latest commercial they see on TV.

According to a report by CBS News on October 22, 2006, the United States makes up just 5 percent of the world’s population, “but it accounts for a whopping 42 percent of the world’s spending on prescription drugs — more than $250 billion just last year.”

And yet, when compared to nearly two dozen other industrialized countries, the US has the highest infant mortality rate and the lowest life expectancy for people who have reached the age of 60, according to a September 20, 2006 report by The Commonwealth Fund’s Commission on a High Performance Health System.

In August 1997, the FDA relaxed the restrictions on television and radio DTC advertising, permitting drug companies to mention both the name of the drug, and the disease or symptoms that the medication treats in the same ad.

Industry critics say the end result of the easing of restrictions has been massive advertising campaigns that regularly promote drugs for off-label unapproved uses, understate risks and overstate benefits, and make efficacy and safety claims that are not backed up by clinical studies.

The most common strategy used these days to mass-market a drug is “disease mongering” to increase the number of potential customers diagnosed with a new disorder. Big Pharma even hires PR firms to come up with the most sellable names for the disorders.

“At Brand Institute, Inc., a Miami marketing firm,” CBS reports, “naming, or re-naming, syndromes for drug companies is 20 percent of the business.”

The key, the company’s president, Jim Dettore, told CBS, is a name that describes the symptom in a nice way, making it OK to seek help, preferably with the client’s drug. “These acronyms allow them to communicate more effectively with less pressure,” Mr Dettore said.

Disease mongering through DTC advertising can dramatically increase the sales of just about any product. For instance, Lamisil is used to treat toenail fungus. The main adverse effect of the fungus is that it turns the toenail yellow and it can hurt, but no one has died of toenail fungus.

However, people taking Lamisil have died from the drug, according to “Pill Pushers,” in on May 8, 2006, “Federal regulators have linked the drug to 16 cases of liver failure, including 11 deaths.”

The Forbes article reports that 10 million Americans have taken Lamisil, at a cost of $850 for a 3-month treatment, even though the drug only cures the problem in 38% of the patients.

The advertising campaign for the drug featured a cartoon character called “Digger the Dermatophyte” being crushed by a giant Lamisil pill.

The ad so overstated the benefits of the drug, Forbes said, that regulators objected and the company was forced to pull the ad. But the campaign was obviously a huge success because in 2004, Lamisil sales increased by 19% to reach $1.2 billion worldwide and held steady in 2005.

Prescription drug advertising has provided a steady stream of revenue for print and broadcast media since the FDA lifted the restrictions. IMS Health, an industry tracking firm, reports that overall in 2004, drug companies spent about $4 billion on DTC advertising.

According to contributing editor, Judy Lieberman, in the July-August 2005, Columbia Journalism Review, the CJR monitored the evening newscasts on ABC, CBS, and NBC for one week in April 2005, and found that network viewers saw an average of 16 ads for prescription drugs and on average 18 commercials for over-the-counter drugs every night.

In 1999, the five networks, including Fox News and CNN, received $569 million in advertising revenue from drug companies, according to TNS Media Intelligence. But by 2004, advertising revenue nearly tripled to $1.5 billion, according to Ms Lieberman.

As far as advertising dollars spent on print media, at the end of 2004, Ms Lieberman found that drug company ads for Time magazine totaled $67 million; $43 million for Newsweek; and the New York Times took in $13 million.

Advertising dollars pay big dividends. A 2003 Harvard Public Health study commissioned by the Kaiser Family Foundation determined that for every $1 spent on direct advertising, drug companies took in an additional $4.20 in sales.

No other drugs in history have received more promotion and media attention than the Cox 2 inhibitors which include Merck’s Vioxx, and Celebrex and Bextra, by GD Searle, a company bought later by Pharmacia. Celebrex went on the market in January 1999, and Vioxx was FDA approved on May 20, 1999.

The study, “Promotion of Prescription Drugs to Consumers: A Look at the Numbers,” in the February 14, 2002, New England Journal of Medicine, found Vioxx to be the most highly promoted drug in 2000 with Merck spending $161 million.

The only real selling point for the Cox 2 inhibitors was the claim by drug makers that the new medications supposedly did not cause stomach bleeding and ulcers that sometimes resulted after lengthily use of painkillers like aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs).

That assertion was untrue and in fact, the FDA refused to allow the companies to make that claim in advertising or the drug’s guidelines for use, since it was not backed up by any clinical studies. The package insert that did accompany the new pain relievers contained the same warning as the older NSAIDs.

But never known to let a little FDA warning stand in the way of profits, in no time at all the drug makers had the mainstream press and medical literature flooded with ghost-written articles and press releases with the names of “experts” attached, describing the bleeding problems and deaths caused by NSAIDs, followed by the effectiveness and safety of the Cox 2 inhibitors.

For instance, Vioxx was approved on May 20, 1999, two days later on May 22, 1999, the Washington Post ran the headline, “FDA Approves Pain Reliever with Fewer Side Effects,” and article reported that NSAIDs cause “107,000 hospitalizations and the death of 16,500 people every year.”

Never mind that the same year, a survey by the Centers for Disease Control reported that less than 6,000 people died the year before from any and all types of gastrointestinal bleeding disorders combined.

However, apparently Merck found a different group of people to survey because on the December 26, 2000, Jim Lahrer News Hour, Dr Roger Perlmutter, who was listed as overseeing basic research at Merck, said, “Each year something in excess of 8,500 deaths and more than 50,000 hospitalizations result from the chronic use of non-steroidal anti-inflammatory drugs.”

He claimed that NSAIDs produced dangerous and even deadly side effects in about 4% of patients, including bleeding in the stomach or intestine. “The result,” Dr Perlmutter said, “is an increase in ulceration and severe gastrointestinal complications.”

At the time of their arrival on the market, Wall Street analysts referred to the launch of the Cox 2 inhibitors as the most successful marketing coup in the history of the pharmaceutical industry.

Drug company sales reps swarmed into medical clinics with free samples galore and millions of patients began demanded prescriptions for the new miracle arthritis pain relievers and sales took off the minute the drugs hit the shelves.

Pain relief drugs that cost pennies a day were history and millions of patients were conned into forking over three to 6 bucks for pills that were no more effective, and as it turns out, much less safe than aspirins.

Reportedly, over 100 million people were prescribed Vioxx and massive DTC advertising has been singled out as the main factor that led to an unusually high number of patients being prescribed the drug before the lethal side effects were known.

In an August 30, 2005, interview with Manette Loudon, career FDA scientist, Dr David Graham said the Vioxx disaster would not have been half as bad if not for DTC advertising. “I submit,” he said, “that the numbers would have been far lower than what they were.”

Due to heavy marketing of new drugs like Vioxx, Dr Graham says, patients and doctors will often use a drug that is no better than others already on the market, even though the FDA does not require that new drugs be equivalent to, or better than, the drugs that are already there. All they have to prove is that a drug works better than a sugar pill, he says.

Merck finally withdrew Vioxx from the market in September 2004, but not before an “estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market life of Vioxx,” according to Dr Graham.

The US national estimate of the case-fatality rate was 44%, he says, which suggests that many of the excess cases attributable to Vioxx use were fatal.

An expert witness in one of the Vioxx trials, the respected biostatistician, Richard Kronmal, from the University of Washington, testified that as early as April 2001, Merck had data that showed a 4-fold increase risk of death in Vioxx patients from a clinical trial that Merck was conducting to determine whether the drug was effective in treating Alzheimer’s and yet the company continued the study until 2003.

“They had evidence that they were potentially killing people and they let that trial go on for another two years,” he said.

According to Merck, as of September 30, 2006, there are close to 24,000 Vioxx-related lawsuits filed against the company on behalf of over 41,000 plaintiff’s groups, and an additional 275 class actions seeking personal injury damages or reimbursement for the costs of buying a drug that Merck misrepresented as being safe and more effective than it actually was.

The Vioxx debacle has placed Merck, the FDA, and the issue of drug safety on center stage and the spotlight is focused on the faulty process by which new drugs are approved and advertised along with the inadequate post approval safety surveillance program.

Lawmakers on both sides of the isle have accused FDA officials of being too cozy with Merck and the over-promotion of Vioxx has led to several pieces of reform legislation aimed at the FDA’s lack of regulatory efforts toward curtailing DTC advertising abuses.

On November 17, 2006, the Senate Committee on Health, Education, Labor, and Pensions, held a hearing and gave Democrats their first chance to exercise their muscle to demonstrate how they will deal with the FDA’s stance on DTC once they become the majority in Congress next year.

The hearing titled, “Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation,” focused on Senate Bill 3807, the “Enhancing Drug Safe and Innovation Act of 2006,” co-sponsored by committee chairman, Senator Michael Enzi (R-WY), and Senator Ted Kennedy (D-MA), the next chairman of the committee.

A prepared statement from Senator Enzi’s office said the Senate Bill will “ensure that drug safety is not an afterthought,” and Senator Kennedy said that as chairman, he plans to hold a series of hearings aimed at FDA oversight early in 2007.

Dr Steven Nissen, MD, from the Cleveland Clinic, testified at the hearing and told the panel that the post marketing surveillance system for prescription drugs functions poorly. “Adverse event reporting,” he notes, “is voluntary and studies show that only 1 to 10% of serious adverse events are ever reported to the Agency.”

And therefore, he informed the committee, “the actual incidence of serious or life-threatened complications cannot be calculated accurately.”

Dr Nissen also said that DTC advertising requires legislative action. “The standard for acceptable DTC advertising,” he told the panel, “should require demonstration of a compelling public health benefit for this type of communication.”

“Drugs with an addiction potential, such as sleeping medication,” he said, “should be specifically prohibited from consumer advertising.”

As it is now, according to Pill Pushers, by Forbes on May 8, 2006, prescriptions for sleeping pills increased 48% in five years to 43 million prescriptions annually, driven by the DTC advertising of Ambien and Lunesta, and sales in the same period rose to $2.76 billion.

Jim Guest, president and CEO of Consumers Union, publisher of Consumer Reports, testified on behalf of Consumers Union, and asked lawmakers to limit advertising of new drugs for three years, instead of the two year requirement in the Senate bill, because most adverse events do not show up until nearly seven years after a drug has been on the market, he said.

However, a Johnson & Johnson vice president, Adrian Thomas, told the committee that a 2-year moratorium on DTC advertising for newly approved drugs “represents a troubling change.”

“Appropriate DTC advertising plays a valuable role in educating patients about diseases and treatments,” Mr Thomas told the panel.

“The value of this education to patients,” he continued, “as well as important First Amendment issues that arise from banning truthful speech, even for a period of time, must be carefully considered before legislating in this area.”

Mr Guest testified that consumer advertising is not an educational tool, but rather a vehicle to mass market drugs before the serious side effects become known. “The direct-to-consumer advertising,” he told the panel, “is not a good way for consumers, physicians or medical providers to be informed.”

Merck Litigation Strategy – Destroy Expert Witnesses

May 22, 2006

Evelyn Pringle

Former Vioxx users could be at risk of developing strokes for years, a prominent scientist said this week after evaluating new data from a 107-page report on patients who were followed for a year after they stopped the drug

“It may be that Vioxx is causing permanent damage to the cardiovascular system, accelerating atherosclerosis or a sustained increase in blood pressure,” said Dr Curt Furberg, a professor of public health at Wake Forest University, and a member of the FDA Safety and Risk Management Advisory Committee, according to a report by Reuter’s news on May 18, 2006.

During his examination of the report, Dr Furberg determined that within the one-year follow-up of the APPROVE study, 7 Vioxx users had strokes, and 2 others had mini-strokes, compared with no strokes in patients taking a placebo.

“These data raise some very important questions because for a while we assumed Vioxx caused temporary problems, and here it is more than that,” Dr Furberg told Reuters. “It could be causing permanent damage.”

“In the past we weren’t quite sure of the stroke risk,” he added, “so stroke is now back on the agenda in a bigger way.”

Also this week the Wall Street Journal reported that heart attack risks for Vioxx users increase long before the 18 month period claimed by Merck. The new report is the 1-year follow-up to the APPROVE trial and includes a graph tracking “confirmed thrombotic cardiovascular events,” that shows that at four months of use, the number of CV events among Vioxx users began to outnumber those in patients who were given a placebo.

On May 18, 2006, CNN’s Moneyline reported that: “Merck is denying news reports that suggest new data from the drug maker indicates Vioxx increased heart attack risks earlier than previously reported and that the risk for stroke persisted long after the patient stopped taking the drug.”

But then when has it ever done anything but deny its wrongdoings?

This appears to be a month of reckoning for Merck because another study published earlier this month in the online edition of the Canadian Medical Journal, Queen’s University researcher Linda L’vesque, along with James Brophy and Bin Zhangat at McGill University in Montreal Canada, found that 25% of Vioxx users who suffered a heart attack did so within 14 days of taking the first dose.

What this all means to Merck’s legal team is that the stakes are getting higher and the company’s SEC filings indicate the drug giant knows it.

Last year, Merck had listed a reserve of $675 million for legal defense expenses related to Vioxx; but in January 2006, the company announced that it had increased the fund by $295 million to cover legal costs through 2007.

According to Merck’s SEC filings, in 2005, the company had worldwide sales of $22 billion, compared to $22.9 billion for 2004. Total sales decreased 4% for the year, which Merck says, reflects a decrease of 7% related to the VIOXX withdrawal, offset by revenue growth in all other products of 3%.

Included in marketing and administrative expenses, the company noted reserves solely for future legal defense costs for Vioxx litigation recorded in the 4th quarter of 2005 and 2004, of $295 million and $604 million, respectively, as well as $141 million associated with the withdrawal of Vioxx recorded in 2004.

According to a January 31, 2006 Merck press release, there are “9,650 lawsuits, which include approximately 19,100 plaintiff groups alleging personal injuries resulting from the use of VIOXX.”

In addition, another 3800 plaintiffs have signed tolling agreements, meaning they have cut a deal with Merck to forego suing in the short term; but should Merck start losing Vioxx lawsuits in marginal cases, attorneys say, those thousands are likely to multiply.

