The Bitter Pill

The Official Blog of UNITE – uniteforlife.org

Taking Zoloft During Pregnancy Linked to Birth Defects

Evelyn Pringle June 7, 2007

Less than a year ago, in July 2006, the FDA issued a Public Health Advisory on a birth defect found to be associated with Zoloft and other selective serotonin reuptake inhibitor antidepressants by a study in the February 2006 New England Journal of Medicine that found a higher risk of a life-threatening lung disorder in infants exposed to SSRIs, stating:

“A recently published case-control study has shown that infants born to mothers who took selective serotonin reuptake inhibitors (SSRIs) after the 20th week of pregnancy were 6 times more likely to have persistent pulmonary hypertension (PPHN) than infants born to mothers who did not take antidepressants during pregnancy.”

PPHN infants have difficulty making the transition from breathing inside the womb to normal breathing after delivery, often leading to respiratory failure that requires mechanical ventilation. Even when treated, between 10% to 20% of babies born with PPHN do not survive.

Between 1998 and 2003, the research team interviewed 377 women who had recently given birth to a baby with PPHN, with questions about medical history and the drugs taken during pregnancy and found that 3.7% of the infants had been exposed SSRIs after the 20th week of pregnancy, or about 6 times the rate among healthy infants in a comparison group born at the same time.

Infants with PPHN typically show abnormal muscle cell growth in their respiratory system. Previous investigations have found that SSRIs tend to accumulate in adult users’ lungs and serotonin can promote the proliferation of certain muscle cells. This may explain how the drugs could have an effect on the developing fetus, according to the study authors in the NEJM.

This birth defect is also not as rare as once thought. After the results of the PPHN study were released in February 2006, the lead author and researcher, Dr Christina Chambers, told the Wall Street Journal that women contacted her from all over the US who had given birth to babies with PPHN after using SSRIs during pregnancy.

Medical experts say its important to recognize that Pfizer promotes Zoloft for many disorders besides depression, meaning women may be taking the drug even though they have never been diagnosed with depression. According to the FDA, in addition to depression, Zoloft is approved to treat obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, and premenstrual dysphoric disorder.

In March 2006, Health Canada issued its own warning, “advising women who are taking antidepressants known as selective serotonin reuptake inhibitors and who are pregnant or intend to become pregnant to discuss the situation with their doctor, due to potential risks to the baby.”

On April 7, 2006, the BBC reported that a Canadian study from the University of Ottawa of almost 5,000 mothers found that SSRI use during pregnancy doubled the risk of delivering a stillborn baby and that women who took the drugs were also more likely to have a premature or low-birth-weight baby.

The study found almost 20% of women who used SSRIs gave birth prematurely, compared to 12% of those who did not use the drugs and that babies born to women using SSRIs were also more likely to have seizures.

On August 25, 2006, Reuters Health reported another Canadian study that found that babies born to women who took SSRIs during pregnancy appear to be at increased risk of having a low birth weight and to develop respiratory distress.

Lead investigator Dr Tim Oberlander told Reuters that “our study was undertaken to distinguish the effects of maternal mental illness — pregnancy-related depression — from its treatment — SSRIs — on neonatal outcomes.”

The research team at the University of British Columbia, Vancouver, examined data for almost 120,000 live births between 1998 and 2001, and found 14% of the mothers who were diagnosed with depression.

The study compared the outcomes of babies born to depressed mothers treated with SSRIs and of those born to depressed mothers who were not treated, and there was a significantly greater incidence of respiratory distress, 13.9% vs 7.8%, and longer hospital stays for infants born to mothers on SSRIs, the team reported in the Archives of General Psychiatry.

Birth weight and gestational age were also significantly less in SSRI infants, and a significantly greater proportion were born before 37 weeks. “These findings are contrary to an expectation that treating depressed mothers with SSRIs during pregnancy would be associated with lessening of the adverse neonatal consequences associated with maternal depression,” Dr Oberlander told Reuters.

Preterm birth is the leading cause of infant mortality in the US, accounting for at least a third of all infant deaths in 2002, and the contribution of prematurity to infant mortality may be twice as high as originally estimated, according to Dr William Callaghan and colleagues in the October 2006 Pediatrics journal.

For the study, the researchers looked at the top 20 causes of infant deaths in 2002 and found that 34% of the deaths occurred in preterm infants, 95% of whom were born before 32 weeks gestational age and weighed less than 3.3 lbs. Two-thirds of the deaths in preterm infants occurred in the first 24 hours of life, the research team found.

The fact that SSRIs are highly addictive also adds to the health risks that a pregnant woman faces if she is already taking Zoloft. “A lot of these medicines are associated with withdrawal syndromes, which can be very problematic for many patients, so stopping is something that needs to be monitored carefully by your doctor,” said Dr Sandra Kweder, deputy director of the FDA’s Office of New Drugs, in a March/April 2006 update on the FDA’s Web site.

But on the flip-side of the coin, continuing to take Zoloft places the infant at risk for withdrawal. A February 2006 study in the Archives of Pediatrics & Adolescent Medicine reports that nearly one-third of infants born to women taking SSRIs show symptoms of withdrawal including tremors, high-pitched crying, gastrointestinal problems and sleep disturbances. The researchers found that 13% of the 60 newborns exposed to SSRIs exhibited severe symptoms of withdrawal.

An earlier study in the February 2004 Pediatrics journal found abnormal heart rhythms, sleeping patterns, and levels of alertness in babies exposed to SSRIs in the womb. Dr Philip Zeskind, a professor of pediatrics at the University of North Carolina-Chapel Hill, and lead author, referred to the results as alarming.

The researchers compared one-day-old babies of mothers who took SSRIs with babies of mothers who did not and looked at sleeping and waking patterns, movements and heart rates. According to the study, infants exposed to SSRIs tended to be locked in one “sleep state” and showed “fewer of the smooth and predictable changes in heart rate that normally occur in newborn infants.”

In July 2004, the rising number of reports prompted the FDA to alter labeling for the entire SSRIs, warning that some newborns exposed to SSRIs and Effexor in the womb had developed problems requiring prolonged hospitalizations, respiratory support and tube feeding.

Critics also say, an important point to consider when weighing the risks and benefits of taking Zoloft during pregnancy, is that most experts who have evaluated all the clinical data on SSRIs say the benefits of the drugs are minimal.

In the July 2005 British Medical Journal, Moncrieff & Kirsch state in part: (1) Recent meta-analyses show [SSRIs] have no clinically meaningful advantage over placebo; (2) Methodological artifacts may account for the small degree of superiority over placebo; and (3) Given doubt about their benefits and concern about their risks, current recommendations for prescribing antidepressants should be reconsidered.

Filed under: 2007, Birth Defects, Pfizer, PPHN, SSRIs, Zoloft

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

Ex-Pfizer VP Peter Rost Takes On Goliath

May 9, 2006

Evelyn Pringle

Beginning in 1997, Pharmacia, currently a subsidiary of Pfizer, sought to boost its sales of the drug Genotropin. To that end, the company illegally marketed the drug to spur growth in short children and as an anti-aging drug for adults looking for the fountain of youth.

In a nutshell, the off-label marketing scheme included: (1) direct payments to doctors; (2) all-expense paid junkets for doctors; (3) financial incentives to distributors: and (4) phony consultant contracts to funnel payments for the off-label promotion.

As a result of the scheme’s success, sales of the Genotropin sky-rocketed and over the years, Medicaid and other public healthcare programs paid millions of dollars for its improper use. The full amount of damage to health care programs is not yet known.

“But this much is certain,” former Pfizer Vice President turned whistleblower, Dr Peter Rost, says, “Pharmacia turned Genotropin into a cash cow by illegally peddling a dangerous drug to make short kids tall and their grandparents young.”

Genotropin is a man-made human growth hormone approved to treat a limited range of hormonal deficiencies. The FDA has never approved the drug to spur growth for children without hormonal deficiencies or to prevent aging.

