The Bitter Pill

The Official Blog of UNITE – uniteforlife.org

Glaxo Fights Against Public Paxil Trials

Evelyn Pringle April 8, 2008

Government attorneys appointed by the Bush Administration have been supporting GlaxoSmithKline in a number of courts across the country in an effort to convince the courts that lawsuits filed by victims of Paxil-induced injuries should be dismissed before ever making it to a jury.

In fact, the Administration has spent a massive amount of tax dollars filing amicus briefs on behalf of just about every drug maker involved in litigation in an attempt to get the lawsuits filed by private citizens thrown out of court.

The government claims that, once a drug and the warnings on its label are approved by the FDA, claims alleging injuries caused by a company’s failure to warn about a risk not listed on the label are preempted.

The Bush Administration says preemption applies even when a company (1) continues to sell a drug when a risk is known; (2) fails to warn when new risks are discovered; (3) fails to send letters notifying prescribing doctors of a known risk, and (4) fails to disclose a known risk to the FDA during the approval process, or anytime for that matter. In essence, if the FDA doesn’t make the companies warn, they’re off the hook.

If the Administration is successful in obtaining immunity for these drug companies, taxpayers will be left to pay not only the costs of medical care for all persons injured by drugs but also the life-long care for persons disabled by a product.

If Americans realized what was happening, there is no way they would approve of their tax dollars being spent to help the richest industry on the planet deprive fellow citizens of their right to a jury trial.

The typical brief against a plaintiff is filed by an army of government attorneys and will include an Assistant Attorney General, a Deputy Assistant Attorney General, a United States Attorney, an Assistant United States Attorney, two Appellate Attorneys from the Department of Justice, the FDA’s Chief Counsel, and the Deputy Chief Counsel, Associate Chief Counsel, and General Counsel for the Department of Health and Human Services.

Glaxo takes things one step further by submitting government amicus briefs that were filed in other cases (not just Paxil cases) and re-files them in virtually every one of the cases filed against the company in order to bolster its preemption arguments.

In O’Neal v GlaxoSmithKline, a case involving the suicide of a 13-year-old Sacramento, California boy, Benjamin Bratt, Glaxo recently used the Bush Administration’s preemption policy to argue that the child’s family should not be allowed to sue Glaxo for failing to warn about the suicide risk.

Benjamin committed suicide on February 14, 1997 by hanging himself. His parents, Terri O’Neal and Barry Bratt, filed a lawsuit alleging that, despite knowledge of suicide risks associated with Paxil prior to 1997, Glaxo concealed the information, failed to warn doctors, the medical community, and the public and all the while the company promoted the drug as safe and effective for children.

In the lawsuit, the Bratt Family alleged that Glaxo should have warned Benjamin’s doctor about the suicide risk both through the label and through other means, such as promotion, advertising, and “Dear Doctor” letters.

On January 30, 2008, federal judge, Frank Damrell, in the US District Court, Eastern District of California, dismissed the case and ruled that all of the family’s claims were preempted. The Bratt family has asked the court to reconsider the ruling. They believe the judge committed error in essentially holding that a drug that is not safe for adults is nonetheless safe for children until proven otherwise.

The family argues that adult clinical trials conducted by Glaxo as far back as 1989 showed an 8 times increased risk of suicidal behavior for Paxil users compared to patients receiving a placebo, but that Glaxo manipulated the data to obscure the risk, and then published the false data in medical journals and articles throughout the 1990′s.

In his ruling, Judge Damrell held that, even if GSK had clinical trial data prior to 1997 that showed an increased risk of suicidality in adults, that data was not sufficient to prove the risk extended to children using Paxil.

The Court held that, because the first clinical trial of Paxil with children did not conclude until 1998, Glaxo could not have known about the suicide risks with kids before that date.

During the January 18, 2008 oral argument on the preemption motion, Judge Damrell himself pointed out that a finding of an increased risk of suicidality in adults would logically apply to children. He specifically stated:

“As a practical matter, if I see there was an association of suicide ideation with anybody and enough of it, the last person I want to see using it is a child. That may not be scientific, but I’m just talking as a grandfather and human being.”

However, in his order, Judge Damrell seems to say the exact opposite:

“That later clinical studies ultimately led to a clear signal of pediatric suicidality, and that these studies arguably reflected the initial data in 1989 and 1991 of similar associations among adults, simply does not provide ‘reasonable evidence’ of the association of pediatric suicidality in February 1997.”

“It is difficult to reconcile Judge Damrell’s statements during oral argument with his ruling,” says senior trial attorney, Ron Goldman of Baum, Hedlund, Aristei & Goldman, the law firm representing the Bratt family.

Baum Hedlund has roughly 30 lawsuits on file involving Paxil-induced suicides and suicide attempts. Over the past 18 years, the firm has handled more than 3,000 cases involving antidepressants, including Glaxo’s Paxil, Eli Lilly’s Prozac and Pfizer’s Zoloft.

The first study Glaxo conducted on children was called Study 329. The study was started in 1994, three years prior to Benjamin’s suicide, and was completed in 1998, nine months after his suicide.

Judge Damrell bought Glaxo’s argument that, because Study 329 wasn’t completed until after Ben Bratt’s death, the company could not have warned of a risk in children prior to that. But, during the four years the study was ongoing, Glaxo received numerous reports of suicidal behavior occurring in children taking Paxil.

Coupled with the risk evident from the adult clinical trials since 1989, the Bratt family argues that Glaxo could have and should have warned of the risk for all people taking the drug long before Benjamin ingested Paxil.

Coincidentally, when the study 329 was finally published, the authors stated that, “The adverse-effect profile of paroxetine in this adolescent population was concordant with that reported in studies of adult patients with depression.”

The Bratt family argues that, the question of whether reasonable evidence of an association existed between Paxil and suicidality in any population at the time of Benjamin’s death is one for the jury.

The question of what Glaxo knew and when Glaxo knew it is also a question for the jury. Glaxo’s attempt to continue the parade down this rabbit trail is simply an attempt to divert attention away from the core issue here. The decisive question in a preemption context for the Court to determine is, “was GSK ever prohibited by the FDA from issuing a warning” thus creating a direct and positive conflict. The answer is unequivocally “NO.”

Judge Damrell also held that, if Glaxo had warned about a suicide risk for kids prior to 1997, such a warning would have been subject to a misbranding action by the FDA.

According to Mr Goldman, “Under no circumstances, given the regulatory scheme, can a drug be considered ‘misbranded’ if the science supports a truthful warning of the risk of suicidality.”

“Under the law,” he says, “it is a drug manufacturer’s duty to warn of risks known or reasonably scientifically knowable.”

“A drug company that fails or refuses to conduct necessary analyses in a scientifically acceptable manner,” he states, “shirks its legal, not to mention ethical and moral, duty to the medical profession and the public.”

According to the US Supreme Court, preemption applies (1) where it is impossible for a private party to comply with both federal and state law; and (2) where the state law stands as an obstacle to the accomplishment and execution of the full purposes and objective of Congress.

“When carefully analyzed, there is absolutely no evidence showing that it would have been ‘impossible’ for Glaxo to warn of this very serious risk, an absolute requirement in cases where conflict preemption is raised,” Mr Goldman contends.

“To the contrary,” he says, “such a warning is in perfect harmony with the FDA regulations and the overarching purpose of the FDA: to promote health and safety in prescription drugs.”

In their brief filed in opposition to summary judgment, the Bratt Family stated: “GSK would like to convince this Court that it is merely a ‘puppet’ when it comes to labeling its multi-billion dollar blockbuster drug, Paxil.”

“According to GSK,” the brief notes, “it is hapless and at the mercy of the FDA when it comes to the content of Paxil’s label.”

Glaxo claims it needed the FDA’s prior approval to issue a warning. However, the attorneys in the Paxil cases point out that Glaxo itself changed the label and sent out a Dear Doctor letter warning about the suicide risk in May 2006, with no prior approval from the FDA. The FDA never objected to the letter or the strengthened warning label.

The FDA, in its amicus briefs, has asserted twisted logic in these cases because the FDA cannot force a company to add a warning to a label. On March 1, 2005, the FDA’s deputy director for the Office of New Drugs, Dr Sandra Kweder, testified at a hearing before the Senate Committee on Health, Education, Labor and Pensions, that the FDA does not have the authority to require a specific label change and that the agency has to negotiate with the companies about how things should be worded, placement, those kinds of things.

During oral argument in SSRI suicide cases, industry attorneys claim that the reevaluation of the suicide risk of all the pediatric studies on SSRIs occurred after Glaxo “voluntarily” offered up the studies to the FDA.

For instance, on December 10, 2007, during oral argument in a case in a federal court in Philadelphia, a Pfizer attorney, Malcolm Wheeler was asked by the court: “What was the tipping point then for the change in position with respect to adolescents and then later extending that to young adults up to age 24?”

Mr Wheeler replied: “The tipping point was because GlaxoSmithKline voluntarily went forward and informed the FDA of some study results and said here are these results.”

“And what the FDA did as a result of that,” he told the court, “was to conduct a new analysis, pooling the data from nine different drugs, not just SSRIs, but nine different antidepressants, to say when we pool all the data from these various antidepressants, does it indicate any signal that suggests that we ought to do something other than what we’ve done in the past?”

However, that is a gross misrepresentation of what actually happened. The truth is, according to FDA documents obtained in litigation, that the European Medicines Agency (EMEA) contacted the FDA in mid-2003 to alert officials about the hidden suicide risk in the pediatric Paxil studies.

According to a June 2, 2003, FDA email written by Dr Russell Katz to Dr Andrew Mosholder, the FDA was notified in May 2003, that suicide events were hidden under the term “emotional lability.” Dr Katz’s email states:

“We have recently become aware of a presumed association between Paxil and suicidality in pediatric patients. We received a call from the EMEA a little over a week ago.

A Dr. Raines told us that the company (GSK) had submitted data that demonstrated that use of Paxil in kids was associated with increased suicidality compared to placebo, and that the company proposed labeling changes.

“I believe she also said that it was in the news, and it was a big issue. Tom and I told her that the company had not informed us of any of this, and we agreed to look into it.”

Dr Katz told Dr Mosholder that the FDA had asked Glaxo to elaborate on the events listed under the term emotional lability and further stated:

“We received this partial response, and almost all of these events related to suicidality. The bottom line is that when data from the controlled trials in depression, OCD, and Social Anxiety are pooled, for “possible suicide related” events occurring during treatment or within 4 days after discontinuation, the rate is 0.14/patient-year on drug, and 0.05/patient-year on placebo, p=0.02.”