There are also numerous lawsuits filed against Merck for claims other than personal injuries. For instance, the Attorney General of Texas, Greg Abbott, has filed a lawsuit seeking $250 million, accusing Merck of defrauding Texas citizens by representing Vioxx as safe when applying for the drug’s approval to be included on the state’s list of drugs approved to be covered for patients on Medicaid.

According to the lawsuit’s complaint, Merck’s failure to disclose the harmful effects of Vioxx, while offering it to the state’s Medicaid program as a safe painkiller, violates the Texas Medicaid Fraud Prevention Act and the Texas Medicaid program reimbursed pharmacists $56 million for Vioxx prescriptions over a five-year period.

In another case, on March 31, 2006, a New Jersey court of appeals upheld a class action lawsuit against Merck filed by private insurers and HMOs, as third-party payors, under the New Jersey Consumer Fraud Act, to recover losses incurred in purchasing Vioxx for their health plans.

The appellate court ruled that Judge Carol Higbee of New Jersey Supreme Court properly exercised her discretion in certifying a nationwide class. “New Jersey’s contacts with this dispute are both extensive and weighty,” the appeals court said, noting the fact that Merck was a New Jersey corporation and that most of Vioxx-related research and marketing efforts took place in the state.

“Given the confluence of New Jersey contacts and interest,” the court stated, “choosing New Jersey as the site for this nationwide class action is not unconstitutionally ‘arbitrary or unfair'”.

On July 29, 2005, Judge Higbee had granted a motion by the International Union of Operating Engineers Local #68 Welfare Fund, a labor union health plan, to allow the lawsuit to proceed as a nationwide class action, based on allegations that Merck engaged in widespread and systematic concealment of data concerning the safety and health risks of Vioxx.

“This Court,” the judge wrote, “sees no reason why the duty to be honest about the safety and usefulness of a drug when marketing it as a product for sale should not extend to the third party payors who actually pay for the purchase of drugs for members.”

Chris Seeger, the lead attorney for the union health plan, states that “the decision applies to all non-governmental third-party payors in the country, including health insurers, unions, and large employers, who paid for Vioxx prescriptions for their plan members.”

“The decision,” he says, “also allows for all such third-party payors in the country to prosecute their allegations of being misled by Merck’s misrepresentations and concealments concerning Vioxx in one class action, rather than in a multitude of individual actions.”

The plaintiffs contend that had they been properly informed of the facts, they would not have included Vioxx on their lists of approved drugs or reimbursed their members for its high cost. In this type of case, the plaintiffs do not have to prove Vioxx caused any injuries or deaths. All they have to prove is that Merck continued to push the sale of the drug after it knew of the increased risks it posed.

Besides recouping costs of purchasing Vioxx for their plan members, if successful, the third-party payors would be entitled to triple damages under the New Jersey Consumer Fraud Act.

That said, Merck must have a lot confidence in its legal team because it reportedly has not reserved any money for liability. Which means it probably plans on using the same trial strategy that has proven somewhat effective so far.

Search out and destroy the credibility of the expert witnesses who might testify for the plaintiffs.

Several of the most feared witnesses provided a preview of their testimony at a November 18, 2004, hearing before the Senate Finance Committee, where the topic was focused on whether the FDA and Merck had failed to protect the public against Vioxx.

In his opening statement, the chairman of the committee, Senator Charles Grassley (R-Iowa), set the parameters for what he called the biggest drug disaster in US history.

“Merck acknowledged that Vioxx carried with it serious cardiovascular risk,” he told the audience, “when it withdrew the drug from the market.”

However, he explained, during “today’s hearing we will hear about the red flags that were raised about those risks in the years before and the years after Vioxx was approved by the Food & Drug Administration.”

The star of the hearing was FDA whistleblower, Dr David Graham, who told the panel that his superiors at the FDA tried to suppress the results of a recent study that determined that Vioxx at low doses was associated with a 50% increase in the risk; and doses of greater than 25 mg a day showed a 370% increase in the risk of heart attacks.

In reviewing the documents on the Vioxx-related studies, a strange coincidence appeared. As it turns out, the report for the above study, authored by Dr Graham, has the exact same date, September 30, 2004, that Merck supposedly “voluntarily” took Vioxx off the market and it says it was sent to Paul Seligman, MD, then acting director of the FDA’s Office of Drug Safety.

“Disturbingly,” Dr Graham wrote in the report, “while evidence of increased cardiovascular risk with rofecoxib continued to accrue following VIGOR in 2000, the only study to examine the gastrointestinal benefits of rofecoxib compared to celecoxib found that the risk of hospitalization for gastrointestinal bleeding was significantly increased in patients treated with rofecoxib.”

“Additionally,” he continued, “this reviewer was unable to identify articles demonstrating a substantial benefit with the high-dose strength of rofecoxib that would counter-balance the level of cardiovascular risk shown in VIGOR or any subsequent observational study, including this one,” he wrote.

Dr Graham’s report and testimony at the hearing led many doctors and scientists, at home and abroad, to conclude that the FDA was in large part responsible for the deaths of tens of thousands of Americans, because it allowed Vioxx to remain on the market for years while Merck made billions of dollars off the sale of the drug.

Critics liken the rise and fall of Vioxx to a masterful public relations coup of aggressive marketing and ineffective regulation. In the months following the hearing, Merck and the FDA, came under attack from experts all over the world. Two months after Vioxx was pulled off the market, Dr Richard Horton, editor in chief of the British medical journal Lancet, wrote: “With Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted, and irresponsible self-interest.”

Other experts demanded an explanation. A team of scientists from the University of Berne, Switzerland, expressed distain in the December 2004 Lancet saying: “Our findings indicate that Vioxx should have been withdrawn several years earlier.”

“The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarize the accumulating evidence need to be clarified,” they said.

In the weeks following the hearing, Dr Graham was interviewed on a series of TV news programs and was also featured in articles in USA Today, Newsweek, the Wall Street Journal, and the Washington Post, leaving a trail of ammunition for attorneys to use in court as far as Dr Graham’s opinions.

However, federal judge Eldon Fallon dealt Merck a major blow in April 2006, when he ordered Dr Graham to testify in a deposition for the Vioxx multidistrict litigation proceedings in response to subpoena issued by attorneys for the plaintiffs.

In addition to Dr Graham, the equally forthright expert witness, Dr Gurkirpal Singh, MD, Adjunct Clinical Professor of Medicine at Stanford University School of Medicine also testified at the November 18, 2004, hearing through a video conference due to health problems.

Dr Singh is a rheumatologist by training with research expertise in drug safety and epidemiology. For the hearing, Dr Singh was asked to review internal company documents and emails between Merck scientists and executives that had been subpoenaed by Congress.

Dr Singh began his testimony by pointing out that as far back as 1996, Merck was already considering the possibility that a clinical trial of Vioxx versus a non-selective NSAID, would find that patients treated with Vioxx would have an increased risk of cardiovascular complications.

“We now know that by November of 1996,” Dr Singh told the panel, “Merck scientists were seriously discussing a potential risk of Vioxx – association with heart attacks.”

At that time, he said, it was not known that Vioxx could cause heart attacks, but the discussion focused on the issue that by inhibiting platelets, other painkillers may protect against heart attacks. Vioxx has no effect on platelets, and thus may seem to increase the risk of heart attacks in studies comparing it to other painkillers, he said.

“This was a serious concern because the entire reason for the development of Vioxx was safety,” he explained. “If the improved stomach safety of the drug was negated by a risk of heart attacks,” Dr Singh said, “patients may not be willing to make this trade-off.”

“Merck scientists,” he told the committee, “were among the first to recognize this.”

“At this point in time,” he said, “scientists should have started a public discussion about this potential trade-off, and designed studies that would more carefully evaluate the risk-benefit ratio of the drug.”

“It appears from the internal Merck e-mails provided to me,” he advised, “that in early 1997, Merck scientists were exploring study designs that would exclude people who may have a weak heart so that the heart attack problem would not be evident.”

“Clinical trials should be designed to test a drug under “real world” circumstances – on patients who are most likely to use the drug,” Dr Singh told the panel.

“Clinical trials should not be designed,” he said, “to selectively favor one outcome over another by excluding people similar to those who would take the drug after its approval.”

“Certainly,” he continued, “clinical trials should not be designed to put marketing needs in front of patient safety – we need to know how a drug behaves in people who are going to take it, even if it “kills the drug”.

Referring to documents provided to him by the Committee, Dr Singh said, “there were many other internal discussions within Merck on these concerns of heart attack-stomach bleed trade-offs, although the practicing physician did not learn of any of this till many years later,” he added.

For instance, one document in 1998 authored by Merck scientist, Dr Doug Watson, presented an analysis of serious heart problems with Vioxx compared to patients enrolled in studies of other Merck drugs and concluded that in women, the risk of heart problems was more than double compared to people not taking any drug in other studies.

“To the best of my knowledge,” Dr Singh said, “these data were never made public.”

“This is when a public scientific discussion of the pros and cons of the medication should have started,” he told the committee.

By 1999, he said, more serious problems were emerging. “By the time Merck had filed for the approval of Vioxx,” he informed the panel, “there were several small studies evaluating the efficacy and safety of Vioxx in patients with pain and arthritis.”

“None of these studies were large enough to study the risk-benefit trade offs of stomach bleeds versus heart attacks,” he explained.

But in a careful review of Merck’s FDA drug application for Vioxx, he told the panel, “Dr. Villalba noticed that “thomboembolic events are more frequent in patients receiving VIOXX than placebo…”.

The review showed that among 412 patients taking a placebo, only one had a cardiovascular event; but among the 1631 patients receiving 12.5 mg or more of Vioxx, 12 had a cardiovascular event.

This meant that not only did Vioxx not inhibit the platelets, Dr Singh said, but for some reason, it was likely to promote heart attacks. “Many scientists would consider this three-fold difference as an early warning sign,” he explained.

“It is my opinion,” he told the panel, “that at this point in time, larger and more definitive studies should have been done before the drug was approved.”

Dr Singh noted that Vioxx was no more effective than any other available pain-killer and at the time, there were nearly 30 such drugs on the market in the US. Celebrex, he said, had no such risk and had been available for 6 months prior to Vioxx.

“There was certainly no emergent need to approve Vioxx without further studies if there were lingering safety concerns,” he said. “The trade-off of heart attacks for the rare instances of stomach bleeds,” he advised, “is not a reasonable one.”

But instead, he reminded the panel, “the drug was approved by the FDA in a priority review within 6 months – with no discussion on the heart attack trade-off.”

“The prescribing physicians,” he noted, “remained unaware of any of these data or discussions, till much later – with the new label change in April, 2002.”

Dr Singh explained, that the VIGOR study was the first public release of information about the heart attack-stomach bleed trade-off. The 500% increase in the risk of heart attacks found in VIGOR stunned him, he said.

At the time that the results were announced, Dr Singh said he was involved in teaching and some of his educational lectures were sponsored by Merck. “I was strongly in favor of this new class of drugs,” he explained, “and before the VIGOR trial, was unaware of any significant heart attack issues.”

Merck’s press release on the study, with a brief mention of the heart attack risk was not enough for him to continue to educate doctors in his lectures Dr Singh said, so he asked Merck for more detailed data, and when he was unable to obtain the information after multiple requests, he added a slide to his presentation that showed a man – representing the missing data – hiding under a blanket.

Up until this time, Dr Singh said, Merck had responded to all of his requests promptly. But when he persisted in his enquiries, he told the committee, “I was warned that if I continued in this fashion, there would be serious consequences for me.”

“I was told that Dr. Louis Sherwood, a Merck senior vice-president, and a former Chief of Medicine at a medical school, had extensive contacts within the academia and could make life “very difficult” for me at Stanford and outside,” he testified.

And as it turns out, Dr Sherwood did call Dr Singh’s superiors at Stanford University to complain.

However, documents that have surfaced in litigation over the past couple of years, reveal that Dr Singh had no idea how important he had become in the minds of Merck officials.

The documents show that for most of June 2000, Merck officials had their heads together trying to come up with a plan to rein in Dr Singh. He presented a major problem because he was widely respected at the FDA and also had connections with large institutional buyers that were vital to Merck sales.

On June 5, 2000, Merck senior business director, Terry Strombom, sent an email that shows Merck found itself caught between a rock and a hard place. “The one thing I am pretty sure of is that Dr. Singh could impact us negatively if he chose to do so,” he wrote. “I would recommend we handle this very carefully… I just don’t think canceling all the programs and walking away completely will serve us well in the long term,” he said.

Another email shows one official acknowledging that Dr Singh’s criticisms about Vioxx were valid. On June 5, 2000, Heather Robertson, a coordinator of health education projects, reported a conversation with Dr Singh’s contact at Merck, (who had since left the company) in an email that said:

“I spoke to Kirsten directly for the first time this past week to learn that Dr. Singh makes a balanced presentation (he must since he is an FDA advisor) but reports product information that is not favorable to Merck… Kirsten feels that no amount of work would change Dr. Singh’s position, and although we may not like to hear about it, his information is scientifically accurate.”

On June 19, 2000, a marketing manager, Susan Baumgartner, wrote an email saying: “Dr. Singh continues to play up the cardiovascular adverse events associated with Vioxx… I think there are many other speakers who deliver good messages, and we should not risk supporting the negative messages that he continues to deliver.”

Merck also had a high-tech surveillance system in place in the medical community where doctors, many with financial ties to Merck, would contact the company whenever they heard criticism. A July 21, 2000, memo reads: “Communication from advocate regarding a program given by Dr. Singh… It was hyper-inflammatory.”

A July 2000 document shows that Merck even knew about the cartoon he used in his lectures and reads: “Received reports that Dr. Singh showed a cartoon of a character hiding under a blanket and asked the audience to speculate about what it is that Merck is trying to hide.”

Other documents show sales reps were gathering information as they made their rounds to doctors’ offices and would use voicemail to relay the data to Merck’s National Service Center. A July 26, 2000 memo reads: “NSC report that at nine meetings in the L.A. area over the last three days, Singh presented sessions that were very unfavorable to Vioxx.”

