The Bitter Pill

The Official Blog of UNITE – uniteforlife.org

Lawmakers Catch Glaxo Hiding Paxil Suicide Risks – Again (Part I)

Evelyn Pringle February 12, 2008

GlaxoSmithKline recently received greetings from a Congressional Committee, asking the company to explain the findings in a report unsealed last month in a lawsuit which shows that Glaxo knew as early as 1989 that Paxil increased the risk of suicidal behavior in patients by more than 8-fold compared to patients who received a placebo.

In a February 6, 2008 letter, Senator Charles Grassley (R-Iowa), ranking member of the Senate Finance Committee, is asking Glaxo to explain why the American public was never adequately informed of this risk until May 2006 in a “Dear Healthcare Professional” letter which reported a “higher frequency of suicidal behavior” associated with Paxil as compared to placebo.

The report showing the 8-fold suicide risk, by Harvard instructor and psychiatrist Joseph Glenmullen, was unsealed on January 18, 2008, by a federal judge in a US District Court in Sacramento, California in the Paxil suicide case of O’Neal v SmithKline Beecham d/b/a GlaxoSmithKline, filed by the surviving family members of 13-year-old Benjamin Bratt.

Dr Glenmullen was retained as an expert in the case by the California-based Baum, Hedlund, Aristei & Goldman law firm.

On January 30, 2008, the court dismissed the lawsuit on the basis of the Bush Administration’s new preemption policy, largely unknown to most Americans, which says that once the FDA approves a drug and its label, citizens may not sue a company for failing to warn about a risk not listed on the label, even in cases like this where the plaintiff can prove that the company knew about the risk and intentionally concealed it.

SSRI’s are antidepressants known as selective serotonin reuptake inhibitors and include Paxil, Eli Lilly’s Prozac, Zoloft by Pfizer and Celexa and Lexapro marketed by Forest Labs. Wyeth’s Effexor, Lilly’s Cymbalta and Glaxo’s Wellbutrin are not considered SSRI’s, but they also carry a warning about an increased risk of suicidality in young people.

Two SSRI suicide cases are now awaiting a joint decision from the Third Circuit Court of Appeals for which oral arguments took place in December 2007.

In the case of Colacicco v Apotex, the US District Court for the Eastern District of Pennsylvania was the first to dismiss a failure-to-warn claim based on the new preemption policy, and in McNellis v Pfizer, the US District Court for the District of New Jersey found no preemption.

Also unbeknownst to most Americans, the Bush Administration is instructing judges to dismiss the lawsuits against the SSRI makers in amicus briefs filed by the government’s top attorneys, who also attend hearings when necessary to argue on behalf of the SSRI makers during oral arguments on motions to dismiss.

In fact, in regard to requiring a warning about suicide, during oral arguments in the Third Circuit, Bush Administration attorney Sharon Swingle told the court that the FDA “had again and again and again made an expert determination that the warning was not appropriate.”

She maintained that the claims were preempted because the SSRI makers were not allowed to add warnings to the label under any circumstances without prior approval from the FDA.

At one point, the court asked an attorney for an SSRI maker, “assume for the moment that you had reasonable evidence of an association between your product and a serious hazard or a serious possibility of an enhanced suicide risk.”

Under federal regulations, “what would be your obligation?”

The attorney stated, “our obligation would be to take that information to the FDA, advise the FDA of the information.”

“It then would be the FDA’s determination whether that represented a substantial relationship,” he told the court.

“So if you had evidence internally that there’s an enhanced risk of suicide, you would go to the FDA,” the court said, and asked, “And how long would that take?”

“I do not know the answer to that, your Honor,” the attorney said, and the court asked, “Could it take months?”

“I imagine it would depend on the seriousness –,” the attorney stated.

“But isn’t there a significant possibility that additional people then might have the same consequence that happened here with McNellis, or with Colacicco and McNellis’s father?” the court asked.

The attorney said, “on the basis of the information that was available we would take it per FDA directive to the FDA and they would make the determination whether the label should be changed.”

“Other people could then,” the court continued, “possibly have an enhanced risk of suicide and other people may commit suicide as a result of taking your product?”

“We would be bound by law to comply with the FDA, then to comply with its directives,” the attorney replied.

“Are they requiring that you go through them first rather than act on your own?” the court asked.

“That’s exactly correct, your Honor, because there is the bigger issue of the –” the attorney stated.

However, at the end of the hearing, Pennsylvania attorney Derek Braslow proved beyond any doubt that the claims made by the Bush Administration attorney and the attorneys for the drug makers were blatant lies, when he informed the court that Glaxo had “independently, strengthened their warning in May 2004 to warn about increased suicidality and worsening depression in everyone, not just children.”

“There was specifically in bold letters a new warning with respect to increased suicidality and worsening depression in May 2004,” he stated.

“Glaxo changed the label on their own without FDA approval,” Mr Braslow told the court.

Glaxo did it again in May 2006, he said, when they sent out a “Dear Healthcare Professional” letter and warned about the increased risk of suicidality and suicidal behaviors with Paxil in persons of all ages.

During oral arguments in the O’Neal case on January 21, 2008, Glaxo’s preemption argument was presented by King & Spalding attorney Mark Brown, who just happens to be a former Associate Chief Counsel for the FDA from the first Bush Administration.

The family intends to ask the court to reconsider the ruling in the O’Neal case, according to a statement by Baum Hedlund.

In his report, Dr Glenmullen sums up the inadequacy of the system, including the FDA, that allowed Glaxo to keep this vital information hidden from prescribing doctors and patients for nearly 2 decades and states, in part:

“One of the most sobering aspects of the story of Paxil-induced suicidality is that GlaxoSmithKline was not forthcoming with its data demonstrating the risk and regulatory agencies like the FDA did not take the initiative to get to the bottom of and expose the true risk.”

“Rather, the impetus came from attorneys and medical experts surprised by what they found in GlaxoSmithKline’s confidential documents, which only came to light through litigation.”

“The GlaxoSmithKline documents that have so-far made it into the public record have in turn been critical to educating patients, the public, and the media about the true risk. The media – particularly the BBC in England – played a crucial role in turning the tide in the history of Paxil-induced suicidality.”

According to Dr Glenmullen, “it was the diligent efforts of plaintiff’s attorneys that forced GlaxoSmithKline to divulge the inaccurate counting method to the FDA.”

Another leading expert on pharmacology, Dr Peter Breggin, warns that an 8-fold increased risk of suicidality in controlled clinical trials could mean 80-fold in actual practice. “We can’t determine exactly how much greater the risk will be in clinical practice but it will be astronomically greater,” he advises.

In actual practice, he explains, many patients are already suicidal when they start taking the drug, increasingly the likelihood that the drug can push them over the edge.

Despite the warnings to watch patients closely, Dr Breggin says, busy doctors do not monitor patients properly. He explains that they are almost never evaluated for suicidality and are often given multiple drugs at the same time, by doctors who know little about their adverse effects on the mind.

Glaxo is facing lawsuits from surviving family members of Paxil suicide victims all over the country and is attempting to use preemption to avoid public trials for good reason. The first case to go before a jury in Wyoming in 2001, involved a man who shot his wife, daughter and infant granddaughter before shooting himself after being on Paxil for just a matter of days.

The trial resulted in a verdict against Glaxo for $6.4 million after the jury weighed the expert testimony of famed pharmacologist Dr David Healy, who presented a summary of Glaxo’s hidden suicide data on Paxil, against the testimony of the industry-funded SSRI defender Dr John Mann, whose name appears on many of the studies issued over the years, some as late as 2007, that steadfastly proclaim that SSRI’s are not linked to suicide and should be prescribed to children.

