The Bitter Pill

The Official Blog of UNITE – uniteforlife.org

Merck Not Losing Sleep Over Vioxx Disaster

Evelyn Pringle June 16, 2006

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

He told the audience how the director of FDA’s office of new drugs suggested that Dr. Graham water down his Vioxx conclusions and how Dr Graham replied that in good conscience he could not. “When Dr. Graham was asked to present his findings at my committee’s Vioxx hearing,” the Senator said, “he was also undermined.”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

But experts say that is definitely not going to happen.

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

Merck Caught Misrepresenting Vioxx Risks Again

May 17, 2006

Evelyn Pringle

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Filed under: 2006, FDA, FDA Crawford, FDA hearing, GAO, Graham, Judge Fallon, Merck, NSAIDs, Vioxx, whistleblower

Ending FDA’s Love Affair With Big Pharma

Evelyn Pringle November 2006

With the Democrats back in power, critics say officials at the FDA and representatives of Big Pharma had better plan on spending much of their time testifying on Capital Hill in Congressional hearings in 2007.

Democrats have spelled out their plans to change how the administration chooses experts to sit on FDA advisory panels and put an end to the suppression of dissenting opinions of FDA scientists.

These panels advise the agency on which drugs should be approved, what their warning labels should say, and how clinical studies should be conducted. The approximately 300 so-called experts make decisions that potentially affect billions of dollars in sales for Big Pharma and the FDA follows their recommendations almost exclusively.

Critics are demanding stricter conflict of interest rules for members of the panels and a November 17, 2006, session of the Senate Committee on Health, Education, Labor, and Pensions, gave the Democrats their first opportunity to indicate how they will deal with the out of control FDA once they become the majority in Congress next year.

The hearing titled, “Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation,” was held to push forward FDA reform legislation Senate Bill 3807, the “Enhancing Drug Safe and Innovation Act of 2006,” previously introduced by outgoing committee chairman, Senator Michael Enzi (R-WY), together with incoming chairman, Senator Edward Kennedy (D-MA). The two Senators began working on the bill when Vioxx was pulled from the market after it was found to cause heart attacks and strokes.

Cleveland Clinic physician-scientist, Dr Steven Nissen, MD, who has served as an expert on FDA advisory panels, testified at the hearing and described “a crisis in public confidence in the FDA following an unprecedented series of revelations about drug and device safety” and referred to the Senate reform bill as a “major step forward.”

“I am a strong supporter of this bipartisan effort to enhance the FDA’s effectiveness and improve drug and device safety,” he said. “I believe that this legislation represents the best chance we have had in a long time to make a real difference for patients in this challenging area.”

Dr Nissen said new laws are needed to strengthen the authority of the FDA. “Currently,” he explained, “the Agency must “negotiate” with industry to make even simple changes in drug labels.”

“I served on a 2001 Advisory Panel that recommended a warning label for Vioxx,” he informed the panel, “but it took 14 months before the FDA could secure agreement from the company to accept a weakly written warning.”

As for enacting new conflicts of interest rules for advisory panels, Dr Nissen testified that improvements “in the Advisory Committee process will help to ensure that FDA consultants are less likely to be influenced by financial conflicts of interest.”

Merrill Goozner, Director of Integrity in Science Center for Science in the Public Interest, testified about the blatant conflicts of interest involving the expert panel that reviewed Vioxx and the other COX-2 inhibitors, and how the panel concluded that Vioxx was safe enough to stay on the market, even though Merck had already removed it from the market.

Mr Goozner told the Senate committee that ten of the 32 scientists on the panel had financial ties to the drugs’ makers. “Had their votes been eliminated,” he said, “two of the drugs in the class would have been voted down by the panel.”

“The best way to solve all these problems,” Mr Goozner stated, “without undermining the quality of the advice offered to the FDA – is to completely eliminate conflicts of interest from these committees.”

Jim Guest, president and CEO of Consumers Union, publisher of Consumer Reports, testified that improvements are needed to help prevent future drug safety disasters and called for a rule specifying that at least 90% of the members on advisory committees who decide whether a drug should be approved be free of conflicts of interest from the pharmaceutical industry.

In “the wake of the Vioxx and Paxil disasters,” he told the committee, where tens of thousands of Americans needlessly suffered, we’ve educated our more than 20 million readers on the need for stronger state and Federal drug safety laws.

During his testimony, Mr Guest pointed out that GlaxoSmithKline had concealed the results of clinical trials linking Paxil to an increased risk in suicidality among adolescents, as proven, he noted, by New York Attorney General, Eliot Spitzer’s successful lawsuit against Glaxo.