Around this same time, Dr Singh made his concerns about Vioxx known to one of Merck’s largest Vioxx buyers, the Department of Veterans Affairs. Reportedly it was at this point that Dr Sherwood elevated himself to the director of damage control and a detailed report began to be compiled on Dr Singh’s activities, with nearly a dozen Merck executives involved.

An October 4, 2000 memo, by a senior regional executive states: “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.”

Less than a month later, Dr Sherwood called Dr Singh’s boss at Stanford University, Dr James Fries.

“I don’t usually receive phone calls on a Saturday at home from representatives of drug companies,” Dr Fries said during an interview with National Public Radio, of a call he received from Dr Sherwood on October 28, 2000. “So it was definitely unusual,” he said.

Dr Fries told NPR he received a call “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, Dr Sherwood hinted there would be repercussions for Stanford if Dr Singh did not stop making negative statements about Vioxx and he was left with the impression that Merck’s financial support to Stanford University was at risk.

Back at Merck, on November 17, 2000, apparently believing his efforts were successful, Dr Sherwood wrote an email to the marketing department that said: “Fries and I discussed getting Singh to stop making the outrageous comments he has in the past few months… I will keep the pressure on and get others at Stanford to help.”

In another email, he specifically directed one Merck executive to pressure Dr Singh himself. “Tell Singh that we’ve told his boss about his Merck-bashing,” he wrote. And tell him, “should it continue, further actions will be necessary (don’t define it.),” he said.

However, after speaking to Dr Sherwood, Dr Fries told NPR he started making calls of his own and learned that Dr Sherwood had called 7 other institutions, including the University of Minnesota, the University of Texas Southwestern and a Harvard teaching hospital, where researchers had raised concerns about the safety of Vioxx.

After Dr Fries learned about those calls, he wrote a letter to Merck CEO, Raymond Gilmartin, and questioned the propriety of Dr Sherwood’s calls in what Dr Fries referred to as, “a consistent pattern of intimidation of investigators by Merck.”

The letter included the warning: “There is a line that you can’t go across. … It had gone over that line.”

In response to questions from his boss, on January 23, 2001, Dr Sherwood wrote a memo saying there was no “orchestrated campaign or specific program” to deal with “problem individuals.”

But then he went on to discuss how he only gets involved if other Merck department heads are unsuccessful in their attempts to “balance” critics. “I will only get involved when our representatives… regional medical directors, Merck research lab physicians… or key individuals in the therapeutic business group have felt frustrated by their inability to reach out or to ‘balance’ selected individuals,” he wrote.

And he boasted about his own importance in dealing with officials at Universities. “Without trying to appear immodest,” Dr Sherwood wrote, “I believe I am the most respected physician in the pharmaceutical industry among academic chairs and deans…”

“Therefore,” he continued, “when I call them on a matter of urgent concern, they generally take it seriously… This has been a source of strength… as I have been able to exert balanced leverage in some difficult situations.”

This slew of internal documents have become a real problem for Merck’s legal team. In fact, in the first Vioxx jury trial decided on August 19, 2005, where a Texas jury awarded the widow of a Vioxx user $253.5 million, the plaintiff’s attorney, Mark Lanier, used many of them to show jurors how hard Merck worked to silence doctors like Dr Singh and the back and forth letters between Merck’s CEO and Dr Fries were very effective in accomplishing that task.

Prior to the trial, in June 2005, Merck’s legal team filed a motion with the court in a feeble attempt to suppress the leaked documents claiming a story in the “national media” had revealed a privileged attorney-client communication that could prejudice a jury against Merck after the Associated Press reported that Merck scientists had contacted company lawyers in 2000 about reformulating Vioxx over concerns it could cause cardiovascular problems.

So anyways, on November 18, 2004, when Dr Singh told the Senate committee, “I learnt that this was a persistent pattern of intimidation by Dr. Sherwood,” he obviously did not yet know the half of it.

But he did say that the harassment stopped after Dr Fries wrote to Merck’s CEO.

Dr Singh told the committee that he had objected to the way Merck published the results of the VIGOR study in the New England Journal of Medicine, because it minimized the significance of heart attacks, but prominently discussed the reduction of stomach bleeds in patients taking Vioxx.

He pointed out how Merck did not mention that patients on Vioxx had more serious adverse events, and more hospitalizations than patients on Naproxen.

But Merck’s misdeeds included more than omissions. Company documents obtained during the congressional investigation, show that in April 2000 Merck developed a “Cardiovascular Card,” and Merck’s sales reps were instructed to refer doctors who raised questions about cardiovascular risks to the card, which claimed that Vioxx was eight to 11 times safer than other similar painkillers.

The card made no reference to the VIGOR study and even though an FDA advisory committee had voted that doctors should be informed of the finding of the VIGOR study in 2001, Merck subsequently sent a memo to sales reps that stated, “Do not initiate discussions of the FDA arthritis committee… or the results of the… VIGOR study.”

In addition, sales reps were told to respond to doctors’ questions about the study by saying, “I cannot discuss the study with you”

In closing his testimony, Dr Singh said, he was especially annoyed when a few weeks before the November 18, hearing, “Merck announced that the published VIGOR data was “preliminary” and that the “final” data was presented to the FDA.”

“To the best of my knowledge,” he said, “the VIGOR paper did not indicate anywhere that the data were preliminary or incomplete.”

“Nor, did I ever see a correction or erratum indicating this fact,” he advised the panel, “up until a few weeks ago, almost 4 years later.”

He also criticized the fact that it took the FDA 2 years to add the heart attack risks to the Vioxx label, and noted that even then, the change supported mostly Merck’s position, not the one advanced by FDA’s own reviewers in public hearings.

“The FDA should regulate the drug companies,” he advised the panel, “not collaborate or negotiate with them if there is any question of public safety.”

Dr Singh also told the committee that it was important to recognize that the APPROVE study that led to the Vioxx withdrawal from the market, was not a safety study, it was an efficacy study, designed to add another indication for Vioxx treatment.

It was not a large enough study to detect a heart attack risk, he explained, “that it did find a risk was a lucky break for patients,” he said, “but this is not what it was designed to do.”

In addition, he told the panel that the FDA approval process needs to be open and subject to public scrutiny and that once a drug is approved, all the data supporting its approval should be put in the public domain.

And since an FDA reviewer had concerns about heart attacks before its approval, Dr Singh said, the FDA could have provided a conditional approval that would have required Merck to complete large safety studies within a certain time frame.

“The failure to conduct large long-term safety studies,” he told the committee, “subjected millions of patients over 4 years to a drug whose safety had been questioned by the FDA even before its approval.”

“This is not the proudest chapter in drug approval in the US,” he concluded.

A group of 12 attorneys, who were appointed by Federal District Judge Eldon Fallon to manage pretrial discovery for all federal lawsuits, has developed a Vioxx trial package that includes a guide for pursing a lawsuit against Merck and contains all the damaging documents and evidence available against the drug giant.

The package also includes parts of video statements made by top Merck officials, and courtroom slides with text and visuals.

It also includes the videotaped deposition testimony of expert cardiologist Dr Eric Topol, one of the first experts to raise questions about the safety of Vioxx and the first expert witness to experience the power of Merck’s wrath.

Shortly after learning that Vioxx had been recalled, in October 2004, Dr Topol, wrote an oped for the New York Times, and posted a column on the New England Journal of Medicine’s web site, and called for a congressional review of what he called the Vioxx “catastrophe.”

“The senior executives at Merck and the leadership at the FDA,” he wrote, “share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health.”

A little over a year later, Dr Topol, testified in a videotaped deposition, first played at a Houston jury trial on December 3, 2005, and said that Vioxx posed an “extraordinary risk,” and that he had urged Merck to conduct more trials.

Dr Topol said that after the 2000 VIGOR study showed patients using Vioxx faced an increased risk of a heart attack, he began his own evaluations after finding “discrepancies” between Merck’s studies and the data submitted to the FDA.

After analyzing 3 Vioxx studies, Dr Topol said he found patients began experiencing higher rates of heart problems “four to six weeks after the start of taking Vioxx.”

“There was not any question about” the link between Vioxx and heart ailments, he told the jury.

Dr Topol, testified that 3 years before the drug was pulled off the market, he and two colleagues published a paper in the Journal of the American Medical Association that raised the issue of whether Vioxx caused heart problems.

Dr Topol pointed out that although they published clear warnings about the cardiovascular risk in 2001, the FDA never ordered a trial to determine the extent of the problem and said Merck countered the JAMA article with a “relentless series of publications” and numerous papers in peer-reviewed medical literature written by Merck employees and consultants.

During his testimony, Dr Topol told the jury how a colleague at the Cleveland Clinic, Richard Rudick, had informed him that Raymond Gilmartin, the former CEO of Merck, had called the Cleveland Clinic board of trustees and complained about Dr Topol in mid-October 2004, after he criticized Merck’s handling of the Vioxx situation in the New York Times and New England Journal of Medicine.

He described how Mr Gilmartin called the chairman of the board, and said “what has Merck ever done to the Cleveland Clinic to warrant this?’

Dr Topol told the jury that Mr Gilmartin’s approach “appalled” him.

Two days after his deposition was played in court, Dr Topol found himself removed as provost and chief academic officer at the Cleveland Clinic medical school.

According to Dr Topol, he was told early in the morning not to attend a meeting of the clinic’s board of governors, because the position of chief academic officer had been abolished.

Dr Tope was somewhat vindicated later in December 2005, with the publication of an “Expression of Concern” by the editors of the New England Journal of Medicine, that charged that the VIGOR, published in the journal in 2000, was submitted to the journal after data on 3 heart attacks and other cardiovascular events among trial participants was deleted by Merck.

According to an article by Amanda Gardner in Health Day Reporter, right after Vioxx was removed from the market, the editors opened a computer diskette that had been submitted with the study and found a blank table with no data – lines had been drawn but not filled in.

“They did not know what should have been in there,” Sandra Jacobs, a spokeswoman for the NEJM said. “It raised some concern, but we didn’t know enough to act on it,” Jacobs added.

On November 21, 2005, Ms Garner says, NEJM’s executive editor, Dr Gregory Curfman, was deposed for a Vioxx trial and during the process, a July 5, 2000 memorandum came to light that indicated that at least 2 of the VIGOR authors knew of the problems 2 weeks before submitting the first of two revisions, and four-and-a-half months before the study was actually published.

Dr Curfman told HealthDay that electronic records showed “a pre-submission version of the study from which data, including the number of heart attacks and deaths, were deleted by a Merck editor two days before submission.”

As a dedicated scientist and health practitioner with nothing to gain, in hindsight, it appears that Dr Topol certainly paid a high price for committing the simple act of truth-telling to protect the public from a dangerous drug and its pusher.

As a small law firm practitioner turned legal reform activist, Attorney Zena Crenshaw is highly critical of Merk’s debilitating cross examinations of experts who essentially claim the company recognized Vioxx’s potential cardiac risks before it went on the market.

Ms Crenshaw is the Executive Director for National Judicial Conduct and Disability Law Project, Inc, a legal reform organization combating abuses of the American legal system that are facilitated by judicial misconduct.

She explains that such is a signature tactic of “mega-corporations” that it seems only “mega-lawfirms” and governmental agencies can neutralize.

Ms Crenshaw says, “the grueling questions help liken American courts to the playgrounds of bullies.”

“Some prescription drug manufacturers,” she says, “clearly bully scientists who challenge their products and ethics.”

“To survive the ordeal emotionally and with credibility intact,” Ms Crenshaw advises, “witnesses for alleged victims need to become smooth courtroom actors, as well as experts in their fields.”

“If the process is not appropriately bridled by judges,” she notes, “the “search for truth” will have much less to do with American jurisprudence than the “quest to win”.”

Merck’s SEC filings on April 27, 2006, list the following upcoming Vioxx trial dates:

Doherty New Jersey Superior Court, Atlantic County June 5, 2006

CA Coordinated California Superior Court, Los Angeles County June 21, 2006

Barnett Eastern District of Louisiana (MDL) July 24, 2006

Kozic Florida Circuit Court, Hillsborough County July 31 – August 25, 2006

Anderson Tribal Court of the Mississippi Band of Choctaw Indians August 7, 2006

Hatch / McFarland New Jersey Superior Court, Atlantic County September 11, 2006

Smith Eastern District of Louisiana (MDL) September 11, 2006

Crook Alabama Circuit Court, Jefferson County, October 26, 2006

Mason Eastern District of Louisiana (MDL) October 30, 2006

Miller or Rigby Texas District Court, Harris County, November 8, 2006

Dedrick Eastern District of Louisiana, (MDL) November 27, 2006

Merck Caught Misrepresenting Vioxx Risks Again

May 17, 2006

Evelyn Pringle

Although Merck has long maintained that the risks associated with Vioxx occur after long-term use, a recent study in the Canadian Medical Association Journal, says the drug may raise the risk of heart attack for patients taking Vioxx for less than 2 weeks.

The study published online this month, found that more than 25% of 239 patients who had heart attacks did so in less than 13 days of being on the drug.

The study followed patients for about two and a half years and included 30,200 Vioxx users and 45,000 Celebrex patients. It found no statistically significant increase in heart attack risk with Celebrex patients.

In addition, on May 12, 2006, Dr Steven Nissen, interim chairman of cardiology at the Cleveland Clinic in Ohio, said Merck recently misrepresented an analysis of data from a follow-up review of patients who participated in the 3-year study called, Approve, that led to Vioxx being pulled off the market on September 30, 2004.

“It’s important that we inform people about this because patients who have taken the drug will need increased surveillance by their physicians and increased awareness of their risks in the year subsequent to stopping the drug. And that risk may extend beyond a year; we simply don’t know,” Nissen told Reuters in a telephone interview.

“In the one year after Vioxx was stopped there was a 75 percent greater risk of having an adverse event,” he said.

“What this means is that, surprisingly, in the year following discontinuation of Vioxx the relative risk remains approximately as high as it was when people were actually taking the drug,” Dr Nissen explained. “That is very clear from the data,” he said.