Genotropin has serious side effects according to the National Institute of Health: “If growth hormone is given to children or adults with normal growth, who do not need growth hormone, serious unwanted effects may occur because levels in the body become too high. These effects include the development of diabetes; abnormal growth of bones and internal organs such as the heart, kidneys, and liver, arteriosclerosis; and hypertension.”

Dr Rost joined Pharmacia in June of 2001 as a VP of Marketing Endocrine Care. One of his primary responsibilities was to oversee the marketing of Genotropin but he did not handle day-to-day marketing activities.

A group of about 70 people reported to Dr Rost, among them a US marketing director with a group of about 22 people under him. The marketing people who sold Genotropin throughout the US reported to the Endocrine Care sales director.

A few days after Dr Rost came on board he received a copy of a letter from his supervisor that discussed the off-label sale of Genotropin and stated that Pharmacia would not promote or encourage the use of the drug outside approved uses.

Dr Rost said he found the letter unusual because “any marketing director would be well aware that it is illegal to promote drugs for off-label indications.” When he asked about it he was told that there had been some problems in the past, but that the issue had since been resolved.

In the fall of 2001, Dr Rost became aware that the company was paying for between 600 and 800 doctors and their spouses to attend an annual meeting at a posh Caribbean resort as part of its marketing of Genotropin. When he expressed concerns, he was assured that the company’s legal department had approved this type of trip.

In early 2002, Dr Rost conducted a profitability analysis of the Genotropin franchise and became uneasy when the senior director of marketing would not disclose key sales and marketing information related to the audit.

During the analysis, Dr Rost learned that Pharmacia paid cash incentives to sales reps for each new patient who was prescribed Genotropin and that 16 of the top 20 earning territories came from the adult team, in spite of the fact that adult sales accounted for only about 10% of total sales. He also learned that they received incentives regardless of whether treatment was on-label or off-label.

Dr Rost then decided to track every new patient to determine exactly how many new anti-aging patients were signed on each month. Based on high number in his analysis, Pharmacia agreed to change the incentive payment plan and exclude payments for any patients from physicians known to engage in off-labeling prescribing.

Later in February 2002, Dr Rost learned that Pharmacia had numerous contracts to sell Genotropin directly to doctors specializing in the anti-aging field, as well as contracts with wholesalers who specialized in servicing the off-label Genotropin market.

Around this same time, he decided to delve deeper into the marketing practices and it soon became clear that his subordinates knew that off-label marketing was illegal, and they were not forthcoming. For instance, the payments to physicians were not revealed until a manager left the company and doctors started to call and ask about their payments.

Dr Rost first approached Pharmacia management in the fall of 2001, and in February 2002, the company started an internal investigation. In March, the firm’s Associate General Counsel informed Dr Rost that she had found that marketing director, Carl Worrell, had engaged in gross misconduct relating to the off-label promotion and that he was not forthcoming during the investigation. Based on their concerns, a decision was made to terminate Worrell’s employment in April 2002.

After he left, Dr Rost discovered documents that showed that Pharmacia had been actively engaged in the off-label marketing since at least 2000. In one example, Dr William Abelove, an anti-aging doctor at a longevity center, had sent a letter to Pharmacia CEO, Fred Hassan, in 2000, and wanted to purchase Genotropin at a discount rate. Mr Hassan forwarded the letter to the marketing departments and by May 1, 2000, Worrell had signed a consulting contract with Dr Abelove to assist in the promotion of Genotropin.

In an effort to ensure that the off-label promotion was terminated, Dr Rost sent an email to the associate director of marketing and her product managers and explained his concerns about continued payments and consultancy agreements, and instructed them not to approve any additional payments without seeing him first.

In May 2002, Pharmacia cancelled contracts that gave rebates to anti-aging doctors and wholesalers who supplied anti-aging clinics but continued to sell to these doctors and wholesalers.

The same month, Dr Rost received a short debriefing of the internal legal review and was assured that appropriate corrective action had been taken.

In July 2002, Pfizer announced the friendly take-over of Pharmacia. With this merger, it became clear to Mr Rost that he would have to address his concerns with Pfizer’s management team. To prepare, Dr Rost started to research the legal statutes related to growth hormones and the False Claims Act, and other laws Pharmacia may have violated.

During the time period of July through September 2002, Dr Rost continued to receive reports about discoveries of kick-backs paid to doctors.

On October 28, 2002, Mr Rost and several marketing directors participated in a meeting with Pfizer that included employees from Pfizer’s medical, marketing, regulatory and legal department, as well as Judith Tytel, Pharmacia’s Senior Corporate Counsel.

The meeting was intended to be an opportunity for Pharmacia employees to provide information to their Pfizer counterparts. At the meeting Dr Rost and his team disclosed that Pharmacia was sponsoring all-expense paid junkets for physicians and that Pharmacia maintained a data base, known as the Bridge Program, that contained detailed information regarding the 30,000 patients who received Genotropin prescriptions.

They also explained that payments were being made to US doctors and discussed how the Bridge Program supplied new patients with free Genotropin for several months while the company assisted in seeking reimbursement.

Following the meeting, several Pfizer executives asked for more information and on November 8, 2002, Dr Rost and several directors, and Associate General Counsel, met with Pfizer representatives and lawyers and reviewed the Bridge Program.

During this time, Dr Rost continued to discuss his concerns with executives and lawyers at Pharmacia and believed that the company was concerned about the potential legal exposure related to the off-label sale of Genotropin.

In response to continued reports indicating illegal activities, Dr Rost repeatedly tried to implement corrective measures. However, he learned that the corporate culture at Pharmacia made it impossible to eliminate illegal conduct because of the financial incentives that drove sales reps to continue it.

Through further investigation, Dr Rost learned that the illegal activities started long before he arrived, and as far back as 1997. He came to conclude that at times, company officers condoned the activities despite knowing that they were illegal.

On April 16, 2003, the merger between Pfizer and Pharmacia was final. Pharmacia directors and officers realized enormous financial benefits. CEO Fred Hassan, received a $9.9 million severance package, 9 other directors received packages worth, in the aggregate, $31.6 million, and company directors were able to obtain early vesting of approximately 6.7 million in stock options.

Pharmacia’s sales were also a shot in the arm to Pfizer. According to Pfizer’s 2003 Annual Report: “Revenues increased 40% to $45,188 million in 2003… Revenue increases in 2003 were primarily due to the inclusion of Pharmacia products,” it said.

The off-label sales paid off extremely well. Between 1997 and 2003, Genotropin generated more than $550 million in sales in the US alone and the company’s database shows that about 60% of adult sales, and 25% to 30% of pediatric sales, were for off-label use.

On May 22, 2003, Dr Rost became aware of the pervasive nature of ongoing illegal activity when he met with a manager of the Bridge Program and was shown documents that confirmed that a massive number of patients were listed with an off-label diagnosis.

In fact, 25% to 30% of the pediatric prescriptions were for off-label use. Dr Rost understood that pediatric patients received significant funding from Medicaid and other government programs.

He was alarmed at the extent of pediatric use – a staggering number, he says, not only due to the medial implications to children but also because it demonstrated that a great percentage of the cost was reimbursed by Medicaid or other governmental programs.

Disturbed by these findings, he decided to file a lawsuit and with Attorney Erika Kelton, and another Phillips & Cohen attorney, started drafting a complaint.

On June 3, 2003, Ms Kelton, informed an assistant US Attorney that Dr Rost would be filing a qui tam action alleging fraud relating to the off-label marketing of Genotropin and delivered a copy of the complaint to the US Attorney’s Office on June 4, 2003.

In the Complaint, Dr Rost provided details of a complex scheme including the nature of the fraud – where it occurred, how it occurred, when it occurred and the persons responsible for its commission. The following is a summary of the complaint’s specific factual allegations:

Approximately 60% of adult sales and 25% of its pediatric sales were for off-label uses.

Pharmacia bribed 16 named distributors to promote off-label usage of Genotropin.