In addition to Dr Healy’s revelations about hidden data showing that Glaxo was aware of the increased risk, Dr Mann’s credibility was likely weighed against the fact that he had received over $30 million in research funding from drug companies between the early 1990’s and the trial in 2001, which was brought out during his testimony by Houston attorney Andy Vickery.

Mr Vickery also established that, roughly 10 years and $30 million earlier, Dr Mann had published a paper stating that SSRI’s could increase suicidality in a small subset of patients.

In his report, Dr Glenmullen states that, since Glaxo had the original data in 1989 that showed a greater than eightfold increased risk, it should have warned doctors and patients about the risk “a decade-and-a-half ago when Paxil was first approved by the FDA.”

The report includes portions of an April 29, 1991 report, written by Glaxo psychiatrist Dr Geoffrey Dunbar, sent to the FDA in response to a specific request for information on suicidality in which Glaxo openly lies in stating: “analyses of our prospective, clinical trials for depression show that patients who were randomized to Paxil therapy were at no greater risk for suicidal ideation or behavior than were patients randomized to placebo or other active control therapies.”

Dr Glenmullen notes the importance of the date that this false data was submitted because the FDA had scheduled a hearing with a nine-member advisory panel for September 20, 1991, to discuss concerns raised a year earlier about the possibility of Prozac making patients suicidal. Paxil was not approved for use in the US until December 2002.

In his report, Dr Glenmullen points out that 5 of the 9 members on the advisory panel had conflicts of interest with drug makers and that 2 psychiatrists, Dr David Dunner of the University of Washington in Seattle and Dr Stuart Montgomery from England, had done research on Prozac for Eli Lilly, and later played crucial roles in Glaxo’s publishing of what he calls “bad” suicide numbers in the Paxil story.

Dr Glenmullen’s report includes portions of a September 19, 1991, memo distributed to over 20 senior staff the day before the hearing with a “Statement to be used to respond to inquiries re Paxil/Suicide,” which claims explicitly that during GlaxoSmithKline’s studies: “the incidence of suicide was lower among patients receiving Paxil than among those receiving placebo.”

This was the statement the company ordered employees to make, even though 5 patients on Paxil committed suicide while no patients in the placebo group did. In addition, Dr Glenmullen points out that, up to 1989, seriously suicidal patients were excluded from Glaxo’s studies, and therefore “anyone who became seriously suicidal during the studies only became so after being given Paxil or a placebo.”

Yet the actual numbers show that there were 40 suicide attempts in the clinical trials by patients taking Paxil compared to 1 suicide attempt in the placebo groups.

Despite the poor quality of the data available to the advisory committee, and despite the many conflicts of interest of its members, one third of the members still voted for a warning in 1991, Dr Glenmullen points out.

Three months later, in December 1991, Dr Dunner, together with Glaxo psychiatrist Dr Dunbar, presented Glaxo’s Paxil data with the “bad” numbers at a meeting of the American College of Neuropsychopharmacology (ACNP) in Puerto Rico.

During the presentation, the doctors told the ACNP: “Suicide and suicide attempts occurred less frequently with Paxil than with either placebo or active control,” according to the Glenmullen report.

The ACNP’s members are considered prominent academic psychiatrists who specialize in pharmacology, and the group has issued a number of position papers over the years which consistently denied a link between SSRI’s and suicidality.

Dr Mann led an ACNP task force which included Dr Fred Goodwin, Dr Charles O’Brien and Dr Robinson, which supposedly reviewed all the clinical trial data on SSRI’s and issued a consensus statement with the position that SSRI’s did not increase the risk of suicidal behavior, which was published in the journal Neuropsychopharmacology in 1993.

In March 1995, Dr Dunner, Dr Montgomery and Dr Dunbar published the paper, “Reduction of suicidal thoughts with paroxetine in comparison with reference antidepressants and placebo,” in the European journal Neuropsychopharmacology. This paper included a table with the “bad” numbers and claimed that other antidepressants were more likely to increase the risk of suicide than Paxil.

The paper specifically states: “Consistent reduction in suicides, attempted suicides, and suicidal thoughts, and protection against emergent suicidal thoughts suggest that Paxil has advantages in treating the potentially suicidal patients.”

On July 5, 1995, Glaxo’s marketing department issued a memo urging its sales force to use the Dunner-Dunbar paper to reassure doctors who were concerned over Paxil-related suicide that there was no need for concern.

The fact is, documents obtained in litigation prove that the FDA has known about the suicide risks of SSRI’s for roughly 23 years. Two years before Prozac was approved, in May 1985, the FDA’s chief investigator, Dr Richard Kapit, wrote: “Unlike traditional tricyclic antidepressants Fluoxetine’s profile of adverse side effects more closely resembles that of a stimulant drug than one that causes sedation.”

“It is Fluoxetine’s particular profile of adverse side-effects which may perhaps, in the future give rise to the greatest clinical liabilities in the use of this medication to treat depression,” he noted.

Dr Kapit’s review described data from 46 clinical trials with a total of 1,427 patients and under the section, “Catastrophic and Serious Events,” he listed 52 cases of “egregiously abnormal laboratory reports which were the reason for early termination,” and “additional adverse event reports not reported by the company were revealed on microfiche.”

“In most cases,” he wrote, “these adverse events involved the onset of an unreported psychotic episode.”

There were ten reports of psychotic episodes including 2 reports of completed suicides, 13 attempted suicides, 4 seizures, and 4 reports of movement disorders. In 1985, Dr Kapit recommended “labeling warning the physician that such signs and symptoms of depression may be exacerbated by this drug”.

When Prozac was approved, no such warning was issued.

Two weeks after the FDA advisory panel met in February 2004 to review the data on SSRI’s to determine whether they were linked to suicide, Dr Healy sent a report to Peter Pitts, Associate Commissioner for External Relations, at the FDA, in response to an invitation by Dr Robert Temple for a submission of the details of studies referred to in the course of a presentation at the meeting.

“A great number of the patient testimonies in the course of the Feb 2nd hearing were from individuals who became suicidal on an SSRI when their underlying disorder was Lyme Disease, migraine or a condition such as social phobia,” Dr Healy pointed out.

He also noted that this had been the case in the 1991 hearings, when it was framed by FDA’s Dr Temple as follows:

“The discussion we heard earlier showed that people who commit suicide are highly likely to have a diagnosis of depression, which means that somebody identified them as in a high-risk category. But there were still a significant number of people who committed suicide without having that sort of diagnosis and I guess I would like some advice or discussion on who those people were.”

“The anecdotes that one hears that are most evocative to me anyway are not the ones where people who have a 20-year history of suicidal ideation and then finally do it – that is not too surprising – it is where they assert that there has never been anything in their minds like that before and yet now they have suddenly become excessively concerned with suicide and may even do it.”

Dr Healy’s analysis submitted to the FDA included the data from the pediatric trials on suicidality and hostility, including some that were concealed for years. To distinguish the difference between suicide caused by SSRI’s verses suicide caused by the underlying depression, he separated the data on children who were treated for depression and children who were treated for obsessive compulsive disorder or social phobia.

The analysis found that SSRI’s can cause some children who are not depressed to become suicidal when taking the drugs for other conditions. From a pool of 931 depressed patients taking SSRI’s versus 811 depressed patients taking placebo, Dr Healy determined that there were 52 suicidal acts by patients on SSRI’s versus 18 in the placebo group.

In a pool of 638 patients taking SSRI’s for other disorders versus 562 patients taking a placebo, there were 10 suicidal acts in the SSRI group versus 1 in the placebo group.