Critics say the cozy relationship between the pharmaceutical industry and the FDA is evidenced by the large number of industry connected members on the agency’s advisory panels. A study conducted by the Public Citizen’s Health Research Group in the April 26, 2006 issue of the Journal of American Medical Association analyzed the transcripts of 221 FDA drug advisory panel meetings that involved 16 committees, listed on the agency’s web site as taking place between January 1, 2001 and December 31, 2004.

The analysis revealed that in 73% of the meetings, at least one member of the panel or one voting consultant disclosed a conflict, and yet only 1% of the members recused themselves from participating.

In all, 28% of committee members and voting consultants disclosed a conflict, the most common involving substantial financial dealings from consulting agreements, contracts or grants, and investments. For instance, the study found that 19% of the consulting agreements were worth over $10,000, 30% of the investments involved over $25,000, and 23% of contracts or grants exceeded $100,000.

In the case of Vioxx, ten of the 32 members on the FDA advisory committee that voted to allow the continued sale of Cox-2 pain drugs, including Vioxx, had previously acted as paid consultants for the drugs’ manufacturers.

And true to form, the members with industry ties voted to return Vioxx to the market. Dr Marcia Angell, a senior lecturer in social medicine at Harvard Medical School and author of “The Truth About the Drug Companies: How They Deceive Us and What to Do About It,” said in a March 10, 2005 editorial in the Boston Globe: “It is hard to see how the panel could have concluded that the benefits were worth those risks, especially given the fact that taking over-the-counter Prilosec in addition to an older pain reliever would probably have provided as much protection from stomach ulcers.”

Dr Angell says advisory committees should not include paid consultants for drug companies. “Their conflict of interest is real, not ‘potential’,” she wrote.

“The excuse that they are indispensable,” she says, “is not only self-serving but insulting to the experts who don’t consult for industry.”

However, in what critics call a rare occurrence, and no doubt because the agency was under intense public scrutiny, in this instance the FDA did not follow the recommendation of its advisory panel and Vioxx was not approved for a return to the market.

In light of the evidence of Merck’s total disregard for patient health that has surfaced in Vioxx litigation thus far, the public needs to take a good hard look at any proposed legislation or action by Congress or the FDA that would shield drug companies from accountability based on the FDA’s approval of a drug.

According to Attorney, Karen Barth Menzies, a partner in the Los Angeles based Baum Hedlund law firm, “the Vioxx public health debacle, has served to highlight deep-seeded problems within the FDA.”

She says, “drug companies are profit-driven and are loath to issue warnings about risks associated with their drugs, even those that become quite clear.”

“And it is precisely for this reason,” Ms Menzies says, “that the public is in such desperate need for an agency that advocates for them, rather than the drug industry.”

The FDA played a big part in the Vioxx disaster and allowed Merck to get away with murder. A new report released on April 24, 2006, by the Government Accountability Office is deeply critical of the FDA’s approach to drug safety and specifically Vioxx, and lists organizational dysfunction, bureaucratic politics, and ineffective enforcement over drug companies as factors compromising drug safety.

The report was commissioned by Senator Charles Grassley (R-Iowa), in response to findings at a November 18, 2004, Senate Finance Committee hearing titled, “FDA, Merck and Vioxx: Putting Patient Safety First,” where reports of mismanagement surfaced regarding the FDA’s failure to implement safety measures to protect the public against the dangers of Vioxx.

Citing “recent controversy about drug safety,” the report illuminates the weaknesses of the FDA in monitoring the safety of drugs once they are approved.

The report states that the FDA “lacks a clear and effective process for making decisions about, and providing management oversight of, postmarket drug safety issues.”

It highlights the communication problems between the two FDA offices that handle postmarket safety concerns and advises that “insufficient communication” between the Office of Drug Safety and the Office of New Drugs “has hindered the decision-making process.”

“Specifically,” the GAO wrote, “ODS management does not always know how OND has responded to ODS’s safety analyses and recommendations.”

Ms Menzies says the FDA has sided with industry for years. “The recent GAO report,” she says, “confirms many of the problems that we have been shouting about for years and illustrates that, contrary to FDA’s preemption arguments, FDA’s decisions must be second-guessed for the safety of the public.”

The report comes almost two years after the hearing that revealed the FDA had not acted promptly to protect the public when it first became aware of information that Vioxx might pose risks to cardiovascular health.

The Senate Finance Committee got involved in the Vioxx matter because it has jurisdiction over the Medicare and Medicaid programs. “Accordingly,” Senator Grassley informed the audience at the start of the November 18, 2004 hearing, “the committee has a responsibility to the more than 80 million Americans who receive health care coverage — including prescription drugs — under these programs.”

“Of the 20 million Americans who reportedly took Vioxx, an untold number are Medicare and Medicaid beneficiaries,” he advised. “I was told that the Medicaid program paid in excess of $1 billion for Vioxx while Vioxx was on the market,” he said.

To demonstrate the value of government payments to Merck, at the beginning of the hearing, Senator Grassley described a June 4, 1999 Merck document titled “IN IT TO WIN IT” that said: “As of yesterday, Vioxx became reimbursable on Medicaid in 42 states with the other 8 states close behind.”

“The Medicaid market was clearly going to be a money maker for Merck,” he said, “and Medicaid has paid Merck well for Vioxx.”

When the FDA approves a drug, Senator Grassley said, it’s considered a “Good Housekeeping Seal of Approval.”

“However,” he told the audience, “what’s come to light about Vioxx since September 30th makes people wonder if the FDA has lost its way when it comes to making sure drugs are safe.”

It looks like the FDA, he said, allowed itself to be manipulated by Merck on labeling changes that became necessary after a review by Merck that’s known as the VIGOR trial.

He explained how Merck completed the VIGOR trial in March 2000 and gave the findings to the FDA in June 2000, and was the subject of an advisory board meeting in February 2001. “But it was April 11, 2002,” he told the audience, “before the Vioxx label was actually changed.”

“During these 22 months,” Senator Grassley said, “Merck aggressively marketed Vioxx, knowing that consumers and doctors were largely unaware of the cardiovascular risks found in the VIGOR trial.”

The bottom line is, consumers should not have to second guess the safety of what’s in
their medicine cabinets,” he said. “The public should feel confident that when the FDA approves a drug, you can bank on it being safe, and if a drug isn’t safe, the FDA will take it off the market.”

The first witness called to testify at the hearing, was Dr David Graham, a scientist with an 18 year career at the FDA, who blew the whistle on the FDA’ s handling of the safety issues related to Vioxx.

Right off the bat, he warned the committee: “we, are faced with what may be the single greatest drug safety catastrophe in the history of this country or the history of the world.”

He called the Vioxx tragedy “a profound regulatory failure.”

“It is important,” Dr Graham said, “that this Committee and the American people understand that what has happened with Vioxx is really a symptom of something far more dangerous to the safety of the American people.”

“Simply put,” he told the panel, “FDA and its Center for Drug Evaluation and Research are broken.”

Dr Graham discussed the studies that demonstrated that Merck and the FDA were aware of the Vioxx risks since before the drug was approved.

He told the panel of a Merck study named 090, that found a nearly 7-fold increase in heart attack risk with low doses of Vioxx conducted before the drug was approved and yet the labeling at the time of FDA approval said nothing about the risks.

In November 2000, he said, the VIGOR study found a 5-fold increase in heart attack risk with high-doses of Vioxx and yet the company said Vioxx was safe.

In fact, it was not until about 18 months after the VIGOR trial was published, that the FDA made a label change to include the heart attack risk, but even then the agency did not place it the “Warnings” section.

“Of note,” Dr Graham told the committee, “FDA’s label change had absolutely no effect on how often high-dose Vioxx was prescribed, so what good did it achieve?”

He informed the panel that a large study in 2002 also reported a 2-fold increase in heart attack risk with high-doses of Vioxx.

In March of 2004, he said another study determined that both high-dose and low-dose Vioxx increased the risk of heart attack and sudden death.

In this study, users of Vioxx were compared with users of another COX-2 inhibitor, Celebrex. The analysis found that Vioxx at doses of 25 mg or less daily was associated with a 50% increase in the risk of heart attack; and doses of greater than 25 mg daily were associated with a 370% increase in the risk of heart attacks.

Yet a report describing these findings was not posted on the FDA website until November 2004, on election day.

“In my opinion,” Dr Graham said, “the FDA has let the American people down, and sadly, betrayed a public trust.”

In regard to injuries, Dr Graham told the panel that Dr Eric Topol of the Cleveland Clinic estimated that there were up to 160,000 cases of heart attacks and strokes due to Vioxx, in an article published in the New England Journal of Medicine.

“This article,” Dr Graham said, “lays out clearly the public health significance of what we’re talking about today.”

At the November 18, 2004 hearing, to illustrate the significance of 100,000 people being affected by Vioxx, Dr Graham presented charts to show that when looking at Florida or Pennsylvania, it would mean that 1% of the entire population would have been affected. For Iowa, the charts showed it would be 5%, for Maine 10%, and for Wyoming 27%.

“If we look at selected cities,” Dr Graham told Senator Grassley who resides in Des Moines, Iowa, “67% of the citizens of Des Moines would be affected, and what’s worse,” he continued, “the entire population of every other city in the State of Iowa.”

The VIGOR study started in January 1999, and included patients over 40, with rheumatoid arthritis who were given either Vioxx or Naproxen. Patients with recent cardiovascular events and patients taking aspirin were excluded from the study.

In the combined outcome of all cardiovascular deaths, heart attacks and strokes, Vioxx patients had higher rates than Naproxen patients. For the outcome of heart attack alone, the rate was five times higher in Vioxx patients than in Naproxen patients

In 1000 patients followed for one year, Vioxx treatment was found likely to be associated with 6 more heart attacks than Naproxen treatment.

Dr Graham said he became concerned about the public health risk after the VIGOR study indicated that the heart attack risk was increased 5-fold in patients who used the high-dose strength of Vioxx.

The safety question was important he explained because (1) Vioxx would be used by millions of patients; (2) heart attack is a fairly common event; and (3) even a small increase in risk could mean that tens of thousands of patients might be seriously harmed or killed.

“If these three factors were present,” Dr Graham said, “I knew that we would have all the ingredients necessary to guarantee a national disaster.”

To get answers, he worked with Kaiser Permanente in California to perform a study that took nearly 3 years to complete and concluded that high-dose Vioxx significantly increased the risk of heart attacks and sudden death and should not be prescribed or used by patients.

“This conclusion,” Dr Graham said, “triggered an explosive response from the Office of New Drugs, which approved Vioxx in the first place and was responsible for regulating it postmarketing.”

The response from senior management in the Office of Drug Safety was equally stressful he said. “I was pressured to change my conclusions and recommendations,” he told the panel, “and basically threatened that if I did not change them, I would not be permitted to present the paper at the conference.”

In fact, one Drug Safety manager recommended that he should be barred from presenting the poster at the meeting, and also said that Merck needed to know about the study results.

Finally, he said they wrote a manuscript for publication in a peer-reviewed medical journal and senior managers in the Office of Drug Safety would not grant clearance for its publication, even though it was accepted by a prestigious journal after rigorous peer review.

“Until it is cleared,” Dr Graham told the panel, “our data and conclusions will not see the light of day in the scientific forum they deserve and have earned, and serious students of drug safety and drug regulation will be denied the opportunity to consider and openly debate the issues we raise in that paper.”

As for the FDA conduct in responding to the studies that showed the dangers of Vioxx, Dr Graham discussed what he referred to as two “revelatory milestones,” in 2004.

“In mid-August,” he said, “despite our study results showing an increased risk of heart attack with Vioxx, and despite the results of other studies published in the literature, FDA announced it had approved Vioxx for use in children with rheumatoid arthritis.”

“Also, on September 22,” he told the committee, “at a meeting attended by the director of the reviewing office that approved Vioxx, the director and deputy director of the reviewing division within that office and senior managers from the Office of Drug Safety, no one thought there was a Vioxx safety issue to be dealt with.”

At this meeting, the reviewing office director asked Dr Graham why he had even thought to study Vioxx and heart attacks because the FDA had made its labeling change and nothing more needed to be done.

At the same meeting, a senior manager from ODS labeled the latest Vioxx study conducted by Dr Graham’s team, “a scientific rumor.”

“Eight days later,” Dr Graham told the panel, “Merck pulled Vioxx from the market.”

“My experience with Vioxx is typical of how CDER responds to serious drug safety issues in general,” he said.

On December 31, 2004, Dr Graham told Inter Press Service that the Vioxx debacle did not phase the FDA. “You have an agency in denial,” he said in the interview with IPS, “the FDA still maintains it made no mistake in the approval or regulation of Vioxx.”

He said, “intimidation of scientists who threaten the status quo at FDA is routine,” and described how, his FDA superior reacted after he sought withdrawal of another arthritis drug called Arava.

“The division director spent the first 10 minutes of that meeting screaming at me,” he said. “Basically, standing up, jugular veins bulging in his neck, eyes sort of bugging out of his head, screaming,” he recalled, “basically trying to intimidate me so that I’d change my conclusion.”

In fact, once Dr Graham went public, history shows that there was a full-court press by FDA officials against the agency Whistleblower.

Dr Steven Galson, the acting director of the FDA drug-evaluation division at the time, told reporters that Graham’s work “constitutes junk science,” and sent an email to an editor at the British medical journal The Lancet, questioning the “integrity” of Dr Graham’s data.

Acting FDA commissioner, Dr Lester Crawford, accused Dr Graham of evading the agency’s “long-established peer review and clearance process,” and another agency official made calls to a Senate staffer, disparaging Dr Graham personally and professionally.

Before the testimony even began at the November 18 hearing, Senator Grassley responded to comments issued the night before by Dr Crawford against Dr Graham.

“News reports today,” Senator Grassley noted, “say the FDA is calling Dr. Graham a “a maverick who did not follow Agency protocols.”

Dr. Graham, he explained, completed an FDA sponsored three-year study under FDA guidance and with Drs. Campen, Levy, Shoor, Ray, Cheetham, Spence and Hui. Dr. Graham’s immediate supervisor said the paper that formed the basis of the study was “… an excellent study and analysis of a complex topic.”

“So the clarifications provided last night by Dr. Crawford,” Senator Grassley said, “appear intended to intimidate a witness on the eve of hearing.”