Under the pretext of participating in a “study,” Pharmacia paid doctors $200 for every patient they prescribed to, including off-label subscriptions, and paid doctors an additional $200 for every year that such patients continued to use Genotropin.

Pharmacia sponsored junkets for physicians and their spouses and awarded substantial “honoraria” as inducements/kickbacks to promote the off-label usage of Genotropin.

Pharmacia provided discounts to doctors working exclusively in the anti-aging area, knowing that they would sell Genotropin off-label for anti-aging treatment and least 18 named doctors signed contracts for such price discounts.

Through contracts and “retainer” agreements, Pharmacia hired persons and entities, some named in the Complaint, to promote off-label use of Genotropin and such “consultants” provided no other services.

The false claims were submitted from 1997 to June 5, 2003 across the US and included false claims and statements made by dozens of named distributors and doctors, and Pfizer’s Bridge Program lists the patients for which the false claims were submitted.

But come to find out, off-label marketing seems to habitual with Pfizer. At the same time that Dr Rost reported the illegal activities, Pfizer was fighting off a whistleblower lawsuit arising out of the off-label marketing of the drug Neurontin, by another company acquired through a merger, in promoting the drug for pain control and Attention Deficit Disorder.

In the end, Pfizer settled the lawsuit and a related criminal case for $430 million.

In a motion filed in attempt to dismiss Dr Rost’s lawsuit, Pfizer states: “After investigating for more than two years, the Justice Department recently declined to intervene in this qui tam complaint.” The inference being that the DOJ does not consider this to be a serious case.

However, a decision by the DOJ not to intervene means nothing. According to a study by the Government Accounting Office, the DOJ has declined to intervene in 72% of all qui tam actions initiated between 1987 and 2005.

A review of Pfizer regulatory filings reveals an ongoing affair with the DOJ. In its Form 10-K for 2003, filed with the SEC on March 10, 2004, Pfizer disclosed the following:

“The company recently was notified that the US Department of Justice is conducting investigations relating to the marketing and sale of Genotropin and Bextra, as well as certain managed care payments.”

In its Form 10-K for 2004, filed with the SEC on February 29, 2005, Pfizer disclosed that: “In late 2003, we received a request for information and documents from the US Department of Justice concerning the marketing of Genotropin as well as certain managed care payments.”

Nine months later, in a Form 10-Q filed on November 9, 2005, Pfizer revealed that: “The U.S. Department of Justice has informed us that it is investigating Pharmacia’s former contractual relationship with a health care intermediary.”

And make no mistake, Pfizer’s legal troubles are far from over. According to Dr Rost’s attorney, Mark Labaton, “a grand jury in Boston is investigating the illegal promotion and marketing of Genotropin based on an investigation conducted by the US Attorney’s office.”

In addition, according to news reports, the US Attorney in the Eastern District of New York also has an active criminal investigation involving Pfizer’s off-label promotion of Lipitor, he says.

Mark Labaton, is a partner at the firm Kreindler & Kreindler, LLP, with offices in New York and LA. The firm handles cases including securities and consumer class actions, and FCA whistleblower, antitrust, and consumer cases.

His resume includes 7 years as an Assistant US Attorney for the Central District of California, where he prosecuted white-collar fraud cases, including whistleblower actions.

Pfizer is the largest pharmaceutical company in the world, and according to Mr Labaton, “Like most large pharmaceutical companies, it is financially and politically powerful.”

“Litigating against such companies is not for the faint-hearted,” he warns.

“But whistleblower lawyers are inspired by their clients,” Mr Labaton says. “Warts and all, these clients are a strong, determined, and courageous lot.”

He claims that “off-label promotion of drugs is a form of quackery that victimizes vulnerable individuals who take these drugs with serious and dangerous side effects for purposes never intended and approved by the FDA.”

“That’s exactly what happened in our case,” he notes.

“Pharmacia and its successor company, Pfizer,” Mr Labaton says, “generated hundreds of millions in revenue by peddling Genotropin to spurt growth in short children and as an anti-aging drug for adults seeking eternal youth.”

“Genotropin was never intended to make short kids tall and their grandparents young,” he said.

In some whistleblower cases, he says, there is one victim – “the taxpayer who foots the bill for the fraud.”

It costs law firms a fortune to go up against the giant drug makers. In the Pfizer Neurontin lawsuit, “the civil/whistleblower plaintiffs in that case took more than 20 depositions and obtained thousands of pages of documents in discovery,” Mr Labaton reports.

But he says he’s not complaining. “The costs to us as lawyers and to our firms can be substantial,” he says, “but these costs pale when compared to what whistleblowers, like Dr. Rost, have to endure.”

“So far,” he points out, “Pfizer has used its muscle to reactively and vigorously oppose Dr. Rost and to make his life tough.”

Dr Rost is indeed being hit from all sides.

On December 30, 2005, he was officially nominated for the “Whiny Whistleblower of the Year” award by a Pharm-backed front group and won. In truth, whether he knows it or not, it is a top honor, when considering that he competed against two of the nation’s most beloved whistleblowers, Dr David Graham of Vioxx fame from the FDA, and Dr Eric Topol, of the Cleveland Clinic.

Dr Rost’s award was announced by Gilbert Ross, MD, who bills himself as a doctor and Executive and Medical Director of the American Council on Science and Health.

That in itself is amazing being that Doctor Ross’ own achievement of ripping off Medicaid to the tune of $8 million was only given the recognition that it deserved last fall.

“Ross actually had to abandon medicine on July 24, 1995, when his license to practice as a physician in New York was revoked by the unanimous vote of a state administrative review board for professional misconduct,” according to the November/December issue of Mother Jones Magazine.

“Instead of tending to patients,” Jones reports, “Ross spent all of 1996 at a federal prison camp in Schuylkill, Pennsylvania, having being sentenced to 46 months in prison for his participation in a scheme that ultimately defrauded New York’s Medicaid program of approximately $8 million.”

For its part, the American Council on Science and Health stopped disclosing its corporate donors in the early 1990s, according to Integrity in Science on its [web site].

However, the companies noted as contributors in ACSH’s 1991 annual report and ACSH’s list of Corporate Donors for 1997 include: Pfizer, Abbott Laboratories, American Cyanamid, Bristol-Myers Squibb, Ciba-Geigy, Eli Lilly, Hoffman-La Roche, Johnson & Johnson, Rhone-Poulenc, Sandoz, Searle, Syntex, Warner-Lambert, Upjohn, and Pharmaceutical Manufacturers Association.

For too many years, off-label marketing offenses resulted in nothing more than a slap on the wrist to drug makers, if that.

The FDA regulated the industry and when it found “off-label” marketing, the agency sent the company a warning letter. Sometimes companies were required to sign a consent degree, but they did not face fines.

In 1991, all that changed. Pharmaceutical giant Genentech started the False Claims ball rolling when the company was caught selling another growth hormone, Protropin, off-label by influencing doctors to prescribe it to children who did not suffer from hormone deficiency.

Genentech was prosecuted under the FCA and paid $50 million to settle the case.

Since then, the government has used the FCA in 15 cases that were settled out of court, but according to Taxpayers Against Fraud, a non-profit advocacy group that assists whistleblowers, 150 more cases are currently pending.

The FCA has become effective in large part due to the reward for whistleblowers who can receive between 15% and 30% of the amount recovered in the lawsuit with the average award being $120,000, according to Taxpayers Against Fraud.

In most cases, off-label marketing is usually not a jailable offense; but it is with Genotropin.

“Growth hormone is different from any other drug,” Dr Rost explains, “distributing the drug for off-label purposes is a crime.”

“Not even a doctor is allowed to prescribe growth hormone for off-label use,” he says.

The Controlled Substances Act states in part: “…whoever knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than the treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services … and pursuant to the order of a physician, is guilty of an offense punishable by not more than 5 years in prison.

“None of us who became employed by Pharmacia asked to be put into an incriminating situation,” Dr Rost points out.