“We have some problems with the methodology they used to capture cases, but this is the major finding, and it has us worried,” he wrote.

“We are planning to look at the NDAs for other SSRIs to see whether or not similar events are being hidden by various inappropriate coding maneuvers, but we’d also like to compare the drugs in other meaningful ways if we can,” Dr Katz informed Dr Mosholder.

A report by Harvard psychiatrist, Dr Joseph Glenmullen, retained by Baum Hedlund as an expert witness in the Bratt case shows that Glaxo knew as early as 1989 that patients who received Paxil in clinical trials showed an 8-fold increased risk of suicidality compared to patients who received placebos. Dr Glenmullen’s report was initially filed under seal, however, on January 30, 2008, the majority of the report was unsealed.

In the report, Dr Glenmullen also notes that, when Glaxo coded suicidal behavior in its computerized database, most of the suicides and suicide attempts were coded as “emotional lability,” which he says is “a technical term for rapid mood swings, for example from crying to laughing.”

Another claim consistently made by both the Bush Administration attorneys and the attorneys for the SSRI makers, is that the FDA’s failure to make the companies issue warnings somehow means the FDA considered and rejected offers by the companies to add warnings about the suicidality risk.

However, Dr Katz specifically notes in his email that Glaxo never offered to add a warning to the label in the US, even after the FDA became aware of the increased suicide risk and discussed the issue with Glaxo.

“The sponsor has not proposed labeling changes and makes a feeble attempt to dismiss the finding,” he told Dr Mosholder in the email.

In the first SSRI case where preemption was raised (the company lost the argument), Motus v Pfizer, the judge wisely observed that, “although the FDA did not require Pfizer to include suicide-related warnings in Zoloft’s label, FDA has not prohibited Pfizer from doing so” and the “FDA never stated that it would be impermissible to include additional warnings.” Likewise, because Glaxo never sought to add a suicide warning, it is not possible that the FDA considered and a suicide warning.

On June 10, 2003, the UK’s Medicines and Healthcare Products Regulatory Agency issued the warning: “It has become clear that the benefits of Seroxat in children for the treatment of depressive illness do not outweigh these risks.”

In the June 11, 2003 New York Times, Gardiner Harris reported that Alan Metz, the vice president for clinical development at Glaxo, said the company was not warning American doctors against using the drug with depressed children in the US.

Dr Metz acknowledged that Paxil was not approved for treating children in the US but that many doctors prescribed the drug for children anyway. Mr Harris pointed out that Glaxo had applied for approval from the FDA to sell Paxil to children with obsessive compulsive disorder and the application was pending at that time.

On June 20, 2003, the Times reported that the FDA’s reanalysis found that the risk of suicidal thoughts and suicide attempts was 3 times greater among children using Paxil, mostly teenagers, than among children given placebos.

On August 12, 2003, the Times ran a commentary by Richard Friedman, a psychiatrist and director of the psychopharmacology clinic at Weill Medical College of Cornell University, which stated in part:

“What is disturbing about the recent report is that the purported link between Paxil and suicidal thinking comes from an unpublished study sponsored by Paxil’s manufacturer, GlaxoSmithKline.”

“In fact, GlaxoSmithKline has published only one of its nine studies of Paxil in children and adolescents to date,” he reported.

In its preemption motion, Glaxo offered nothing to support the claim that the FDA had considered, much less rejected, a proposal to add a warning about the increased suicide risk for kids. In fact, the studies in question were not submitted to the FDA until 2002, when Glaxo sought approval for new uses of Paxil, meaning it would have been impossible for the FDA to have considered whether a warning was appropriate based on a risk known only to Glaxo.

To support their argument that the FDA had never rejected a Glaxo proposed warning, the Bratt family brief states: “None of the GSK employees in the past 14 years who have, or had, responsibility for communicating with the FDA regarding Paxil could point to any specific, proposed suicide or suicidality language that was rejected by the FDA.

In his report, Dr Glenmullen explains how Glaxo successfully avoided having to include a warning on the label when it obtained FDA approval for Paxil in 1992:

“GlaxoSmithKline’s ‘bad’ Paxil data made it look as if patients randomized to Paxil were no more likely to become seriously suicidal when, in fact, the correct data shows patients on Paxil were eight times more likely to commit or attempt suicide.”

“One again,” he states, “GlaxoSmithKline’s ‘bad’ Paxil numbers carried the day: The FDA approved Paxil on December 29, 1992 with no warning to doctors or patients of the significant increased risk of suicidal behavior.”

The FDA’s Dr David Graham, most famous for exposing the risks associated with Vioxx, says the government’s attempts to immunize drug companies must not succeed. In an August 30, 2005 interview with Manette Loudon, the lead investigator for Dr Gary Null, (author of numerous books including “7 Steps To Overcoming Anxiety and Depression”), Dr Graham was asked about his views on attempts to pass tort reform.

“I think it’s dangerous and wrong,” he stated. “We already have an FDA that’s been neutralized by industry and sees industry as its client.”

Dr Graham said the agency is not going to protect the average citizen from the consequences of unsafe drugs, so the only alternative is the legal system. “That’s the only way we have of getting companies to change their behavior,” he said and, “tort reform would remove that threat as well.”

“It’s basically giving companies immunity because now the people who are injured by the drugs can’t recover damages that might actually mean something to industry,” he advised.

“I mean $250,000 for damages; they blow that in one ad campaign,” he stated. “To them, that’s nothing.”

“But a lawsuit for multiple millions of dollars has more of an impact,” he added.

“Now, is that optimal?” he said. “No.”

“But the fact is that since we have a regulatory agency that doesn’t regulate and we have a public health agency that doesn’t protect the public, we have thousands of people who are being injured by products that the FDA knows are unsafe,” he told Ms Loudon.

He pointed out that the FDA knew there was a big problem with Vioxx in mid 2000, and did nothing about it. If the FDA is not going to exercise control over companies, he said, there has to be a system in place “that reins companies in.”

In addition to the agency’s failure to protect the public against Vioxx, Dr Graham also discussed the FDA’s attempts to conceal the increased suicide risks that were found in the reevaluation of the pediatric SSRI studies in early 2004. “The FDA had suppressed a report written by a colleague of mine in drug safety and had prevented him from presenting this information in an advisory committee meeting,” he explained.

“That information leaked to the media,” Dr Graham continued, “embarrassing the FDA because it had been caught suppressing very important information – that most of the antidepressants don’t work for treating children.”

He told Ms Loudon that someone in his supervisory chain at the FDA even initiated a criminal investigation to identify the person who had leaked the information to the media.

With the SSRIs, he says, the FDA should have insisted on a signed informed consent form, that said three things: (1) these are the antidepressants available and only Prozac has been shown to work for children; (2) all the other drugs are no better than placebos; and (3) all these drugs appear to have the ability to increase the risk of suicidal behavior.

As a parent, he stated, if I saw that in writing and the doctor was going to write the prescription for some drug other than Prozac, I could say, “Doc, why are you putting my child on a drug that doesn’t work in kids.”

According to Dr Graham, the FDA did not want patients to have that information, so it refused to require signed informed consent. And, the companies didn’t want parents to have that information because all of a sudden the lucrative “off-label” use of the drugs would have dried up.

Dr Graham also explained that, if the FDA pulls a drug off the market due to safety issues, it not only hurts the marketing of the drug, but also calls into question why it was approved in the first place.

“Therefore,” he said, “you get this culture of cover-up, this culture of suppression, this culture of denial, and this culture that demonstrates above all else that industry is the client and not the American people.”

Most Americans do not realize that a preemption decision on whether to throw out a lawsuit largely hinges on the judge assigned to the case. Attorneys James Beck and Mark Herrmann run the “Drug and Device Law” blog and they post their personal views on topics that arise in the defense of pharmaceutical company product liability litigation.

On May 17, 2007, they posted a piece called, “Picking Spots In Preemption Cases.” The bloggers lamented that “two adverse preemption decisions over the last couple of weeks [ ] have us scratching our heads.”

The opinions referred to were Barnhill v Teva Pharmaceuticals, No 06-0282, (SD Ala Apr 24, 2007), and Kelly v Wyeth, 2007 WL 1302589 (Mass Super Apr 12, 2007).

In their blog, Mr Beck and Mr Herrmann discuss the importance of filing preemption motions with judges who are already known to be unsympathetic to private plaintiffs who sue drug companies.

“With respect to Kelly,” they state, “the most salient point for us is why a preemption motion was brought at all in a state trial court in Massachusetts – a known pro-plaintiff jurisdiction.”

“There’s certainly no history of success with preemption motions in prescription medical product cases in Massachusetts,” they point out.

“Part of preemption strategy is choosing the jurisdictions in which such motions would have a reasonable likelihood of success,” they explain.

“In plain English, you gotta pick your spots,” the attorneys advise.

“If defendants go running helter skelter into courts filing preemption motions no matter how hostile the jurisdiction – well, the result is going to be decisions like Kelly,” they warn.

“That doesn’t do the filing defendant any good,” they state. “Nor does it do anyone else defending prescription drug cases any good.”

On the other hand, in the September 2007 paper, “The Truth about Torts: Using Agency Preemption to Undercut Consumer Health and Safety,” legal scholars, William Funk, Sidney Shapiro, David Vladeck and Karen Sokol, of the Center for Progressive Reform, discuss the importance of jury trials, and the tort system in general.

“It is less susceptible to disproportionate influence by large companies and trade associations than the federal regulatory system,” they note and explain:

“When agencies respond to such influence by failing to regulate, or by adopting inappropriately weak regulations, the tort system becomes the primary legal vehicle for consumers to obtain protection from dangerous products and services.”

“Because tort decisions are made by juries, and because plaintiffs’ lawyers have the necessary skill and incentives to seek appropriate levels of protection for consumers and patients, the civil justice system puts individual consumers on the same footing as large corporations,” according to the paper.

“Unlike the regulatory system,” the authors explain, “the civil justice system makes it possible for members of the general public to be directly involved in governing.”

“This is a crucial distinction,” they note, “since individuals normally lack the same incentives as politically appointed government officials to resolve regulatory problems in favor of regulated entities.”

