Glaxo Fights Against Public Paxil Trials

By Evelyn Pringle

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

"Now, is that optimal?" he said. "No."

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Evelyn Pringle
evelyn-pringle@sbcglobal.net

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