The criminal penalties were a result of the 1988 and 1990 amendments to the Food, Drug and Cosmetic Act, that made off-label sale of human growth hormone to treat age-associated illnesses illegal, according to a report in the October 26, 2005 Journal of the American Medical Association.

In the JAMA article, authors Dr Thomas Perls, director of the New England Centenarian Study at Boston Medical Center; Dr Neal Reisman, clinical professor of plastic surgery at Baylor College of Medicine, who is also an attorney; and S. Jay Olshansky, professor of epidemiology at the University of Illinois at Chicago School of Public Health discuss the little known law.

According to the article, human growth hormone can be legally prescribed for only 3 conditions: HGH deficiency-related syndromes that cause short stature in children, adult deficiency due to rare pituitary tumors and their treatment, and muscle-wasting disease associated with HIV/AIDS.

According to Dr Olshansky, “off-label use for many drugs is a normal and accepted practice in medicine, but that is not true for growth hormone. According to laws instituted by Congress more than 10 years ago, HGH can only be distributed for indications specifically authorized by the Secretary of Health and Human Services, and aging and its related disorders are not among them.”

“The use of HGH as an alleged anti-aging intervention is a major public health concern not just because it is illegal,” Dr Olshansky explains, “but also because its provision for anti-aging is not supported by science and it is potentially harmful.”

People are spending a fortune on HGH under the belief that it reverses aging. “On the contrary, responsibly conducted and peer-reviewed science indicates that HGH could in fact accelerate aging and shorten lifespan,” according to Dr Perls.

“It is associated with very high rates of serious adverse effects,” he advised, “and long-term use could increase one’s risk of cancer.”

In 2004, sales of HGH totaled $622 million (nearly 213,000 prescriptions) not including sales on anti-aging Web sites. “These data suggest that a very large proportion of HGH sales are for illegal uses,” Dr Perls noted.

Logically, the vast majority of prescriptions should be for children, but according to the study, 74% of prescriptions in 2004 were for people 20 and older, and 44% were for people between the age of 40 and 59.

Filed under: 2006, Genotropin, HGH, Pfizer, Protropin, Rost, whistleblower

Lethal Defects Of Bjork-Shiley Heart Valve

Evelyn Pringle April 24, 2006

An estimated 25 million Americans have one kind of medical implant or another. However an analysis of implant recalls over 10 years show that the average number of recalls per year was 40 and by 2001, the number rose to 117.

The FDA regulates the implant industry, but many products reach the market with insufficient clinical testing, followed by very little oversight.

By law, the FDA is supposed to inspect medical-device manufacturing plants every 2 years, but according to an August 11, 2002, report by the Star-Ledger, “it visits U.S. plants on average once every five years, and overseas plants once every 13 years.”

In addition, of the 3,500 proposed medical devices reviewed by the FDA in 2001, the Ledger determined that 98% were approved under an expedited process that requires no clinical testing.

Implants include heart valves, pacemakers, stents, hip and knee joints, orthopedic plates and screws, and breast enhancements. However, devices recalled most often have been heart related implants which made up nearly 40% of all recalls during the 10 year period between 1992 and 2002 investigated by the Ledger.

Perhaps the most infamous recall case on record involves the Bjork-Shiley Convexo-Concave mechanical heart valve. Shiley, Inc manufactured the valves and Pfizer purchased Shiley in 1979.

The product came on the market in 1979, and was recalled in November 1986, after the struts that held the device in place began fracturing.

When the strut breaks, the heart contracts and explodes, and without emergency surgery, the person can die within minutes. Due to fear and anxiety arising from the risk of a fracture at any moment, the injury to patients is lifelong.

According to the August 17, 1995, New England Journal of Medicine, by December 31, 1994, “564 complete strut fractures had been reported to the manufacturer, approximately two thirds of which were fatal.”

The JAMA article also noted that there was no reliable diagnostic methods to detect valves that may be at risk for strut fracture.

As of April 1, 2003, according to CBS News, approximately 12,000 people had filed claims for wrongful death and personal injury in a class-action lawsuit against Pfizer. Under the terms of a settlement agreement, CBS said victims could receive somewhere between $500,000 and $2 million, depending on age, income, and family status. At the time of the settlement there were an estimated 40,000 living heart valve recipients.

Early on when lawsuits were filed, Pfizer insisted on secrecy agreements. Corporations in products liability cases often insist that material turned over in litigation be kept confidential, even when the product is dangerous and remains on the market.

As a result of the secrecy agreements in this case, crucial information about the valves was not revealed to doctors or the FDA, and patients continued to receive the implants long after the company detected the defects. Federal law requires a company to report a known hazard and in this case, the secrecy fostered the evasion of laws designed to protect consumers.

It later became known that company inspectors had found poor welds on the valves, but rather than throw them out, they ordered the valves to be ground down and polished to look smooth, after which they were sold all over the world.

As it turns out, employees at the factory intentionally filled out paperwork to disguise the practice of polishing over the cracks and an internal memo that surfaced, written by a supervisor, complained about the policy that disguised cracked valves.

As more documents turned up, one showed that in 1980, Dr Viking Bjork, whose name helped sell the valves, had written to Pfizer demanding corrective action and threatened to publish cases of valve failures.

In response, a Pfizer executive telexed Dr Bjork and said: ‘ATTN PROF BJORK. WE WOULD PREFER THAT YOU DID NOT PUBLISH THE DATA RELATIVE TO STRUT FRACTURE.’ His reason for holding off was: ‘WE EXPECT A FEW MORE.’

In 1990, a Congressional report concluded that the company had “aggressively marketed the device despite internal knowledge of serious problems in the manufacturing and quality assurance procedure.”

Had the dangers with the valve been known, thousands of deaths and injuries, as well as the related economic costs, could have been avoided because doctors would not have implanted the valve in thousands more patients.

In March 1992, the FDA instructed Shiley to notify physicians that the risk of fracture could be five times higher than previously thought.

“When a critical device such as a heart valve is found to have a problem that could result in death or serious injury, FDA has an obligation to see that doctors and patients are notified so that they can consider the new information in deciding on a course of action,” said FDA Commissioner David Kessler, MD at the time.

The FDA also told Shiley to send letters to patients who received the faulty device to inform them of the increased risks. By that time, the FDA had already received about 350 reports of fractures among the roughly 82,000 valves implanted worldwide.

Some patients were advised to undergo explantation, to remove the defective valve and replace it with another valve. However, explantation was a risky procedure for which few patients were eligible.

The conduct by Pfizer of suppressing the fact that the valves were defective eventually came under intense scrutiny by the Department of Justice and a Congressional oversight committee.

According to the charges in a lawsuit filed by the DOJ under the False Claims Act, Pfizer-Shiley made false statements to the FDA to obtain approval of the valve, and again later to keep the product on the market. Specifically the DOJ said Shiley:

* falsely asserted the valve caused fewer blood-clotting complications than other models

* falsely asserted a series of manufacturing changes had corrected a serious design defect

* did not provide FDA with all the data it had concerning fractures during testing

* argued – to keep marketing the valve after the problem became evident – that the fracture risk was outweighed by the purported blood-clotting advantage, which did not prove to be as significant as represented to FDA

* rebuilt scrap valves

* rewelded valves an excessive number of times

* polished, rather than rewelded, cracked valve struts

* falsified employee identification numbers on cards attached to bags of reworked valves, including more than 3,000 “baggie cards” with inaccurate identification numbers.

In a 1994, Pfizer agreed to pay $10.75 million to settle the false claims case. The company also agreed to pay for medical costs the government had incurred, or would otherwise incur in the future, through Medicare, Medicaid, CHAMPUS, federal hospitals, or other programs due to fracture or replacement of the valve.

The DOJ announced the settlement on June 30, 1994, and estimated its total value to be close to $20 million.