They also note that, “although corporate interests expend significant resources in an attempt to populate the judiciary with industry-friendly judges in states where judges are elected, there is simply no way to ‘capture’ all the judges throughout the country’s numerous state and federal, trial and appellate courts.”

“Moreover, even where judges are elected, citizens serving on juries are responsible for making decisions about liability,” the paper concludes.

(Written as part of the SSRI Antidepressant Litigation Monthly Round-Up, Sponsored by Baum, Hedlund, Aristei & Goldmans’ Pharmaceutical Antidepressant Litigation Department)

Filed under: 2008, Baum, Fraud, Glaxo, Graham, Paxil, Preemption, suicide

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 Forbes.com 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.”

Filed under: 2006, advertising, disease mongering, DTC, Graham, NSAIDs, population, prices, Vioxx

Merck Not Losing Sleep Over Vioxx Disaster

Evelyn Pringle June 16, 2006

Merck’s top management team reportedly remains unphased by Vioxx litigation woes. In fact, Prudential Equity Group analyst, Timothy Anderson, says Merck’s Chief Executive, Richard Clark, specifically told him that “Vioxx does not keep him up at night.”

According to Mr Anderson, “the company believes that lower court cases will be overturned on appeal, and it is even considering trying to reintroduce Vioxx.”

“A reintroduction might help Merck’s legal case,” Mr Anderson states, “as long as the FDA or its advisers do not decide that Merck’s risks really do outweigh its benefits,” he said in a June 21, 2006, article in Forbes.com.”

Critics say that’s not even a remote possibility because the FDA is still under fire for its own part in the Vioxx disaster and it wouldn’t dare pull a stunt like that.

When it comes to saving Merck in the Vioxx litigation, the FDA is at odds with some of the most powerful leaders in Congress. Senator Charles Grassley (R-Iowa), chairman of the Senate Finance Committee, is on record as saying the Vioxx debacle has shown that the FDA has gotten too cozy with drug companies to conduct proper oversight.

“The Vioxx example showed that the FDA and Merck were too close for comfort,” he said in a speech. “Testimony and documents at our Finance Committee hearing showed that the FDA allowed itself to be manipulated by Merck.”

Documents indeed reveal that the FDA knew about the problems with Vioxx very early on. A memo written by Shari Targum, MD, Project Manager for the Division of Anti-inflammatory Drug Products, clearly shows that as of November 18, 1999, the Data and Safety Monitoring Board of the VIGOR study, a committee independent from Merck, was concerned over the deaths from cardiovascular events in the Vioxx group, compared to the group taking another painkiller.

This memo documents a clear date of recognition by the FDA of when cardiovascular events were brought to the attention of Merck.

Admittedly, if it was up to the Bush administration, the FDA would allow Vioxx back on the market today. Bush does everything in his power to protect the profits of Big Pharma, the industry most responsible for his 8-year rent free lease of the White House.

Under Bush, the FDA has in fact become Big Pharma’s chief enabler when it comes to getting away with murder. A newly released report on June 26, 2006, titled, “Prescription for Harm: The Decline in FDA Enforcement Activity,” says that FDA enforcement actions have declined by 50% since Bush took office.

“The number of warning letters issued by the agency for violations of federal requirements,” the report said, “has fallen by over 50%, from 1,154 in 2000 to 535 in 2005, a 15-year low.”

“During the same period,” it noted, “the number of seizures of mislabeled, defective, and dangerous products has declined by 44%.”

Bush has never hesitated to utilize the FDA in the Big Pharma protection racket. For instance, on January 18, 2006, the FDA issued new regulations for labeling prescription drugs, supposedly aimed at providing doctors and patients with clearer information about their risks. But in the preamble to the regulations, the FDA inserted a claim that lawsuits alleging a failure to warn of known or reasonably knowable risks are preempted by federal law.

Also, amicus briefs filed by FDA attorneys appointed by Bush, on behalf of the drug companies, have tried to claim that because private lawsuits threaten to disrupt the nation’s system of drug regulation, federal standards preempt requirements established by state judges and lawmakers, and that if a state court finds that a drug is unsafe, it is in direct conflict with the conclusion reached by the FDA.

With Bush using the FDA to do the dirty work, Republicans lawmakers up for reelection this fall, don’t have to make a spectacle of themselves fighting for such blatant industry-friendly legislation during an election year.

A partner in the LA based Baum Hedlund law firm, attorney Karen Barth Menzies, has been litigating claims against drug companies for more than a decade and says “the Vioxx public health debacle has served to highlight deep-seeded problems within the FDA.”

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

“Medicine is no longer about health,” Ms Menzies notes, “its about market share and profits.”

Since Bush took office, the FDA has sent out its legal squad to assert the preemption argument on behalf of drug companies in attempt to defeat private citizens in lawsuits numerous times. However, Ms Menzies’ team of Baum Hedlund attorneys has knocked the FDA briefs out of the ball park in a several cases, including Witczak v Pfizer and Motus v Pfizer.

But “the FDA’s legal arm has continued to intervene in private civil lawsuits on the side of drug companies,” she says, “arguing that FDA’s decisions should not be second-guessed by anyone, the federal preemption argument.”

In the past 15 plus years, Ms Menzies notes, the FDA has been worse than “comatose” as the New York Times recently described the agency. “It has sided with industry and become an adversary against consumers,” she points out.

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

In light of recent disasters like Vioxx that have resulted in large part due to a lack of regulatory oversight, Ms Menzies contends that the “FDA’s decisions must be second-guessed for the safety of the public.”

Medical experts agree that the FDA must be second-guessed. “With an FDA that regularly displays incompetence and negligence in its deliberations about the efficacy and safety of medications,” says Dr Grace Jackson, author of, Rethinking Psychiatric Drugs: A Guide to Informed Consent, “it cannot possibly be the case that this federal agency possesses the institutional expertise to which courts or litigants should now defer.”

“Indeed,” she notes, “if the FDA is preempting anything, it is the sound practice of medicine, and the integrity of American health care.”

It will truly be a fatal day for the concept of separation of powers when a federal agency like the FDA can wield the power to enact federal law by filing legal briefs in private lawsuits, funded by tax dollars, to defeat American citizens who are already up against one of the most profitable industries on earth.

Moreover, if FDA attorneys are going waste tax dollars, the least they can to is come up with a few valid arguments. The argument that drug companies are not allowed to warn the public by adding a new warning to a label when dangers become known because it would violate FDA regulations, is ridiculous. There is not now, and there has never been, a law that prevents a drug maker from strengthening a warning or labeling consistent with the company’s specific regulatory ability to do so under 21 CFR 314.70(c)(6)(iii)(A).

The guy responsible for this silly argument is the FDA’s Chief Counsel, Daniel Troy, recruited straight off of Pfizer’s legal team, was Big Pharma’s inside man until he quit the FDA in the fall of 2004.

Instead of going after the drug companies for killing off citizens with lethal drugs in the name of profits, he devoted much of his time filing Joe Tax Payer funded briefs, on behalf of his former industry clients, and even invited drug company attorneys to submit their cases to him for amicus brief consideration.

On March 1, 2004, Jessica Rae Dart, an attorney involved in civil litigation against Pfizer, filed an affidavit in support of a plaintiff’s motion and described a lecture she attended by Mr Troy that clearly shows him offering the FDA’s services to trial lawyers representing drug companies.

On December 15, 2003, Ms Dart said, Daniel Troy, Chief Counsel of the FDA, headed a discussion for pharmaceutical firms and defense attorneys titled, “The Case for Preemption” at the 8th Annual Conference for the In house Counsel and Trial Attorneys, Drug and Medical Device Litigation” in New York City.

During Troy’s “Case for Preemption” talk, she said, Troy stated that he was the initiator behind all the FDA Amicus Briefs and/or Statement of Interest filed on behalf of manufacturers “since the new administration” took over. Specifically, he stated, “I am not the only one who decides,” but “I am the initial proposer.”

According to the affidavit, Troy made it clear that he wanted to file more amicus briefs on behalf of the drug companies and actually invited members of the defense attorney’s audience to approach him with requests for briefs, stating “we can’t afford to get involved in every case,” we have to “pick out shots,” so “make it sound like a Hollywood pitch.”

However, in an obvious effort to try and level the playing field for the little guy, in 2004, Representative, Maurice Hinchey (D-NY), chastised the administration for taking the FDA in a radical new direction, “seeking to protect drug companies instead of the public,” and persuaded the House to cut $500,000 from the budget of the chief counsel’s office as a penalty for the FDA’s aggressive opposition to citizen’s lawsuits.

Although the FDA’s current Chief Counsel, Sheldon Bradshaw, might not have the direct and visible financial links to Big Pharma of his predecessor, critics say, he certainly does not represent a changing-of-the-guard in political leadership at the FDA.

“In fact,” Attorney Menzies says, “following in his predecessor’s footsteps, Bradshaw submitted a legal brief in support of Pfizer’s federal preemption arguments.”

Judges across the nation have flat-out rejected the FDA’s argument. A Minnesota court said it declined “to treat statements from a single FDA legal brief as declarations afforded the preemptive force of law.”

A California court ordered the brief stricken from the record calling it “hearsay and irrelevant,” and an Illinois judge said it “contains nothing more than legal argument by [FDA] counsel.”

Most recently, in a June 6, 2005, Vioxx court hearing, the FDA’s position on preemption hit a major road block with New Jersey State Court Judge, Carol Higbee, who is handling the Vioxx cases, when she labeled the FDA’s Final Rule’s preamble “a political statement by the FDA.” She scoffed at the agency’s preemption claim and said:

“It is contrary to the U.S. Supreme Court’s decisions. It is contrary to all the law on preemption. … In addition to being contrary to the law of the land, it is also contrary to the Constitution of the United States.”

Judge Higbee ended her comments by throwing cold water on any planned attempt by Merck’s legal team to give the preemption argument a whirl, by telling them right-out in open court: “I am not going to allow you to use it.”

Speaking to the Consumer Federation of America in March 2005, Senator Grassley, basically said the FDA can’t be trusted to protect citizens against dangerous drugs like Vioxx because the agency is to “cozy” with companies like Merck.

Based on a clinical trial that took place in 2000, he told the audience, both the FDA and Merck were aware that heart attacks were 5 times more likely in patients taking Vioxx than among those taking a similar drug, but the FDA did nothing to change the labeling on the drug for nearly two years, while Merck aggressively marketed Vioxx on nightly TV.

