Inventor of ADHD confesses “ADHD is a prime example of a ficticious disease”. The APA turns the hoax Ïnternet Addiction Disorder” into a DSM billing bible diagnosis!
At the request of Congress, GAO is seeking information regarding cases in which state foster children have been prescribed psychotropic medication outside of federal regulations or accepted medical standards of practice. These may include very young foster children prescribed certain kinds of psychotropic drugs, children prescribed psychotropic drugs in dosages that exceed accepted standards, children prescribed psychotropic drugs for purposes other than a medically accepted indication, or children taking numerous psychotropic drugs concurrently. If you have information about state foster children being prescribed psychotropic medication outside of regulatory and/or medical guidance and are willing to provide details, please e-mail GAO at FosterKids@gao.gov.
Evelyn Pringle April 8, 2008
Government attorneys appointed by the Bush Administration have been supporting GlaxoSmithKline in a number of courts across the country in an effort to convince the courts that lawsuits filed by victims of Paxil-induced injuries should be dismissed before ever making it to a jury.
In fact, the Administration has spent a massive amount of tax dollars filing amicus briefs on behalf of just about every drug maker involved in litigation in an attempt to get the lawsuits filed by private citizens thrown out of court.
The government claims that, once a drug and the warnings on its label are approved by the FDA, claims alleging injuries caused by a company’s failure to warn about a risk not listed on the label are preempted.
The Bush Administration says preemption applies even when a company (1) continues to sell a drug when a risk is known; (2) fails to warn when new risks are discovered; (3) fails to send letters notifying prescribing doctors of a known risk, and (4) fails to disclose a known risk to the FDA during the approval process, or anytime for that matter. In essence, if the FDA doesn’t make the companies warn, they’re off the hook.
If the Administration is successful in obtaining immunity for these drug companies, taxpayers will be left to pay not only the costs of medical care for all persons injured by drugs but also the life-long care for persons disabled by a product.
If Americans realized what was happening, there is no way they would approve of their tax dollars being spent to help the richest industry on the planet deprive fellow citizens of their right to a jury trial.
The typical brief against a plaintiff is filed by an army of government attorneys and will include an Assistant Attorney General, a Deputy Assistant Attorney General, a United States Attorney, an Assistant United States Attorney, two Appellate Attorneys from the Department of Justice, the FDA’s Chief Counsel, and the Deputy Chief Counsel, Associate Chief Counsel, and General Counsel for the Department of Health and Human Services.
Glaxo takes things one step further by submitting government amicus briefs that were filed in other cases (not just Paxil cases) and re-files them in virtually every one of the cases filed against the company in order to bolster its preemption arguments.
In O’Neal v GlaxoSmithKline, a case involving the suicide of a 13-year-old Sacramento, California boy, Benjamin Bratt, Glaxo recently used the Bush Administration’s preemption policy to argue that the child’s family should not be allowed to sue Glaxo for failing to warn about the suicide risk.
Benjamin committed suicide on February 14, 1997 by hanging himself. His parents, Terri O’Neal and Barry Bratt, filed a lawsuit alleging that, despite knowledge of suicide risks associated with Paxil prior to 1997, Glaxo concealed the information, failed to warn doctors, the medical community, and the public and all the while the company promoted the drug as safe and effective for children.
In the lawsuit, the Bratt Family alleged that Glaxo should have warned Benjamin’s doctor about the suicide risk both through the label and through other means, such as promotion, advertising, and “Dear Doctor” letters.
On January 30, 2008, federal judge, Frank Damrell, in the US District Court, Eastern District of California, dismissed the case and ruled that all of the family’s claims were preempted. The Bratt family has asked the court to reconsider the ruling. They believe the judge committed error in essentially holding that a drug that is not safe for adults is nonetheless safe for children until proven otherwise.
The family argues that adult clinical trials conducted by Glaxo as far back as 1989 showed an 8 times increased risk of suicidal behavior for Paxil users compared to patients receiving a placebo, but that Glaxo manipulated the data to obscure the risk, and then published the false data in medical journals and articles throughout the 1990’s.
In his ruling, Judge Damrell held that, even if GSK had clinical trial data prior to 1997 that showed an increased risk of suicidality in adults, that data was not sufficient to prove the risk extended to children using Paxil.
The Court held that, because the first clinical trial of Paxil with children did not conclude until 1998, Glaxo could not have known about the suicide risks with kids before that date.
During the January 18, 2008 oral argument on the preemption motion, Judge Damrell himself pointed out that a finding of an increased risk of suicidality in adults would logically apply to children. He specifically stated:
“As a practical matter, if I see there was an association of suicide ideation with anybody and enough of it, the last person I want to see using it is a child. That may not be scientific, but I’m just talking as a grandfather and human being.”
However, in his order, Judge Damrell seems to say the exact opposite:
“That later clinical studies ultimately led to a clear signal of pediatric suicidality, and that these studies arguably reflected the initial data in 1989 and 1991 of similar associations among adults, simply does not provide ‘reasonable evidence’ of the association of pediatric suicidality in February 1997.”
“It is difficult to reconcile Judge Damrell’s statements during oral argument with his ruling,” says senior trial attorney, Ron Goldman of Baum, Hedlund, Aristei & Goldman, the law firm representing the Bratt family.
Baum Hedlund has roughly 30 lawsuits on file involving Paxil-induced suicides and suicide attempts. Over the past 18 years, the firm has handled more than 3,000 cases involving antidepressants, including Glaxo’s Paxil, Eli Lilly’s Prozac and Pfizer’s Zoloft.
The first study Glaxo conducted on children was called Study 329. The study was started in 1994, three years prior to Benjamin’s suicide, and was completed in 1998, nine months after his suicide.
Judge Damrell bought Glaxo’s argument that, because Study 329 wasn’t completed until after Ben Bratt’s death, the company could not have warned of a risk in children prior to that. But, during the four years the study was ongoing, Glaxo received numerous reports of suicidal behavior occurring in children taking Paxil.
Coupled with the risk evident from the adult clinical trials since 1989, the Bratt family argues that Glaxo could have and should have warned of the risk for all people taking the drug long before Benjamin ingested Paxil.
Coincidentally, when the study 329 was finally published, the authors stated that, “The adverse-effect profile of paroxetine in this adolescent population was concordant with that reported in studies of adult patients with depression.”
The Bratt family argues that, the question of whether reasonable evidence of an association existed between Paxil and suicidality in any population at the time of Benjamin’s death is one for the jury.