The settlement also brought to a close a case that the Congressional Subcommittee on Oversight and Investigations had been following for years. Since the late 1980s, the Subcommittee had been investigating the shortcomings of the FDA, and the implant industry, in medical device regulation and had zeroed in on the heart valve case.

According to the committee, despite the occurrence of fractures during clinical trials, the FDA approved the valve after a short premarket approval process. The Subcommittee said that the FDA had been unable, or unwilling, to critically and independently assess clinical data and that instead, the agency relied upon an “Honor System” which trusted the company to report problems with the valves.

Although there was an aggressive campaign to locate valve recipients, the General Accounting Office determined that only about 14,000 patients were located; which means the defective valves remain implanted in thousands of patients.

Filed under: 2006, Bjork-Shiley Heart Valve, medical devices, Pfizer, settlement

SSRIs – Wonder Drugs From Hell

Evelyn Pringle February 7, 2006

The Glenn McIntosh family has to introduce 12-year-old Caitlin, with a photograph because that is all they has left. Caitlin committed suicide 8 weeks after being prescribed the SSRIs, Paxil and Zoloft.

“We were told that antidepressants like Paxil and Zoloft were wonder drugs, that they were safe and effective for children. We were lied to,” Caitlin’s father said.

According to Glenn, his daughter was a straight “A” student, an artist, and a talented musician who loved animals and wanted to be a veterinarian.

With the onset of puberty, Caitlin seemed to be having trouble coping, and was also having sleeping problems due to a mild seizure disorder.

“We wanted to help, of course,” her father explains, “so we took her to our family physician, who prescribed her Paxil.”

Right off the bat, Caitlin did not do well on Paxil, so the doctor took her off the drug. About a week later the family went to see a psychiatrist and Caitlin was put on Zoloft.

According to Glenn, “She then started having strong suicidal ideations, along with severe agitation known as akathisia and hallucinations, and she was put in the adolescent ward of a mental hospital to balance her meds.”

Once she entered the hospital, the situation got worse as Caitlin was put on more and more psychiatric drugs to treat symptoms and behaviors that Glenn says he now realizes were caused by the SSRIs to begin with.

When she was released from the hospital, the downward spiral continued until the day that Caitlin used her shoe laces to hang herself in a bathroom at school.

“Let me be very clear about something,” Glenn said, “the dramatic and severe symptoms that led to my daughter’s suicide manifested only after she started taking antidepressant drugs.”

“The pharmaceutical companies have known for years that these drugs could cause suicide in some patients,” Glenn said. “Why didn’t we?”

Grieving the loss of their 14-year-old daughter Dominique, Lorraine and Robert Slater also make the point that, “informed parental consent is only possible as long as full disclosure is made by the pharmaceutical companies, the FDA, and the medical community.”

“How can teenagers be allowed to be given antidepressants that were never approved for adolescent consumption, only for adults?” Lorraine wants to know. “How come the medical profession doesn’t fully disclose the possible harmful and fatal effects of medication as well as watch carefully for diverse effects on its adolescent population?”

Shortly after she was prescribed Celexa, Dominique attempted suicide. She was treated by several mental health professionals after her initial adverse reaction to the first SSRI.

And, each time they met with professionals, her parents explained that the drugs seemed to maker Dominique’s condition worse rather than better. Unfortunately, as so often happens, the adverse reactions and behaviors caused by the SSRIs, were treated as a worsening of an underlying condition and Dominique was prescribed other drugs from the same class.

“Dominique’s mind and behavior were slowly being altered to the point that she became very agitated, irrational, ultimately suicidal,” her mother recounts, “because none of the so-called medical professionals acknowledged the drug’s role in her irrational and suicidal behavior or properly withdrew her from their suicidal effects.”

On February 6, 2003, Dominique was switched to the SSRI Effexor, and during the two weeks that followed, her doctor doubled the dose.

The morning of February 21, 2003, Robert dropped his daughter off at school and they said goodbye as usual. Around 11 am, Dominique told her teacher she needed to go outside for some fresh air. She left classroom and never returned.

Next to nothing is known about Dominique’s activities from the time she left school on February 21, until her body was found 3 weeks later in the Delta Mendota canal in California on April 14, 2003.

Lorraine is still racked with guilt and blames herself for giving her daughter the prescribed medication. “How can you imagine I feel, knowing now that I was slowly poisoning my daughter every day as I was dispensing her antidepressant medication?” she said.

Tom and Kathy Woodward’s daughter, Julie, who had no history of suicide or self-harm, hung herself in a matter of days after being prescribed Zoloft. “Julie began experiencing akathisia almost immediately,” Tom recalls.

But he knew nothing about Zoloft’s side effect of “akathisia” at the time. The doctor had stressed that Zoloft was safe and had very few side effects. He never advised Tom and Kathy about the possibility of violence, self-harm, or suicidal acts and the information they received with the drug never mentioned self-harm or suicide either.

According to her parents, Julie was a young woman who had everything to live for. Just weeks before her death, she had scored high on her SATs and was excited about starting college.

However, “instead of picking out colleges with our daughter, my wife and I had to pick out a cemetery plot for her,” Tom said. “Instead of looking forward to visiting Julie at school, we now visit her grave,” he added.

Like so many other cases of suicides of young people on SSRIs, Julie’s body apparently could not handle the drug. “We now know from a blood test from the coroner’s office, that she was not metabolizing the drug,” Tom said.

Tom and Kathy are angry at government officials. “The FDA has placed the interests of the drug industry over protecting the American public,” Tom said, “if the trials don’t favor a drug, the public never hears of them.”

“It is clear that the FDA is a political entity,” he continued, “and its leadership has protected the economic interests of the drug industry.”

Tom believes that suppressing unfavorable studies should be illegal, “the drug industry must be compelled to produce all of their findings and studies,” he said.

Cheryl and Mark Miller lost their 13-year-old son, Matthew to suicide, after a psychiatrist gave him Zoloft. His parents were told that Matt had a chemical imbalance that could be helped by a new, wonder drug called Zoloft.

“It was safe, effective, only two minor side effects were cautioned with us – insomnia, indigestion,” they said.

While on the drug, Matt became agitated, could not eat, sleep, or sit still. The night before the family was set to leave for vacation, Matt hung himself in a bedroom closet from a hook, barely higher than he was tall.

“To commit this unthinkable act,” Mark said, “he was able to pull his legs up off the floor and hold himself that way until he lost consciousness.”

His parents had no warning of their son’s plan to kill himself. Mark had never spoken about suicide or threatened to commit suicide.

Mark and Cheryle have since learned that Matt’s doctor has served as “a well-paid spokesman for Pfizer,” the maker of Zoloft.

Terri Williams’ 14-year-old son, Jacob, was an exceptional athlete and participated in both the varsity and junior varsity football teams at his school.

In September 2000, Jacob seemed to lose interest in school activities except for football, and a conflict arose with regard to his grades and school attendance. As a result, his parents attended a conference in October 2000, at which the school administrator suggested that Jacob might be depressed and recommended seeking medical help.

Terri contacted Jacob’s pediatrician and made an appointment for the same afternoon. The doctor prescribed Prozac, and three weeks later increased the dose.

Shortly after he started taking the drug, Jacob complained of having strange bad dreams and shortly after the dose was increased, his mother noticed an aggressive behavior which had not been there before. “Jacob also became destructive and destroyed some of his favorite things,” Terri said.

When questioned, Jacob told his mother, “I don’t know what is making me do this.” Terri wrote it off to normal adolescent behavior and did not pursue the issue further.

On December 5, 2000, Terri found Jacob’s body hanging from the rafter in their attic. He had hung himself with his own belt. He left a letter on the ladder leading up to the attic for his parents, thanking them for giving him 14 years of a happy life.

After her son’s death, his friends told Terri that they had noticed the same changes in Jacob, that he had become short tempered and verbally aggressive.

“Had I known that this was a potential side effect, suicide,” Terri said, “I would have never allowed my son to take the drug Prozac.”