Dr Crawford knows there’s a problem, he told the audience, “and would better serve the FDA by spending time on the problem rather than going after congressional witnesses who helped identify the problem in the first place.”

Earlier in the year, on March 10, 2005, Senator Grassley gave a speech to the Consumer Federation of America and praised the FDA whistleblower and described how the FDA stonewalled concerns raised by Dr Graham after a study found an increased risk of heart attacks and strokes with Vioxx and said:

“Dr. Graham warned the FDA of the cardiovascular risks of Vioxx, the FDA approved the use of Vioxx for children. The director of FDA’s office of new drugs suggested that Dr. Graham water down his Vioxx conclusions. Dr. Graham replied that in good conscience he could not. When Dr. Graham was asked to present his findings at my committee’s Vioxx hearing, he was also undermined.

“Dr. Graham did testify before the advisory committee and his science was subjected to public scrutiny from his peers. … In the end, the scientific process prevailed. But again, not before Dr. Graham’s supervisors attempted to intercede.”

In the speech, Senator Grassley said FDA whistleblowers are patriots.

“Think about the guts it takes to undermine your career,” he said, “and to go against your supervisors at a huge federal agency, and in this case, the multi-billion-dollar drug companies.”

“Whistleblowers are the rare birds who refuse to go along to get along,” he told the audience. “The only thing they’re guilty of is “committing truth,” he said.

“Unfortunately,” Grassley told the audience, “it appears that some drug companies are placing greed ahead of drug safety. In this fraudulent environment, the FDA’s mission is more important than ever before. The FDA absolutely has to do a top-notch job on ensuring drug safety,” he said.

The FDA “needs to demonstrate that it is unequivocally committed to the scientific process – and those who speak up on its behalf — when it comes to drug safety and that nothing gets in the way of that, whether it’s pressure from profit-oriented drug makers or institutional ego that doesn’t want to admit a mistake,” Grassley warned.

“The one and only client of the FDA must be John Q. Public,” he declared.

Four months later, on July 18, 2005, Senator Grassley took to the floor of the Senate to explain why he would vote against the nomination of Dr Crawford to head the FDA, and gave a caustic speech about the FDA’s relationship with drug companies as a whole, and Dr Crawford’s conduct in the position of a temporary commissioner, and said in part:

“During the last 18 months, this country’s confidence in the FDA has been shaken. It has been shaken not because of one isolated incident or one isolated whistleblower. It has been shaken because multiple drug safety concerns have been exposed by more than one courageous whistleblower.

“My oversight of the FDA leads me to the conclusion that there are cultural and systemic problems at the FDA. Unfortunately, Dr. Crawford has long been part of that same culture and system. The evidence is overwhelming that the FDA must change to better protect the American people. Dr. Crawford does not appear willing to be the man to change the FDA.

“During Dr. Crawford’s tenure, I have witnessed the suppression of the scientific process and the muzzling of scientific dissent. First, with Dr. Mosholder finding a link between anti-depressants, children and suicide. And second with Dr. Graham’s allegations regarding the FDA, Vioxx and post-marketing safety generally.

“Dr. Graham’s testimony before the Finance Committee suggests that the problems are systemic. Oversight of the FDA exposed the cozy relationship that exists between the FDA and the drug industry. It revealed that the FDA negotiated for almost two years with Merck about how to change the Vioxx label so people would know about the risk of heart attacks.”

In the end, Dr Crawford did become the FDA Commissioner in July 2005, but not for long. This Lester Crawford saga gives to new meaning to the phrase of “what goes around comes around.”

After less than 3 months on the job, in a September 23, 2005 letter to President Bush, Crawford announced his resignation from the FDA and said it was “effective immediately.”

In public, Crawford explained his departure by saying it was time for someone else to lead the agency. On September 28, 2005, reported that Crawford said he decided to leave the agency because he was tiring after three years at the agency. “He denies that financial conflicts of interest had anything to do with his decision to resign,” Forbes noted.

However, Senators Mike Enzi (R-Wyo) and Edward Kennedy (D-Mass) disputed that claim and asked the HHS Inspector General to investigate Crawford’s resignation to see whether he left due to an undisclosed financial conflict of interest.

Less than a month later, on October 26, 2005 the Wall Street Journal reported that as late as 2004, Crawford or his wife “owned stock in companies that make or distribute products regulated by the agency.”

According to the Journal, Crawford or his wife held shares in several companies whose business is regulated by the FDA, as late as 2004, when Crawford was acting commissioner, quoting financial disclosure forms obtained by the Journal.

When Crawford began work at the FDA in 2002, the Journal said, he held stock in many companies, including Merck, Pfizer, and Johnson and Johnson. But he told ethics officials that he sold those stocks in 2002, along with stock he held in Kimberly-Clark, which makes medical devices.

Crawford also reported the sale of his stock in the company Teleflex Inc in 2002, which also makes medical devices, although “later forms show that he or his wife continued to own some shares,” the Journal reports.

On the same day that the Journal’s article was published, the Kaiser Daily Health Policy Report reported that the HHS Inspector General had confirmed that it had launched an investigation into Crawford’s departure from the FDA.

About 3 months after that, on February 8, 2006, Crawford’s new employer was revealed when the Washington Post reported that Crawford, “whose sudden resignation last fall after less than three months in office remains a mystery, has joined a lobbying firm that specializes in food and drug issues.”

“Crawford is listed as “senior counsel” to the firm Policy Directions Inc.” the Post said.

A few of the firm’s clients listed in the article, include Merck, Altria Group Inc, formerly Philip Morris Companies, and the industry’s trade group, the Pharmaceutical Research and Manufacturers of America.

According to the Post, “Crawford is barred from lobbying former colleagues at the FDA for a year, but he can give clients strategic advice about food and drug issues and can lobby members of Congress.”

Less than a month later, on March 3, 2006, the Houston Chronicle reported that before he abruptly resigned, Crawford sold more than $50,000 in shares of Teleflex Inc, “a company that makes medical devices, according to financial disclosure forms” obtained by The Associated Press.

“As head of the FDA,” the Chronicle noted, “Crawford oversaw the regulation of medical devices.”

And on April 29, 2006, the Washington Post reported that the “former commissioner of the Food and Drug Administration is under federal investigation amid accusations of financial improprieties and making false statements to Congress.”

The criminal investigation was disclosed at a hearing in a civil suit filed against the FDA over its handling of the emergency contraceptive Plan B, according to the Wall Street Journal on May 1, 2006. It seems Crawford was scheduled to be questioned under oath in the trial, but his attorney Barbara Van Gelder asked for a delay, saying she would instruct Crawford to invoke his Fifth Amendment rights.

Van Gelder said that Crawford is under criminal investigation and that the issue of his financial disclosures “is within the grand jury.”

As for how things are going these days for Dr Graham, in April 2006, he was interviewed by Life Extension Magazine and described his life as “surreal” since the Vioxx scandal broke and discussed what its like to face the same people every day who tried to destroy him for simply telling the truth.

“It’s very difficult,” he said. “I periodically have to sit down with supervisors who I knew in November were lying to Congress about me, lying to The Lancet about me, and who tried to prevent my getting protection as a government whistleblower.”

“They were doing hateful things,” he explained, “and now they pretend nothing happened.”

Dr Graham did say that the mistreatment comes only from senior management. “At the staff level,” he said, “I’m very respected and supported.”

“If anything, esteem for me has increased because they realize I told the truth,” he told Life Extension. “They know the reality of what we’re dealing with.”

In April 2006, in what has to be one of Merck’s worst nightmares, a federal judge ordered Dr Graham to testify at a deposition in the Vioxx multidistrict litigation. The MDL was created to consolidate pretrial proceedings for the thousands of lawsuits filed by users of Vioxx.

The FDA attempted to block Dr Graham’s testimony by filing a motion to quash the Plaintiff’s subpoena on grounds that his deposition would divert the agency’s time and resources, and cripple its ability to fulfill its statutory mandate, and said there was no need to depose Dr Graham, given his public statements already made.

However, Judge Eldon Fallon denied the motion and said: “This court does not see how the deposition of one employee during nonworking hours would cripple the FDA’s ability to function.”

He also noted that none of the documents in the public record could “express Dr. Graham’s opinion with the clarity and tone as he personally can in his deposition.”

Latest Celebrex Court Ruling 50/50

Evelyn Pringle September 18 2006

According to Pfizer, Celebrex is still selling like hot cakes with worldwide sales of $471 million in the second quarter of 2006, representing growth of 17% over the same period last year, with sales in the US of $355 million.

“We continue to expect full-year Celebrex revenues of at least $2 billion, an ambitious target given the ongoing pressures in the arthritis market,” Pfizer told shareholders in its Second Quarter 2006 SEC filing.

Notwithstanding the fact that the FDA asked Pfizer not to run ads to promote more use of Celebrex, and that the company previously granted that request, Pfizer is right back at it. In April 2006, it began advertising Celebrex “in alignment with our new Direct-to-Consumer (DTC) advertising principles, highlighting Celebrex’s unique clinical profile and benefits,” Pfizer wrote in its First Quarter 2006 SEC filing.

Celebrex is a COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) used for pain relief, marketed and sold by Pfizer, Pharmacia, and GD Searle. Over the past several years, these drug makers have been hit by a massive number of lawsuits filed all over the US.

A majority of plaintiffs are represented in class actions. The procedure for filing a class action is to file suit with one or several named plaintiffs on behalf of a putative class which must consist of a group of individuals or entities that have suffered a common wrong.

Several putative class actions have been filed by consumers seeking damages from the purchases of Celebrex as a result of Pfizer’s deceptive marketing scheme. In September 2005, all of the purchase claims, as well as the product liability personal injury actions, were transferred to Judge Charles R Breyer in the US District Court for the Northern District of California, by the Multi-District Litigation Panel, In Re: Bextra and Celebrex Marketing Sales Practices and Product Liability Litigation, MDL Docket No 1699, No 05-1699, (ND CA)

At the plaintiffs’ request, the court allowed the filing of a Purchase Claims Master Celebrex Complaint which includes four claims for relief: (1) RICO; (2) state consumer protection laws; (3) unjust enrichment; and (4) breach of warranty.

The complaint seeks damages on behalf of a national class of all Celebrex End-Payors located in the US, including Consumers and Third-Party Payors who purchased and/or paid for Celebrex not for resale during the period from December 1, 1998 through the present.

The Prescription Access Litigation Project filed a Celebrex class action in California in February 2005, as well as a nationwide case in April 2005, which are included in the MDL proceeding.

PAL plaintiffs allege that, to increase its sales, Pfizer launched a massive deceptive advertising campaign to convince consumers that Celebrex was a premium drug that offered significant benefits over older, cheaper pain relievers. When in fact, PAL alleges, not only did Celebrex offer no safety benefits to the majority of consumers, it actually increased their risk of death from a heart attack or stroke.

According to PAL, in December 2004 and in February 2005, Pfizer disclosed two separate studies showing that Celebrex users have an increased risk of cardiovascular events and that had Pfizer revealed the risks of Celebrex, of which it was aware since 1999, consumers would not have been willing to pay the high price for Celebrex.

PAL alleges that Pfizer convinced consumers to pay a higher price than they would have paid if they had known the risks, if they would have purchased Celebrex at all. The suits seek recovery for consumers who purchased Celebrex at the inflated price made possible only by Pfizer’s massive deceptive advertising campaign.

The plaintiffs specifically allege that the marketing scheme was deceptive because Pfizer (1) suppressed data showing the cardiovascular risks associated with Celebrex; (2) falsely claimed that Celebrex caused fewer gastrointestinal side effects than traditional NSAIDs; and (3) falsely claimed that Celebrex provided superior pain relief and safety over traditional NSAIDs.

The plaintiffs maintain that as a result of the marketing success, Pfizer was able to sell Celebrex “at a premium price over NSAIDs and to have it become a standard treatment option as opposed to use of less expensive NSAIDs.”

According to the lawsuits, Celebrex sells for $2.53 to $6.45 per day, depending upon the dose, while NSAIDs sell for $0.21 to $0 .31 per day.

The plaintiffs allege that if Pfizer had not engaged in the wrongful marketing, advertising and promotion of Celebrex, they would have paid for other equally effective and less expensive medication.

On March 31, 2006, Pfizer filed a motion to dismiss the case. Plaintiffs opposed the motion, and a hearing and status conference was held on June 30, 2006.

In moving to dismiss the failure-to-warn claims, Pfizer argues that the claims are preempted because they conflict with the Food, Drug and Cosmetic Act (“FDCA”) and the authority of the Food and Drug Administration (“FDA”) to regulate warnings about prescription medicine and the promotion of such medicine.

On August 16, 2006, the Court ruled that claims that Pfizer failed to warn about the cardiovascular risks were preempted by the FDA’s authority to determine prescription drug labels, and that those claims were dismissed but with permission for plaintiffs to amend the complaint.

In opposing the motion, the plaintiffs argued that because the FDA’s preemption statement appears in a preamble to a Final Rule, and is not itself a regulation or even an interpretative rule, the Court should ignore the FDA’s view.

The plaintiffs asserted that Congress had not delegated authority to the FDA to opine on the preemptive effect of its regulations. However, the court ruled that Congress has delegated the responsibility for administering the FDCA to the FDA, and that such responsibility implies the authority and expertise to determine which state laws conflict with its regulations.

The plaintiffs asked the court to consider the inconsistency of the FDA’s position when determining what weight to give the current preemption view and highlighted the FDA’s statements in 1998, that its labeling regulations establish minimum standards, and that in 2000, when the FDA published the proposed drug labeling rule to which the preemption preamble is now attached, that the FDA determined that the proposed labeling rule does not preempt state law.

The following year, the plaintiffs argued, only after a change in administrations, did the FDA begin for the first time to submit amicus briefs arguing in favor of preemption.

The court noted the drastic change but said it made no difference. “While the FDA’s current view of the preemptive effect of its labeling regulations is a 180-degree reversal of its prior position,” the Court stated, “the Supreme Court has recognized that an agency’s view of the preemptive effect of its regulations may change over time as the agency gains more experience with the interrelationship between its regulations and state laws.”