Describing whistleblowers as “patriots” who risk their careers in the interest of public safety, Senator Grassley recounted the controversy over Vioxx that was fueled in large part by the efforts of FDA scientist, Dr David Graham, to shed light on the drug’s potential risks.

Senator Grassley described how the FDA “disregarded and stonewalled” concerns raised by its own scientist. “Dr. Graham completed a study that found an increased risk of heart attacks and strokes in patients taking Vioxx,” he told the Federation. “His immediate supervisor, however, dismissed this study as ‘scientific rumor.’”

“The very same month that Dr. Graham warned the FDA of the cardiovascular risks of Vioxx,” Senator Grassley continued, “the FDA approved the use of Vioxx for children.”

He told the audience how the director of FDA’s office of new drugs suggested that Dr. Graham water down his Vioxx conclusions and how 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,” the Senator said, “he was also undermined.”

News reports that day show that acting FDA Commissioner Lester Crawford called Dr Graham a “maverick who did not follow agency protocols.”

“This statement,” Senator Grassley told the Federation, “made on the eve of the hearing, could logically serve no purpose other than to intimidate Dr. Graham.”

The Vioxx matter became the focus of the Senate Finance Committee, basically because of the drug’s cost to public health care programs, and the Committee is responsible for oversight of the Medicaid and Medicare programs.

During a November 18, 2004, hearing, the ranking Democrat on the finance committee, Senator Max Baucus, discussed the tax dollars wasted on Vioxx: “In the 5 years that Vioxx was on the market, Medicaid spent more than $1 billion on the drug,” he said.

In addition, he complained about the fact that government programs are now paying the medical bills for patients harmed by Vioxx. “Medicaid bears the cost of any additional medical care necessary when drugs cause injury,” Senator Baucus said.

Merck’s last CEO, Raymond Gilmartin, resigned on May 5, 2005, the same day that another Congressional Committee, the House Committee on Government Reform, released more than 20,000 pages of documents showing how Merck continued to promote Vioxx long after it was aware of the safety problems.

Documents released that day at a Reform Committee hearing on Merck’s marketing practices, described in detail how Merck directed its 3,000-strong sales force to avoid discussions about the cardiovascular risks identified in the 2000 VIGOR study. During visits with doctors, sales reps were instructed to rely on a “Cardiovascular Card” that claimed Vioxx was actually protecting the heart rather than damaging it. The sales reps were specifically trained on how to speak, smile, and position themselves most effectively when talking to doctors.

If doctors asked about Vioxx increasing the risk, the sales reps were instructed to give them a pamphlet written by Merck’s marketing department that claimed Vioxx was eight times safer for heart patients than similar pain medications, and omitted Merck’s findings that Vioxx produced a 5-fold increase in the risk of heart attack and stroke compared with naproxen, the other painkiller used in the study.

The company’s training efforts were obviously successful because Vioxx was approved by the FDA in May 1999, and the drug reached $2 billion in sales in two years, faster than any drug in Merck’s history.

In 2000, the same year the VIGOR study was completed, Vioxx was the most heavily advertised drug in the US with $160.8 million spent on mass media promotion. And the blitz paid off well. In one year, retail sales of Vioxx rose from $329.5 million in 1999, to $1.5 billion in 2000, up 360%, according to a November 2001, report by the National Institute for Health Care Management.

For the same year, Pepsi only spent $125 million advertising its products. Vioxx also beat out Budweiser’s spending of $146 million, and matched Dell Computer’s ad expenditures of $160 million. And by far, the drug beat out Nike’s advertising budget of $78.2 million for shoes, and Campbell soup’s $58 million.

The increase in Vioxx sales from 1999 to 2000 accounted for 5.7% of the one-year increase in total prescription drug spending, more than any other single drug, the report said, and Vioxx was the 13th best selling drug in 2000.

In 2003, Merck upped the anti even more and spent 499.8 million on Vioxx promotion including the cost of sales reps detailing office and hospital-based physicians, advertising in medical journals and the retail value of samples passed out to doctors, according to IMS Health, Integrated Promotional Services in April, 2004. In return Vioxx saw growth of 24% and became the 6th best selling drug.

What’s that old saying about the bigger they are the harder they fall?

Nowadays, instead of spending hundreds of millions of dollars promoting Vioxx, shareholders are paying hundreds of millions a year for attorney fees. As of December 31, 2004, in its 2005 annual report, Merck said it had a reserve of $675 million solely for its future legal defense costs related to Vioxx. And in the fourth quarter of 2005, Merck said it recorded another charge of $295 million to increase the reserve.

“This reserve is based on certain assumptions,” the annual report said, “and is the best estimate of the amount that the Company believes, at this time, it can reasonably estimate will be spent through 2007.”

There is no money listed anywhere in Merck’s financial filings set aside to pay damages to any injured party, at least through 2007. The whole wad goes for Vioxx “legal defense costs.”

And to think, Republicans have the nerve to say that personal injury attorneys who go up against attorneys with a war chest of close to $700 million a year are financial gluttons.

However, thanks to a helpful group of plaintiff’s attorneys, going up against Merck in jury trials is getting bit easier. The group put together what they call a pre-made Vioxx trial package, complete with a guide to pursuing a claim against the corporate giant.

The package reportedly organizes and edits all of the information that shows Merck knew about the dangers of Vioxx but failed to inform consumers and includes the most damaging documents and evidence available against the drug maker. The package is offered on a small contingency fee basis and costs nothing until the lawsuit is won.

This month, Merck’s legal eagles were hit up once again when the New England Journal of Medicine issued a correction to a paper it published last year on Vioxx that mistakenly said that heart risks only became apparent after 18 months. The Journal editors deleted the 18 month statements saying a statistical error by Merck undermined the evidence for them.

All through litigation thus far, Merck’s main argument has been that the risk to patients from Vioxx did not begin until after 18 months of use, and with one sweep of the pen, the NEJM blew a hole in that defense.

But then juries are not buying into the 18 month defense in any event. In the first jury trial, in August 2005, the jury held Merck liable for the death of Vioxx victim, Robert Ernst, age 59, who died after only taking Vioxx for eight months.

Internal company documents introduced at the trial showed that Merck was aware of the problems with Vioxx as early as 1997. Attorney, Mark Lanier, showed jurors documents and e-mails to prove that Merck scientists knew about the cardiovascular risks (CVs), two years before the drug was approved.

For instance, one 1997 email written by Merck scientist Dr Alise Reicin, said: “The possibility of increased C.V. events is of great concern.”

“I just can’t wait to be the one to present those results to senior management,” he wrote.

As evidence to prove that physicians were deliberately misled, the jury was shown a 2001 Dear Doctor letter, in which Merck specifically stated that in the largest study ever of more than 4000 patients taking Vioxx, only 0.5%, or about 20 patients, had incurred CVs, when in fact, 14.6% of the patients, or 590, had cardiovascular problems, according to a Merck report submitted to the FDA.

It was also proven at trial that in April 2001, the doctor who prescribed Vioxx to Mr Ernst, had received the letter with the fraudulent statistics.

Mr Lanier played a video for the jury that showed sales reps were told that Vioxx did not increase heart attacks and were trained to view doctors concerns about CVs as “obstacles” to be avoided or dismissed. Another training document told sales reps to play “Dodgeball” if doctors raised questions about CVs.

In a more recent on-going trial, on July 5, 2006, more damaging testimony against Merck was given by Dr Lemuel Moye, a professor of biostatistics at the University of Texas, in a California case filed by a 71-year-old, Stewart Grossberg, who told the jury that Merck’s clinical trials conducted as far back as 1996, showed patients taking Vioxx were at risk for heart attacks and strokes, long before the drug went on the market, and that after reviewing the trials, he concluded that Vioxx carried more risks to patients than benefits.

But legal experts say that back in April 2006, Merck received the worst news possible when it lost an appeal to deny certification of a Vioxx-related class action lawsuit. They says the court’s decision to certify third-party payers, like health insurance companies, HMOs, and unions, has to be the most disturbing development for the company to date.

By ruling against Merck, the court gave the OK to apply New Jersey’s consumer fraud statutes to all members of the class, even to plaintiffs from states that have different laws. Experts predict that the consequences of this ruling will be profound and far-reaching, and the costs to Merck potentially staggering.

In light of the verdict in the April 2006, trial of Cona v Merck and McDarby v Merck, in which the jury said Merck violated New Jersey’s consumer fraud statute because it misled physicians about the cardiovascular risks of Vioxx and concealed information about those risks from doctors, experts say, the appeals court’s ruling might just turn out to be the nail in the coffin for Merck.

Christopher Seeger, the lead lawyer in the class action filed by HMOs, insurers, and unions, says that Judge Higbee, who is overseeing about 5,000 Vioxx cases, should apply the findings of this jury to the class action, which he said could be worth $10 billion.

Mr Seeger told Bloomberg News on April 5, 2006, that this was devastating for Merck: “This jury just said ‘Yes’ to consumer fraud, so I think we go right to damages.”

Mr Seeger is referring to collateral estoppel a situation in which the judgment in one case prevents, or estops, a party from litigating the same issue in future cases. Because of the consumer fraud verdict, Mr Seeger contends that Merck may now be permanently bound by the jury’s ruling.

Indeed, Bloomberg says, a judge could decide that the ruling that Merck failed to warn of Vioxx’s risks could be applied to thousands of future trials in New Jersey, leaving the jury to decide only whether Vioxx caused specific heart attacks.

Barry Turner is an academic lawyer in the UK who has taught medical ethics and for a number of years has been involved in litigation activities related to the pharmaceutical industry.

He has been advocating the use of federal and state false claims statutes against Big Pharma for years. “I take the view that because of the harsh penalties imposed when these actions are successful,” he explains, “that this is the legal strategy that will work against these people.”

“PI suits,” he says, “may very well be morally righteous but they will never make this industry change its ways.”

“What is at issue,” he continues, “is that companies factor litigation costs into ‘research and development’ and other costs of sales, so it does not hurt them to pay out in damages, what they already budgeted for.”

“The Federal and State False Claims Act actions are different,” he notes, “a drug company hit by a big one of these will have to pay out colossal amounts in fines and damages, hundreds of millions in most cases,” he says, “and these come out of profits.”

“Then the stock will go down,” he explains, “and they can be hit again under the Sarbanes Oxley Act.”

“And if anyone thinks that Sarbanes Oxley is feeble legislation,” he says, “they can always ask the Enron executives.”