And the sad fact is, the FDA could have warned Terri, because by 1998, according to the FDA’s adverse reaction reporting system, Prozac alone had already accumulated over 40,000 adverse reaction reports, including over 2,100 deaths, far more than any other drug in the history of the reporting system.

Filed under: 2006, Celexa, Effexor, FDA, Glaxo, Lexapro, Paxil, Pfizer, Prozac, SSRIs, suicide, Wellbutrin, Zoloft

Lawmakers Say FDA Better Clean Up Its Act

Evelyn Pringle February 2007

For six years, the Bush administration has placed pharmaceutical industry interests ahead of public interest by appointing persons with strong ties to drug companies to high level positions at the FDA, and as a result, Congressional investigations and a recent survey indicate that the health and safety of all Americans is being compromised. 

On July 20, 2006, the Union of Concerned Scientists published the results of a survey that showed an insidious political influence of science within the FDA. According to the UCS press release, the survey was co-sponsored by Public Employees for Environmental Responsibility (PEER), and was sent to 5,918 FDA scientists.

The survey found that 61% of the responding scientists knew of cases where the “Department of Health and Human Services or FDA political appointees have inappropriately injected themselves into FDA determinations or actions.”

In responding to the survey, one scientist wrote: “Over the last several years I have noticed a significant increase in the number of decisions that have become politicized (e.g., increasing requests to review even simple regulations and changes, both by Congress and the Commissioner’s office and to make apparently politically-motivated changes in language and sometimes to alter bottom line results), and I think the integrity of scientific work could be improved by minimizing the ‘politics’ of the process.”

Out of the nearly 1000 scientists who responded, close to one-fifth or 18.4%, said they had “been asked, for non-scientific reasons, to inappropriately exclude or alter technical information or their conclusions in a FDA scientific document.”

In addition, 40% of the scientists said they fear retaliation for voicing safety concerns in public and more than one-third said they did not feel they can express safety concerns even inside the agency.

The survey also found that only 47% think the “FDA routinely provides complete and accurate information to the public,” and 81% agreed that the “public would be better served if the independence and authority of FDA post-market safety systems were strengthened.”

In a complaint aimed at the FDA’s Office of Regulatory Affairs, one scientist said it should “not ostracise scientists or black ball them because their foresight sees a problem with a drug, device, food, biologics, etc. that possess a potential hazard to health now or in the future.”

In response to the concerns raised by FDA scientists, the UCS recommends:

–  Accountability: FDA leadership must face consequences if they side with commercial or political interests and not with the American people.

–  Transparency: Scientific research and reviews should be open so any undue manipulation is immediately apparent.

–  Protection: Safeguards must be put in place for all government scientists who speak out.

“These disturbing survey results make it clear that inappropriate interference is putting people in harm’s way,” said Dr Francesca Grifo, Senior Scientist and Director of UCS’s Scientific Integrity Program, in the press release.

“All federal scientists,” he said, “need protections so they can speak out when their science is manipulated, and all federal agencies need fully functioning independent advisory committees.”

“FDA leaders,” Dr Grifo noted, “should act now to improve transparency and accountability and renew respect for independent science at the agency.”

“FDA leadership,” he stated, “must understand and support independent science and it is up to Congress to hold them accountable.”

But nothing about this survey is news to FDA officials. By use of the FOIA, the UCS and PEER, recently obtained a copy of a previously unpublished survey by the Health and Human Services Office of Inspector General from late 2002, that polled 846 FDA scientists, and with nearly half responding determined that:

Nearly one in five said that they “have been pressured to approve or recommend approval” for a drug “despite reservations about the safety, efficacy or quality of the drug”

Two-thirds lacked confidence that the FDA “adequately monitors the safety of prescription drugs once they are on the market”
 
Only 12% of the responding scientists were completely confident that FDA “labeling decisions adequately address key safety concerns,” and 30% were not at all or only somewhat confident
 
More than one-third were not at all or only somewhat confident that “final decisions adequately assess the safety of a drug”
 
Despite the above results, the report published by the OIG in March 2003, included the conclusion that FDA scientific reviewers “have high confidence in decisions FDA makes.”

On August 8, 2006, the UCS briefed acting FDA Commissioner, Andrew von Eschenbach, on the latest survey and discussed the political inference at the FDA. To restore integrity, UCS recommended that Dr von Eschenbach adopt and enforce three basic commitments:

(1) to ensure that data or results are never softened for any audience. Rigorous scientific debate must be valued at the FDA;

(2) to pledge to support scientists who speak out by taking adverse employment action against any manager who retaliates against a reviewer; and

(3) to commit to a culture that supports a collaborative process of testing and challenging scientific hypotheses.

Along with the recommendations, the group’s August 8, 2006, press release said, “The FDA must allow an open scientific process and recognize the need for scientists to pose and answer questions without consequences related to their status at the FDA.”

Critics claim that a major issue that needs to be addressed involves the rampant conflicts of interest among members of the FDA’s advisory panels who have financial ties to the pharmaceutical industry. In November 2005, a new law was passed that required members of the committees to disclose all financial ties to drug companies.

The categories for disclosure were broken down into dollar amounts and time frames, such as less than $10,000 a year or between $10,000 and $50,000 a year. After reviewing the financial disclosure forms, the FDA is permitted to grant waivers that allow experts to sit on panels even if they have financial ties to a drug company.

However, on April 21, 2006, the Boston Globe discussed the practical effects of the law since it was enacted and reported that FDA critics “say the new transparency has changed little, and scientists who have conflicts of interest can still guide FDA decision making.”

In less than 6 months after the law went into effect, the Globe determined the FDA had granted close to 100 waivers.

One of the latest FDA fiascoes, involves the approval of the antibiotic, Ketek, despite serious concerns about the drug’s safety and lack of efficacy, by top officials with full knowledge that the studies submitted to support its approval were fraudulent.

Several employees at told FDA officials that the liver damage associated with Ketek was known to its maker, Sanofi-Aventis, early in clinical trials but was covered up.

According to the FDA’s senior scientist, Dr David Graham, who blew the whistle on the agency’s mishandling of the Vioxx debacle, Ketek is at least as toxic to the liver as three other drugs that have been removed from the market and the FDA’s original approval of the drug was based on a study that the agency’s top officials knew was fraudulent.

Internal FDA emails that surfaced during the investigation show that at least four FDA safety officials, Dr David Graham, Dr Charles Cooper, Dr David Ross and Dr Rosemary Johann-Liang, had voiced serious concerns about the safety of the drug.

“I tried to argue that given Aventis’s track record in which they have proven themselves to be nontrustworthy that we have to consider the possibility that they are intentionally doing a poor job of collecting the postmarketing data to protect their drug sales,” Dr Cooper said in an email.

“It’s as if every principle governing the review and approval of new drugs was abandoned or suspended where telithromycin is concerned,” Dr David Graham wrote in an email that recommended Ketek’s “immediate withdrawal.”

“We don’t really know if the drug works;” he said, “no one is claiming it works better than other, safer drugs; and we’re flying blind as far as safety goes, except for our own A.D.R. data that suggests telithromycin is uniquely more toxic than most other drugs.”

In May 2006, Dr Johann-Liang called for a halt to tests of Ketek in children with ear infections, arguing that cutting the duration of ear pain by one day was hardly worth risking death.

The FDA’s actions in regard to Ketek are being investigated by Senator Charles Grassley’s (R-Iowa), Senate Finance Committee, and by Representatives, Edward Markey of Massachusetts, and Henry Waxman of California, ranking Democrats on the House Government Reform Committee.

In May 2006, the lawmakers released a statement that said although “the FDA has consistently assured the public of Ketek’s safety and efficacy, public documents obtained and examined by Representatives Markey and Waxman’s staff indicate that the approval process for this drug was seriously flawed.”

As Chairman of the Senate Committee, Senate Grassley has called for a “major overhaul and a culture change at the highest levels” of the FDA. In a May 1, 2006, press release, he noted concerns over the FDA’s complicity with the drug maker and its subsequent failure to ensure the integrity of a study on the benefits and risks of Ketek.