“Moreover,” the judge continued, “the Supreme Court has never held that a court may not give weight to an agency’s view of the preemptive effect of its own regulations simply because that agency’s view changed contemporaneously with a change in administration.”

The plaintiffs also unsuccessfully argued that the FDA’s failure to comply with Executive Order 13132, regarding consultation with local officials about a possible conflict with state law should be considered.

The court disregarded plaintiffs’ allegation that Pfizer withheld material cardiovascular risk data from the FDA, saying it “does not change the preemption analysis.” The law is well established that a claim premised on a drug manufacturer’s failure to provide data to the FDA is preempted, the court wrote citing a US Supreme Court case.

“Plaintiffs’ state law failure-to-warn-claims,” the judge said, “conflict with the FDA’s determination of the proper warning and pose an obstacle to the full accomplishment of the objectives of the FDCA.”

In its conclusion, that court stated that, “Plaintiffs’ claims that Pfizer’s promotion of Celebrex was unlawful because it failed to warn of the drug’s cardiovascular risks are preempted because they conflict with the FDA’s determination of what warnings are substantiated by the scientific evidence.”

“Accordingly,” the court ruled, “the failure-to-warn of cardiovascular risk claims are dismissed with leave to amend.”

A point not mentioned that indicates the court’s faith in the FDA’s ability, or inclination, to protect the public against dangerous drugs promoted by profit driven drug makers is misplaced, is the fact that it took the FDA two years to negotiate a label change to warn consumers about Vioxx during which time, the FDA’s own career scientist, Dr David Graham, said tens of thousands of people were needlessly injured or killed.

Legal experts say its difficult to gauge how the California decision will effect other Celebrex cases because different judges in different states can mean different results.

According to attorney, Ted Parr, of the Washington DC firm, Ury & Moskow, “State court judges are likely to reach conclusions regarding preemption that are inconsistent, both with the federal court and with each other to some extent.”

“Some cases will be dismissed, and others will not,” he states.

For instance, he points to the Pennsylvania Paxil case, Colacicco v Apotex, Inc, where the court dismissed the entire lawsuit, since, under Pennsylvania state law, failure-to-warn is the only cause of action available.

On the other hand, in another Pennsylvania case, Mingus v Wyeth, Mr Parr states, “the plaintiff withdrew her failure-to-warn claim and agreed to proceed only on claims for negligence and strict product liability based on design defect under Ohio law; in that case, the court denied the defendant’s preemption motion.”

“We really do not know yet,” he advises, “how extensive the preemption problem will be nationwide.”

“Two federal courts in the 8th Circuit have rejected preemption motions,” he points out.

The fact that studies might come out, like has happened in Vioxx litigation, that show Pfizer knew about the heart risks might not even make a difference, according to Mr Parr.

“The defendants will no doubt argue that the FDA’s enforcement mechanisms are exclusive,” he explains. “Therefore, even if it were shown that Pfizer engaged in outright willful fraud,” he said, “the plaintiffs’ claims could still be dismissed.”

As for whether all Celebrex plaintiffs will be permitted to amend their complaints, the answer is once again a mixed bag. “Some plaintiffs may have an opportunity to amend their claims;” Mr Parr states, “others will not, depending upon the interpretation of preemption and decision of the court and differences in state laws.”

In moving for a dismissal of the GI claims, Pfizer argued that the plaintiffs’ theory of liability, that Pfizer falsely claimed that Celebrex had fewer GI complications than other NSAIDs, and was more effective, was preempted because it stands as an obstacle to the accomplishment of the objectives of the FDCA.

Pfizer maintained that the FDA requires companies to submit all advertising to the
FDA’s Division of Drug Marketing, Advertising, and Communications, and that the
DDMAC reviews the ads for compliance, and has the authority to require a company to stop running a particular ad or to run a corrective promotion.

According to Pfizer, the FDA has “necessarily determined” that the unobjected to ads are accurate and strike a fair balance between the benefits and risks of Celebrex; therefore, any claim that such ads were deceptive conflicts with the FDA’s determination and are impliedly preempted.

The court acknowledged that Pfizer has submitted its challenged ads to DDMAC and, with a few exceptions, the DDMAC did not object to the ads.

However, the judge stated, “there is nothing in the record from which the Court could conclude that the FDA has actually reviewed all of the submitted advertisements, let alone conclude that the FDA’s review means that it has definitively determined that the advertisement was not misleading.”

The court pointed out that the FDA’s silence is significant here because when “the FDA believes that its regulations preempt state law it says so.”

“The FDA has been silent with respect to the preemption of lawsuits challenging false claims in prescription drug advertisements,” the court wrote. “This silence suggests that the FDA does not intend its review of promotional materials to preempt false advertising claims.”

The plaintiffs’ claims are premised on the assertion that the ads imply that Celebrex is superior to other NSAIDs because it has fewer GI symptoms, a claim which the FDA expressly determined would be false and misleading.

Pfizer argues that particular ads identified in the complaint are consistent with the FDA-required label and therefore any claims based on those ads are preempted.

Pfizer is actually arguing, the judge said, that certain ads were not misleading as a matter of law, that the ads do not imply GI superiority or greater efficacy than other NSAIDs.

The court said it declined to make such a determination on the limited record and briefing currently before the Court.

Pfizer also argued that the FDA should initially decide whether the ads are misleading because plaintiffs’ claims fall within the “primary jurisdiction” of the FDA.

The court determined that the false advertising claims do not implicate the primary jurisdiction doctrine. “The issue is not whether Celebrex has fewer GI complications than other over-counter NSAIDs;” the court stated, “the FDA has already determined that it does not.”

“The issue,” it explained, “is whether contrary to the FDA’s findings, Pfizer nonetheless falsely claimed that Celebrex was superior.”

Courts and juries frequently decide similar false advertising claims, the court noted.

In its conclusion, the court stated that, “Pfizer has not established that the FDA has determined that all of Pfizer’s promotional material strikes a “fair balance” and are not false and misleading.”

“Accordingly,” the court ruled, “Pfizer’s motion to dismiss the false advertising claims on conflict preemption grounds is denied.”

There is certainly ample evidence to present to a jury to back up the claims that the Celebrex makers engaged in false advertising and over-promotion of Celebrex, within the walls of the various FDA offices alone.

First off, Pfizer’s claim that Celebrex ads were preapproved by the FDA is dead in the water. On December 1, 2005, Tom Abrams, director of the DDMAC, said in an interview for Pharmaceutical Executive that although FDA regulations require companies to submit advertising material at the time of first use, his office receives an average of 53,000 promotional items a year and his staff of 35 cannot handle that volume of screening.

“DDMAC has limited resources and we use our limited resources as effectively as we can to do our job,” he said.

In fact, Mr Abrams says the biggest misconception is that the FDA approves all ads before they are released, and most ads are launched without the agency reviewing them. In fact he states, “Often, we’re seeing it at the same time as the American public.”

According to Mr Abrams, when the FDA determines that an ad violates regulations, the agency sends the company either a notice of violation letter or a warning letter. Notice letters are issued for the least serious offenses and warning letters are issued for serious or repetitive violations and request that the company stop the promotion, and disseminate corrective messages.

FDA records show that Celebrex received seven citations for false or misleading promotions between 1997 and 2005. In 1997, before Celebrex even obtained FDA approval, the FDA accused Celebrex maker at the time, GD Searle, of touting the drug on the internet as “a breakthrough in arthritis therapy,” and suggesting that it caused no gastrointestinal bleeding.

The claim of no gastrointestinal risks was not approved for the label when the FDA approved Celebrex and yet, Searle, Pharmacia and Pfizer, have each been cited for stating or implying in promotional materials that Celebrex worked better than other pain relief drugs because it posed no gastrointestinal risks.

In fact, when the FDA approved Celebrex it specifically warned that any promotional activities “that make or imply comparative claims about the frequency of clinically serious GI events compared to NSAIDs or specific NSAIDs will be considered false and/or misleading . . .”

Furthermore, the FDA required the Celebrex label to include the warning that “serious gastrointestinal toxicity can occur at any time, with or without warning symptoms, in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs).”

In 2005, the FDA required the Celebrex label to include a boxed warning stating: “NSAIDs, including CELEBREX, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.”

Claims that portray Celebrex as a superior pain reliever are also false and misleading because the FDA has stated that, “none of the comparative studies with naproxen, ibuprofen, and diclofenac to-date has been designed to demonstrate superiority or a specified degree of similarity in a rigorous way.”

One Celebrex TV ad found to be false and misleading promoted the drug for use in treating osteoarthritis or rheumatoid arthritis, and shows a woman playing a guitar with a voice-over saying, “With Celebrex, I will play the long version.” The FDA sent Pfizer a “warning” letter on this ad stating:

“While the Guitar TV ad suggests a direct benefit to this patient’s wrist/hand/finger joints related to movement and flexibility, it fails to state the actual approved indication (e.g., relief of signs and symptoms of osteoarthritis).”

The FDA also pointed out that this ad failed to include any risk information about Celebrex, thus omitting the major side effects and contraindications, and said the omission of this information implies that there are no risks, which overstates the drug’s safety.

The FDA determined that another TV ad was misleading and warranted a warning letter that began with the announcement: “Celebrex presents, arthritis tips.”

The ad features a woman dressed as doctor stating: “Arthritis is the most wide-spread crippling disability in the United States today. Arthritis is the predominant cause of activity limitations and is a major determinate of nursing home institutionalization for the elderly.”

“One out of every 7 people and 1 in every 3 families is affected by arthritis,” the ad states. “If you feel any pain or discomfort in your joints, contact your local doc.”

The commercial concludes by saying: “These arthritis tips have been brought to you by Celebrex.”

The FDA said that this ad is product-specific, and misleading because it omits important information about the drug’s safety and effectiveness and makes unsubstantiated claims. The FDA said the ad promotes Celebrex by name at the beginning and end and that using the term arthritis tips clearly suggests that the drug is an arthritis treatment.

The totality of this presentation, the FDA letter advised, suggests that Celebrex is an effective treatment for preventing or modifying the progression of arthritis, such that crippling disability and nursing home institutionalization may be avoided, when in fact, Celebrex is indicated only for relief of the signs and symptoms of OA and RA and is not indicated for disease modification (i.e., altering the course of the progression of arthritis).

“Moreover,” the FDA said, “we are not aware of substantial evidence or substantial clinical experience demonstrating that treatment with Celebrex will prevent crippling effects or disability due to arthritis or prevent nursing home institutionalization of elderly patients with arthritis.”

“Therefore,” the letter warned, “your Arthritis Tips TV ad greatly overstates the proven benefits of Celebrex.”

The FDA also noted that the ad fails to disclose any risk information and omits the major side effects and contraindications, including warnings and precautions, which implies that there are no risks to the patient who takes Celebrex, thus overstating its safety.

In the same letter the FDA warmed that a Celebrex print advertisement also made unsubstantiated claims with respect to less expensive alternative drugs. The print ad features the headline “Strength They Can Stay With” and shows a chart comparing Celebrex, Ibuprofen and Naproxen, titled “6-Month Patient Persistency Rate.”

Over the chart is the statement, “In a study of approximately 1 million patients, persistency rates of different OA/RA treatments were assessed at 6 months.” The line below the Celebrex logo says, “Proven strength that lasts.”

The FDA said these claims imply that Celebrex is more effective (i.e., stronger) than ibuprofen and naproxen for treatment of osteoarthritis or rheumatoid arthritis and that
patients “stay with” or are more compliant with Celebrex therapy than with the other products. “We are not aware of substantial evidence or substantial clinical experience to support these claims,” the FDA wrote.

The cited retrospective retail pharmacy database analyses by NDC Health, the FDA advised, do not contain any data or information demonstrating that patients found Celebrex to be more effective than the other products, or that patients will be more “persistent” or compliant with Celebrex therapy.

Moreover, the agency said, the information did not note the indication for which the drug was prescribed, so the suggestion that these rates reflect specifically OA/RA patients is misleading.

In addition, the FDA said, the analyses do not account for factors that affect persistence or compliance such as cost insurance coverage, side effects, dosage regimen, and ease of use.

“Therefore,” the agency wrote, “the analyses do not constitute substantial evidence or substantial clinical experience demonstrating that OA/RA patients are more compliant with Celebrex or stay on Celebrex longer because it is more effective than other products for the treatment of OA or RA.”

Experts say these overly aggressive promotional campaigns are causing great harm to consumers. Former FDA commissioner, David Kessler, told the San Francisco Chronicle, February 27, 2005, that the rapid adoption of new drugs — fueled by heavy promotional campaigns — is an inherent threat to the public.

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

In recent years, though, he said, new medicines explode into widespread use before they build up a safety track record. Mr Kessler is credited with preventing the widespread use of drug TV commercials when he was commissioner.

“Many more people are going to be exposed,” he warned in the Chronicle. “That’s the nightmare.”

Patients who suffer from chronic pain, like Sandy Lambrecht, say Pfizer and other drug companies take advantage of their suffering. “Excruciating relentless pain is indeed a strong motivator,” she states.

“That’s why so many of us finally give in and take drugs that may indeed harm us even further,” she explains, “we are that desperate.”

Sandy says chronic pain sufferers keep up with the news about pain drugs like Celebrex but when the doctor says take it or go without, they take it. “We are not stupid,” she states, “we know that we are being coerced into taking drugs pushed by these unconscionable criminals.”

Her medicine cabinet still has half-empty bottles of Vioxx, Celebrex and Bextra. Last month she found out that she has heart problems, but has no way of knowing if its related to one of those drug or all 3. “And it’s not likely I’ll ever find out,” she says.

“We pay a price that is rarely considered in law suits,” Sandy notes, “and we never get recognition – let alone any compensation – for simply being in such tragic situations.”

Sandy contends that the few dollars still being spent on the disabled should not be used to boost drug companies profits. “I’ve long known that the real criminals are not the few people who take advantage of social programs,” she states, “its the greedy corporations whose legions of unscrupulous lawyers and salesmen exploit the most vulnerable of our society.”