“As well as defrauding the taxpayer,” Mr Turners notes, “the consequences of these deliberate and deceitful acts hurts shareholders when the litigation causes serious downturns in stock value.”

“This is a violation of Sarbanes Oxley,” he says, “and sooner of later there will be a major action here.”

In each of the cases Merck has lost, the juries have ordered the drug giant to pay large punitive damage awards, creating additional problems for the company. Punitive damages are awarded to punish a defendant and deter future misconduct. They are not covered by insurance because the conduct is an intentional act on the part of the insured; and the intent of punitive damages would be lost if a defendant could avoid payment simply by buying more insurance.

In the state of New Jersey, punitive damages are allowed to be as much as 5 times the amount of compensatory damages. The Texas $229 million punitive damage award against Merck, even when reduced, will still be about $26 million. Legal analysts say no company could avoid financial ruin if ordered to pay tens of thousands of $26 million punitive damage awards.

Punitive damages provide a basis for a derivative lawsuit seeking damages for conduct that compromised the value of the investments of shareholders. These types of lawsuits are being filed for much less than what Merck pulled with Vioxx.

For instance, in March 2005, a class action lawsuit was filed in the US District Court for the District of Massachusetts, on behalf of shareholders in Elan Corp PLC, after the company’s withdrawal of the multiple sclerosis drug Tysabri, with many of the same allegations that can be made against Merck.

The complaint alleges that Elan failed to disclose and misrepresented material adverse facts in connection with Tysabri including serious immune-system side effects and that the information was concealed in order to fast track Tysabri for FDA approval.

In any event, notwithstanding that Merck continues to contend that it will try every single case, legal analysts say, state courts will never be able to handle the trials for the lawsuits already filed, much less the additional cases still being filed on a regular basis.

“At some point courts are going to be clogged with these cases and judges will start to put pressure on Merck and the plaintiffs to settle these cases,” according to John Leubsdorf, professor of law at Rutgers Law School, on CNN Moneyline on April 26, 2006.

“The only scenario in which they won’t settle,” he says, “is if they win so much that all the plaintiffs go away.”

But experts say that is definitely not going to happen.

Filed under: 2006, FDA, FDA Crawford, Graham, Merck, Preemption, stroke, Troy, Vioxx, whistleblower

Merck Legal Team Makes Killing Off losing Vioxx Strategy

Evelyn Pringle June 5, 2006

Not much has changed at Merck since Vioxx was pulled off the market. The only difference for shareholders is that instead of spending hundreds of millions of dollars a year to promote Vioxx, the attorney’s fees are now costing hundreds of millions of dollars a year.

As of December 31, 2004, Merck had established a reserve of $675 million solely for legal defense costs related to Vioxx, according to the company’s 2005 annual report.

During 2005, the report said, Merck spent “$285 million in the aggregate in legal defense costs worldwide” related to Vioxx.

In the fourth quarter of 2005, Merck recorded a charge of $295 million to increase the reserve solely for its future legal defense costs related to Vioxx, the report said, to $685 million as of December 31, 2005.

“This reserve is based on certain assumptions,” Merck told shareholders, “and is the best estimate of the amount that the Company believes, at this time, it can reasonably estimate will be spent through 2007.”

That said, the company has not set aside one dime for potential damage awards in Vioxx trials through 2007. Which means the only good news to report as far as Merck’s legal strategy of a case by case defense of thousands of lawsuits in the years ahead, is that the company’s legal team will keep raking in dough while Merck slowly goes under.

We now know that tens of thousands of people died, and many more were injured, because Merck concealed the information about the adverse effects of Vioxx. But to date, Merck has not paid one red cent in damages. And the appeals process initiated by Merck attorneys, guarantees that that money awarded to any plaintiff so far will be years away. And even then, experts say, the close to $300 million in damages awarded will be reduced to $48 million by caps on punitive damages.

In addition to the thousands of personal injury and wrongful death claims, Merck also faces class actions, filed on behalf of prescription drug plans and insurance carriers seeking treble damages, that experts say could expose Merck to multi-billion dollar verdicts.

The plaintiffs in the class actions allege that Merck misrepresented the safety profile of Vioxx, ignoring clear and early warning signs of its risks in order to continue its sale, and that had they known the truth, they would not have included Vioxx as an approved drug or agreed to reimburse plan members for its high cost. They also contend that Vioxx was no more effective than over-the-counter painkillers already on the market.

In seeking reimbursement, these plaintiffs will not have to prove that Vioxx caused any injuries or deaths. All they will have to show is that Merck continued to push Vioxx after it knew about the drug’s increased risks.

And on top of the class action monsters, there is the pesky little matter of lawsuits filed on behalf of the individual states that also have the potential to expose Merck to billion dollar damage awards. The state actions are similar to the class actions and seek repayment for money paid for Vioxx by state run health care programs like Medicaid.

The damages sought are huge. For instance, Texas Attorney General, Gregg Abbott, is seeking $168 million and says he can prove total damages in excess of $250 million over five years in payments for Vioxx.

According to Merck’s 2005 annual report, “The Company has received a Civil Investigative Demand from a group of the Attorneys General of 31 states and the District of Columbia who are investigating whether the Company violated state consumer protection laws when marketing Vioxx. The Company is cooperating with the Attorneys General in responding to the Civil Investigative Demand.”

The state of New York’s Controller, Alan Hevesi, claims his state’s retirement fund lost $171 million when Merck’s stock value dropped and that teachers, policemen, and firefighters have lost $287 million all total from their retirement funds.

The NY suit alleges that Merck violated federal securities laws by failing to disclose information about the safety risks of Vioxx. “The New York State Common Retirement Fund is exactly the kind of sophisticated and knowledgeable financial institution that the Congress, in the 1995 Private Securities Litigation Reform Act, intended to lead such class action suits,” Mr Hevesi said in a press release.

The NYSCRF is reportedly the second largest public pension fund in the US, in terms of membership and assets, with more than 970,000 retirees, beneficiaries and members and over $120 billion in assets.

“Merck must be held legally responsible for its actions,” Mr Hevesi noted in his press release. “These actions have put lives at risk and cost shareholders billions of dollars.”

Experts say that for Merck’s “no pay” strategy to work, the company would have to win virtually every one of the of individual lawsuits and then hope that such success would help defeat the claims by state health care programs, and the insurance and healthcare plans. Which they say is absolutely impossible because Merck has already admitted that consumers who used Vioxx over 18 months were exposed to an increased risk.

Billion dollar awards could easily drain Merck’s insurance coverage and punitive damages based on evidence that shows the company withheld, manipulated, and misrepresented the results of clinical studies, and therefore willfully marketed Vioxx, are not covered by insurance and must be paid by Merck directly.

According to attorney, Barry Turner, “Merck may be holding its own at the moment but the fact is that the lying and deceit cannot continue indefinitely without some major blow to stockholder funds.”

“I do think that Merck will get burned over this one,” he says, “if their lawyers are dumb enough to fight each personal injury case.”

Even though insurance does not cover punitive damages, Mr Turner says, “personal injury litigation costs are factored into so called R&D and marketing costs and the end user price covers all of this money.”

“But the securities actions are different,” he says. “Anyone who thinks this strategy is going to help the stockholders is crazy,” he warns.

He predicts that Merck will soon start trying to settle PI cases with confidentiality clauses. “This would mean less payouts,” he says, “and less knock on effect as other plaintiffs and their lawyers stand by to watch the action before running their own cases.”

The fact is, that in every new trial, the lawyers for the plaintiffs introduce more embarrassing evidence. For instance, in a California trial that began last week, a former Merck employee, testified that the company did not inform federal authorities about two clinical trials in which users of Vioxx were found to be more likely to die than people given a placebo.

Dr Edward Scolnick, the former head of Merck’s research laboratories, said in a videotaped deposition played for the jury, that he did not believe the numbers were coincidental. “It’s not likely due to chance,” he said.

Dr Scolnick testified that people on Vioxx died at a rate 4 times higher than those who didn’t receive the drug in one trial, and the rate was 2 1/2 times higher in the other. Both studies were done in 2001 to see if Vioxx could help Alzheimer patients.

He said Merck did not turn over results to the FDA when company officials met with an FDA representatives in April of that year and that he was not aware of the trial results at the time.

The juries have also viewed internal documents that show Merck training its sales reps to avoid answering tough questions from doctors about the adverse effects of Vioxx on the heart. In one training manual, each of the last four pages of potential questions that doctors might ask, the manual said “DODGE!” to avoid answering.

In the first trial in Texas, the plaintiff’s attorney, Mark Lanier, presented documents showing that Vioxx sales reps at one time received a $ 2,000 bonus if one of the doctors they met with prescribed Vioxx more than 55% of the time, and that the rep was paid another $2,000 if the rate exceeded 61%.

Mr Lanier also showed the jurors a Merck SEC filing that said Merck’s CEO Gilmartin was making about $3 million in salary and bonuses in 2000, when the company received the results of the clinical study in which Vioxx users suffered 5 times as many heart attacks as those taking naproxen.

In March 2006, Merck lost a major legal battle that had the company’s attorneys kicking and screaming, when US District Judge Eldon Fallon ordered FDA scientist, Dr David Graham to testify in a deposition in response to a subpoena from attorneys for Vioxx plaintiffs.

A major part of Merck’s legal strategy has been to continuously point out that Vioxx had been approved by the FDA. Experts say, Dr Graham’s testimony will throw a monkey-wrench into that strategy because it will reveal the long-fought battles over the deliberate concealment of the safety risks of Vioxx within the FDA itself.

Judge Fallon said the deposition would be limited to material relevant to the up-coming federal trial in July 2006, and Dr Graham’s previous public statements. In the deposition, Dr Graham alleged that Merck dragged its feet about changing the label on Vioxx to warn of the increased risk of heart attacks.

So now in their latest run-up-the-costs tactic, Merck attorneys have filed a motion to limit the use of Dr Graham’s deposition claiming it goes beyond anything Dr Graham previously said and therefore portions of it should not be heard by a jury.

Merck’s memorandum filed with the motion, asks the court to exclude the following: “The two-year period for coming up with the revised label for a problem as serious as high risk of heart attacks with Vioxx, this is an extraordinary long period of time, and the only explanation based on my long experience at FDA is that there was foot dragging by the company.”

But this statement is not new. Dr Graham publicly discussed the failure by Merck and the FDA to warn the public and add a new label to Vioxx while testifying at a congressional hearing a couple years ago on November 18, 2004.