The question of what Glaxo knew and when Glaxo knew it is also a question for the jury. Glaxo’s attempt to continue the parade down this rabbit trail is simply an attempt to divert attention away from the core issue here. The decisive question in a preemption context for the Court to determine is, “was GSK ever prohibited by the FDA from issuing a warning” thus creating a direct and positive conflict. The answer is unequivocally “NO.”
Judge Damrell also held that, if Glaxo had warned about a suicide risk for kids prior to 1997, such a warning would have been subject to a misbranding action by the FDA.
According to Mr Goldman, “Under no circumstances, given the regulatory scheme, can a drug be considered ‘misbranded’ if the science supports a truthful warning of the risk of suicidality.”
“Under the law,” he says, “it is a drug manufacturer’s duty to warn of risks known or reasonably scientifically knowable.”
“A drug company that fails or refuses to conduct necessary analyses in a scientifically acceptable manner,” he states, “shirks its legal, not to mention ethical and moral, duty to the medical profession and the public.”
According to the US Supreme Court, preemption applies (1) where it is impossible for a private party to comply with both federal and state law; and (2) where the state law stands as an obstacle to the accomplishment and execution of the full purposes and objective of Congress.
“When carefully analyzed, there is absolutely no evidence showing that it would have been ‘impossible’ for Glaxo to warn of this very serious risk, an absolute requirement in cases where conflict preemption is raised,” Mr Goldman contends.
“To the contrary,” he says, “such a warning is in perfect harmony with the FDA regulations and the overarching purpose of the FDA: to promote health and safety in prescription drugs.”
In their brief filed in opposition to summary judgment, the Bratt Family stated: “GSK would like to convince this Court that it is merely a ‘puppet’ when it comes to labeling its multi-billion dollar blockbuster drug, Paxil.”
“According to GSK,” the brief notes, “it is hapless and at the mercy of the FDA when it comes to the content of Paxil’s label.”
Glaxo claims it needed the FDA’s prior approval to issue a warning. However, the attorneys in the Paxil cases point out that Glaxo itself changed the label and sent out a Dear Doctor letter warning about the suicide risk in May 2006, with no prior approval from the FDA. The FDA never objected to the letter or the strengthened warning label.
The FDA, in its amicus briefs, has asserted twisted logic in these cases because the FDA cannot force a company to add a warning to a label. On March 1, 2005, the FDA’s deputy director for the Office of New Drugs, Dr Sandra Kweder, testified at a hearing before the Senate Committee on Health, Education, Labor and Pensions, that the FDA does not have the authority to require a specific label change and that the agency has to negotiate with the companies about how things should be worded, placement, those kinds of things.
During oral argument in SSRI suicide cases, industry attorneys claim that the reevaluation of the suicide risk of all the pediatric studies on SSRIs occurred after Glaxo “voluntarily” offered up the studies to the FDA.
For instance, on December 10, 2007, during oral argument in a case in a federal court in Philadelphia, a Pfizer attorney, Malcolm Wheeler was asked by the court: “What was the tipping point then for the change in position with respect to adolescents and then later extending that to young adults up to age 24?”
Mr Wheeler replied: “The tipping point was because GlaxoSmithKline voluntarily went forward and informed the FDA of some study results and said here are these results.”
“And what the FDA did as a result of that,” he told the court, “was to conduct a new analysis, pooling the data from nine different drugs, not just SSRIs, but nine different antidepressants, to say when we pool all the data from these various antidepressants, does it indicate any signal that suggests that we ought to do something other than what we’ve done in the past?”
However, that is a gross misrepresentation of what actually happened. The truth is, according to FDA documents obtained in litigation, that the European Medicines Agency (EMEA) contacted the FDA in mid-2003 to alert officials about the hidden suicide risk in the pediatric Paxil studies.
According to a June 2, 2003, FDA email written by Dr Russell Katz to Dr Andrew Mosholder, the FDA was notified in May 2003, that suicide events were hidden under the term “emotional lability.” Dr Katz’s email states:
“We have recently become aware of a presumed association between Paxil and suicidality in pediatric patients. We received a call from the EMEA a little over a week ago.
A Dr. Raines told us that the company (GSK) had submitted data that demonstrated that use of Paxil in kids was associated with increased suicidality compared to placebo, and that the company proposed labeling changes.
“I believe she also said that it was in the news, and it was a big issue. Tom and I told her that the company had not informed us of any of this, and we agreed to look into it.”
Dr Katz told Dr Mosholder that the FDA had asked Glaxo to elaborate on the events listed under the term emotional lability and further stated:
“We received this partial response, and almost all of these events related to suicidality. The bottom line is that when data from the controlled trials in depression, OCD, and Social Anxiety are pooled, for “possible suicide related” events occurring during treatment or within 4 days after discontinuation, the rate is 0.14/patient-year on drug, and 0.05/patient-year on placebo, p=0.02.”
“We have some problems with the methodology they used to capture cases, but this is the major finding, and it has us worried,” he wrote.
“We are planning to look at the NDAs for other SSRIs to see whether or not similar events are being hidden by various inappropriate coding maneuvers, but we’d also like to compare the drugs in other meaningful ways if we can,” Dr Katz informed Dr Mosholder.
A report by Harvard psychiatrist, Dr Joseph Glenmullen, retained by Baum Hedlund as an expert witness in the Bratt case shows that Glaxo knew as early as 1989 that patients who received Paxil in clinical trials showed an 8-fold increased risk of suicidality compared to patients who received placebos. Dr Glenmullen’s report was initially filed under seal, however, on January 30, 2008, the majority of the report was unsealed.
In the report, Dr Glenmullen also notes that, when Glaxo coded suicidal behavior in its computerized database, most of the suicides and suicide attempts were coded as “emotional lability,” which he says is “a technical term for rapid mood swings, for example from crying to laughing.”
Another claim consistently made by both the Bush Administration attorneys and the attorneys for the SSRI makers, is that the FDA’s failure to make the companies issue warnings somehow means the FDA considered and rejected offers by the companies to add warnings about the suicidality risk.
However, Dr Katz specifically notes in his email that Glaxo never offered to add a warning to the label in the US, even after the FDA became aware of the increased suicide risk and discussed the issue with Glaxo.
“The sponsor has not proposed labeling changes and makes a feeble attempt to dismiss the finding,” he told Dr Mosholder in the email.