When these data sets were combined, there were 62 episodes of suicidality in the 1,569 patients on SSRI’s versus only 19 episodes in the 1,373 patients on a placebo.

In his submission to the FDA, Dr Healy also explained that he had conducted his own trial on Zoloft in 2000 with 20 “healthy volunteers,” meaning they had no mental disorder when entering the trial, and two of the Zoloft patients became suicidal. This type of study provides the strongest evidence of drug-induced suicidality because it’s impossible for drug companies to claim that a patient became suicidal as a result of the underlying depression.

Seven years ago, during the Wyoming jury trial involving the tragic Paxil-induced murder-suicide, the man’s physician testified that he may not have prescribed Paxil if a warning regarding homicide and suicide had been added to the drug’s label.

In his report released last month, Dr Glenmullen offers the following heart-wrenching conclusion to the court: “It is my opinion to a reasonable degree of medical probability that if GlaxoSmithKline had provided a warning all these years, Benjamin Bratt would still be alive today.”

On April 24, 2004, the Lancet medical journal published an editorial entitled, “Depressing Research,” with the following comments that surely ring doubly true today for the Bratt family, as well as all the other families whose children committed suicide while on SSRI’s:

“It is hard to imagine the anguish experienced by the parents, relatives, and friends of a child who has taken his or her own life. That such an event could be precipitated by a supposedly beneficial drug is a catastrophe. The idea of that drug’s use being based on the selective reporting of favourable research should be unimaginable.”

Filed under: 2008, Baum, Braslow, Breggin, Colacicco, FDA, FDA hearing, Fraud, ghostwritten, Glaxo, KOL, Mann, Paxil, Preemption, SSRIs, Study 329, suicide, Vickery

FDA and Big Pharma Gang Up On Joe Citizen

Evelyn Pringle November 6, 2006

The botched safety processes at the FDA have had an extremely negative impact on the nation’s public health and tens of thousands of people have died as a result of its negligent handling of the Vioxx debacle alone.

Americans today can no more trust what’s in their medicine cabinets than could the pioneers in the 1800s who filled their medicine chests when the snake oil salesmen came to town.

The FDA is now apparently claiming infallibility by telling consumers that if it says a drug is safe and the warnings on a drug’s label are sufficient, no consumer can bring a lawsuit against a drug’s maker in a state court for injuries caused by a drug, even if it is shown that the drug company actively concealed information about known injuries associated with the drug not only from consumers, but from the FDA as well.

Throughout the FDA’s 100 year history, state consumer protection laws have played an important role in protecting Americans from unsafe pharmaceutical products, and consumer protection advocates are rightfully questioning whether the FDA can or will provide the same protection.

Its no secret that the Bush-sanctioned FDA is bent on protecting drug company profits and doesn’t care enough about protecting consumers from unsafe drugs. A March 2006 report to Congress issued by the Government Accountability Office, after an investigation of the FDA ability to monitor drug safety, said the FDA’s performance was undermined by infighting between drug evaluation administrators whose allegiance is with industry and the Office of Drug Safety.

According to Attorney, Jim Gottstein, who recently scored a major victory in the Alaska Supreme Court protecting patients in state institutions from forced drugging with psychiatric medications, “the fact that current leaders of the FDA have taken the extraordinary step of interjecting the FDA into cases to argue pre-emption, leaves no doubt that it has abdicated its duty to protect the public from unsafe drugs in favor of protecting pharmaceutical profits.”

State lawmakers are also crying foul over the FDA’s arrogant undermining of state consumer protection laws because under Executive Order 13132, the FDA is required to consult with state authorities about the effects of regulations it issues on states. In the original proposed rule, the FDA specifically said that the regulation would not preempt state laws so state officials had no chance to object to the preemption rule.

According to the National Conference of State Legislatures, the preemption language in the preamble to the Final Rule is a thinly veiled attempt on the part of the FDA to confer upon itself authority it does not have by statute and does not have by way of judicial ruling. The NCSL called the FDA’s action an abuse of agency process and a complete disregard for our dual system of government.

According to Baum Hedlund attorney, Karen Barth Menzies, “the FDA’s statement is nothing more than the policy position of appointed officials with an agenda unrelated to public safety.”

“As such,” she says, “it should have zero preemptive effect.”

When Congress enacted the Federal Food, Drug, and Cosmetic Act in 1938, it specifically rejected a proposal to include a private right of action for damages caused by products regulated by the FDA, on the grounds that a right of action already existed under state common law.

The new FDA preemption rule provides no exceptions even in cases like Vioxx where the FDA asked the company to change the warning label based on reports of serious adverse effects, and a drug maker like Merck refuses to change the label for more than 18 months while many more patients are killed and injured.

In addition, the FDA contends that the agency’s approval of the drug label preempts not only claims related to label warnings but also claims related to false advertising.

Given the on-going heated debate over the FDA’s ability to police the pharmaceutical industry as a whole, critics say it is a particularly inappropriate time to eliminate the role that private citizen lawsuits in state courts play.

But then again, what can we expect when the agency’s top attorney, Daniel Troy, is recruited directly from Pfizer’s stable of lawyers. Troy began the administration’s preemption war against Joe Citizen to protect Big Pharma profits as soon as he set up shop at the FDA, by filing amicus briefs on behalf of drug companies, including Pfizer.

Even though Pfizer had been one of his clients and Troy’s firm was paid over $350,000 for work he performed in the year before he was appointed chief counsel, Troy agreed to file a brief in support of Pfizer on behalf of the FDA, arguing, unsuccessfully, that state tort claims should be preempted.

He later justified writing the brief by claiming that he did not become involved in the case until after the 1-year period in which government employees may not participate in cases involving former clients. In hindsight, the 1-year grace period reportedly expired less than a month before Troy agreed to go to bat for his former client.

In stark contrast to Troy’s pro drug company stance, in a 1996 speech, the Clinton appointed FDA chief counsel, Margaret Jane Porter, said the FDA had a “longstanding presumption against preemption” and that “FDA’s view is that FDA product approval and state tort liability usually operate independently, each providing a significant, yet distinct, layer of consumer protection.”

When simply filing amicus briefs did not work because no judge accepted the FDA’s at best feeble and at worst ridiculous arguments, in January 2006, the FDA added the preamble to the new drug labeling rules stating that the Food, Drug and Cosmetic Act “pre-empts conflicting or contrary state law.”

Judges are having mixed reactions to the FDA’s preemption position. In a stinging rebuke, New Jersey judge, Carol Higbee, during a June 6, 2006 hearing involving Vioxx lawsuits, called the Final Rule’s preamble “a political statement by the FDA.”

As for the claim that state lawsuits should be preempted, she 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,” she stated, “it is also contrary to the Constitution of the United States.”

She ended her comments by telling Merck’s Vioxx attorneys, “And I am not going to allow you to use it.”

On June 2, 2006, the Associated Press reported that a federal judge had refused to dismiss a lawsuit filed against Pfizer and Wyeth, on behalf of the parents of an 11-year-old boy who committed suicide after taking the antidepressants Zoloft and Effexor.

The judge rejected the preemption argument stating: “Federal labeling laws are minimum standards; they do not necessarily shield manufacturers from state law liability.”

“Defendant’s pre-emption argument ultimately fails because Congress has not expressed a specific intent to pre-empt state consumer-protection laws in the area of prescription-drug labeling,” the court said.

“In the absence of Congress’s express statement,” the judge stated, “defendant must overcome the presumption against implying congressional pre-emptive intent. It has not done so.”