Furthermore, he told the committee, the hidden trials also revealed that Paxil was actually less effective than placebos among adolescents.

Mr Guest also told the committee that these abuses by drug companies have not ended. As recently as September 29, 2006, he noted, the FDA released a Public Health Advisory that said Bayer, maker of Trasylol, failed to inform an advisory committee during a hearing held 8 days earlier to discuss Trasylol, of a new study that revealed an increased risk of death, serious kidney damage, congestive heart failure and stroke.

In addition, Mr Guest described problems created by fraud and falsification of studies used in the drug approval process. “In the recent case of Ketek,” told the panel, “the FDA found multiple instances of fraud in the company’s clinical trial of about 24,000 patients, some cases of which the maker Sanofi already knew about yet failed to notify the agency.”

Internal FDA emails that surfaced during a previous Congressional investigation revealed that the FDA was aware of the dangers with the drug and 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 Ketek (telithromycin).

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

On the Republican side of the isle, the Democrats have a strong ally in Senate Finance Committee chairman, Senator Chuck Grassley (R-Iowa), who also has been one of the FDA’s most out-spoken critics since the Vioxx and SSRI disasters.

His latest focus has been on the FDA’s handling of the Ketek debacle. In a May 1, 2006 press release, Senator Grassley expressed concerns over the FDA’s complicity with the drug company and its subsequent failure to ensure the integrity of a study on the benefits and risks of Ketek. In another statement released on June 29, 2006, he said, “Ketek is another example where the F.D.A. accommodated a drug maker and turned a blind eye to serious safety concerns.”

Critics say the worst conflicts of interest within the FDA are the result of major Big Pharma influence over the Bush appointed officials at the top.

According to Robert Brava-Partain, an associate attorney at the national law firm of Baum Hedlund, the FDA has become an “approval factory” for drugs that are ineffective and dangerous. “This factory is manned by doctors who, in any other setting,” he says, “would have irreconcilable conflicts of interest with the companies the agency is supposed to be monitoring.”

And at the top of the factory, he says are, “political appointees who make no apologies for engaging in promanufacturer advocacy.”

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

According to the Globe, Manning paid Dr Gottlieb a monthly retainer of $12,500 for nine months for work involving 8 companies, and he was also paid $9,000 for consultant work for VaxGen, a company that won an $878 million government contract to supply the US with 75 million doses of anthrax vaccine.

Dr Gottlieb and Dr Nissen recently went head to head when they both participated in a debate on the topic: “Government Science Panels: Fair and Balanced?” moderated by National Public Radio’s Snigdha Prakash, and sponsored the Center for Science in the Public Interest, reported on August 2, 2006, by Russell Mokhiber and Robert Weissman, in Common Dreams.

To his credit, Dr Nissen can never be called a back-stabber because while sitting next to fellow panelist, Dr Gottlieb himself, Dr Nissen very candidly described the conflicts of interest which he described as “evident at the highest levels of the FDA.”

“For years,” he said of the 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,” he noted, “creating another conflict.”

“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, after that, Dr Nissen stated, “the administration appointed Scott Gottlieb as deputy commissioner.”

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

Dr Gottlieb’s reply to Dr Nissen’s remarks, was basically that he would not dignify the comments with a response.

This month, Dr Gottlieb presented an early Xmas gift to one of his former employers, Inamed Corp, when the FDA announced that it would lift restrictions on the sale of silicone gel breast implants on November 17, 2006.

Firms that Dr Gottlieb was involved with prior to his gig at the FDA, according to the Boston Globe, include “Inamed Corp., one of two companies seeking to return silicone gel implants to the market.”

As for the last FDA commissioner, 2 months after Mr Crawford was confirmed, MSNBC announced: “Embattled Food and Drug Administration Commissioner Lester Crawford abruptly resigned Friday, telling his staff that at age 67 it was time to step aside.”

In a resignation letter to Bush on September 23, 2005, Mr Crawford said his resignation was “effective immediately.”

On October 26, 2005, the Wall Street Journal stated: “As late as 2004, former Food and Drug Administration head Lester Crawford or his wife owned stock in companies that make or distribute products regulated by the agency.”

Six months later, on April 29, 2006, the New York Times reported that Mr Crawford, was under criminal investigation by a federal grand jury over allegations of financial improprieties and false statements to Congress, quoting his lawyer, Barbara Van Gelder.