In the first SSRI case where preemption was raised (the company lost the argument), Motus v Pfizer, the judge wisely observed that, “although the FDA did not require Pfizer to include suicide-related warnings in Zoloft’s label, FDA has not prohibited Pfizer from doing so” and the “FDA never stated that it would be impermissible to include additional warnings.” Likewise, because Glaxo never sought to add a suicide warning, it is not possible that the FDA considered and a suicide warning.
On June 10, 2003, the UK’s Medicines and Healthcare Products Regulatory Agency issued the warning: “It has become clear that the benefits of Seroxat in children for the treatment of depressive illness do not outweigh these risks.”
In the June 11, 2003 New York Times, Gardiner Harris reported that Alan Metz, the vice president for clinical development at Glaxo, said the company was not warning American doctors against using the drug with depressed children in the US.
Dr Metz acknowledged that Paxil was not approved for treating children in the US but that many doctors prescribed the drug for children anyway. Mr Harris pointed out that Glaxo had applied for approval from the FDA to sell Paxil to children with obsessive compulsive disorder and the application was pending at that time.
On June 20, 2003, the Times reported that the FDA’s reanalysis found that the risk of suicidal thoughts and suicide attempts was 3 times greater among children using Paxil, mostly teenagers, than among children given placebos.
On August 12, 2003, the Times ran a commentary by Richard Friedman, a psychiatrist and director of the psychopharmacology clinic at Weill Medical College of Cornell University, which stated in part:
“What is disturbing about the recent report is that the purported link between Paxil and suicidal thinking comes from an unpublished study sponsored by Paxil’s manufacturer, GlaxoSmithKline.”
“In fact, GlaxoSmithKline has published only one of its nine studies of Paxil in children and adolescents to date,” he reported.
In its preemption motion, Glaxo offered nothing to support the claim that the FDA had considered, much less rejected, a proposal to add a warning about the increased suicide risk for kids. In fact, the studies in question were not submitted to the FDA until 2002, when Glaxo sought approval for new uses of Paxil, meaning it would have been impossible for the FDA to have considered whether a warning was appropriate based on a risk known only to Glaxo.
To support their argument that the FDA had never rejected a Glaxo proposed warning, the Bratt family brief states: “None of the GSK employees in the past 14 years who have, or had, responsibility for communicating with the FDA regarding Paxil could point to any specific, proposed suicide or suicidality language that was rejected by the FDA.
In his report, Dr Glenmullen explains how Glaxo successfully avoided having to include a warning on the label when it obtained FDA approval for Paxil in 1992:
“GlaxoSmithKline’s ‘bad’ Paxil data made it look as if patients randomized to Paxil were no more likely to become seriously suicidal when, in fact, the correct data shows patients on Paxil were eight times more likely to commit or attempt suicide.”
“One again,” he states, “GlaxoSmithKline’s ‘bad’ Paxil numbers carried the day: The FDA approved Paxil on December 29, 1992 with no warning to doctors or patients of the significant increased risk of suicidal behavior.”
The FDA’s Dr David Graham, most famous for exposing the risks associated with Vioxx, says the government’s attempts to immunize drug companies must not succeed. In an August 30, 2005 interview with Manette Loudon, the lead investigator for Dr Gary Null, (author of numerous books including “7 Steps To Overcoming Anxiety and Depression”), Dr Graham was asked about his views on attempts to pass tort reform.
“I think it’s dangerous and wrong,” he stated. “We already have an FDA that’s been neutralized by industry and sees industry as its client.”
Dr Graham said the agency is not going to protect the average citizen from the consequences of unsafe drugs, so the only alternative is the legal system. “That’s the only way we have of getting companies to change their behavior,” he said and, “tort reform would remove that threat as well.”
“It’s basically giving companies immunity because now the people who are injured by the drugs can’t recover damages that might actually mean something to industry,” he advised.
“I mean $250,000 for damages; they blow that in one ad campaign,” he stated. “To them, that’s nothing.”
“But a lawsuit for multiple millions of dollars has more of an impact,” he added.
“Now, is that optimal?” he said. “No.”
“But the fact is that since we have a regulatory agency that doesn’t regulate and we have a public health agency that doesn’t protect the public, we have thousands of people who are being injured by products that the FDA knows are unsafe,” he told Ms Loudon.
He pointed out that the FDA knew there was a big problem with Vioxx in mid 2000, and did nothing about it. If the FDA is not going to exercise control over companies, he said, there has to be a system in place “that reins companies in.”
In addition to the agency’s failure to protect the public against Vioxx, Dr Graham also discussed the FDA’s attempts to conceal the increased suicide risks that were found in the reevaluation of the pediatric SSRI studies in early 2004. “The FDA had suppressed a report written by a colleague of mine in drug safety and had prevented him from presenting this information in an advisory committee meeting,” he explained.
“That information leaked to the media,” Dr Graham continued, “embarrassing the FDA because it had been caught suppressing very important information – that most of the antidepressants don’t work for treating children.”
He told Ms Loudon that someone in his supervisory chain at the FDA even initiated a criminal investigation to identify the person who had leaked the information to the media.
With the SSRIs, he says, the FDA should have insisted on a signed informed consent form, that said three things: (1) these are the antidepressants available and only Prozac has been shown to work for children; (2) all the other drugs are no better than placebos; and (3) all these drugs appear to have the ability to increase the risk of suicidal behavior.
As a parent, he stated, if I saw that in writing and the doctor was going to write the prescription for some drug other than Prozac, I could say, “Doc, why are you putting my child on a drug that doesn’t work in kids.”
According to Dr Graham, the FDA did not want patients to have that information, so it refused to require signed informed consent. And, the companies didn’t want parents to have that information because all of a sudden the lucrative “off-label” use of the drugs would have dried up.
Dr Graham also explained that, if the FDA pulls a drug off the market due to safety issues, it not only hurts the marketing of the drug, but also calls into question why it was approved in the first place.
“Therefore,” he said, “you get this culture of cover-up, this culture of suppression, this culture of denial, and this culture that demonstrates above all else that industry is the client and not the American people.”
Most Americans do not realize that a preemption decision on whether to throw out a lawsuit largely hinges on the judge assigned to the case. Attorneys James Beck and Mark Herrmann run the “Drug and Device Law” blog and they post their personal views on topics that arise in the defense of pharmaceutical company product liability litigation.
On May 17, 2007, they posted a piece called, “Picking Spots In Preemption Cases.” The bloggers lamented that “two adverse preemption decisions over the last couple of weeks [ ] have us scratching our heads.”