In regard to the death and injuries caused by those failures, he in fact said: “I strongly believe that this should have been, and largely could have been, avoided.”

Maybe Merck would rather have the jury listen to how Dr Graham put the number of people injured by Vioxx into perspective, when he told members of the Senate committee that instead of side-effects from Vioxx, to picture the number of people as if it were airline crashes.

“If there were an average of 150 to 200 people on an aircraft,” he told the panel, “this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky.”

“This translates to 2-4 aircraft every week,” he noted, “week in and week out, for the past 5 years.”

Merck also does not want the jury to hear Dr Graham say that Vioxx should not have been approved to begin with and that after learning the results of the VIGOR study in 2000, that Merck should have done a large study to determine whether Vioxx damaged the heart or blood vessels; and that an FDA official had recommended “at least” a warning label for the drug.

There is nothing new about these allegations either. Dr Graham made basically the same charges when he told the committee that the FDA “views the pharmaceutical industry it is supposed to regulate, as its client, over-values the benefits of the drugs it approves and seriously under-values, disregards and disrespects drug safety.”

Dr Graham also pointed out that even when the FDA did try to take measures to limit harm, the agency lacked the enforcement authority to make companies comply. In the case of Vioxx, he said it took more than 2 years to get Merck to add the increased risk of heart attack and stroke to its label.

In their memorandum, Merck attorneys complained because: “Much of Dr Graham’s testimony is an elaboration of why and how he believes the FDA is ‘broken.’”

“However,” they wrote, “Congress (not the jury) is the only body that can address Dr Graham’s concerns.”

Well then perhaps Merck should call members of congress to testify at future Vioxx trials to explain how Merck got top FDA officials to protect Vioxx profits by concealing the health risks associated with Vioxx that were revealed in damaging studies as far back as 2000.

In a statement following the verdict in first trial, Senator Grassley was quick to point out the FDA’s involvement in the Vioxx disaster. “Those running the nation’s public safety agency repeatedly dismissed the concerns of their own scientists and seemed to do everything possible to keep the public in the dark about emerging problems with Vioxx,” he said.

“The Food and Drug Administration was also negligent in the Vioxx case,” Senator Grassley declared.

A hearing on Merck’s motion is scheduled for July 5, 2006, to decide what parts of Dr Graham’s deposition will be allowed in during the trial of a suit brought by retired FBI agent, Gerald Barnett, who had a heart attack in September 2002.

Sooner rather than later, the steady stream of multi-million dollar judgments is bound to enrage Merck shareholders who have already suffered massive losses in their investments since October of 2004.

When Vioxx was pulled off the market in September 2004, the drug’s $2.5 billion in annual sales equaled 11% of Merck’s revenues. When news of the recall broke, Merck shares plunged $12 to $33, wiping out $28 billion of stock value in one day for investors, pension funds and mutual funds.

Stock value dropped another $2.35 per share, or 7.7%, following the first jury’s verdict for the plaintiff in Texas on August 19, 2005.

Up until then, analysts had estimated Vioxx liability to be as high as $18 billion. But by the following Monday morning after the verdict, analyst, David Moskowitz, from Friedman, Billings, Ramsey & Co, told CNBC that he had raised his forecast for Merck’s total tab from $11 billion to $50 billion.

Critics says, Merck is misleading investors by not making any provision whatsoever for the Vioxx liabilities in financial statements. In its annual report, regarding Vioxx litigation for 2006, Merck said:

“The Company has not established any reserves for any potential liability relating to the VIOXX Litigation. Unfavorable outcomes in the VIOXX Lawsuits or resulting from the VIOXX Investigations could have a material adverse effect on the Company’s financial position, liquidity and results of operations.”

Overall, there appears to be no good news out there for Merck shareholders. According to the January 27, 2006, Business Week Online, research from Morgan Stanley and Danish investment bank, Jyske Bank, estimates that patent expirations this year will equal 25% of Merck’s 2005 sales as major medicines face generic competition.

And in the meantime, more and more angry consumers are saying civil damage awards are not a enough punishment for Merck and that top management people who allowed the Vioxx disaster to happen should be in jail.

Although unbeknownst to most people, criminal charges are being considered that could lead some of the culprits in that direction.

In New Jersey, the $9 million punitive damage award against Merck in April 2006, resulted in the case being referred to the state’s Attorney General. Under the New Jersey Punitive Damage Act, any time there is a punitive damage award there must be an investigation “as to whether a criminal act has been committed by the defendant.”

By now, there’s certainly plenty of evidence in the public domain to prove that criminal acts were committed. For starters, the Attorney General can review the victims revealed in a 2004 study, lead by FDA scientist, Dr Graham, that says Vioxx caused as many as 140,000 heart attacks and strokes and killed as many as 55,000 people.

Filed under: 2006, FDA, FDA hearing, Graham, Judge Fallon, Merck, stroke, Vioxx

FDA Used to Shield Big Pharma From Lawsuits

Evelyn Pringle May 12, 2006

In January 2006, the FDA announced the Bush administration’s latest gift to Big Pharma in a statement that said people who believe they have been injured by drugs approved by the FDA should not be allowed to sue drug companies in state courts.

“We think that if your company complies with the FDA processes, if you bring forward the benefits and risks of your drug, and let your information be judged through a process with highly trained scientists, you should not be second-guessed by state courts that don’t have the same scientific knowledge,” said Scott Gottlieb, the FDA’s deputy commissioner for medical and scientific affairs.

To soften the blow, the agency’s claim of federal preemption was included as a preamble to the long sought after new drug labeling guidelines. In response to the FDA’s statement, Senator Edward Kennedy (D-MA) issued a statement of his own that said: “It’s a typical abuse by the Bush Administration – take a regulation to improve the information that doctors and patients receive about prescription drugs and turn it into a protection against liability for the drug industry.”

The ploy was also readily recognized by state lawmakers and trial lawyers as another attempt to reduce the public’s ability to hold Big Pharma accountable. “Eliminating the rights of individuals to hold negligent drug companies accountable puts patients in even more danger than they already are in from drug company executives that put profits before safety,” said Ken Suggs, president of the Association of Trial Lawyers of America.

“The fact that the drug industry can get the FDA to rewrite the rules so that CEOs can escape accountability for putting dangerous and deadly drugs on the market is the scariest example yet of how much control these big corporations have over our political process,” Mr Suggs told the Washington Post.

According to Attorney Mark Labaton, a partner at the firm Kreindler & Kreindler, LLP, with offices in New York and LA, “the Administration’s recent efforts to misuse federal rulemaking in the pharmaceutical and other areas to eviserate consumer rights is a big step backward.”

“The new FDA rules to limit consumers’ rights,” he says, “are part and parcel of a larger effort to deny persons injured by unsafe products – be they drugs, cigarettes or automobiles – any form of redress.”

“Clearly,” Mr Labaton notes, “this Administration and its supporters want to slam the courthouse doors on working men and women injured by unsafe products.

He says its ironic that “an Administrative that calls itself “compassionate” and “conservative” consistently turns its back on “limited government” and “states rights” when it comes to protecting the rights of seriously injured consumers.”

Upon learning of the FDA’s power grab, the National Conference of State Legislatures, a bipartisan group that represents state lawmakers, accused the FDA of trying to seize authority that it did not have. The organization bases its opposition, in part on the following:

“FDA has usurped the authority of Congress, state legislatures and state courts. There is no statutory authority in the FDCA for FDA to preempt state product liability laws as they relate to prescription drugs.

“Instead of seeking valid congressional authority, unelected agency officials are seeking to preempt state product liability laws by writing this preemption into a final rule, thereby undermining state policy and judicial decision made in this area.

“State tort laws and civil justice systems serve as an important check on federal standards. Our civil justice system establishes a duty of care that protects citizens when the federal government is too slow to act or when federal standards are insufficient. States have the ability to achieve greater protections for their citizens through successful product liability lawsuits.”

In an earlier gift delivered to Big Pharma in December 2005, Republican leaders, and specifically Senator Bill Frist (R-TN), attached protective provisions to a Department of Defense appropriations report that gave the industry “unprecedented immunity,” according to Democratic lawmakers who described the underhanded move as follows:

“Republican leaders added provisions to the conference report after cutting a back-room deal in the middle of the night. The conference report grants sweeping immunity to drug companies for injuries caused by vaccines and drugs and for the administration of those vaccines and drugs, even if they are made with flagrant disregard for basic safety precautions.

“Moreover, the compensation program is a sham, leaving people who become injured from a drug or vaccine without recourse.”

Since 2002, Senator Frist had tried numerous times to insert this rider in Homeland Security Bills after thousands of lawsuits were filed by parents who believe the mercury-based preservative thimerosal, contained in childhood vaccines until recently, caused autism and other neurological disorders in their kids.

The rider could save Big Pharma hundreds of millions, if not billions of dollars.

The latest revelation on this little stunt came on May 8, 2006 when the Tennessean reported that vaccine industry officials helped shape legislation behind the scenes that Frist secretly amended into a bill, according to e-mails obtained by Pubic Citizen, a public advocacy group.

The industry group, called the Biotechnology Industry Organization, wanted the vaccine liability language in the bill, the e-mails proves.

“At Senator Frist’s staff’s request, this morning, BIO (Tom and I) participated in a meeting with three other industry representatives (Sanofi and an outside counsel who works for both Pfizer and Roche, I believe), administration staff (HHS, DoJ and WH Leg Affairs), and Liz Hall to further discuss liability,” BIO official Dave Boyer wrote in a November e-mail obtained by Public Citizen.

Other E-mails and documents show that BIO met privately with Frist’s staff and the White House to figure out ways to give drug makers protection from people injured by vaccines.

“The lack of any restriction on jury trial is problematic,” the BIO analysis said. “Where injured parties have no other avenue for relief, juries are likely to find ways to award damages.”

In another e-mail, Boyer described a meeting in which Karl Rove said it was “important to the President that a bill move this year,” and said “they had invited industry to discuss what they understood to be a few key remaining points” of contention.

Republicans members of Congress had tried on several occasions to enact similar legislation of its own, but with voters already so angry over soaring drug costs, they finally had to back off.

With less than 3 years left in office, and the Democrats positioned to take over Congress in the fall elections, Bush had to find a way to repay Big Pharma so he came up with the bright idea to utilize the FDA and kill 2 birds with one stone.