In what can only be viewed as a rare ruling, In Bextra and Celebrex, on August 16, 2006, the US District Court for the Northern District of California dismissed the state law failure-to-warn claims saying they conflict with the FDA’s determination of the proper warning and pose an obstacle to the full accomplishment of the objectives of the Food, Drug and Cosmetic Act.

The court attempted to justify the FDA’s “180-degree reversal of its prior position” on preemption, by noting that an agency’s view may change over time and especially with a change in administration.

But in New Jersey on September 29, 2006, a federal district court in McNellis v Pfizer Inc, refused to allow the preemption defense and based on the fact that the text of FDA regulations had remained unchanged for years, ruled that the regulations did not conflict with New Jersey’s failure-to-warn laws.

The court also said that FDA regulations allow increased warnings when new risks emerge and that the Food, Drug and Cosmetic Act does not contain a preemption clause.

Following the McNellis decision, on October 16, 2006, a federal court in Pennsylvania refused to grant the drug maker’s preemption motion in Perry v Novartis Pharma Corp, noting concerns about the effectiveness of the FDA’s monitoring of recently approved drugs, making the availability of state tort suits an “important backstop to the federal regulatory scheme.”

On October 5, 2006, the 2nd Circuit Court of Appeals was also critical of the FDA’s preemptive reach stating, “[W]hatever deference would be owed to an agency’s view … an agency cannot supply, on Congress’s behalf, the clear legislative statement of intent required to overcome the presumption against preemption,” in Desiano v Warner-Lambert et al.

Three weeks later, on October 28, 2006, the Associated Press reported another state court victory against preemption in a case where Wyeth was ordered to pay nearly $6.8 million to a Vermont women after the Vermont Supreme Court upheld a lower court’s ruling.

The court’s decision said federal labeling requirements “create a floor, not a ceiling” for state regulation, noting that the FDA regulations allow drug companies to go beyond required warnings.

“When further warnings become necessary, the manufacturer is at least partially responsible for taking additional action, and if it fails to do so, it cannot rely on the FDA’s continued approval of its labels as a shield against state tort liability,” the court wrote.

Peter Lurie, deputy director of the health research group at Public Citizen, told the Associated Press that the case appeared to mark a push-back against efforts by the industry, the administration and the FDA to preempt state regulation of prescription drugs.

“If you have a wide enough berth that you can strengthen the label,” he said, “you can’t use the FDA-approved label as an automatic protection against lawsuits.”

Since May 2006, all eyes in the legal field have been on the appeal in the case of Colacicco v Apotex, Inc, – F Supp 2d -, 2006 WL 1443357 (ED Pa), in the 3rd Circuit Court of Appeals, where the lower court ruled against a man whose wife committed suicide after taking Paxil.

Joseph Colacicco filed a lawsuit against both drug makers alleging that his wife committed suicide in October 2003, just 21 days after she began taking Paxil for mild depression with claims of wrongful death, negligence and a failure to warn her doctor of a link between Paxil and an increased risk of suicide.

In moving for dismissal, Paxil maker, GlaxoSmithKline, and Paxil generic maker, Apotex, relied on the FDA’s position that state failure-to-warn claims are preempted.

The judge ruled that the defendants were entitled to a dismissal of all claims because the FDA controls the content of warnings and requires generic drug makers to use the same labeling as approved for the drug’s original maker.

In this case, the judge on his own initiative, asked the FDA to submit an amicus brief. And in response, on the tax payer’s dime, the FDA wrote a brief asking the court to rule against the American citizen and dismiss the lawsuit against the drug companies.

In fact the FDA was the strongest supporter of preemption in this case because according to the attorneys handling the case, Glaxo itself barely addressed the preemption issue during oral arguments on the motion.

In a decision that experts predict may end up before the US Supreme Court, the judge ended up dismissing the claims without ever considering whether the FDA regulations pose a conflict to the plaintiff’s state tort claims.

Attorneys Derek Braslow, Harris Pogust and Matthew Leckman from the Conshohocken, Pennsylvania firm of Pogust & Braslow are representing the plaintiff in the case.

Attorney, Harris Pogust, says the judge’s ruling “could potentially do away with all failure-to-warn pharmaceutical cases”

The FDA action he notes, “does not seem to be a public health concern as much as a political concern.”

According to Mr Braslow, “the Judge readily admits that he did not analyze whether there is or was a conflict between state law and federal law and surmises that he probably would not find a conflict if he actually did the analysis.”

“But, the Judge explained,” he said, “that it doesn’t matter – if the FDA says there is preemption, then there must be preemption. Far be it for a Judge to interpret the law.”

“The Bush-era FDA,” Mr Braslow notes, “in a complete reversal of the position it took in its 2000 rule proposal, has now officially cemented its role as a pawn for the pharmaceutical industry.”

“It was not that long ago,” Mr Braslow points out, “that the FDA came forward with amicus briefs on behalf of the consumer in prescription drug litigation.”

“Now,” Mr Braslow says, “an argument first put forward in a couple Zoloft suicide cases, has become the primary argument in every prescription drug case, and could,” he warns, “potentially, mean the end for anyone seeking recourse from injuries resulting from prescription drugs, no matter how fraudulent the drug company’s conduct.”

“Make no mistake,” he states, “the position taken by the Bush-era FDA is an attempt by the current administration to achieve tort reform for the benefit of big pharma and at the expense of the injured consumer, without the consent of Congress.”

“The Bush-era FDA takes this position,” he warns, “unconcerned by the reality that preemption would allow drug companies to peddle their drugs with impunity and avoid being justifiably called into court for deceiving the public about the safety and effectiveness of those drugs.”

“Notwithstanding the FDA’s position on preemption,” Mr Braslow says, “courts examining this issue, if they take any time to actually look at the FDA regulations in question, would realize that there is no conflict between federal drug regulations and state tort claims.”

“Federal drug regulations specifically mandate drug companies to strengthen their drug’s label,” he explains, “as soon as there is reasonable evidence of an association of a serious hazard with their drug.”

“A state tort claim,” Mr Braslow points out, “does not force a drug company to take any action that is not already permitted by federal regulations.”

“Because federal regulations for prescription drugs are minimum standards,” he notes, “federal regulations can never conflict with a state common law claim.”

“The District Court erred,” he states, “in abdicating to FDA legal opinion, as opposed to interpreting the law.”

“What the Colacicco court did,” he says, “was improperly abdicate to the FDA’s legal opinion.”

Critics say it’s time for the FDA to get back to protecting consumers from dangerous products, rather than protecting the profits of the pharmaceutical industry.

According to career scientist, Dr David Graham, in a 2005 interview with Jeanne Lenzer in the journal Public Library of Science, “The pharma-FDA complex has to be dismantled and the American people have to insist on that, otherwise we’re going to have disasters like Vioxx that happen in the future.”

Filed under: 2006, Baum, Braslow, Colacicco, FDA, Preemption, Supreme Court, Troy

Shelhigh and FDA Play Blame Game Over Sale of Contaminated Devices

Evelyn Pringle May 2007

On April 17, 2007, the FDA issued a press release to announce that US Marshals had seized all implantable medical devices from Shelhigh, Inc, in Union, NJ, after finding “significant deficiencies in the company’s manufacturing processes.”

“The deficiencies,” the agency said, “may compromise the safety and effectiveness of the products, particularly their sterility.”

According to the FDA, if not sterile, the use of these devices poses a reasonable probability of serious adverse events or death.

But critics say the real story here involves the FDA’s knowledge about the safety hazards at Shelhigh dating back to at least 2000, and the fact that it allowed patients to be implanted with the firm’s devices for basically 7 years.