The opinions referred to were Barnhill v Teva Pharmaceuticals, No 06-0282, (SD Ala Apr 24, 2007), and Kelly v Wyeth, 2007 WL 1302589 (Mass Super Apr 12, 2007).
In their blog, Mr Beck and Mr Herrmann discuss the importance of filing preemption motions with judges who are already known to be unsympathetic to private plaintiffs who sue drug companies.
“With respect to Kelly,” they state, “the most salient point for us is why a preemption motion was brought at all in a state trial court in Massachusetts – a known pro-plaintiff jurisdiction.”
“There’s certainly no history of success with preemption motions in prescription medical product cases in Massachusetts,” they point out.
“Part of preemption strategy is choosing the jurisdictions in which such motions would have a reasonable likelihood of success,” they explain.
“In plain English, you gotta pick your spots,” the attorneys advise.
“If defendants go running helter skelter into courts filing preemption motions no matter how hostile the jurisdiction – well, the result is going to be decisions like Kelly,” they warn.
“That doesn’t do the filing defendant any good,” they state. “Nor does it do anyone else defending prescription drug cases any good.”
On the other hand, in the September 2007 paper, “The Truth about Torts: Using Agency Preemption to Undercut Consumer Health and Safety,” legal scholars, William Funk, Sidney Shapiro, David Vladeck and Karen Sokol, of the Center for Progressive Reform, discuss the importance of jury trials, and the tort system in general.
“It is less susceptible to disproportionate influence by large companies and trade associations than the federal regulatory system,” they note and explain:
“When agencies respond to such influence by failing to regulate, or by adopting inappropriately weak regulations, the tort system becomes the primary legal vehicle for consumers to obtain protection from dangerous products and services.”
“Because tort decisions are made by juries, and because plaintiffs’ lawyers have the necessary skill and incentives to seek appropriate levels of protection for consumers and patients, the civil justice system puts individual consumers on the same footing as large corporations,” according to the paper.
“Unlike the regulatory system,” the authors explain, “the civil justice system makes it possible for members of the general public to be directly involved in governing.”
“This is a crucial distinction,” they note, “since individuals normally lack the same incentives as politically appointed government officials to resolve regulatory problems in favor of regulated entities.”
They also note that, “although corporate interests expend significant resources in an attempt to populate the judiciary with industry-friendly judges in states where judges are elected, there is simply no way to ‘capture’ all the judges throughout the country’s numerous state and federal, trial and appellate courts.”
“Moreover, even where judges are elected, citizens serving on juries are responsible for making decisions about liability,” the paper concludes.
(Written as part of the SSRI Antidepressant Litigation Monthly Round-Up, Sponsored by Baum, Hedlund, Aristei & Goldmans’ Pharmaceutical Antidepressant Litigation Department)
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.”
Evelyn Pringle February 13, 2008
Apparently, GlaxoSmithKline is still trying to hide damaging information about Paxil, because 9 pages of a report released from under a court order last month, are not available to the public. However, Senator Charles Grassley has instructed Glaxo to provide him with the full report by February 14, 2008.
In the report, which is dated roughly 6 months ago on June 29, 2007, Harvard Professor, Dr Joseph Glenmullen reveals that Glaxo had clinical trial data since 1989 which showed that Paxil increases the risk of suicide by more than 8-fold compared to patients who received a placebo.
The report was submitted in O’Neal v Glaxo, a lawsuit filed in a California federal court by the surviving family members of Benjamin Bratt who committed suicide at age 13 while on Paxil. The family is represented by the California law firm of Baum, Hedlund, Aristei & Goldman.
On January 30, 2008, the judge dismissed the case on the basis of the new preemption policy of the Bush Administration, but the family intends to ask the court to reconsider the ruling, according to Baum Hedlund.
In his report, Dr Glenmullen also makes a plea for public disclosure of all information that remains sealed under court orders on the basis of Glaxo’s claim that the documents contain trade secrets and states:
“Given the importance of GlaxoSmithKline’s internal documents, it is unfortunate that so many of the documents cited in this report and the attached Appendix are still confidential.”
“Given the stakes for public health and safety, GlaxoSmithKline should not be permitted to claim the documents are proprietary trade secrets.”
“All the documents should be made part of the public record so the full story of Paxil-induced suicidality can be told and the additional necessary steps can be taken to fully protect patients and the public.”
Dr Glenmullen also mentions a companion report related to children and adolescents and a “Specific Causation Report” in the case of Benjamin Bratt, and Senator Grassley has instructed Glaxo to provide him with a copy of that report as well.
In what can only be viewed as an eerily prophetic comment, in a letter back on September 16, 2004, to the Secretary of Health and Human Services, and the acting FDA Commissioner at the time, Senator Grassley warned: “I intend to keep the FDA’s feet to the fire to insure that the American public is knowledgeable about the risks of SSRI’s.”
SSRI’s refer to antidepressants known as selective serotonin reuptake inhibitors that include Paxil, Eli Lilly’s Prozac, Zoloft by Pfizer and Celexa and Lexapro marketed by Forest Labs, along with their generic counterparts. Lilly’s Cymbalta, Wyeth’s Effexor and Glaxo’s Wellbutrin are often referred to as SSRI’s but they are slightly different chemically. However, the new antidepressants all carry the same warnings about the suicide risks.
Senator Grassley’s letter followed the vote by an FDA advisory committee for a black box warning about the increased risk of suicide with kids to be added to the drugs’ labels.
His angry tone, and not so subtle threat, was due to the fact that, during the advisory committee meeting, it became apparent that not only Glaxo, but all the SSRI makers, had concealed and misrepresented clinical trial data for years in the published medical literature which clearly indicated that there was an increased risk of suicidality with SSRI use.
In fact, as soon as Glaxo’s was asked about the hidden studies by regulators in the UK, Glaxo issued a “Dear Doctor” letter to physicians in England saying Paxil should not be prescribed to children because it “failed” to work any better than a placebo and frequently caused “hostility, agitation, emotional lability (including crying, mood fluctuations, self-harm, suicidal thoughts, and attempted suicides.)”
Glaxo did not issue any such warning to doctors in the US.
The paper that garnered the most wrath from pharmacology experts all over the world was published in the July 2001 issue of the Journal of the American Academy of Child and Adolescent Psychiatry on Paxil study 329, which was conducted from 1993 through to late 1995 or early 1996, according to a leading pharmacology expert, Dr David Healy.