On October 16, 2006, the Associated Press said that Mr Crawford had agreed to plead guilty to charges of failing to disclose a financial interest in firms regulated by his agency. “The Justice Department accused the former head of the Food and Drug Administration in court papers,” the article stated, “of falsely reporting that he had sold stock in companies when he continued holding shares in the firms governed by FDA rules.”

After leaving the FDA, Mr Crawford quickly moved on to a job with a firm called Policy Directions, Inc. A few of the firm’s accomplishments for clients listed on its Web site are: (1) achieved FDA advisory committee support for a product that had originally been voted down; (2) Interceded with FDA when the agency failed to provide final approval for client’s product because it had granted orphan drug status for a product by another company and client’s product was approved; (3) created a coalition of six biotechnology firms to promote legislation advantageous to client and meet with agency officials to prevent onerous rulemaking; (4) wrote industry-coalition draft of legislative authority for a regulatory agency that was included in final bill; (5) created and led coalition of universities, research institutions, pharmaceutical and biotechnology companies to lobby Congress to stop a federal agency from costly and ineffective rulemaking; and (6) led an industry coalition that stopped several negative amendments to agriculture/FDA appropriations bills.

On its Web site, the firm also states, “PDI has longstanding relationships with key personal and committee staffs in Congress, as well as with critical players at important agencies within the Administration.”

That appears to be an understatement since Mr Crawford joined the company. The firm should put modesty aside and inform potential clients that it now has inside information about the status of each and every drug, device, and company regulated by the FDA.

Although Mr Von Eschenbach has served as acting commissioner since Mr Crawford left in disgrace, critics say the likelihood of his confirmation as the permanent commissioner is not a done deal, especially now that Senator Grassley is protesting his confirmation and became the third Republican to join the campaign to block the nomination.

As for the Senator’s reasons, it seems that Mr Von Eschenbach has refused to cooperate with Senator Grassley’s investigation into the FDA’s approval of Ketek and has refused requests for agency documents and interviews with FDA staff, even after subpoenas were issued, according to a November 16, 2006 letter that Senator Grassley sent to Senate Majority Leader Bill Frist (R-TN).

“I am extremely disturbed,” Senator Grassley wrote, “by the Acting Commissioner’s continued failure to comply with the committee’s subpoenas over the past six months.”

There are three major FDA advisory committee meetings scheduled for December, 2006 to review: drug-eluting stents on December 7-8; SSRI use and adult suicidality on December 13; and Ketek on December 14-15.

But it does not appear that the FDA is too worried about improving the public image of the advisory panels because reports from persons wanting to speak at the SSRI hearing say the FDA is refusing to allow enough time for public comments and is refusing to release the complete list of names for members of the panel until the day before the hearing making it impossible to determine whether they have financial ties to SSRI makers.

Filed under: 2006, Avandia, FDA, FDA Crawford, Gottlieb, Ketek, Manning, Paxil, SSRIs, Trasylol

FDA – The Rest of the Story

Evelyn Pringle March 7, 2007

The 12,000-employee FDA regulates products that account for more than $1.5 trillion in yearly sales, or about a 10th of the US economy. Besides food and drug safety, the agency also enforces regulations covering medical devices and cosmetics.

The FDA is part of the executive branch of government and therefore, any filing of reports by companies where critically important safety data is willfully omitted is a criminal offense under US Code: 18 USC 1001- Fraud and False Statements, according to Barry Turner, a professor of law and medical ethics in the UK.

Mr Turner explains that concealing dangerous side effects is a willfully misleading act and that any company that engages in a course of action that involves withholding data about adverse reactions is committing a crime.

However, in order to find a company guilty of fraud, there would probably have to be a showing that FDA officials were not involved in the underlying act, and this is where the whole case would fall apart because Big Pharma has so successfully infiltrated the nation’s top regulatory agency that there are no “clean hands” so to speak.

Since the Bush administration took over the FDA, there has been several unsuitable Commissioners. Mark McClellan was the official leader in 2003, but after being embarrassed on 60 Minutes when asked why Canadian drugs were not safe enough to be imported for use by Americans, he moved on to a less visible position.

After that, Lester Crawford served as Acting Commissioner until his nomination for full-time Commissioner was approved in August 2005. However, Mr Crawford’s tenure was also short-lived and he abruptly resigned two months after he was confirmed.

About a year later, on October 2006, Mr Crawford pleaded guilty to charges of having a conflict of interest and false reporting of information about his stock holdings with pharmaceutical companies during the years he was employed at the FDA. Going back to 2002, investigators found that Mr Crawford had filed 7 false reports with the government ethics office and Congress.