This route would spare Republicans the task of trying to pass pro-industry legislation in an election year and still reward Big Pharma for the more than $80 million that Republicans received from drug makers over the past decade.

Since 2000, the top drug corporations, their trade group, and their employees gave more than $10 million to 527 organizations, tax-exempt political committees which operate in the grey area between federal and state campaign finance laws, according to Drug Lobby Second to None, July 7, 2005, M. Asif Ismail.

Nearly $87 million of the contributions went to federal politicians, with almost 69% going to Republicans. Top recipients include Bush, with upwards of $1.5 million, and members who sit on committees that have jurisdiction over pharmaceutical issues, reports Drug Lobby Second to None.

During Bush’s campaigns, 21 pharmaceutical industry executives and lobbyists achieved “Ranger” or “Pioneer” status, which means they raised at least $200,000 or $100,000, respectively, during the 2000 or 2004 campaigns.

According to Public Citizen, the group included 5 executives from brand-name drug companies, 6 officials from HMOs, the CEO of a pharmacy services company that runs a PBM, the head of a direct-mail pharmacy, and 8 Washington lobbyists who represent drug companies and HMOs.

Frist is never shy when it comes to calling in markers from drug companies. In November 2004, when he wanted to take a victory tour celebrating the newly elected Republican senators, “A Gulfstream corporate jet owned by drug maker Schering-Plough was ready to zip the Senate majority leader to stops in Florida, Georgia and the Carolinas,” according to the April 25, 2005 USA Today

Frist’s PAC reimbursed Schering $10,809, the equivalent of a commercial first-class fare, but that was only a fraction of the cost of a charter flight, which would have cost 3 times that much. Besides, the cost was almost a wash because Schering had donated $10,000 to Frist’s committee in 2003-04, according to USA Today.

Its also worth pointing out that Big Pharma was the largest contributor to the National Republican Senatorial Campaign Committee while Frist chaired the Committee.

The ever-growing number of lawsuits in state courts has created a nagging fear in drug makers. Local juries and elected judges in state courts are much more likely to go against drug giants than juries and appointed judges in federal courts which is a one of the main reasons why Big Pharma wants all cases moved to federal courts.

Vioxx set off the industry’s worst nightmare when users or their heirs began filing lawsuits all over the US. According to the January 24, 2006, Associated Press, Merck currently faces 9,200 Vioxx lawsuits, with about 4,050 in federal courts and the rest in state courts.

But Vioxx by far is not the only worry for Big Pharma. These days, every major drug company has litigation problems involving one or more FDA-approved products and a few prominent law firms have taken up the battle for plaintiff’s in state courts.

For instance, since 1990, the Los Angeles based Baum Hedlund Law Firm has been handling SSRI (selective serotonin reuptake inhibitor) suicide/violence cases and served on the Plaintiffs’ Steering Committee in the first SSRI-suicide litigation involving Prozac, the first SSRI approved by the FDA.

Baum Hedlund partner, Karen Barth Menziess, has been litigating claims involving injuries stemming from SSRIs such as Prozac, Paxil, Zoloft and, more recently, Lexapro/Celexa, for over a decade.

She heads a team of attorneys, who have successfully defeated Pfizer’s and the FDA’s preemption arguments in a number of cases, including Motus v Pfizer and Witczak v Pfizer.

In addition to her court activities, Ms Menziess has testified about the dangers of SSRIs before the California State Assembly and the FDA’s Psychopharmacologic Drugs Advisory Committees and met with members of Congress regarding the risk of antidepressant induced suicidality and preemption issues.

Ms Menziess wrote an article discussing the ill-effects of preemption in Mealey’s Emerg. Drugs & Devices 27 (2006), titled, “Preamble To FDA Final Rule: FDA’s Latest Effort To Immunize Drug Manufacturers From Tort Liability At The Expense of Consumer Safety,” and stated in part:

“Pharmaceutical industry lobbying efforts and zealot tort reformers have sired a new wave of brazen attempts to shield drug manufacturers from tort liability.

“The preemption language in the preamble to the Final Rule is but the latest attempt. Preemption has become the argument du jour and politically appointed regulatory officials the mouthpieces. The crafty messages sound of consumer protection, but are just the opposite. Limiting the liability of drug companies will not improve public safety.

“The FDA s purported position on preemption assumes that the FDA is infallible and that negligent misconduct by pharmaceutical companies should be the sole purview of FDA. Recent regulatory failures demonstrate that FDA is neither infallible nor does it have the capability of policing drug manufacturers negligent misconduct.”

The Bush administration went up against a tough opponent in Baum Hedlund when it turned to the courts, and had the FDA file amicus briefs hoping the courts would rule in favor of preemption, but those attempts also failed.

Ms Menziess explains some of the history of the FDA’s intervention into lawsuits she was involved in stating: “Until his resignation in late 2004, FDA Chief Counsel, Daniel Troy, was the pharmaceutical industry’s ‘inside man,’ filing legal briefs on behalf of former clients such as Pfizer (the maker of Zoloft) and soliciting defense attorneys to submit their cases for government amicus brief consideration.”

“Although the newly appointed Chief Counsel, Sheldon Bradshaw, lacks the blatant pharmaceutical industry ties that Troy had,” she advises, “he clearly was not selected to his position because of a sudden change-of-heart in the political leadership or direction of the FDA.”

“In fact,” Ms Meziess says, “following in his predecessor’s footsteps, Bradshaw submitted a legal brief in support of Pfizer’s federal preemption arguments.”

The FDA filed its first brief in favor of a manufacturer of SSRIs in September 2002 in Motus v Pfizer, one of Baum Hedlund’s cases in California, which was pending in the 9th Circuit Court of Appeals.

Daniel Troy, who was the FDA’s Chief Counsel at the time, was contacted by Pfizer’s national counsel, Malcolm Wheeler, in the summer of 2002 requesting that the government get involved in this private lawsuit to help Pfizer with its preemption argument related to Zoloft-induced suicidality.

Despite the fact that Pfizer had been one of his clients and Troy was paid over $358,000 for work he had conducted for Pfizer in the year he took office, Troy acquiesced, arguing that there was no impropriety in doing so because he did not become involved until after the required 1-year period in which government employees may not participate in official activities involving former clients.

From public accounts, it appears that the 1-year “grace period” elapsed less then a month before Troy entered the fray.

Troy argued in the FDA brief that, even though Pfizer never sought to strengthen Zoloft’s warning label concerning suicidality, any warning, no matter how worded, that suggested a link between Zoloft and suicidality would have been false and misleading, would have misbranded the drug, and the FDA would have rejected any effort by Pfizer to use such a warning.

The 9th Circuit never decided the preemption issue, instead ruling on another appellate issue, which concluded the case on unrelated grounds.

Nevertheless, Menzies said that Pfizer has continued to use the brief in its battle against Zoloft-induced suicide cases, arguing that the lawsuits are federally preempted and should be dismissed.

But Judges across the US have been rejecting Pfizer’s arguments, as well as the FDA brief itself. A federal judge in Texas pointed out that the law “allows, even encourages, manufacturers to be proactive when learning of new safety information related to their drug.”

“Manufacturers, not the FDA, are tasked with the responsibility of taking proactive steps once a manufacturer learns of ‘reasonable evidence of an association of a serious hazard with a drug,’” the judge stated.

A state court judge in California ordered the FDA brief stricken from the record, calling it “hearsay and irrelevant.”

In an Illinois case, the judge said the brief “contains nothing more than legal argument by [FDA] counsel.”

In a Zoloft suicide case in Minnesota, the court rejected Pfizer’s arguments, stating that it “declines to treat statements from a single FDA legal brief as declarations afforded the preemptive force of law.” The same judge also called Pfizer’s arguments “perverse” and a “public policy argument gone awry.”

Ms Menziess notes that the FDA’s legal stance on preemption is “particularly egregious in the wake of congressional investigations involving FDA failures to protect the public health, in particular related to antidepressants.”

Without state liability laws, she says, drug companies will be able to escape liability for injuries and deaths caused by drugs like SSRIs and Vioxx.

Baum Hedlund currently represents approximately 50 victims and their families in cases involving alleged antidepressant-induced suicide and suicide attempts, over one third of whom are children and adolescents.

As with Vioxx, the risks associated with SSRIs were also kept hidden. Ms. Menziess’ litigation has evidence from as far back as the 1980′s that people taking SSRIs were at a heightened risk of suicidality, and not just children, she notes.

In fact, in the early 1990s, it was the FDA safety officer Dr David Graham, of recent Vioxx fame, who raised concerns about the risk between antidepressants and suicidality, but no one listened, Ms Menziess says.

Fourteen years later, the FDA finally ordered black box warnings labels on SSRIs alerting physicians about the increased risk of suicidality. Ms Menziess describes the FDA during these years as “complacent, ignoring its own internal scientist when they raise concerns, and in the pocket of industry.”

She believes that the FDA would never have confronted the issue had it not been for the public outcry from victims, consumer groups, courageous experts willing to place their careers on the line, investigative reporters and pressure from certain members of Congress; and yes, she says, “lawyers uncovering the drug industry’s dirty little secrets through legal discovery and speaking out about the dangers.”

Ms Menziess points out that “the antidepressant controversy and resultant congressional investigations, and later, the Vioxx public health debacle, have served to highlight deep-seeded problems within the FDA.”

Over the past couple of years, a growing number of lawmakers have been turning up the heat on both the FDA and the industry in response to their combined failure to reveal the problems found in studies conducted on drugs like SSRIs and Vioxx.

At one point, Senator Charles Grassley (R-IA), Chairman of the Senate Finance Committee, came right out and accused the FDA of suppressing studies in order to protect industry profits and the careers of certain FDA officials.

“The Vioxx example showed that the FDA and Merck were too close for comfort,” Senator Grassely told Health News on March 12, 2005. “Testimony and documents at our Finance Committee hearing showed that the FDA allowed itself to be manipulated by Merck,” he said.

The results of a trial that took place in 2000, surfaced that showed that the FDA and Merck were aware that heart attacks were 5 times more likely in patients taking Vioxx than among those taking a similar drug, Senator Grassley pointed out, but the FDA did nothing to change the labeling for nearly 2 years, he said, while Merck marketed its product on nightly TV.

On November 18, 2004, Senator Grassley drew enormous media attention when he held hearings on Vioxx, and FDA scientist, Dr Graham, testified that he determined that Vioxx may have caused tens of thousands of heart attacks and strokes but that his superiors at the FDA pressured him to keep quiet.