In the press release, the FDA says it inspected the Shelhigh facility last fall, and warned the firm in a meeting that failure to correct the violations could result in an enforcement action. The agency also noted that it had sent two previous warning letters to the firm about manufacturing deficiencies and other violations.

However, on its web site, Shelhigh has posted a response to the public statements made by the FDA and squarely points the finger of blame at the agency for allowing the sale of the potentially contaminated devices to continue.

“If the FDA truly believes what it claimed,” Shelhigh states, “then the FDA is negligent and guilty of professional misconduct for permitting the use of Shelhigh products during the 10 weeks when 2-3 FDA inspectors were present at the Shelhigh facility and for 4 months afterwards.”

But the history of the controversy at the center of this blame game goes back a lot further than last fall. According to the complaint filed in US District Court of New Jersey by the US Attorney for the District of New Jersey, to support the seizure of Shelhigh‘s products, the first FDA warning letter referred to in the agency’s press release was sent 7 years ago on April 26, 2000, and the second warning letter was sent December 14, 2005.

In assessing blame, its necessary to understanding that FDA regulations require device makers to have systems in place to accept and analyze all complaints received from doctors and hospitals and to forward all complaints that indicate that a device failure may have contributed to the injury or death of a patient to the FDA.

The first warning letter proves that on April 26, 2000, the FDA was aware that patients who were implanted with Shelhigh devices were developing serious infections that required surgery to remove the devices and that Shelhigh refused to investigate the adverse events to determine whether its products were contaminated.

In the letter, the FDA said, Shelhigh “failed to evaluate” complaints of patients who developed infections which required surgical removal of the implant to determine whether the infection was due to the malfunction of the device.

The agency also pointed out that despite the fact that there were 4 separate event reports filed with Medwatch from one source that involved patients with infections so severe that the device had to be explanted, there “was no written evaluation or investigation of these Medwatch complaints,” by Shelhigh.

The letter also stated that there were 43 problems related to infections of implanted devices reported by the firm’s distributor, Classic Medical on October 14, 1999, which “were not recorded and evaluated as product complaints.”

Jumping ahead to the FDA’s latest list of safety violations, they include Shelhigh’s failure to (1) adequately monitor critical manufacturing environments for possible microbial contamination; (2) properly test products for sterility and fever-causing contaminants; (3) scientifically support product expiration dates; and (4) manufacturing products in a poorly constructed and maintained clean room where sterilized devices are further processed.

On April 18, 2007, the FDA sent out a Dear Healthcare Provider letter stating, “This is to notify you that all medical devices manufactured by Shelhigh … were manufactured under conditions that may have contaminated the devices and may result in devices that fail to function for the expected life of the products.”

The FDA also said, it was aware of published reports of premature or accelerated failure associated with some devices and the products could potentially be contaminated with bacteria, fungi, and endotoxin. The letter recommended that providers assess the overall health status of each patient, and provide the testing, monitoring and care appropriate to each patient’s individual case.

On April 19, 2007, the FDA issued a public advisory for patients stating: “Devices manufactured by Shelhigh, Inc. may have been implanted during various surgical procedures, including open-heart surgery for valve replacement; and repair of soft tissue structures during abdominal, pelvic, heart, lung, brain, shoulder, and spine surgery.”

The advisory warns that patients vulnerable to infection and those at high risk for complications include the critically ill, children, the elderly, and pregnant women.

Noting that the devices have been available since 1997, the FDA tells patients, “The number of these devices that may be contaminated or experience problems isn’t known at this time,” and problems “could occur at anytime, and may become apparent to you and your physician during routine examination.”

According to the agency, the seizure last month involves many products and includes pediatric heart valves and conduits, described as “tube-like devices for blood flow,” surgical patches, arterial grafts, dural patches, which aid in tissue recovery after neurosurgery, and annuloplasty rings, used to help repair heart valves.

The FDA may not know how many devices have been sold but in the May 3, 2007, Star-Ledger, Shelhigh’s marketing director, Douglas Goldman reported that, “thousands and thousands of the company’s implants have been used since Shelhigh began distributing products 10 years ago.”

The FDA’s warning to patients amounts to a life-sentence of worry and medical care because the devices are permanently implanted into infants, children and adults and the agency advises doctors to monitor patients for infections and proper device functioning throughout “the expected lifetime of the device.”

The meeting referred to in the FDA press release took place almost a year ago on June 16, 2006, and according the complaint filed with the court, “the firm was again warned by FDA that continuation of the violative conduct could result in seizure, injunction, and/or civil money penalties.”

The inspections referred to in the press release took place between October 11 – December 20, 2006, and “revealed that the methods used in, and the facilities and controls used for, the manufacture, design, packing, storage, and installation of the devices do not comply” with safety regulations, according to the complaint.

“Because the firm’s devices are implanted into patients,” it states, “ensuring continued sterility is critical.”

However, ensuring sterility was apparently not a priority to the FDA being it permitted the hazardous devices to be implanted for 7 years. The complaint was not filed until April 16, 2007, and in it, the FDA now claims, “the firm allowed at least four lots of devices that failed sterility testing to be released for distribution in the last two years.”

This is certainly a bizarre allegation considering that the FDA allowed the sale of the devices in the same two years. On April 24, 2007, the arrogant founder of the Shilhigh, Shlomo Gabbay, MD, blasted the FDA on this point in a press release stating:

“There is absolutely no FDA recall of our devices which the FDA claims may cause patient injury. If our products were truly questionable as the FDA is leading the Public to believe, the FDA could have requested a remedy at any time – why haven’t they?”

Legal experts are not amused by the public spectacle of the firm and the FDA arguing over who’s to blame for knowingly implanting patients with potentially contaminated devices.

Attorney, Derek Braslow, of the Pennsylvania Law Firm, Pogust & Braslow, has plenty of experience fighting for the “little guy” against the giant drug companies in large part because of the fact that the industry friendly FDA, under the Bush Administration, refuses to protect the public from dangerous products placed on the market by an industry comprised of the most generous Bush campaign contributors.

In this instance, Attorney Braslow says the conduct of both Shelhigh and the FDA is “outrageous.”

“This is another example of a pharmaceutical company placing profits over people and further,” he says, “why we cannot continue to rely on the FDA to protect Americans from dangerous drugs and devices.”

“Instead of feigning worry about Americans importing contaminated drugs from Canada,” he notes, “our government should be more concerned about the contaminated products in its own backyard.”

“I doubt that even the Senate’s proposed new drug safety legislation will end up being strong enough to prevent this kind of outrageous conduct,” he warns.

“As far as I’m concerned,” he says, “the FDA’s action is too little, too late.”

But Mr Braslow also says, “the failure of the FDA does not give this company a free pass.”

“Shelhigh must be held responsible for its criminal conduct,” he points out, “not only by the government but by those patients it injured.”

According to the FDA, at the time of the seizure, Shelhigh was asked several times to voluntarily recall all of the products that remained on the market but declined to do so. On May 2, 2007, the FDA sent a letter to Shelhigh formally requesting the recall of all devices including those in hospital inventories.

On May 3, 2007, Mr Gabbay issued his own press release and callously refused to recall the devices to prevent the possibility of more implant victims. “This is the first formal request by the FDA for Shelhigh to recall its products,” he said, “and since the FDA allegations are unfounded, Shelhigh has no intention to initiate a product recall.”

“The FDA,” he said, “should understand that it must prove its allegations before it can make a request and their newest statements do not provide any further factual support for their claims.”

Mr Gabbay and the FDA can argue over blame until the cows come home but the cold hard truth is that nobody will ever know how many serious injuries and deaths have occurred over the past 7 years that were not rightly attributed to the company’s contaminated devices and the FDA’s failure once again to protect the public.