Last month, on February 27, 2007, Judge Deborah Robinson, sentenced Mr Crawford to three years of supervised probation, 50 hours of community service, plus fines of roughly $90,000 for lying about the stocks that he and his wife owned in companies that were regulated by the FDA.

The judge would not agree to let Mr Crawford off the hook as easily as proposed. “While the total fine exceeds what the parties agreed to,” she said at the hearing, “the fine is well below the maximum under the statute.”

The Bush administration’s original nomination of Mr Crawford was nearly derailed a number of times. On July 18, 2005, a member of the administration’s own party, Senator Charles Grassley (R-Iowa) took to the Senate floor to respond to the nomination and gave a caustic critique of the FDA as a whole and Crawford’s conduct specifically.

“My oversight of the FDA,” he stated, “leads me to the conclusion that there are cultural and systemic problems at the FDA.”

“Unfortunately,” he said, “Dr. Crawford has long been part of that same culture and system.” Senator Grassley also elaborated further in stating:

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

“Oversight of the FDA exposed the cozy relationship that exists between the FDA and the drug industry. It revealed that the FDA negotiated for almost two years with Merck about how to change the Vioxx label so people would know about the risk of heart attacks.”

The evidence is overwhelming, Senator Grassley said, that the FDA must change to better protect the people. “Dr. Crawford,” he stated, “does not appear willing to be the man to change the FDA.”

A few months earlier, several Democrats had also raised strong objections to the nomination. On April 6, 2005, following a closed-door meeting, Senators Patty Murray (D-Wash) and Hillary Rodham Clinton (D-NY), members of the Senate Health Education and Labor Committee, announced their intention to place a “hold” on Dr Crawford’s nomination, citing the FDA’s failure to act on a host of public health issues, including the Plan B contraceptive approval, during his tenure as Acting Commissioner.

On June 15, 2005, Senators Murray and Clinton delayed consideration of the nomination by the full Senate. “At a time when the FDA needs a strong leader to restore its reputation,” Senator Clinton said in a statement, “I fear that Dr. Crawford’s record demonstrates a lack of vision and drive to ensure that the FDA upholds its gold standard of drug regulation.”

“He has failed,” she explained, “to address the concerns raised by his own employees about the needs of the agency.”

“And he cannot provide assurances,” she continued, “that the FDA will make science, not ideology or other interests, the cornerstone of its decision making.”

“The Senators’ hold will remain,” the statement said, “in effect until FDA issues a yes or no decision on the over-the-counter application of Plan B emergency contraceptives.”

“We are asking FDA to explain,” they Senators stated, “why they are delaying an over-the-counter application for Plan B that even their own Advisory Panel overwhelmingly recommended for approval.”

“I fear that the case of Plan B,” Senator Murray noted, “highlights a leadership problem at FDA – a leadership that can be biased or open to undue influence.”

On July 15, 2005, Senators Clinton and Murray lifted the hold after receiving assurance from Health and Human Services Secretary, Mike Leavitt, that the FDA would act on the Plan B application by September 1, 2005.

Once the nomination was confirmed, that assurance turned out to be meaningless and September 1, came and went. However, 23 days later, Dr Crawford resigned after serving only two months as Commissioner, and Andrew von Eschenbach became the Acting Commissioner.

The emergency contraceptive at the center of the controversy, Plan B, had been available with a prescription since 1999. In 2003, Barr Laboratories sought FDA approval to sell it over-the-counter, arguing that it could reduce the number of unintended pregnancies and abortions as an emergency contraceptive to be used within 72 hours of unprotected sex.

On May 6, 2004, Mr Crawford rejected a 23 to 4 vote by the FDA’s Advisory Committee for Reproductive Health Drugs to approve over-the-counter sale of Plan B, in effect overruling a scientific consensus that overwhelmingly found the drug safe and effective.

At the time, critics accused FDA officials of ignoring scientific evidence due to pressure from social conservatives, and they of course denied the allegations.

However, much of the outrage that erupted a year later when it came time for Mr Crawford’s confirmation as Commissioner, was fueled by Dr David Hager, an obstetrician-gynecologist, and a Bush appointee to the FDA Advisory Committee, who was known to be one of the 4 members that voted against the approval of Plan B.

In 2002, the original appointment of Dr Hager was for chairman of the Advisory Committee. However, the nomination drew an onslaught of protests due to his ideological views such as refusing to prescribe contraceptives to unmarried women and advocating the use of prayer for the relief of premenstrual syndrome.