Critics agree that consumers have been ripped off when it comes to Cox-2 inhibitors. “Though billed as super aspirins,” says Merrill Goozner, author of, The $800 Million Dollar Pill, “the Cox-2 inhibitors provided no more pain relief than over-the-counter aspirin, ibuprofen, or prescription naproxen, which were the most popular NSAIDs on the market.”

“This inconvenient fact,” he says, “was overlooked by the new drugs’ marketers.”

In the spring of 2002, then Pfizer CEO, Henry McKinnell, awarded PhRMA’s highest research award to the four scientists who developed Celebrex stating:

“Thanks to their pioneering work, millions of people throughout the world who were once crippled with arthritis can now work, walk, garden, and do all the little things that make life worthwhile.”

Mr McKinnell said all this, even though, as Mr Goozner points out, “they were no more able to perform those tasks than if they had popped a couple of over-the-counter ibuprofen.”

Pfizer has been one of the foremost proponents of the position that many FDA rules limiting drug advertising violate the company’s First Amendment right to free speech. That argument has made headway in a number of court cases, former deputy commissioner, Mary Pendergast, acknowledged to the San Francisco Chronicle on February 7, 2005.

However, according to Ms Pendergast, the FDA could still win a case for promotional limits by producing enough evidence to show public health could be at risk.

“You don’t have a First Amendment right to lie, to say false and misleading things,” she points out.

Pfizer Celebrex Lawsuits – 1500 and Counting

Evelyn Pringle September 5, 2006

The first Celebrex trial, originally set for June 6, 2006, has been delayed indefinitely, reportedly to give attorneys more time to gather information. Although no new trial date has been set, legal analysts now predict that Celebrex trials will begin in early 2007.

The delay was requested by a federal judge in San Francisco, where Pfizer is facing around 1,500 lawsuits related to its painkillers Celebrex and Bextra, according to Bloomberg News. In light of the studies on Celebrex that have surfaced over the past year, any media update should say 1,500 lawsuits and counting.

The lawsuits filed actually list defendants involved in the development, manufacturing and distributing of Celebrex as Pfizer Inc, Pharmacia Corp, Monsanto Co, and GD Searle & Co.

On August 30, 2006, Health Day News doused Pfizer’s last hope of ever finding a reason to justify the over-prescribing of Celebrex when it reported that the “final word on whether the cox-2 painkiller Celebrex might be used to prevent colon cancer is a definite “no,” according to the long-awaited results of two major studies.”

“Both of the three-year trials found that the drug reduced the occurrence of precancerous polyps called adenomas in people at risk for colon cancer,” Health Day wrote, “but it more than doubled patients’ risk for heart attack and other serious cardiovascular events.”

“The message is that celecoxib has no role as a chemotherapeutic agent — in people with adenomas or in people among the general population,” said Dr Bruce Psaty, a professor of medicine, epidemiology and health services at the University of Washington in Seattle, who co-authored an editorial on the two studies, published in the August 31, 2006, New England Journal of Medicine.

According to Dr Psaty, the take home message is that the cardiovascular risks “far outweighed even the most optimistic projections about the drug’s cancer-prevention properties.”

More bad news was reported a week earlier on August 24, 2006, by MedPage Today, in the results of a Canadian study that found women who take NSAIDs (nonsteroidal anti-inflammatory drugs), such as Celebrex, during the first trimester of pregnancy have twice the risk of having babies with congenital anomalies, particularly cardiac septal defects, researchers reported.

Of 1,056 women who filled prescriptions for NSAIDS during the first trimester of pregnancy, 8.8% had infants with congenital abnormalities, compared with 7% of 35,331 women who did not use NSAIDs, said Anick Berard, PhD, of Sainte-Justine Hospital, and colleagues, in the September 2006, issue of Birth Defects Research Part B.

And a few months ago on March 1, 2006, the Scotsman reported: “In a study involving more than 4,000 patients, Celebrex, which is the most commonly used Cox-2 inhibitor, was found to increase the risk of heart attacks by 2.26 times.”

The leader of the study, Professor Richard Beasley, from the Medical Research Institute of New Zealand, warned that, “Given the popularity of this in the treatment of arthritis, drug regulators must undertake an up-to-date risk assessment based on the findings presented here.”

The study was published in the Journal of the Royal Society of Medicine and reported that in addition to the increased risk when compared to a placebo, the use of Celebrex also had a 1.88-fold increase in the risk of heart attacks when compared with other painkillers.

According to a November 16, 2005, study conducted in Denmark, presented to the American Heart Association, people who have survived a previous heart attack and take Celebrex are at an increased risk of death, especially if they take Celebrex at higher doses.

The lead researcher, Dr Gunnar Gislason, stated that people with heart disease or history of heart attack should not use Celebrex. The study showed that heart disease patients who take 200 mg of Celebrex a day are more than four times more likely to die.

The first Celebrex trial that was delayed involves the case of Rosie Ware, an Alabama woman who alleges that a stroke at age 53, in February 2005, was caused by Celebrex and that the stroke has resulted in medical, hospital, and after-care costs of “substantial sums of money.”

Ms Ware is represented by the law firm of Beasley, Allen, Crow, Methvin, Portis & Miles, in Montgomery, AL. On February 28, 2006, Attorney Jere Beasley told the Wall Street Journal that his client, a nonsmoker whose health was “very good” before her stroke, took Celebrex for back pain and was left disabled and unable to work after the stroke.

Mr Beasley also told the Journal that he is undeterred by the fact that Celebrex has been deemed safe by federal regulatory agencies. “I don’t think that makes much difference,” he said. “The FDA is just an extension of the drug industry.”

Ms Ware alleges in her lawsuit that had it not been for Pfizer’s overly aggressive marketing campaign with misleading claims about the safety and efficacy of Celebrex, she would never have taken it to begin with.

This allegation is pretty much verified by a study published on January 24, 2005, in the Archives of Internal Medicine, titled, “National Trends in Cyclooxygenage-2 Inhibitor Use Since Market Release,” which concludes that the “aggressive marketing techniques to patients and physicians” caused a growth not only in use of COX-2 inhibitors but also in overall market demand, resulting in the use of such drugs by patients who did not need them.

The study in Archives found that 63% of patients who received COX-2 inhibitors were at a low risk for developing the ulcers and gastrointestinal problems that the drugs were supposed to prevent, and that the marketing campaign played a significant role in the over-use of COX-2 inhibitors for this type of patient.

In both the non-risk and at-risk population, the study found, Celebrex was neither more effective or safer than NSAIDs, meaning that there was a small population for which it might be a superior product, but for the vast majority of users, its use was excessive.

According to Merrill Goozner in the new best-selling book, “The $800 Million Pill:”

“Sales exploded the instant the FDA gave the okay for the drugs’ makers to rev up their marketing machines. Commercials featuring frisky seniors flooded the airwaves. Detailers inundated doctors with free samples. Millions of people pestered their physicians to give them prescriptions for the new drugs, requests that fell on receptive ears.”

Mr Goozner states that, “Wall Street’s stock analysts considered the rollouts of Celebrex and Vioxx the most successful drug launches in pharmaceutical industry history.”

“Within a year of its launch,” he notes, “Celebrex was generating more than $2 billion a year in sales for Pharmacia and its comarketer Pfizer.

“Arthritis pain relief medicine that had once cost pennies a day,” he says, “was now costing millions of patients and their insurers nearly three dollars a pill.”

Celebrex in fact, has no proven superiority over other NSAIDs and yet it sells for anywhere between $2.50 to $6.50 per day depending on the dose, while NSAIDs sell for $0.21 to $0.31 per day which means Pfizer has made billions of dollars off Celebrex by charging an outrageous price for a drug that in reality is not even better than over-the-counter drugs that cost pennies per pill and have been on the shelves for years.

Had the truth been known about the drug’s lack of safety and efficacy, critics says, Celebrex would have sold for a price similar to other NSAIDs and would not have become a standard in the treatment of arthritis and other forms of pain relief.

In 2004, Pfizer spent $117 million promoting Celebrex and sales reached $3.4 billion worldwide, according to the April 28, 2006, New York Times. The following year, after advertising of Celebrex ceased, sales dropped 48% to $1.73 billion in 2005, the WSJ reports.

Although scrutiny over marketing practices intensified following the Vioxx recall, violations of advertising regulations have been getting worse, according to Tom Abrams, director of the FDA’s Division of Drug Marketing, Advertising, and Communications, speaking in an interview for Pharmaceutical Executive on December 1, 2005.

FDA regulations require drug companies to submit promotional materials to the FDA at the time of first use which means Mr Abrams and his staff of 35 receive an average of 53,000 promotional pieces a year, he estimates.

He says the biggest public misconception is that the FDA screens and approves all ads before they are released but that most ads are launched without the agency reviewing them first. “We get complaints from consumers and physicians who call us up and say, ‘Tom, how can you allow that TV ad to be on?'” Mr Abrams said during the interview.

“They’re flabbergasted,” he says, “when we say, ‘We didn’t approve it before it went on TV.’ Often, we’re seeing it at the same time as the American public. DDMAC has limited resources and we use our limited resources as effectively as we can to do our job.”

He told Pharmaceutical Executive that competing marketing campaigns within the pharmaceutical industry have become fierce. “Currently, industry spends $25 billion a year on promotion,” he said in the interview.

“I think it is going to continue to increase,” he added.

When the FDA determines that ad is violating regulations, it sends the drug company either a notice of violation letter or a warning letter. Notice of violation letters are untitled and are issued for the least serious offenses. “They pretty much tell companies, ‘Stop what you’re doing and don’t do it again,” says Mr Abrams.

Warning letters, he explains, request that the drug company stop the promotion and disseminate corrective messages, and are issued for more serious or repetitive violations.

Over the years, the misleading and deceptive ads for Celebrex have led to regular correspondence between Pfizer and the FDA.

Since its arrival on the market, Celebrex has been promoted as having the ability to improve the quality of life with ads in which patients go from not being able to work or do much of anything, to being able to work and do everything else pain-free.

In one infomercial, Celebrex patients talk about being able to “do anything,” “do as much as I want to do,” being “back to doing what I do,” and such. They talk about “enjoying life” again, how the drug improved their “quality of life,” and how the drug “gave them back their lives.”

One person states that “you can be free,” and another says that Celebrex “brought new vitality in life.”

Such claims portray Celebrex as a superior pain relief drug when in fact, the FDA has stated that, “none of the comparative studies with naproxen, ibuprofen, and diclofenac to-date has been designed to demonstrate superiority or a specified degree of similarity in a rigorous way.”

Typical of the phony “improve the quality of life” commercials is a TV ad that promotes the use of Celebrex for osteoarthritis or rheumatoid arthritis, with a woman playing a guitar. The visuals focus on her hands and fingers and playing ability with a voice-over saying, “With Celebrex, I will play the long version.”

Combined, the image and voice-over imply that there is a direct benefit to the woman’s wrist, hand, and finger joints so that she can now play the long version and that prior to taking Celebrex she could not.

This misleading ad earned the drug maker the most serious FDA “warning letter” stating: While the Guitar TV ad suggests a direct benefit to this patient’s wrist/hand/finger joints related to movement and flexibility, it fails to state the actual approved indication (e.g., relief of signs and symptoms of osteoarthritis).

It also fails to include any risk information about Celebrex, the FDA said, thus omitting the major side effects and contraindications (including warnings and precautions). Omission of this information, the warning letter said, implies that there are no risks to the patient who takes Celebrex which overstates the drug’s safety.

The Canada’s regulatory agency were also keeping a close watch on Celebrex and apparently so were consumers. On November 4, 2004 a class action lawsuit was filed in Canada alleging that Celebrex caused cardiovascular related side effects and on November 28, 2004, Canada’s Adverse Drug Reaction Monitoring Program confirmed 14 Celebrex related deaths.

About 2 weeks later in mid-December 2004, the announcement came that a clinical trial investigating a new use of Celebrex to prevent colon polyps, conducted by the National Cancer Institute and Pfizer, was discontinued because of an increased risk of cardiovascular events in patients taking Celebrex versus those in the group taking a placebo.

Patients in the trial who were taking 400 mg of Celebrex twice a day were found to have a 3.4 times greater risk of cardiovascular events compared to patients taking a placebo and patients taking the 200 mg dose had a risk that was 2.5 times greater.

The news of this study came a mere 10 weeks after Merck’s recall of Vioxx, when a study found that Vioxx doubled the risk of heart attack and stroke among patients taking the drug to prevent colon polyps.

In fact, on September 30, 2004, in response to Merck’s announcement, Pfizer issued a press release bragging that over 27 million patients in the US had been prescribed Celebrex since it was approved and said people should use it instead of Vioxx.

“Because of its outstanding long-term safety profile and broad indication base including osteoarthritis, rheumatoid arthritis and acute pain, Celebrex is an appropriate treatment alternative,” said Dr Joe Feczko, Pfizer’s president of worldwide development.

The press release claimed that a recent FDA sponsored study of 1.4 million patients, found that those patients who received Celebrex demonstrated no increased risk of cardiac events. “Pfizer is confident in the long-term cardiovascular safety of Celebrex,” Dr Joe Feczko stated.

Well, that glory was short-lived because in January 2005, following a sharp decline in new prescriptions for Celebrex after the December 2004 study was revealed, Pfizer investors filed a federal class action lawsuit against Pfizer in Connecticut alleging that the company misled investors about the safety of Celebrex.

A former Vice President of Pfizer turned whistleblower, Peter Rost, says shareholders were rightfully upset and estimates that the fiasco probably cost Pfizer $3-4 billion.

As for the potential damages to the company from all the lawsuits filed, Mr Rost states companies like Pfizer usually carry some insurance but says, “Most comes out of shareholders pockets.”

He predicts that more hidden studies and documents will pop up during litigation.

And that too seems likely being Pfizer has been forced to acknowledge that a study that was testing Celebrex as a treatment for Alzheimer’s disease between 1997 to 1999, showed patients taking Celebrex quadrupled their risk for a heart attack compared to those patients taking a placebo.

The study found patients on Celebrex had a 3.6 times greater occurrence of a serious heart event compared to those on a placebo, according to an analysis of the data by the patient advocacy group, Public Citizen.