Twenty academics, considered to be the tops in their field, signed off on the study. The main authors of paper on the study were later found to be in constant contact with Glaxo when the media began reporting that the data published was fraudulent, and include Dr Martin Keller, Dr Neil Ryan and Dr Karen Wagner.
In the paper, the authors write: “Of the 11 patients only headache (one patient) was considered to be related to the treatment,” and Paxil is “generally well tolerated and effective.”
However, when the actual study was analyzed in 2003, it showed suicidal acts by 5 out of 93 children on Paxil compared to no suicidal acts in the 89 children who received placebo.
On January 29, 2007, the BBC’s Panorama broadcast, “Secrets of the Drug Trials.” Attorney Karen Barth Menzies obtained many of the secret Paxil documents that were quoted during litigation, and she explained how Glaxo found ways “to blow up out of proportion the supposed benefits in Study 329 and downplayed the negative findings.”
Glaxo recruited the opinion leaders to put their names on the published 329 study, she said, because they were academics whom everybody looked up to, and the company knew that doctors would be far more likely to prescribe Paxil after listening to these doctors than they would be if approached by Glaxo salespersons.
One letter that was quoted, revealed that these so-called opinion leaders never even wrote a paper. The letter was from a ghost writer to Dr Keller, informing him that all the necessary materials were enclosed for him to submit the study to a journal for publication. The packet even included a cover letter, with instructions telling Dr Keller to: “please re-type on your letterhead. Revise if you wish.”
Dr Wagner, along with Dr Graham Emslie, was also responsible for publishing papers on studies that resulted in Prozac’s approval for children, and Dr Wagner and Dr Keller were also investigators on Zoloft studies and several of the unpublished Paxil studies.
In the October 4, 1999 Boston Globe, Alison Bass reported that in 1998, as a professor at Brown University, Dr Keller was forced to forfeit “hundreds of thousands of dollars” in state grant money and was paid more than $500,000 in consulting fees in 1998, most of it from companies whose drugs he touted in medical journals and at conferences.
In the report, Ms Bass pointed out that Keller was a valuable resource for the University, and had brought in about $14.4 million in research funding from drug companies and federal agencies since 1993.
According to the report, in 1998, the year Keller published 3 studies with colleagues in the Journal of the American Medical Association and the Journal of Clinical Psychiatry touting the efficacy of Zoloft, he received $218,000 in personal income and more than $3 million in research funding from Zoloft maker Pfizer.
Several ethicists contacted by the Globe said Keller’s unusually large consulting fees, a total of $556,000 in 1998 and $444,000 in 1997, constitute the most serious potential conflict they’ve heard of yet, Ms Bass noted.
Dr Wagner received an onslaught of criticism from experts all over the world when she misrepresented trial data in a paper on Zoloft, claiming it was safe and effective for use with children. On November 29, 2004, Barry Meier wrote, “Contracts Keep Drug Research Out of Reach,” in the New York Times, and reported that over the past decade, Dr Wagner from the University of Texas Medical Center in Galveston had led or worked on some 20 studies published in medical journals and had also “attracted a large number of industry-financed studies, including those aimed at testing whether antidepressants approved for use in adults were safe and effective in children and adolescents.”
In a financial filing with the university in December 1999, Mr Meier found the same month that a Zoloft trial began recruiting patients, Dr Wagner disclosed that she had received more than $10,000 from Pfizer but she did not provide details.
She also did not respond to written questions about the payments but a lawyer for the school, told Mr Meier that Dr Wagner had told him that Pfizer had paid her $20,500 during the course of the Zoloft trial.
Mr Meier also noted that academic researchers routinely receive speaking and consulting fees from companies whose products they test and at Galveston the financial threshold for such a review is $10,000. But the school lawyer, told Mr Meier that the center had been unable to locate records related to Pfizer’s payments to Dr Wagner.
Glaxo’s study 329 was successfully used to promote Paxil for children, and sales to kids skyrocketed to $55 million in 2002 alone. It also served as the smoking gun in a lawsuit filed against Glaxo by New York Attorney Elliot Spitzer, charging Glaxo with fraud for promoting the off-label use of Paxil to children while concealing and misrepresenting the data from 5 studies that showed the increased suicide risks and the fact that Paxil did not work with children. Glaxo settled out of court to shut that lawsuit down within 2 months.
In 2003, after reviewing the same fraudulent studies, the UK banned the use of Paxil with children, and the FDA scheduled an advisory committee meeting in February 2004 to review the data on all SSRI’s.
In response to the announcements by the regulatory agencies, the American College of Neuropsychopharmacology (ACNP), which designated a Task Force in the early 1990’s to review the SSRI trial data, and subsequently published an position paper saying SSRI’s were not linked to suicide, appointed a new Task Force in September 2003, to study the matter again.
This Task Force was made up of many of the same authors whose published papers were under attack for being fraudulent and included Dr John Mann, Dr Graham Emslie, Dr Karen Wagner, Dr Neal Ryan, Dr Andrew Leon, Dr Fredrick Goodwin, Dr David Shaffer, Dr Beardslee, Dr Jan Fawcett, Dr Herbert Meltzer and Dr Ross Baldessarini.
Two weeks before the advisory committee meeting, the Task Force issued a report, once again claiming SSRI’s did not cause suicide, and began making what many experts condemned as preemptive statements in the media to influence the advisory committee to vote against adding a warning about the risk of suicide to SSRI labels.
On January 21, 2007, WebMd’s headline on the internet stated: “Group Finds No Suicide-Antidepressant Link”.
“Our conclusion is that when you look at the SSRI’s as a group, there is evidence they are effective for treating depression in children and adolescents,” Dr Mann told WebMD.
“Instead of being a risk for suicidal behavior, they are potentially therapeutic,” he stated.
In fact, the $30-million Dr Mann, who admitted under oath in a jury trial that it was possible that he got over $30 million in research funding from drug companies over a 10-year period, said the group found strong evidence that SSRI’s help depressed kids and that suicide rates started going down when SSRI’s became available.
He claimed that a 14-year study showed a decline in suicide rates in kids. “Across 15 countries there has been a 33% decline in suicide rates amongst youths,” he told WebMD.
“Doctors must go on treating depression, and SSRI’s appear to be a reasonable choice,” he stated.
The FDA even allowed Task Force members Dr Andrew Leon and Dr Neil Ryan to participate as voting members of the February 2, 2004 advisory panel.