“The estimates range from 88,000 to 139,000 Americans,” Dr Graham told the committee. “Of these, 30 to 40 percent probably died,” he advised. “For the survivors,” he added, “their lives were changed forever.”

To put the number of injuries into perspective, Dr Graham told members of the committee that instead of side-effects from a drug, to think of it as if they were talking about jetliners.

“If there were an average of 150 to 200 people on an aircraft,” he said, “this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky.”

“This translates to 2-4 aircraft every week,” he advised, “week in and week out, for the past 5 years.”

“If you were confronted by this situation,” Dr Graham asked the panel, “what would be your reaction, what would you want to know and what would you do about it?”

He noted the problems with the FDA’s reliance on a 95% paradigm. In other words, he said, a drug is considered safe “until you can show with 95% or greater certainty that it is not safe.”

The scientist condemned the FDA’s failure to acknowledge the Vioxx risks sooner. “I strongly believe that this should have been, and largely could have been, avoided,” Dr Graham told the committee.

Ms Menziess often cites his testimony to demonstrate that the FDA’s position on preemption is wrong and states: “Dr. Graham’s testimony illustrates why FDA approval and subsequent post-marketing acquiescence should have no preemptive effect.”

The Vioxx matter caught the attention of the Senate Finance Committee basically because of the drug’s cost to government programs like Medicaid and Medicare. The committee is responsible for oversight of the two programs.

At the November 18, 2004 hearing, Senator Max Baucus discussed the high-costs related to the drug: “In the 5 years that Vioxx was on the market, Medicaid spent more than $1 billion on the drug,” he said.

In addition to the prescription costs, government programs are now paying for the damage caused by Vioxx. “Medicaid bears the cost of any additional medical care necessary when drugs cause injury,” Senator Baucus pointed out.

By far, the Vioxx debacle is the most serious public health failure to occur since the FDA took on the authority for safety oversight of medical products in 1938.

On September 3, 2005, Shane Ellison, a former pharmaceutical chemist turned whistleblower and author of the book, “Health Myths Exposed,” gave an interview to Crusador Magazine and discussed Vioxx and the problems within the FDA.

According to Mr Ellison, the FDA and Merck knew about the dangers of Vioxx for at least 4 years before it was pulled off the market. “Instead of removing the drug immediately,” he said, “they kept it on the drug market for matters of wealth not health.”

Mr Ellison says compliant politicians have “democratized” the industry. “This means that drug approval is a matter of 51% telling the other 49% that deadly drugs are safe and necessary,” he reports. “Science and choice no longer prevail at the FDA or at pharmaceutical companies,” he added.

“To go against the 51% means losing your career,” Mr Ellison explains. “Therefore, the majority of scientists choose to please drug companies, not the general public.”

To substantiate this allegation, Dr Ellison points to Dr Curt Furberg, a member of the FDA’s drug safety advisory committee. Dr Furberg went public with findings that Bextra also caused heart attacks and strokes and said studies “showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information,” in the British Medical Journal.

“Immediately thereafter,” Mr Ellison said, “Dr. Furberg was barred from serving on the panel that was responsible for considering the safety of cyclo-oxygenase-2 (COX 2) inhibitors.”

“The end result being more votes in favor of COX 2 inhibitors, the drug company wins by votes – not science,” he told Crusador.

Another relevant, but little-mentioned fact, is that many FDA officials end up working for Big Pharma. “The old joke is that the FDA is sort of like a showcase for a future job in the drug industry,” Robert Whitaker, author of Mad In America, said in an August 2005 interview with Street Spirit.

“You go there, you work awhile, then you go off into the drug industry,” he said, “the progression that people make, in essence they’re making good old boy network connections, so they’re not going to be so harsh on the drug companies.”

In addition, when leaving office many federal employees and members of Congress go to work for Big Pharma in one area or another. For instance, of the 1,274 people registered to lobby in Washington for drug companies in 2003, according to an April 2005 report by the Center for Public Integrity, 476 are former federal officials, including 40 former members of Congress.

Critics say the Prescription Drug User Fee Act, is in large part to blame, for the current problems within the FDA. The Act allows the agency to collect a fee from a drug company seeking approval for a new drug. In return, the FDA is expected complete the review process within 12 months.

User fees now account for about 40% of the approval process, which means the FDA is dependent on drug companies for nearly half of its funding. This situation creates a major conflict of interest according to Dr Graham: “This culture views the pharmaceutical industry it is supposed to regulate as its client. It overvalues the benefits of the drugs it approves, and seriously undervalues, disregards and disrespects drug safety,” he told members of Congress.

Another problem he said is that even when the FDA does try to take measures to limit harm, the agency lacks the authority to force drug companies to comply. For example with Vioxx, he said, it took more than 2 years to get Merck to add the increased risk of heart attack and stroke on the label.

Then there is the matter of the conflicts of interests involving the FDA panels that advise the agency on which drugs should be approved, what their warning labels should say, and how studies should be conducted.

The approximately 300 experts on the 18 committees make decisions that affect billions of dollars in sales and with very few exceptions the FDA follows their advice.

Members of the panels are supposed to be free of conflicts of interest relating to products they consider but they rarely are. For example, in February 2005, when the hearings were held to determine whether the COX-2 inhibitors should be allowed to remain on the market, a panel mired with conflicts was exposed. Out of the 32 voting members, ten had served as consultants to Merck and Pfizer in recent years.

This revelation prompted Senator Mike Enzi, (R-WY), the chairman of the Health, Education, Labor and Pensions Committee, along with Senators, Edward Kennedy (D-MA), and Richard Durbin (D-IL), to ask the General Accounting Office to look into the FDA’s practice of letting scientists serve on panels when they have conflicts of interest.

“We are concerned about the process that supports FDA’s decisions to waive conflicts of interest rules for scientists with financial ties to the manufacturers of the products under consideration, or their competitors,” said their letter to the GAO in September 2005.

“These practices appear to have undermined the public’s faith in the objectivity and fairness of FDA’s advisory committees,” they wrote. The Senators specifically referred to the conflicts among the panels that studied the Cox-2 inhibitors like Vioxx.

According to Ms Menziess, “The FDA’s preemption argument, if successful, would take away the sole means by which American consumers may obtain compensation for drug-induced injuries caused by a drug company’s failure to warn.”

“Civil lawsuits uncover internal company documents to which not even the FDA has access,” she explains.

“The tort system provides an important check on the regulatory process and on drug companies’ compliance with law.”

“Preemption,” Ms Menziess warns, “would close off one of the few avenues by which we learn of safety and efficacy information that pharmaceutical companies do not publish or hide from FDA.”

Filed under: 2006, FDA, FDA hearing, Graham, Pfizer, Preemption, SSRIs, Vioxx, Zoloft

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

Filed under: 2006, FDA, FDA hearing, Graham, MEDICAID, Merck, NSAIDs, stroke, Vioxx, whistleblower

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UNITE News

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Protect babies from drugs

Eli Lilly Funds Depression Screening Initiatives

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Matthew Schultz killed by Effexor. Two hours old.

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Big Pharma Victim

  • I haven't been on in awhile thanks to all those who followed 3 years ago
  • @LindsayRush yay IOWA! 3 years ago
  • Another rainy day here in IOWA. Well at least i had a good time swimmin yesterday. 3 years ago
  • Hey everyone hope you have a great day! THanks to all the new followers :) and for those that continue to follow 3 years ago
  • srry if I dont get on here much I mostly just look at my facebook acct. thanks to all the new followers! 3 years ago

The Indiana Star

Christiane Schultz

  • Is not coping well at all. Loss sucks! 4 years ago
  • is scared to bond with this baby, just in case. 4 years ago
  • Happy 6 months today baby. I love you Matthew. 4 years ago
  • Living with loss, sucks. 4 years ago
  • Thinking I need to discuss plans for this baby soon or I will be having it in my doctors office. Where do I deliver? 4 years ago

Amery Schultz

Seeking Parents in Missouri for Celexa / Lexapro Class Action – Call 800-827-0087

TWEET FOR LIFE

BREATH – The Official Blog of MADNAP – momsandmeds.com

RSS BREATH

  • Dan Jenski - ADDicted
    Reblogged from The Bitter Pill: Kickstarter is a website for artists to use to raise money and complete awesome projects. The best thing to come to the informed consent movement since Thomas Szasz could just be the new, upcoming film by Dan Jenski, "ADDicted" which basically gives Ritalin, Adderall, Concerta and the like a great […]
  • Zoloft Fails to Outperform Placebo: Class Action
    Reblogged from The Bitter Pill: In the studies submitted to the FDA for approving Zoloft (a drug that has killed numerous families, babies, mothers, children), the drug maker covered up the fact that Zoloft failed to outperform placebo, according to a new consumer fraud lawsuit filed by the firms Baum, Hedlund Aristei & Goldman and […]
  • Antidepressants Again Linked to Preterm Birth & Seizures
    In what was more than likely originally an attempt to prove that depression causes birth complications, researchers from Yale, Tufts, et al found in two new studies that antidepressants increase the risk of preterm birth and seizures. Read more at this link on the newly redesigned UNITE website.
  • Who Could Do This On Purpose
    Read this blog to find out
  • Canadian Regulation on Fetal Exposure to Psychotropic Drugs – Public Input Needed
    Canadian Regulation on Fetal Exposure to Psychotropic Drugs – Public Input Needed (Cross-Posted on The Bitter Pill blog) Amery and Christiane Schultz have been asked to provide input on proposed recommendations regarding psychotropic drugs in pregnancy in Canada. Amery & Christiane are hard-working activists affiliated with UNITE and MADNAP. Please send […]

UNITE ARCHIVES – Victims & Survivors Against The MOTHERS Act: YouTube Playlist

Videos: Psych Drugs, Birth Defects, Infant Death, Violence & Suicide

UNITE ARCHIVES – Add Your Group To The Coalition Against The MOTHERS Act

CADIMA: 54 Groups and Counting!

UNITE ARCHIVES – The MOTHERS Act Citizen Voting Area on Open Congress

Status: 76% AGAINST S. 324 The MOTHERS Act. Vote & Comment.

UNITE ARCHIVES – Join the Coalition Against The MOTHERS Act on Facebook!

3,271 Facebook Members and Counting!

UNITE ARCHIVES – Stop The Dangerous and Invasive MOTHERS Act!

13,500 Signatures and Counting!

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