Filed under: 2007, Braslow, FDA, medical devices, Shelhigh

Battle of Device Maker Shelhigh and FDA Rages On Part I

Evelyn Pringle May 2007

In a court hearing on May 15, 2007, US District Court Judge William Martini in New Jersey informed medical device maker Shelhigh that it was unlikely that he will allow the release of any inventory seized by US Marshals at its Union City plant, after the FDA found “significant deficiencies in the company’s manufacturing processes.”

A seizure is an enforcement action taken as a last resort to remove a dangerous product from commerce. The FDA initiates the action by filing a complaint with the District Court where the product is located and a US marshal is then directed by the court to take possession of the goods until the matter is resolved. The complaint against Shelhigh was filed on April 16, 2007

The US Marshal did not physically remove the devices from the plant but rather “seized them in place,” meaning Shelhigh cannot remove, attempt to remove or in any way interfere with the products without the prior written permission from the US Marshal. The firm’s products have also been embargoed by the state of New Jersey.

Shelhigh sought an emergency hearing on a request for some of the quarantined materials to be released for export to Spain and Italy. Shelhigh says the majority of its business results from exports and claims the company will go under and have to lay off its 50 employees if it is not permitted to export devices to other countries.

In its request, Shelhigh argued that the firm’s tissue-based products imported to other countries are exempt from the FDA’s rulings but Judge Martini disagreed and said, “I’m inclined to agree with the government interpretation,” during the hearing.

Its difficult to understand how Shelhigh believes it has a legal leg to stand in light of the FDA’s last 7 years of warnings, threats, and promises. Investigators documented deficiencies in the firm’s Union City facility in 2000 and 2005, and those inspections resulted in warning letters to Shelhigh in April 2000 and December 2005.

A December 14, 2005 warning letter spelled out what Shelhigh was facing. Your failure to comply with any post-approval-requirement, the FDA explained, constitutes a ground for withdrawal of the Human Device Exemption and commercial distribution of a device that is not in compliance with these conditions is a violation of the Federal Food, Drug, and Cosmetic Act.

“Federal agencies are advised of the issuance of all Warning Letters,” the FDA wrote, “about devices so that they may take this information into account when considering the award of contracts.”

“Additionally,” it said, “no premarket approval applications for Class III devices to which the Quality System regulation deficiencies are reasonably related will be approved until the violations have been corrected.”

Also, in language highly relevant to this case, the letter warned that, “no requests for Certificates to Foreign Governments will be granted until the violations related to the subject devices have been corrected.”

The FDA instructed Shelhigh to take “prompt action” to correct the problems. “Failure to promptly correct these deviations,” it warned, “may result in regulatory action being initiated by the Food and Drug Administration without further notice.”

“These actions include, but are not limited to, seizure, injunction, and/or civil money penalties,” the FDA stated.

An FDA warning letter is supposed to signal that a company had better clean up its act or the ax is going to fall. In the case of Shelhigh, the FDA refuses to explain how the firm managed to keep selling defective devices for 7 years..

And to this day the company is openly defying the FDA and showing no remorse for its part in this fiasco. In fact, orders are still coming in for Shelhigh products, according to Mike Furgal, vice president of sales, in a report by Thomas Gaudio for NJBiz.com on May 15, 2007.

“We have a number of distributors,” he states, “throughout the United States and the rest of the world that are shipping products to accounts that are asking for it.”

“The products are continuing to be implanted around the entire country and outside the United States,” Furgal told Mr Gaudio.

And for its part, according to Mr Gaudio, the FDA would not comment on why it waited 5 years between warning letters and then nearly a year-and-a-half between the December 2005 letter and the seizure, or why it then waited 2 more weeks after the seizure to send Shelhigh a formal request for a product recall.

The tissue-based products manufactured by Shelhigh are used in surgical settings including open heart surgery in adults, children and infants, and to repair soft tissue during neurosurgery and abdominal, pelvic and thoracic surgery, according to an FDA press release on April 17, 2007.

In a letter to health care providers on April 18, 2007, the FDA noted published reports of premature or accelerated failure associated with some Shelhigh devices and said they could potentially be contaminated with “bacteria, fungi, and endotoxin.”

A public health advisory was issued the next day telling patients: “Devices manufactured by Shelhigh, Inc. may have been implanted during various surgical procedures, including open-heart surgery for valve replacement; and repair of soft tissue structures during abdominal, pelvic, heart, lung, brain, shoulder, and spine surgery.”

In addition to the warning letters, the FDA’s press release noted that Shelhigh had been warned to correct the problems at its facility at a meeting but did not mention that the meeting took place last June 16, 2006. That date was revealed in the complaint filed in court and alleges, “the firm was again warned by FDA that continuation of the violative conduct could result in seizure, injunction, and/or civil money penalties.”

According to the legal filing, the fall 2006 inspections revealed ongoing problems that included manufacturing devices in a poorly constructed and maintained clean room, failure to adequately monitor for possible microbial contamination, failure to properly test products for sterility, failing to scientifically support product expiration dates and failing to properly train employees.

As an example of employee misconduct, the complaint alleges that a Shelhigh employee fabricated “test results on retained samples and presented the data to an FDA investigator because she could find no record of the original test results.”

The complaint also explains that employee training “must include the consequences of improper performance so that the personnel will be aware of the effects that their actions can have on the safety and effectiveness of the device and know what process and product defects can occur as a result of deficient practices, procedures, or conditions.”

But then the December 2005 letter cited the firms failure to ensure that all employees were trained to adequately perform their assigned responsibilities, and to document the training. “Specifically,” the letter said, “your employees training records do not specify what procedures each employee was trained on, and how their training relates to the procedures that apply to their areas of responsibility.”

The FDA’s complaint also says, Shelhigh illegally made design changes to a device that is implanted in infants and children without notifying the FDA. Reporting changes is required to create a history of evolution of the design and such records “are integral to failure investigations and preventing the repetition of errors and the development of unsafe or ineffective designs,” according to the complaint.

But this allegation is nothing new either. The April 2000 warning letter noted that Shelhigh devices were not in conformance with the Quality System/Good Manufacturing Practice Regulations, and noted that there was no “Master Device Record” for one device.

The FDA letter specifically stated: “Design controls for the Uropatch are lacking with regard to the following: Design history file; Design plan; Design inputs; Design outputs; Design review, Design verification and Design validation.”

In addition, the second warning letter in 2005, following inspections on April 28 through May 16, 2005, and July 21 through August 10, 2005, cited the company’s failure to follow its “own written procedures for design control” in order to confirm that the changes made to certain devices were controlled to include validation or where appropriate, verification prior to their implementation, and a failure to demonstrate that the device history records for certain devices were manufactured in accordance with the device master records.

According to Vince Boehm, who monitors FDA enforcement activities, “It is surreal that the first FDA warning letter in this case was sent 7 years ago on April 26, 2000, and the second warning letter was sent December 14, 2005.”

“This horror story,” he says, “documents the crass outcomes of the Prescription Drug User Fee Act.”

“The PDUFA,” he notes, “puts all the cards in the manufacturers hands, and leaves the FDA impotent to act on it’s own to remove a dangerous product.”

A 2002 statute extended user fee policies to cover medical devices. This month the Senate passed FDA reform legislation but the bill did not give the FDA the much needed control over medical devices.

“The new version of the law, Mr Boehm says, lacks the crucial authority to permit the FDA to act on it’s own to remove dangerous or harmful products.