The day after a September 2004 advisory committee finally voted to add a black box warning to the SSRI labels, on September 14, 2004, Senator Grassley issued a press release stating that the FDA “needs to learn an important lesson from what’s developed this year on the matter of kids and antidepressants.”
“Transparency in government is the best policy,” he noted. “Parents and doctors should not be left in the dark, and especially when information that’s available could be a matter of life and death.”
“Given the scientific findings,” he added, “it’s obvious that the strongest label warning for this class of drugs is critically important for the health and safety of young Americans.”
“These measures are especially critical,” he said, “since I also understand from previously released studies and from the Advisory Committee’s own deliberations that only one of the nine antidepressant drugs has been proven to provide any benefit to children and adolescents.”
“In fact,” he pointed out, “in almost all cases, the FDA’s own data demonstrates that these drugs actually perform no better than do placebos.”
In a September 16, 2004, letter, Senator Grassley asked the FDA to “very quickly and fully consider” the recommendations for the black box and med guides, “before the lives of more children are needlessly lost because parents and others lack adequate, readily understandable information when they most need it.”
He also brought up the issue of informed consent and said he was curious about the FDA’s rationale for not requiring doctors to provide a clear, informed consent document that parents must read, understand and sign before accepting a prescription, as the FDA had done with the drug Lotronex, due to a 1 in 300 risk of ischemic colitis in patients.
In the case of antidepressants, Senator Grassley pointed out, “a suicide-related event involving Prozac (fluoxetine) is about 1 in 15 according to the TADS study, and about 1 in 30 for all SSRI’s, according to FDA’s own study.”
The letter said that the informed consent form should at least include the following points: (1) Only Prozac has been shown to be effective in treating depression in children and adolescents, and is the only drug approved for this; (2) All others have been shown to be no different than a placebo, and their use in the treatment of children and adolescents is not an approved use; (3) All antidepressants increase the risk of suicidality, and (4) The risk of a suicide event (planned or actually attempted) is one for every 15 to 30 children and adolescents taking the antidepressant.
Senator Grassley also asked what the FDA planned to do about educating doctors and the public about the risk-benefits of antidepressants, especially in children. Obviously, the short answer to that question more than three years later is, not a thing.
In fact, in the January 17, 2008, Wall Street Journal, David Armstrong and Keith Winstein reported that, “the effectiveness of a dozen popular antidepressants has been exaggerated by selective publication of favorable results, according to a review of unpublished data submitted to the Food and Drug Administration.”
“As a result,” they wrote, “doctors and patients are getting a distorted view of how well blockbuster antidepressants like Wyeth’s Effexor and Pfizer Inc.’s Zoloft really work,” in discussing research led by Erick Turner, a psychiatrist at Oregon Health & Science University, published in a study in New England Journal of Medicine.
They also point out that sales of antidepressants total about $21 billion a year.
In all the studies, old and new, which promote the off-label sale of SSRI’s for children with claims that the drugs work and do not cause suicide, almost without fail, the same names appear as investigators and authors. A complete listing includes Dr John Mann, Dr Martin Keller, Dr Graham Emslie, Dr Frederick Goodwin, Dr Karen Wagner, Dr Neal Ryan, Dr Charles Nemeroff, Dr David Dunner, Dr Andrew Leon, Dr John March, Dr David Shaffer, Dr John Rush, Dr Mark Olfson and Dr Robert Gibbons.
This time around, in addition to going after Glaxo for concealing and misrepresenting the data that showed an 8-fold increased risk of suicide, somebody needs to take the bull by the horns and see to it that these industry-funded quacks get thrown in the slammer.
It’s also more than apparent that a few FDA officials belong there as well.
Evelyn Pringle November 7, 2007
Since August 2006, as part of an on-going, multistate investigative effort by approximately 30 states, Eli Lilly has received civil investigative demands or subpoenas seeking a broad range of documents relating to the company’s marketing and promotion of the antipsychotic drug
Zyprexa, and more states are expected to join the effort.
In addition, a total of ten states are now suing Lilly for Medicaid fraud to recover the cost of Zyprexa purchases for persons covered by the program, along with the past and future costs of treating Zyprexa-related illnesses. Alaska, Arkansas, Louisiana, Mississippi, Montana, New Mexico, Pennsylvania, Utah and West Virginia have filed cases thus far.
Zyprexa belongs to a new generation of antipsychotic drugs known as “atypicals” which arrived on the US market in 1994, beginning with Risperdal, marketed by Johnson and Johnson subsidiary Janssen. Other drugs in this class include Seroquel, sold by AstraZeneca; Geodon, by Pfizer; Abilify, from Bristol-Myers Squibb and Clozaril, marketed by Novartis.
For the first four years that Zyprexa was on the market in the US, it was only approved to treat adults with schizophrenia, and it was not until 2000 that the FDA approved the drug for adults in the manic phase of bipolar disorder.
However, in a matter of a few short years, Lilly turned Zyprexa into its best-selling product, despite the drug’s extremely limited approved uses, by influencing doctors to prescribe the drug off-label.
In addition to prescribing a drug for unapproved uses, off-label can mean treating an approved condition for a longer duration of time, or prescribing a drug in combination with other drugs, or at a different dosage, or to a different patient population such children or the elderly, other than those specified on the FDA-approved label.
According to Lilly’s SEC filings, the Office of the US Attorney for the Eastern District of Pennsylvania has also advised Lilly that it has commenced a civil investigation related to the company’s marketing and promotion of Zyprexa, and a “number of State Medicaid Fraud Control Units are coordinating with the EDPA in its investigation of any Medicaid-related claims relating to Lilly’s marketing and promotion of Zyprexa.”
Lilly has also received subpoenas from the Office of the Attorney General of the State of Illinois, and the Florida Office of the Attorney General, Medicaid Fraud Control Unit, asking for documents relating to sales, marketing and promotion of Zyprexa.
Lilly’s SEC filings also report that the company has received requests for information related to the company’s marketing and promotion of Zyprexa from the offices of Representative Henry Waxman, Chairman of the House Committee on Oversight and Government Reform, and Senator Charles Grassley, the ranking Republican on the Senate Finance Committee.
Collectively, the Medicaid fraud lawsuits allege that Lilly illegally influenced doctors to prescribe Zyprexa off-label to patients, including children, for conditions such as behavior and mood disorders, eating disorders, anxiety, post traumatic stress disorder, insomnia, PMS, Alzheimer’s, Tourette’s syndrome, dementia and other unapproved indications.