Critics said they objected to Dr Hager holding a position where he could have an impact on decisions affecting women’s health, and finally to put an end to the controversy, the administration announced that Dr Hager would serve on the committee but not as chairman.

In May 2005, the media began reporting that after the Committee voted to approve Plan B, the FDA had asked Dr Hager to write a minority opinion advocating against the recommendation and submit it to Dr Crawford.

On May 12, 2005, the Washington Post, quoted a sermon given by Dr Hager at Asbury College in Kentucky, in which Dr Hager discussed his part in the FDA’s decision to reject the advisory panel’s recommendation.

“I was asked,” he stated, “to write a minority opinion that was sent to the commissioner of the FDA.”

“For only the second time in five decades,” Dr Hager said, “the FDA did not abide by its advisory committee opinion, and the measure was rejected.”

“I argued from a scientific perspective, and God took that information, and he used it through this minority report to influence the decision,” he stated.

“Once again,” Dr Hager told the audience, “what Satan meant for evil, God turned into good.”

Less than two weeks later, on May 23, 2005, fifty-one members of congress sent a letter to Dara Corrigan, Acting Principal Deputy Inspector General at the Department of Health and Human Services requesting an investigation of the FDA’s request for a opinion from Dr Hager during consideration of Barr’s application to allow OTC sales of Plan B.

After an investigation, the Government Accountability Office said the decision not to approve Plan B was highly unusual, made with atypical involvement from high level FDA officials, and likely was made months before the formal announcement.

On May 30, 2005, as Paul Harvey would say, The Nation magazine published “the rest of the story,” in an article titled, “Dr. Hager’s Family Values,” by Ayelish McGarvey, which stated in part:

“In both his medical practice and his advisory role at the FDA, his ardent evangelical piety anchors his staunch opposition to emergency contraception, abortion and premarital sex.

“Through his six books–which include such titles as Stress and the Woman’s Body and As Jesus Cared for Women, self-help tomes that interweave syrupy Christian spirituality with paternalistic advice on women’s health and relationships–he has established himself as a leading conservative Christian voice on women’s health and sexuality.”

However, Linda Carruth Davis, co-author of, Stress and the Woman’s Body, is Dr Hager’s former wife of 32 years, and told the Nation that her ex-husband’s public moralizing on sexual matters clashed with his deplorable treatment of her during their marriage.

In the article, Ms Davis revealed that Dr Hager had repeatedly sodomized her without her consent for years. “I probably wouldn’t have objected so much, or felt it was so abusive if he had just wanted normal sex all the time,” she explained to Ms McGarvey.

“But it was the painful, invasive, totally nonconsensual nature of the sex that was so horrible,” Ms Davis said.

For seven years, she told the Nation, Dr Hager sodomized her while she slept, roughly once a month until their divorce in 2002. Sometimes, Ms Davis said, she fought him off and he would quit for a while, only to circle back later that same night, and at other times, she would just try and get it over with.

At other times, she said, she attempted to avoid his predatory advances by sleeping in other rooms, or trying to stay awake until he was asleep, but nothing worked.

According to Ms McGarvey, “As disturbing as they are on their own, Linda Davis’s allegations take on even more gravity in light of Hager’s public role as a custodian of women’s health.”

“Some may argue that this is just a personal matter,” she wrote, “between a man and his former wife–a simple case of “he said, she said” with no public implications.”

“That might be so,” she continued, “if there were no allegations of criminal conduct, if the alleged conduct did not bear any relevance to the public responsibilities of the person in question, and if the allegations themselves were not credible and independently corroborated.”

“But given that this case fails all of those tests,” Ms McGarvey states, “the public has a right to call on Dr. David Hager to answer Linda Davis’s charges before he is entrusted with another term.”

“After all,” she correctly points out, “few women would knowingly choose a sexual abuser as their gynecologist, and fewer still would likely be comfortable with the idea of letting one serve as a federal adviser on women’s health issues.”

The day after the Nation published the story, Dr Hager resigned stating: “I will no longer be on the advisory committee after June 30.”

According to Ms McGarvey, Ms Davis had told a handful of people about the abuse during her marriage, and several longtime confidantes confirmed that she had told them at the time it was occurring. Ms Davis’ attorney and a close friend of 25-years also spoke to Ms McGarvey on the record, and several others spoke to her off the record.

As for Dr Hager, he told the reporter, “My official comment is that I decline to comment.”

Filed under: 2007, Bush, David Hager, FDA Crawford, Plan B, sex, von Eschenbach

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