The Senator called it “mystifying” on May 16, 2006, that the FDA would continued to provide information that it knew was fraudulent, and warned that he planned to keep the pressure on the FDA to provide more information about Ketek’s approval and post-market surveillance.

“It’s no surprise to learn that the FDA didn’t listen to Dr. Graham on the dangers of Ketek,” Senator Grassley was quick to point out. “The FDA has made it their business to discredit Dr. Graham and others who aren’t willing to cater to the drug companies,” he noted.

In October 2001, doctors began enrolling subjects for the Ketek clinical trial known as Study 3014, and were paid $100 for each patient that signed up. The participating doctors would also receive another $150 when the study results were submitted, and a final $150 when all questions related to the study were resolved, according to the May 1, 2006, Wall Street Journal.

On July 24, 2002, drug maker Aventis submitted the results of the study to the FDA, but when FDA officials submitted the study to the advisory committee for review, they did not disclose that the Division of Scientific Investigation and Office of Criminal Investigation was investigating the integrity of the study.

The misconduct that took place during the clinical trials is so serious that critics say it calls the validity of the entire study into question. For instance, the doctor who signed up the 3rd highest number of patients, was in a chronic state of cocaine addiction while conducting the clinical trial, and was arrested and found to have cocaine hidden in his underwear, while holding his wife hostage with a gun, the same month the study results were submitted to the FDA.

Another doctor who participated in the study was totally disqualified as an investigator and prohibited from conducting any clinical trials in the future, and another who signed up 150 patients was cited for 20 violations of the study’s instructions.

Dr Anne Campbell, the doctor with the highest number of subjects in the study, was sentenced to nearly 5 years in prison in March 2004, after being charged in a 21-count indictment over her misconduct.

Senator Grassley is demanding a face-to-face interview with the FDA investigator who discovered the fraud and misconduct in the trials, who he contends “is key to understanding what the FDA did when it became clear that the safety study required by the FDA in order to approve the drug was fraudulent and faulty.”

This investigator authored a March 25, 2004, memorandum from the Division of Scientific Investigations titled, “DSI Recommendations on Data Integrity,” that states in part, that Study 3014 involved “multiple instances of fraud” and that “the integrity of data from all sites involved in [the] study … cannot be assured with any degree of confidence.”

After months of trying unsuccessfully to get an interview, Senator Grassley finally marched right over to the Department of Health and Human Services headquarters and asserted a congressional right to speak to the investigator.

After a brief conversation with senior officials, he left mad as a hornet. “This is extraordinary to me,” he said outside HHS headquarters. “I haven’t had to go to an agency like this since 1983 to get information I requested.

“I smell a cover-up,” he stated.

On June 22, 2006, Senator Grassley publicly announced a not too subtle warning to officials at the agency. “Two years ago I called a congressional hearing to probe the FDA’s handling of the withdrawn painkiller Vioxx,” he said in a statement.

“It might be time,” he warned, “to round up another oversight hearing after the runaround I got recently at the FDA.”

“The FDA,” he wrote, “refused to allow me to question an internal investigator who is leading an inquiry into alleged fraud involved with clinical trials for the antibiotic Ketek.”

“So for only the second time in 23 years,” he said, “I resurrected in June my unconventional means to fulfill my Constitutional oversight responsibilities.”

He said, “I appeared at the FDA’s doorstep,” and noted that agency officials refused to let the investigator speak to him.

However, he warned, “Bureaucratic stonewalling won’t deter this U.S. Senator.”

“I won’t rest,” Senator Grassley said, “until the light of day exposes what ought to be available for public consumption.”

“It all boils down to keeping the government accountable,” he wrote, “to the people and strengthening the public trust in government.”

In another statement released on June 29, 2006, he stated, “Ketek is another example where the F.D.A. accommodated a drug maker and turned a blind eye to serious safety concerns.”

Over the past couple of years, the suppression of the scientific process and the muzzling of scientific dissent at the FDA became evident first when officials forced Dr Andrew Mosholder to suppress a link he found between SSRI antidepressants and suicide in children, and Dr Graham went public with allegations about the FDA’s mishandling of the Vioxx matter.

On March 10, 2005, Senator Grassley gave a speech to the Consumer Federation of America and said these two whistleblowers had done more to shake up a complacent FDA than probably anybody in recent history and relayed parts of the story saying:

“Early last year I heard that the FDA was muzzling one of its own scientists. In February 2004 the FDA held a meeting to decide whether there was a link between some antidepressant drugs and suicidal behavior in kids.

“Dr. Andrew Mosholder – the FDA’s expert in this area — concluded there was a link. However, FDA management disagreed. So, when Dr. Mosholder stuck by his findings, his supervisors canceled his presentation to an advisory committee.

“Instead of allowing Dr. Mosholder to present his findings publicly and subject them to committee scrutiny, the scientific process and his peers, the FDA effectively muzzled him.”

But despite the FDA’s best efforts, Senator Grassley said, Dr Mosholder wouldn’t be silenced and months later he was proven right.

Citing information from the Department of Justice, he told the audience that there are currently under seal in the neighborhood of 100 whistleblower cases involving allegations against over 200 drug companies.

“During the past four years,” he stated, “the department recovered nearly 2 and a half billion dollars from whistleblower cases against drug companies.”

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

In an August 30, 2005, interview with Manette Loudon, the lead investigator for Dr Gary Null, Dr Graham discussed how FDA officials attempted to suppress the results of his study on Vioxx a year earlier. According to Dr Graham, prior to his Senate testimony in mid-November of 2004, there was an orchestrated campaign by senior FDA managers to intimidate him so that he would not testify about the adverse affects of Vioxx to Congress.

One attack he says, came when the acting FDA Commissioner, Lester Crawford, contacted the editor of the Lancet, a UK medical journal, and told him that Dr Graham had committed scientific misconduct and that the journal should not publish the paper that he had written showing that Vioxx increased the risks of heart attack.

The second attack came from other high level officials, he said, who contacted Senator Grassley’s office in attempt to prevent Senator Grassley from calling him as a witness.

And the third he says came from senior FDA officials who contacted Tom Devine, Dr Graham’s attorney at the Government Accountability Project, and attempted to convince him that the GAP should not represent Dr Graham because he was guilty of scientific misconduct.

According to Dr Graham, these officials posed as whistleblowers themselves, and told Mr Devine that Dr Graham was a “bully,” a “demigod,” and a “terrible person” that could not be trusted.

In one more last ditch effort to thwart Dr Graham’s testimony the week before he testified, he says, the acting Commissioner offered him a job in the Commissioner’s Office to oversee the revitalization of drug safety if he would just leave the Office of Drug Safety.

“Obviously he had been tipped off,” Dr Graham said in the interview, “by people in the Senate Finance Committee who are sympathetic to the FDA’s status quo that I was going to be called as a witness.”

To preempt his testimony, he told Ms Loudon, he was offered a job “which basically would have been exile to a fancy title with no real ability to have an impact.”

According to Dr Graham, by allowing Vioxx to stay on the market, the FDA is responsible for 140,000 heart attacks and 60,000 dead Americans. “That’s as many people as were killed in the Vietnam War,” he points out.

He says the FDA could have prevented many of the heart attacks and deaths simply by banning the high dose Vioxx back in 2000 when the agency learned about the results of the VIGOR Study. “But the FDA did nothing for almost two years,” he states. “They were “negotiating” with the company over a label.”

“The FDA made bad decisions,” Dr Graham said, “based of its culture and its institutionalized biases that favor industry, and as a result thousands of Americans died.”

During a July 18, 2005, speech on the Senate floor, Senator Grassley proclaimed, “this country’s confidence in the FDA has been shaken.”

It has not been shaken, he said, by one isolated incident or whistleblower. “It has been shaken because multiple drug safety concerns have been exposed by more than one courageous whistleblower.”