“Under the PDUFA,” he notes, “the FDA has only one option, to haggle, haggle and haggle some more with maker of a dangerous product.”

“In the case of Shelhigh,” he points out, “it took seven years of haggling.”

“This puts the FDA in a perfect “out” position,” he says, “because the FDA can always tell an injured patient protesting an injury or death of a loved one that their hands were tied.”

Filed under: 2007, Braslow, FDA, medical devices, Shelhigh

Battle of Device Maker Shelhigh and FDA Rages On Part II

Evelyn Pringle May 2007

In response to references about warning letters dating back 7 years in the FDA’s complaint filed in New Jersey US District Court to initiate the seizure of all products made by device maker Shelhigh, on its web site, the company claims the old letters don’t count.

“Past warning letters,” it notes, “do not apply to the recent seizure action, and the content of the 7 year old, 2000 warning letter was addressed.”

“The complaint,” the firm says, “filed by the FDA that lead to product seizure included different claims which Shelhigh believes are unsupportable and not related to any realistic possibility of unacceptable risks to patients.”

If given the opportunity to review the FDA warning letters issued in April 2000 and December 2005, Shelhigh patients might not agree being that they mirror the allegations in the complaint filed in April 2007.

The April 2000 letter shows the FDA knew then that patients were developing serious infections that required surgical removal of the devices and that Shelhigh refused to investigate the adverse events to determine whether the products were contaminated.

Because the sales of Shelhigh devices date back to 1997, the FDA now says the number of defective products is not known but warns that problems “could occur at anytime, and may become apparent to you and your physician during routine examination.”

Another violation listed in the latest complaint alleges that Shelhigh only provided documentation to the FDA to support a 3-year shelf-life for its products but, “the firm’s labeling claims a four year shelf-life for all devices.”

FDA regulations require device makers to establish and maintain adequate procedures for the health, cleanliness, personal practices, and clothing of employees who work in areas where their contact could adversely affect the product and the complaint alleges that adequate requirements “were not established and maintained.”

By law, companies must have systems in place to receive and analyze all complaints received from health care providers and must notify the FDA of complaints that indicate that the failure of a device may have contributed to a death or injury.

However, in the April 2000 letter, the FDA reported that the company had “failed to evaluate” complaints of patients who developed infections which required surgical removal of the implant to determine whether the infection was due to malfunction of the device.

The letter noted that there were 4 separate Medwatch reports by one source that involved infections so severe that the device had to be explanted but there “was no written evaluation or investigation of these Medwatch complaints.”

The letter also reported that forty-three problems related to infections were reported by the firm’s distributor on October 14, 1999, and “were not recorded and evaluated as product complaints.”

The FDA said there was insufficient documentation to support Shelhigh’s decision that the product malfunctions were not reportable. “Your position that the infections were due to user technique,” the letter said, “does not abrogate your responsibility to report these events.”

In each of the complaints, the FDA said, “documentation was lacking to indicate that these incidents were fully reviewed, evaluated and investigated, in order to conclude that the reported failures were due to user error, rather than device nonconformance.”

Two complaints, the letter said, reported infection of implanted devices, which required surgical intervention to explant and documentation was lacking or insufficient to support the conclusion that these events were procedure-related and not product-related.

With all that said in the April 2000 letter, 5 years later in the December 2005 letter, the FDA once again cited Shelhigh’s failure to maintain complaint files. “Specifically,” the agency said, “no complaint files were maintained for the years 2000, 2002, 2003, 2004, and 2005.”

“For example,” the letter states, “your firm received oral communication of problems by phone or from physicians during conferences where these complaints are not reported in your complaint log.”

And this time the FDA pointed out that Shelhigh had still failed to review and evaluate complaints dating back to 1999 to determine whether an investigation was necessary. “Specifically,” the FDA wrote, “your firm has failed to adequately investigate and follow-up on all complaints that were received from physicians by phone or during conferences from 1999 to the present.”

You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the Food and Drug
Administration without further notice.

As noted above the December 2005 letter ended with the idle threat that the company needed to take “prompt action” to correct the violations or the company could be subject to sanctions including “seizure, injunction, and/or civil money penalties.”

Well so much for that warning because following the seizure of the company’s products on April 24, 2007, the fearless Shelhigh founder, Dr Shlomo Gabbay, issued a press release stating there is “absolutely no FDA recall” of our devices which the FDA claims may cause injury.

On May 2, 2007, the FDA took the bait by sending Shelhigh a letter requesting a recall of all the firm’s medical devices which remained in inventories on the market and warned doctors, hospitals, and consumers of the potential risks associated with Shelhigh devices.

The next day, Dr Gabbay issued another press release announcing Shelhigh was refusing to conduct a recall. The company’s web site said it had “no intention to initiate a recall,” and posed the question: “if the alleged problems were as severe as the FDA claims, why did it wait 6 months to act?”

At least in part, attorney Derek Braslow of the Pennsylvania law firm of Pogust & Braslow agrees that the FDA’s inaction is glaringly clear. “All of this could have been avoided,” he states, “if the FDA had only followed up on its own warnings.”

But ultimately, he says, Shelhigh must be held accountable. “The company was aware of serious problems at its facility,” he points out, “and failed to address them, failed to warn physicians, and continued to sell its product to unsuspecting doctors, all the while knowing its products were unsafe.”

Business analysts say Shelhigh is playing with fire by engaging in a public battle with the FDA, and its competitors are jumping for joy on the side lines. Datamonitor, a business information firm, lists the top competitors as Medtronic, Baxter International, and Bio Vascular.

Kenneth Reid, publisher of Washington Information Source, which monitors FDA enforcement actions, told Newhouse News Service in The Times, on May 13, 2007, that Shelhigh’s aggressive stance is fraught with risks.

Mr Reid notes that the FDA has the power to put the firm out of business as well as work with the European Medicines Agency to block overseas sales. “Shelhigh can fight the FDA, but they do so at their own financial peril,” he said.

“The regulators are much more in tune with each other than ever before,” he told the Times. And if Europe or the United States takes action, “the other will react,” he added.

Filed under: 2007, Braslow, FDA, medical devices, Shelhigh

FDA Colludes With Merck To Avoid Vioxx Liability – Part II

Evelyn Pringle June 2007

Legal experts say the recent court ruling in Bush’s home state of Texas that failure-to-warn claims against Merck by Vioxx victims in state courts are preempted is particularly egregious due to the FDA’s failure to protect the public against Merck’s deceptive mass-marketing of Vioxx as a safe drug for basically 5 years.

In a nutshell, the FDA’s position on preemption means that states cannot force drug companies to warn consumers about any safety risks associated with a drug other than what the FDA says is required.

In the case of Vioxx, under the Texas statute cited by the judge, all the FDA would have to do to stop the dismissal of the lawsuits filed by citizens in state courts is acknowledge that Merck withheld or misrepresented safety information about the drug to the FDA.

As the judge said in his April 19, 2007 opinion, “plaintiffs can still avail themselves … if the FDA determines that required information was withheld.”

In the end, the judge granted Merck’s motion to dismiss the failure to warn claims because “someone other than the FDA is being asked to make the determination,” and plaintiffs cannot rebut the presumption of preemption “unless and until the FDA makes the required findings..”

The proof for these finding can easily be found in the agency’s own actions against Merck for making misleading statements about the safety and efficacy of Vioxx. For example, on September 17, 2001, the FDA sent Merck a Warning Letter about its promotion of Vioxx and described numerous instances where Merck lied about the risks associated with the drug and specifically the heart attack risks.