On January 24, 2005, Public Citizen petitioned the FDA to immediately remove Celebrex from the market and a week later on January 31, 2005, Citizen accused Pfizer of burying the study. Sidney Wolfe, director of Public Citizen’s Health Research Group, said “there is no excuse for this study not being made more public.”

Critics say this study proves that the drug makers knew that Celebrex was a total fraud before the drug even hit the shelves.

According to Merrill Goozner, author of the $800 Million Dollar Pill, the only legitimate selling point for the Cox-2 inhibitors was the claim that they would eliminate the ulcers and deaths that on rare occasions resulted from the prolonged use of generic painkillers.

“Yet the FDA didn’t allow them to claim that in their advertising or literature,” he points out, “since the clinical trials failed to turn up evidence that the new drugs were safer than NSAIDs.”

“The package insert, which goes out with every prescription,” he notes, “contained the same warning label as all the other NSAIDs.”

Critics predict that Vioxx, Celebrex and Bextra will go down in history as a shining example of the danger posed by allowing the unbridled promotion of prescription drugs to both doctors and patients.

Experts blame the doctors for over-prescribing and being so gullible to trust the information in promotional materials furnished by drug companies. On June 22, 2000, Dr Marcia Angell, wrote in the New England Journal of Medicine:

“Unfortunately, many doctors do indeed rely on drug-company representatives and promotional materials to learn about new drugs, and much of the public learns from direct-to-consumer advertising. But to rely on the drug companies for unbiased evaluations of their products makes about as much sense as relying on beer companies to teach us about alcoholism. The conflict of interest is obvious.”

“The fact is,” she said, “marketing is meant to sell drugs, and the less important the drug, the more marketing it takes to sell it.”

“Important new drugs do not need much promotion,” she wrote.

Pfizer Makes List of Worst Corporate Evildoers

Evelyn Pringle March 6, 2006

On January 3, 2006 the Global Exchange Report named the top fourteen “Worst Corporate Evildoers” in the world for 2005. Pfizer, one of the most profitable drug companies on earth, with sales over $52 billion in 2004, made the list of Evildoers.

Pfizer’s participation in the cover-up of the deadly side effects of Bextra surely contributed to its membership. Because the drug was promoted and sold off-label for so many unapproved uses, the company made hundreds of millions of dollars in pure profits during Bextra’s short life on the market. However, experts predict that when all is said and done, the total amount of the drug’s damage to consumers will be in the billions.

Bextra belongs to the same class of drugs as Vioxx and Celebrex, known as Cox-2 inhibitors. Millions of people world-wide have taken these drugs.

It is now apparent that Pfizer knew Bextra was associated with extremely harmful side effects long before it was yanked off the market. However, Pfizer had good reason to stall its inevitable removal after Vioxx was recalled.

Bextra was on the market for about 3.5 years, but did not reach its full sales potential until Vioxx was eliminated from the competition. After the Vioxx recall, in one month alone, Bextra prescriptions went from 1.15 million in September 2004, to 1.48 million in October. All total for 2004, Pfizer generated sales of about $1.3 billion.

The marketing history of Bextra involves a train of suspicious conduct. On November 16, 2001, the drug’s original maker, Pharmacia won FDA approval for treatment of pain associated with osteoarthritis, adult rheumatoid arthritis and menstrual pain only and immediately went into overdrive promoting the drug for off-label use.

In July 2002, Pfizer acquired Bextra from Pharmacia in a $58 billion dollar deal that was not approved by the FTC until the following year in April 2003.

An FDA Talk Paper on the agency’s web site on November 15, 2002, announced new warnings on Bextra and said, “labeling is being updated with new warnings following postmarketing reports of serious adverse effects including life-threatening risks related to skin reactions – including Stevens Johnson Syndrome, and anaphylactoid reactions.”

The following month, the “Congress of California Seniors,” filed a lawsuit against Pharmacia in a Superior Court in Los Angeles, alleging the company had illegally promoted Bextra for off-label use.

According to the group, after the FDA refused a request to approve Bextra for pain related to impacted molars, Pharmacia helped fund a study that claimed Bextra could be useful in fighting acute dental pain and got it published in dental journals which led to the suit alleging secretive encouragement of ‘off label’ uses and attempting to circumvent the FDA’s refusal.

On November 2, 2003, after a year-long analysis of prescribing records, Knight-Ridder reported that more than half of Bextra pills sold were for off-label use.

About 5 months later, on March 14, 2004, Pfizer disclosed in a regulatory filing that the Justice Department was investigating the company’s marketing practices of Bextra for uses not approved by the FDA.

In October, 2004, the New England Journal of Medicine carried two editorials calling for renewed scrutiny of all Cox-2 inhibitors to assess whether the other drugs also caused heart problems.

In one editorial, cardiologist, Eric Topol, one of the first people to raise a red flag on Vioxx, from the Cleveland Clinic in Ohio, called for a government investigation into why Merck and the FDA allowed Vioxx to remain on the market for so long after its association with heart risks were revealed.

The FDA’s inaction was also noted by the Washington Post pointing out that in the late 1990s, the FDA took action when safety concerns were raised by withdrawing 10 drugs within 3 years. “But until the Vioxx withdrawal, only one other drug had been pulled since the Bush administration began, leading some to conclude that the agency had made a quiet policy change that emphasized “benefit” and sought to manage “risk” less intrusively,” the Post said on April 11, 2005.

As it turns out, Pfizer knew Bextra was every bit as dangerous as Vioxx and that the incidence of heart attack and stroke among patients using Bextra was more than 2 times that of patients taking placebos, which was revealed in a study presented on November 9, 2004, during the annual meeting of the American Heart Association in New Orleans.

Dr Curt Furberg, a professor at Wake Forest University School of Medicine, helped conduct the study and said: “Basically, we showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information.”

On November 18, 2004, Dr David Graham, head of the FDA’s Office of Drug Safety, testified before the Senate Finance committee and listed Bextra as one of five drugs whose safety needs ”to be seriously looked at.”

On December 9, 2004, the FDA announced that Bextra would come with a new bolded warning contraindicating its use in patients undergoing coronary artery bypass graft (CABG) surgery.

The FDA knew Bextra was being widely marked for off-label use. Its December 9, Talk Paper, noted that Bextra was “not approved for use in the treatment of postoperative pain of any type;” but added: “however, FDA believes that these new findings should be made available to healthcare professionals and patients, and the bolded warning specifically contraindicates Bextra for treatment of pain immediately following CABG.”

The FDA also ordered a black boxed warning on the label stating that patients taking Bextra had reported serious, potentially fatal skin reactions, including Steven-Johnson Syndrome and toxic epidermal necrolysis.

Come to find out, as of November 2004, the FDA had received reports of 87 cases of SJS associated with Bextra. Thirty-six patients required hospitalizations, and 4 people died. Twenty involved patients with a known allergy to sulfa.

Although the other Cox-2 selective inhibitors also showed a risk for SJS, the FDA found reported cases to be greater with Bextra.

SJS is a devastating reaction affecting the skin and mucous membranes, causing severe burning, blistering and sloughing of involved tissue. SJS commonly causes blindness and results in death in 10 to 30 percent of the cases, according to a December 12, 2004 press release by the SJS Foundation.

People also develop SJS as a reaction to other commonly prescribed drugs, including antibiotics, anti-convulsants, and non-steroidal inflammatory drugs (NSAIDS), including over-the-counter drugs such ibuprofen products.

On January 26, 2005, Jean Farrell McCawley, the founder of the SJS Foundation testified before a joint meeting of the FDA’s Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee.

Ms Farell-McCawley told the panel that although SJS was referred to as a rare skin reaction, since 1995, the SJS Foundation had been notified of far more cases of the condition than those recorded by the FDA.

By one estimate, each year, SJS effects three to eight people per million in the US. However, the frequency is thought to be much higher since the FDA acknowledges that only between one and 10% of all adverse drug reactions are reported each year.

“SJS is not as rare as we are led to believe,” Ms Farrell McCawley advises. “During the winter months, we learn of 15 new cases a week, and that’s only people with Internet access,” she says.

It is hard to imagine a more severe adverse drug reaction than SJS. In the April 2005 SJS Newsletter, SrA Tanner Claybaugh published a letter describing what his sister, Mollie, went through after developing SJS as a reaction to children’s Advil.

Shortly after taking drug, Mollie developed blisters and rashes all over her body and was hospitalized. “She was put in the Intensive Care Unit (ICU) where there were countless machines keeping her alive,” SrA says.

“After about a weeks time,” he continued, “she was put in the burn unit as if she had burns from a fire, but the allergic reaction was the cause of her third degree burns.”

She was hanging on to life by a thread for weeks. “Back and forth she went,” her brother said, “from the burn unit to ICU.”

“As soon as her condition improved it worsened,” he noted. “It was always the same pattern entering ICU,” he recalls, wash your hands with warm water and soap and then put on medical mask and gloves.

“I was an 11 year old boy,” he wrote, “who had to do this just to watch my sister through a glass door of an isolation room.”

Mollie’s head had to be shaved and her skin was covered in blisters. “Her whole body was wrapped in gauze to stop the bleeding blisters,” SrA recalls.

“I remember sitting in her burn unit room watching two therapists lift her up and try to sit her in a wheelchair,” he said and described how drops of blood would fall from Mollie’s burnt flesh.

SrA says Mollie could not even scream out in pain. “All she could do is cry because her vocal cords had been burned,” he said.

After five months in the hospital Mollie was allowed to go home.

“Our living area transformed into that of a hospital room,” SrA said, “it had a ventilator for her tracheotomy, IV stand, stomach tube stand, heart rate monitor, and medications galore.”

Therapists came everyday and a nurse was always with Mollie giving her care. She required surgeries almost every other week to stretch her esophagus and the ligaments in her feet and hands. She also had cornea surgery.

According to SrA, today Mollie cannot walk, see, or talk very well. “She is fed through a stomach tube and it’s hard for her to breath,” he says.

Before SJS, Mollie was a dancer. “She was suppose to perform in the opening show for the 1996 Olympics in Atlanta,” her brother says. However, the room where she used to practice her dance moves and back flips has now become a rehabilitation center.

SrA says Mollie cannot receive any more therapy because of the healthcare budget cuts so his mother became a nurse to take care of Mollie.

SrA believes there needs to be more public awareness of the dangers associated with the drugs that cause this horrible reaction.

In January 2005, the Bextra related cardiovascular problems were back in the news when the results of two trials were released that showed the drug tripled the incidence of heart attack and stroke in coronary bypass graft surgery patients.

On February 14, 2005, the Associated Press reported that while Vioxx and Celebrex increased patients’ risk of heart attack and stroke by about 20 percent, Bextra increased the risk by 50%, citing a study by WellPoint Inc.

In April 2005, Pfizer finally took Bextra off the market at the request of the FDA. At the same time, the FDA told Pfizer to include a black box warning on Celebrex.

In a prepared statement, Pfizer reported that the FDA said Bextra’s risk to the heart was not distinguishable from other drugs and that it was the skin reaction that led to the decision.

The FDA advisory said it “concluded that the overall risk versus benefit profile is unfavorable and has requested that Pfizer, the manufacturer of Bextra, voluntarily withdraw Bextra from the market.”

The FDA explained that the request to recall the drug was based on:

1) The lack of adequate data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse CV events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use.

2) Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The risk of these reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa allergy, and after both short- and long-term use.

The FDA also cited a lack of any demonstrated advantages for Bextra compared with other NSAIDs and instructed patients taking Bextra to contact their physicians and consider alternative treatments.

At the same time, FDA officials said all painkillers in the category known as “nonsteroidal anti-inflammatory drugs,” or NSAIDS, would have to carry stronger warnings about risks of heart attack, stroke, ulcers, internal bleeding or skin reactions, the Philadelphia Inquirer announced on April 9, 2005.

The warnings affected dozens of medications sold by prescription, as well as over-the-counter, with worldwide sales of at least $18.7 billion, according to the British pharmaceutical research firm Lead Discovery.

The drugs included Wyeth’s biggest-selling over-the-counter product Advil, which had sales of $620 million in 2004, Wyeth spokesman Doug Petkus told the Inquirer.

Teva Pharmaceutical’s ibuprofen, diclofenac and naproxen were included as also McNeil’s biggest-selling NSAID Motrin.

A report in the San Francisco Chronicle on February 27, 2005, said the “painkillers Vioxx, Celebrex and Bextra may go down in history as a classic example of the danger posed by aggressive industry promotion of prescription drugs to both patients and doctors.”

“In 2003,” the report said, “their manufacturers spent more than $1.5 billion to promote the drugs through television spots, print ads and pitches to doctors,” the report wrote.

And the $1.5 billion turned out to be a sound investment because by 2003, combined sales of the 3 drugs topped $5.3 billion, according to IMS Health, a pharmaceutical information and consulting company.

People who helped derail this deadly money train by standing up to the giant drug makers responsible for marketing this class of drugs often end up with a bitter pill. In the third civil lawsuit against Vioxx, Dr Topel gave testimony against Merck in a deposition and less than a week after his videotaped testimony was played in a Houston courtroom, he lost his title as chief academic officer of the Cleveland Clinic’s medical college.

On December 10, 2005, Dr Topol told the New York Times he was fired as a result of going up against Merck and said in part:

“The hardest thing in the world is just trying to tell the truth, to do the right thing for patients, and you get vilified. No wonder nobody stands up to the industry.”

But the icing on the cake for the Cox-2 inhibiter saga came on December 2, 2005, when Gooz News ran an article titled, “Pricey Pain Pills No Better at Reducing Tummy Distress.”

“It looks like the billions spent on expensive new Cox-2 inhibitors,” Gooz said, “was wasted – and not just because Vioxx was the likely cause of tens of thousands of heart attacks among its users.”

Citing a report in the British Medical Journal that day, Gooz said that “Cox-2 inhibitors do not reduce the gastrointestinal side effects of over-the-counter pain pills like ibuprofen.”

“This was the whole rationale for justifying the drug industry’s massive investment in this new class of medicines,” Gooz noted, “since they don’t reduce pain any more effectively than older pain pills.”