“Dr. Graham’s testimony before the Finance Committee,” he told members of Congress, “suggests that the problems are systemic.”

“Oversight of the FDA,” Senator Grassley advised, “exposed the cozy relationship that exists between the FDA and the drug industry.”

“It revealed that the FDA negotiated for almost two years with Merck,” he said, “about how to change the Vioxx label so people would know about the risk of heart attacks.”

According to Dr Graham, the Vioxx disaster would not have been as severe in the absence of direct-to-consumer advertising. “I submit,” he told Ms Loudon, “that the numbers would have been far lower than what they were.”

Due to heavy marketing of new drugs, Dr Graham says, lots of patients and doctors will use a new drug that is no better than another drug already on the market, even though the FDA does not require that new drugs be at least equivalent to, or better than, the drugs that are already there. All the drug maker has to prove is that a drug works better than a sugar pill, he says.

Silencing scientists to protect the industry has become habitual under the current politically appointed rulers of the FDA. According to Shane Ellison, author of “Health Myths Exposed,” pharmaceutically compliant politicians have “democratized” the drug 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,” he warns, “no longer prevail at the FDA or at pharmaceutical companies.”

Mr Ellison is a former pharmaceutical industry chemist who says he felt a responsibility to reveal the truth about the industry’s sordid tactics after he witnessed first-hand how they deceive the public, according to a September 3, 2005, interview with Crusador Editor, Greg Ciola.

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

As an example, Mr Ellison discussed Dr Curt Furberg, a member of the FDA’s drug safety advisory committee. Dr Furberg, he says, came forward to reveal that Bextra also caused heart attack and stroke. In the British Medical Journal, Dr Furberg said that his studies showed Bextra to be no different than Vioxx, and warned that Pfizer was trying to suppress that information.

“Immediately thereafter,” Mr Ellison said, “Dr. Furberg was barred from serving on the panel that is 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,” Mr Ellison told Crusador.

In the case of the pain relieving Cox-2 inhibitors, the FDA’s advisory committee was stacked with experts with ties to the drug makers. Of the 32 advisers who would vote on the drugs, it has since become known that 10 of panel members had consulted in recent years for Vioxx maker, Merck, or Pfizer who made Celebrex and Bextra.

While the committee voted unanimously that all of the drugs significantly increased the risk of heart attack and stroke, in a 17-15 vote the panel said the FDA should allow Vioxx to remain on the market. A tally of the votes showed that without the 9 votes of the 10 members who consulted for the drug makers, the committee would have voted 14 to 8 to ban Vioxx.

However, the panel’s recommendation was met with scorn and outrage by medical experts and researchers alike in the media, and in a rare occurrence, the FDA went against the recommendation of its advisory panel and refused to allow Vioxx to remain on the market.

Critics also accuse the FDA of not properly monitoring the marketing activities of the pharmaceutical industry. An investigation by the House Committee on Government Reform found that since December 2001, there has been a sharp decline in enforcement actions taken against drug companies for illegally promoting their products.

The investigation determined that from 1999 to 2001, the FDA sent out 250 “Notice of Violation” or “Warning” letters to drug companies; but for the time period of 2002 through 2004, the agency sent out only 70 letters, which amounts to a reduction of more than two-thirds.

Since the Vioxx and SSRI debacles, Senator Grassley has jumped on the FDA every time there has been any indication that officials might be putting the industry’s interest over public safety. Earlier this year, he wrote a letter to the FDA saying he was concerned that it might be “dropping the regulatory ball” on stimulant drugs, prescribed to treat ADHD.

Specifically, he wrote, “I’m concerned FDA’s regulatory responsibilities haven’t kept pace with the explosion of prescriptions written to treat 2.5 million children with these drugs.”

Despite psychiatric and cardiovascular risk signals associated with the drugs, he noted, it appears the FDA has failed to promptly respond to their possible adverse effects. “Such events,” he wrote, “may include sudden unexplained deaths, strokes, cardiovascular irregularities or aggression, anxiety and depression.”

Sales of drugs, he said, “have zoomed to the moon, jumping from $759 million to $3.1 billion between 2000 and 2004.”

“And yet,” he wrote, “the FDA seems to have adopted a wait-and-see approach before charting a course of action to study these risks.”

In early February 2006, he noted, that an advisory panel had recommended adding the strongest black box warning to ADHD drugs to alert patients about the possible cardiovascular side effects.

“The recommendation,” Senator Grassley wrote, “brings even more urgency to the controversy surrounding the explosion of prescriptions being filled with these medicines.”

“As the debate unfolds,” he warned agency officials, “I will continue to closely track the FDA and urge its timely, thorough review of these drugs.”

“With millions of Americans, mostly children, regularly taking these medications,” he added, “it is essential the FDA leaves no stone unturned to investigate and review this class of drugs.”

No doubt in response to all the intense scrutiny from members of Congress, in late July 2006, the FDA outlined a series of changes it plans to make in the methods used to evaluate clinical trials. One of the proposed changes would require a drug company to notify the FDA immediately if it believes a researcher has committed fraud during a clinical trial.

As it is now, drugs companies are trusted to remove unreliable data and are not required to report any fraudulent activity to the FDA until they actually submit the application.

The agency also says it plans to clarify which adverse events in clinical trials must be reported to the review boards that monitor the studies. Other proposed change includes the standardization of forms used to collect information and a revision of the rules on how patients may qualify to participate in clinical trials.

However, people who are tempted to think that the FDA is capable of changing under the agency’s current team of politically appointed officials, had better think again.

According to an article by Russell Mokhiber and Robert Weissman, for Common Dreams on August 2, 2006, Dr Steven Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, was recently a member of a panel debating the topic of: “Government Science Panels: Fair and Balanced?” which was moderated by National Public Radio’s Snigdha Prakash, and sponsored the Center for Science in the Public Interest.

Dr Nissen spoke about the conflict-of-interest problems “evident at the highest levels of the FDA,” the article says.

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

“Then the administration appointed Andrew Von Eschenbach as interim commissioner, creating another conflict,” he noted.

“In his role as director of the National Cancer Institute,” Dr Nissen said, “Von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict.”

But even worse, he said, “the administration appointed Scott Gottlieb as deputy commissioner.”

“He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter,” Dr Nissen stated.

“Between them,” he said, “Drs. Von Eschenbach and Gottlieb have whined incessantly about the need to speed drug development.”

“So while the American people worry about the safety of drugs,” he continued, “the top FDA leadership tells us we need faster drug approval.”

On November 12, 2005, the Boston Globe reported that prior to his job at the FDA, Dr Gottlieb worked for the PR firm of Manning Selvage & Lee and that his clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the maker of Ketek, and the parent company to the nation’s sole flu vaccine maker.

According to the Globe, the Manning PR firm paid Dr Gottlieb a monthly retainer of $12,500 for nine months, for working on projects that involved eight companies. Other firms regulated by the FDA that he was involved with include Inamed Corp, a company seeking the return of silicone gel implants to the market.

Between May and July 2005, Dr Gottlieb also was paid $9,000 for consultant work performed for VaxGen, a company that won an $878 million government contract to supply the US with 75 million doses of anthrax vaccine.

In any event, no matter who’s in charge, the Senator from Iowa is keeping the heat on. In July 2006, he wrote a letter to the Daniel Levinson, the Inspector General at the Department of Health and Human Services, asking for an investigation into whether Dr Brian Harvey of the FDA, conspired against Dr Graham by providing Merck with details about Dr Graham’s presentation on Vioxx, prior to the hearing in 2004 to help the company refute his testimony.

“It is no secret that Dr. Graham was and is a critic of the FDA,” he wrote to Inspector. “However,” he said, “that does not mean the FDA should scheme with drug sponsors to discredit its own employees.”

Filed under: 2007, Avandia, Bextra, FDA, Gottlieb, Graham, Ketek, Manning, Merck, Pfizer, SSRIs, Vioxx, whistleblower

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