The letter said Merck was misrepresenting the risks of Vioxx to both the public and doctors. “Your minimizing these potential risks and misrepresenting the safety profile of Vioxx raise significant public health and safety concerns,” the FDA said.

And this was not the first time Merck was warned about making misleading claims in promoting Vioxx. “Your misrepresentation of the safety profile of Vioxx,” the FDA Letter said, “is particularly troublesome because we have previously, in an untitled letter, objected to promotional materials that also minimized Vioxx’s safety profile.”

The promotional activities described in the letter included audio conferences, events in which a doctor gave a Merck sponsored presentation to other doctors, statements made by sales representatives at professional conferences, and a press release.

The press release in fact claimed that Vioxx had “a favorable cardiovascular safety profile,” a claim that the FDA called “simply incomprehensible.”

Company documents that surfaced in litigation prove that Merck intentionally concealed the heart risks of Vioxx from prescribing, with a specific sales training manual that instructed sales representatives to “dodge” if doctors asked about the cardiovascular risks of Vioxx.

The company’s illegal promotional activities were extremely profitable for Merck but lethal for consumers. According to the May 13, 2006 New York Times, twenty million Americans took Vioxx between 1999 to 2004 and epidemiologists “estimate that the drug may have caused 100,000 heart attacks during the five years it was on the market.”

The Bush-appointed FDA officials’ preemption position reverses a long standing policy of allowing states to provide additional remedies for citizens against the marketers of unsafe drugs, over and above the minimal protection afforded by the FDA.

“The FDA admittedly does not have the resources or manpower to achieve a perfect record,” says Baum Hedlund attorney Karen Barth Menzies, “nor does it provide remedies to the victims when it fails.”

“State product liability laws,” she notes, “provide remedies and an invaluable safeguard.”

In addition, she says, preemption eliminates one of the few methods available to obtain safety and efficacy information about a drug that companies do not publish and often hide from the FDA. “Civil lawsuits,” Ms Menzies points out, “have uncovered internal company documents to which not even FDA is privy.”

According to Pennsylvania Attorney Derek Braslow, state tort claims do not force a drug company to take any action that is not permitted by FDA regulations. “Federal regulations,” he says, “specifically mandate drug companies to strengthen their drug’s label as soon as there is reasonable evidence of an association of a serious hazard with their drug.”

“The reality of preemption,” he says, “allows drug makers to peddle unsafe products and avoid being sued for deceiving consumers about the safety and effectiveness of the drugs.”

“The position on preemption taken by the Bush-era FDA,” Mr Braslow says, “is an attempt to achieve tort reform for the benefit of the pharmaceutical industry without the consent of Congress.”

Other legal experts view the actions of the current FDA the same way. “The fact that the leaders of the FDA have taken the extraordinary step of interjecting the agency into private lawsuits and arguing preemption,” says Alaskan Attorney Jim Gottstein, “leaves no doubt that the FDA has abdicated its duty to protect the public in favor of protecting pharmaceutical profits.”

The FDA’s past collusion with Merck to keep Vioxx on the market to increase profits is no secret. In the December 2004, British medical journal, Lancet, a team of scientists from the University of Berne, Switzerland reported: “Our findings indicate that Vioxx should have been withdrawn several years earlier.”

The study pooled data from 5,273 patients who participated in 18 clinical trials conducted before 2001 and found that Vioxx patients had 2.3 times the risk of heart attacks as patients taking placebos or other pain medications.

“The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarize the accumulating evidence needs to be clarified,” the authors stated.

Dr Richard Horton, editor-in-chief of Lancet wrote: “With Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted, and irresponsible self-interest.”

And its a matter if public record that Merck concealed safety information from the FDA. In a November 18, 2004 hearing before the Senate Finance Committee to evaluate the FDA’s handling of the Vioxx disaster, Dr Gurkirpal Singh, Adjunct Clinical Professor of Medicine Department of Medicine, Division of Gastroenterology and Hepatology at Stanford University, testified by video conference and said Merck knew all about the health risks of Vioxx long before the drug was approved.

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

At that time, he said, it was not known that Vioxx itself caused heart attacks, but the discussion focused on the issue that by inhibiting platelets, other painkillers might protect against heart attacks while Vioxx had no effect on platelets.

“This was a serious concern because the entire reason for the development of Vioxx was safety,” Dr Singh explained.

He noted that Vioxx was no more effective than older NSAIDs and if the improved stomach safety of the drug was negated by a risk of heart attacks, patients might not have been willing to make the trade-off.

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

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

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

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

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

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

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

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

He said larger, definitive studies should have been conducted before the drug was approved. “After all,” he noted, “the drug was no more effective than any other available pain-killer – and there were nearly 30 such drugs available in the US.”

Instead, Dr Singh told the panel, the drug was approved in a priority review within 6 months – with no discussion on the heart attack trade-off. “The prescribing physicians,” he said, “remained unaware of any of these data or discussions, till much later – with the new label change in April, 2002.”

Dr Singh also described a pattern of intimidation by Merck similar to what the Committee heard about from other experts who dared to speak out on Vioxx. He said he persisted in his enquiries about Vioxxx, and “was warned that if I continued in this fashion, there would be serious consequences for me.”

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

“But as a research scientist,” he testified, “I felt that it was unethical for me not to discuss my concerns in public.”

Dr Singh said, “Dr. Sherwood called several of my superiors at Stanford to complain.”

“Subsequently,” he said, “I learnt that this was a persistent pattern of intimidation by Dr. Sherwood.”

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

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

Another expert, Dr Bruce Psaty, Professor of Medicine at the Cardiovascular Health Research Unit at the University of Washington, also testified at that hearing and delivered a summary of Vioxx’ history that underscored the conflict of interest between the FDA and Merck and offered recommendations to avoid similar fiascos in the future.

He also testified that the “failure to conduct large long-term randomized trials in a more timely fashion permitted millions of Americans to use a drug whose cardiovascular safety profile was in question.”

Overall Dr Psaty said, Merck intentionally designed studies to only bring out the positives. “If I were to give a test to my students and ask what thing could you do to design a study to not find harm, and to find benefits,” he noted, “Merck would have gotten an A-plus.”

He also pointed out that the FDA’s review of the VIGOR study occurred in February 2001, but yet the revisions to the Vioxx label were not completed until April 11, 2002.

At November 17, 2006, hearing by the Senate Committee on Health, Education, Labor, and Pensions, to advocate for FDA reform legislation, the “Enhancing Drug Safe and Innovation Act of 2006,” prominent cardiologist, Dr Steven Nissen, of the Cleveland Clinic, described “a crisis in public confidence in the FDA following an unprecedented series of revelations about drug and device safety.”

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

Merck has continued to mislead doctors and former Vioxx users about the risks of the drug. On May 12, 2006, Reuters reported that Dr Nissen said Merck misrepresented an analysis of data from a follow-up review of patients involved in the trial that led to Vioxx being pulled off the market and that patients were at a high risk of heart attacks and stroke long after they stopped taking the drug.

“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,” Dr Nissen told Reuters in a telephone interview.

“And that risk may extend beyond a year;” he added, “we simply don’t know.”

“In the one year after Vioxx was stopped there was a 75 percent greater risk of having an adverse event,” Dr Nissen told Reuters.

Speaking to the Consumer Federation of America in March 2005, Senator Grassley, basically said the FDA cannot be trusted to protect Americans against drugs like Vioxx because the agency is to “cozy” with the drug makers like Merck.

“The very same month that Dr. Graham warned the FDA of the cardiovascular risks of Vioxx,” he pointed out, “the FDA approved the use of Vioxx for children.”

Filed under: 2007, Braslow, FDA, Merck, Preemption, Vioxx

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