The lawsuits also allege that Lilly concealed the adverse effects associated with Zyprexa, including drastic weight gain, high blood sugar levels, diabetes and pancreatitis.
Other serious adverse effects known to be associated with Zyprexa include Parkinson-like symptoms, akathisia, tardive dyskinesia, dystonia, hypotension, constipation, tachycardia, seizures, liver abnormalities, white blood cell disorders and death.
The Mississippi lawsuit alleges that about 10% of Zyprexa patients have developed diabetes, some of whom are children, even though Zyprexa “has never been approved for, nor found to be effective, in the treatment of children.”
An estimated 1,500 Utah Medicaid patients who took Zyprexa have developed diabetes, according to the lawsuit filed on May 29, 2007, by state attorney general David Stallard.
Utah is seeking damages including $5,000-$10,000 for each prescription that was “not medically necessary.”
Lilly recently attempted to get the Utah case dismissed, in part by arguing that the allegations of off-label promotion and failure to warn were preempted by FDA regulations under a new rule put in place by the Bush Administration, largely viewed as a gift to the pharmaceutical industry.
In 2006, the FDA published a preamble to new prescription drug labeling rules in which it asserted that its approval of the labeling would prevent the filing of lawsuits in state courts premised on a theory that a drug company should have provided additional warnings on a drug’s label.
However, the Utah court ruled against Lilly on this issue and stated, in part: “In fields traditionally occupied by the states, such as health and safety regulation, there is a strong presumption against federal preemption,” and Lilly “has not overcome this strong presumption.”
Pennsylvania alleges that the state spent millions of dollars “for non-medically accepted indications and non-medically necessary uses of Zyprexa,” as well as “significant sums of money for the care and treatment” of patients injured by the drug.
Montana’s complaint charges that, “Lilly management participated, encouraged and authorized the unlawful payment of illegal kickbacks to physicians in order to continue generating sales of Zyprexa.”
The Montana lawsuit is asking for reimbursement on behalf of all citizens who purchased Zyprexa, and not only patients covered by public health care programs, because under the law in that state, the attorney general can request treble damages and attorneys’ fees on behalf of all consumers.
There are also several RICO class actions filed against Lilly on behalf of union insurance plans, pension funds, and other private health insurers, which accuse Lilly of violating racketeering laws and allege the drug maker engaged in illegal marketing schemes to promote the sale of Zyprexa for off-label uses and seek to recover the cost of purchasing the drug, as well as treble damages, punitive damages and attorneys’ fees.
On June 28, 2007, Lilly lost a motion for a summary judgment dismissal of the RICO claims, based on the preemption argument, when District Court Judge Jack Weinstein for the Eastern District of New York ruled against the company, In re Zyprexa Products Liability Litigation, 2007 WL 1851161.
In a written ruling rejecting Lilly’s argument that state law failure-to-warn claims are preempted, Judge Weinstein wrote that “the regulation of public health is an area traditionally occupied by the states, supporting a presumption against preemption.”
“Under the present organization of the pharmaceutical industry, the official federal Food and Drug Administration (FDA), and the plaintiffs’ bar,” he stated, “the courts are arguably in the strongest position to effectively enforce appropriate standards protecting the public from fraudulent merchandising of drugs.”
The Judge also noted that Congress had not stated an intent to preempt these claims. “The FDA cannot be allowed to usher in such a sweeping change in substantive law through the back door,” he wrote.
The Medicaid fraud lawsuits allege that many children have been turned into customers for the off-label prescribing of Zyprexa. A recent October 7, 2007, report from the Florida Agency for Health Care Administration entitled, “The Use of Antipsychotic Medications with Children,” found that pediatric use of antipsychotics increased in the late 1990’s and early 2000’s, largely due to the arrival of the atypicals on the market.
The report noted that one study documented a 75% increase with commercially insured children aged 0 to 17 from 1997 to 2001, and another study of the managed care population from 1996 to 2001 found a 127% increase among children aged 0 to 18.
The study also reported that antipsychotic use in the Medicaid populations was three to four times higher than commercial populations in the late 1990’s, and in one program in the Midwest, the rate of prescriptions grew 304% between 1996 and 2001.
The authors said the analysis showed that the drugs are being used to treat a broad spectrum of disorders, and some of the disorders, such as attention deficit hyperactivity disorder and major depression, “clearly do not call for antipsychotic treatment.”
In the 0 to 5 age group, the study found that more than 53% of the drugs were prescribed for ADHD, even though antipsychotic use with children under 6 “should be considered only in very rare circumstances.”
A report in the May 10, 2007, New York Times revealed some of the known adverse events that occurred in children who were prescribed antipychotics in 2006 alone. The FDA received reports of 29 children dying, and at least 165 other serious side effects in children, where an antipsychotic was listed as the primary suspect, according to the Times.
The FDA acknowledges that its reporting system only picks up between one and ten percent of the adverse events that take place, which means the number of deaths and injuries above must be multiplied many times over to obtain an accurate estimation of how many children have been harmed by the drugs.
Evelyn Pringle November 10, 2007
Several Zyprexa-related class actions have been filed against Eli Lilly on behalf of the company’s shareholders charging Lilly, and certain of its officers and directors, with violations of the Securities Exchange Act.
On April 2, 2007, the Schiffrin Barroway Topaz & Kessler law firm issued a press release to announce a class action filed on behalf of all purchasers of Lilly stock between March 28, 2002, and December 22, 2006, alleging that Lilly disseminated false and misleading statements regarding Zyprexa.
More specifically, it alleges that Lilly was aware of a “clear link” between Zyprexa and diabetes, failed to warn the public and engaged in an illicit scheme to offset a drop in sales that was certain to occur when reports of side effects emerged, by creating a marketing plan which included the evaluation and pursuit of sales for Zyprexa based on “off-label” uses, in direct violation of Lilly’s own code of conduct.
The complaint further alleges that concealing the side effects and engaging in an illegal marketing campaign subjected Lilly to substantial regulatory fines, penalties and other legal action, compromising the company’s overall financial condition and prospects.
According to the complaint, between 2002 and 2004, sales of Zyprexa grew from $3.69 billion to $4.42 billion, and between July 18, 2002, and May 7, 2004, Lilly’s stock value increased from $43.75 per share to $76.95.
But when public warnings were issued about the safety of Zyprexa, the lawsuit alleges, sales slowed and share prices dropped from $76.95 to $50.34 between May 7, 2004, and October 25, 2004, representing a loss of market capitalization of over $30 billion.
Another shareholder’s complaint claims that Lilly had knowledge of a link between Zyprexa and extreme weight gain and diabetes and when sued by private individuals who developed these adverse effects, “the Company adamantly refused to acknowledge any wrongdoing.”
Still another lawsuit alleges that Zyprexa does cause such side effects, and to a greater extent than its competitors, and the “revelations sharply curtailed the sales growth of Zyprexa and resulted in thousands of product liability lawsuits against Lilly and hundreds of millions of dollars in settlements.”
A number of Zyprexa cases have been filed against Lilly in other countries as well.
In private litigation, almost all of the federal lawsuits are part of a Multi-District Litigation proceeding before Judge Jack Weinstein in the Federal District Court for the Eastern District of New York.
Since June 2005, Lilly has entered into out-of-court settlements with approximately 30,200 claimants in the US for about $1.2 billion, and there were still about 350 lawsuits covering about 540 claims pending at the time of the company’s August 7, 2007, SEC filing.
However, on June 29, 2007, Rob Waters and Margaret Cronin Fisk reported in Bloomberg News that Lilly “may attract more lawsuits alleging it failed to warn users that a psychiatric drug was linked to diabetes after the pharmaceutical company received a letter from US regulators.”
They report that Lilly was told in March that the FDA would delay the approval of Symbyax, which contains both Zyprexa and Prozac, for hard-to-treat depression because the agency wanted more information about the risk of diabetes in the prescribing label. Symbyax was already approved for bipolar disorder.
In a letter obtained by Bloomberg, the FDA stated: “We are concerned that the proposed labeling is deficient with regard to information about weight gain and high levels of sugar and fat in the blood of patients who took the drug.”
“We do not feel that current labeling for either Symbyax or Zyprexa provides sufficient information on these risks,” the agency wrote.
According to Bloomberg, the FDA said Lilly’s proposed prescribing information for Symbyax failed to disclose that almost half of the patients who had high or borderline blood sugar levels when they started taking the drug ended up with levels high enough to be considered diabetic and that was over nine times the number of patients on placebos.
“We were troubled that this important information was not included in your proposed label,” the agency said.
“The FDA’s request,” Bloomberg points out, “may bolster plaintiffs’ suits against the Indianapolis company over side effects tied to Zyprexa,” attorneys told the reporters.
“When the FDA says something damning about the warnings of a drug, it’s admissible as evidence on the reasonableness of the manufacturer’s decisions,” said David Logan, dean of the Roger Williams University School of Law, in an interview with Bloomberg.
“It would likely carry some weight with juries,” he stated.
Experts say, in light of all the studies which have shown that the older cheaper antipsychotics work as well or better than atypicals for schizophrenia patients, it’s difficult to understand why Zyprexa is still being prescribed for those patients.
An October 2006 study in the Archives of General Psychiatry, funded by the British government and lead by Dr Peter Jones, a psychiatrist at the University of Cambridge, compared treatment outcomes for schizophrenia patients with the older antipsychotics with treatment results from the new atypicals and found the quality of life of patients was slightly better with the older drugs.
The study was conducted on behalf of Britain’s National Health Service to determine whether the increased cost of the new atypicals was justified and involved 227 patients who were assigned to two groups and evaluated by researchers who did not know which medication the patients were taking for over a year.
In the October 3, 2006, Washington Post, Dr Jones said a conservative interpretation of the data suggests that there is no difference, “so the notion you would pay 10 times as much would be difficult to justify.”
“Why were we so convinced?” he asked, referring to the widespread belief that the new drugs were worth the cost. “I think pharmaceutical companies did a great job in selling their products,” he said.
Experts are quick to point out that earlier studies in the US had produced the same results. In 2003, the Department of Veterans Affairs found there was no difference in compliance, symptoms or overall quality of life in patients treated with the older drug Haldol compared with Zyprexa, and a September 2005 government-funded study in the New England Journal reported that patients taking the older drug perphenazine did as well as patients on the new drugs and patients on atypicals experienced more side effects.
“The story of these newer antipsychotic drugs is a story that reveals an institutional gap,” according to Dr Robert Rosenheck, who was involved in both US studies, in the Post on October 3, 2006.
“It should not have needed 10 years to get three government studies,” he noted.
The fact is, Lilly promoted Zyprexa as being more effective than the older drugs with less side effects right from the start. On November 14, 1996, the FDA’s Division of Drug Marketing, Advertising and Communications sent a letter to Lilly addressing the company’s misrepresentations of the risks and benefits of Zyprexa in an October 2, 1996, promotional teleconference conducted by Dr Gary Tollefson, Vice President of Lilly Research Laboratories.
During the conference, the FDA said, Dr Tollefson made the false claim that Zyprexa did not cause the Parkinsons-like side effects observed in patients who received Haldol, and even though the FDA labeling for Zyprexa included weight gain as an adverse effect, during the conference Dr Tollefson claimed that it usually occurred in patients who were underweight to begin with, making it sound like weight gain was actually a benefit of the drug, according to the FDA letter.
In addition to the many serious health problems found to be associated with Zyprexa in recent years, experts say the suicide rate amongst Zyprexa patients is also high. According to an analysis of the FDA’s adverse event reports by Dr Gregory Warren, an independent researcher and statistician, since Zyprexa came on the market in 1996, there have been 532 suicide reports on the drug filed by health care professionals.
UK psychiatrist and professor Dr David Healy, one of the world’s leading authorities on pharmacology, says there has been a ten- to twenty-fold increase in the rate of suicide among patients diagnosed with schizophrenia since antipsychotics were first introduced.
All that said, apparently no amount of litigation will slow the off-label prescribing of Zyprexa. In 2006, sales were $4.3 billion, and for the second quarter and first half of 2007, US sales of Zyprexa increased 4% and 5%, respectively, and international sales increased 14% during both periods, according to the SEC filings.
Critics say going after the drug makers is not enough, that it’s time to sue the doctors who prescribe drugs off-label. Alaska human rights attorney Jim Gottstein says psychiatrists are seldom held legally responsible for their failure to adequately inform patients about the true efficacy and harms of the drugs they prescribe.
“This has likely lulled them into a false sense of security,” he notes, “because there are various factors at work which could loosen a tidal wave of legal cases against doctors who do not adequately inform their patients about the benefits and harms, including the efficacy of other approaches and of nontreatment.”