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."
Showing posts with label FDA hearing. Show all posts
Showing posts with label FDA hearing. Show all posts
Sunday, August 8, 2010
FDA Officials Form Hit Squad to Protect Avandia Profits
Evelyn Pringle August 2007
The FDA's latest campaign to protect the profits of a drug company over the safety of Americans is unprecedented, and the organizers include a gang of current and former FDA officials largely credited with turning the nation's regulatory beagle into a lapdog for Big Pharma under the Bush Administration.
FDA spokesman Douglas Arbesfeld, apparently the industry's new inside guy, kicked off the campaign by sending an e-mail to journalists which was intended to discredit Dr Steven Nissen and the Cleveland Clinic. Dr Nissen's study appeared online on May 21, 2007, in the New England Journal of Medicine and warned that GlaxoSmithKline's diabetes drug Avandia increased the risk of heart attacks by 43% and death from cardiovascular events by possibly 64%.
The talking points for the media were obviously agreed upon ahead of time because the stories that appear on the internet refer to Dr Nissen with names like "St Steven", "Patron Saint of Drug Safety" and "Saint Steven the Pure."
In his email to journalists, Mr Arbesfeld pasted portions of an article which appeared on the Heartwire website, containing umpteen critical comments about Dr Nissen and the Avandia study, as well as comments made by an anonymous blogger on the internet which said that business at the Cleveland Clinic is run similar to a Mafia TV series. The full bog states:
"Wake up pharmaceutical companies, this is a call from Dr. Nissen, if you don't hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company."
"The Cleveland Clinic was one of the most respected names in medicine, now they are positioning themselves as candidates to take over for a new series on HBO to replace the Soprano's — the Clinico's 'next week who should we wack ......' — Bata bing bata boon. Comment by Brian A - May 22, 2007."
However, it could just as easily be inferred that Mr Arbesfeld authored the slanderous blog and supplied it to Heartwire with the intention of quoting it later from a “reputable” web site. For its part, Heartwire has since removed what it says are "unsubstantiated remarks about Dr Nissen and the Cleveland Clinic", and states: "In retrospect we regret that we published those sentences, as they do not meet the highest standards of journalistic or scientific integrity or credibility."
The smear campaign has federal lawmakers up in arms. At a June 6, 2007, hearing before the House Oversight and Government Reform Committee, in response to questions about Mr Arbesfeld sending the e-mail under his official title of FDA spokesman, FDA Commissioner Andrew von Eschenbach told the lawmakers, "It was an inappropriate and unfortunate act on the part of an individual which has been addressed through disciplinary procedures."
Dr Nissen is none to happy about the stunt either. "I'm a pretty tough guy," he told ABC News on May 30, 2007, "but I'll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is -- it's an outrage."
As for his part, Mr Arbesfeld told the Boston Globe that the email reflected his own personal views and not the FDA's. Any assertion that the email reflected his own personal views is not quite credible considering that his previous employment was always promoting the views of the industry.
A few articles in the media mentioned that Mr Arbesfeld worked for Johnson & Johnson, but his employment with public relations firm Manning Selvage & Lee was not noted. On December 16, 1999, the Healthcare Marketing & Communications Council reported that Mr Arbesfeld had joined Manning as Senior Vice President in New York.
On January 5, 2001, the firm issued a press release to announce the promotion of Mr Arbesfeld and others and referred to Manning as "one of the largest healthcare practices worldwide and has a broad array of clients including Allergan, Amgen, Eli Lilly and Company, Genentech, Hoffmann La-Roche, Kaiser Permanente, Novartis, Pharmacia and Procter & Gamble."
In reading the press release, Mr Arbesfeld's email expertise is apparently a bi-product of his work for Manning. "In this role," it said, "Arbesfeld will help healthcare clients maximize internet-relations in the marketing and communications mix, and will expand the Practice's strategic e-product offerings."
On August 5, 2002, he identified himself in a Reuters article as representing none other than Glaxo, along with six other drug giants including Bristol-Myers, Aventis, J&J, AstraZeneca, Abbott Labs and Novartis, in a campaign to promote the "Together Rx" prescription drug card program for senior citizens. In 2005, the Reporters Handbook listed him as the contact person for J&J subsidiaries, Janssen Pharmaceutica, Ortho-McNeil Pharmaceutical and Ortho Biotech Products.
Less than a week after Mr Arbesfeld's hatchet job on Dr Nissen, ex-FDA Deputy Commissioner Dr Scott Gottlieb planted an editorial in the May 29, 2007, Wall Street Journal entitled, "Journalist Malpractice," accusing the New England Medical Journal of intentionally publishing the Nissen study to make the FDA look impotent. "The publication was timed," he wrote, "to get ahead of the Food and Drug Administration's more careful evaluation of the same issues."
"The journal seemed bent on beating the FDA to the punch," Dr Gottlieb claimed.
"The goal?" he said, "Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals."
The only problem with the Nissen-NEJM conspiracy theory is that the issue under investigation in Congress right now is why the FDA did not warn the public about Avandia heart risks six months before the Nissen study was ever published.
In the end, when it comes to "Journalistic Malpractice," the larger question would seem to be how was it that so many industry shills were able to get the major media outlets and medical journals to immediately publish commentaries and editorials attacking the NEJM and the Nissen research with headlines splashing all over the internet.
In his editorial, Dr Gottlieb notes that there are "questions" whether Avandia is associated with heart risks, but says they are "so far unsupported by more rigorous, randomized studies and extensive review by the FDA and other authorities around the world."
"When it comes to the issue du jour, drug safety," he wrote, "no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval."
There is no doubt much truth to this assertion, but the problem is that the industry insiders running the FDA refuse to act on the advice of the agency's top scientists. In a July 26, 2007, speech on the Senate floor, Senator Charles Grassley (R-Iowa), of the Senate Finance Committee, said that, in the case of Avandia, "Not only did the FDA disregard the concerns and recommendations from the office responsible for post-marketing surveillance, but I have found that it also attempted to suppress scientific dissent."
In the past two months, he told his fellow senators, "I've had to write to the FDA regarding the suppression of dissent from not one but two FDA officials involved in the review of Avandia."
The Heartwire website conveniently echoed Dr Gottlieb's sentiments by featuring portions of a May 23, 2007, unsigned editorial from the medical journal The Lancet, which claimed that the verdict on Avandia should await the results of a Glaxo sponsored trial called RECORD, not due out until 2009.
"Taken together," the editorial said of Dr Nissen's findings, "these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone's safety."
"But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase 3 trial designed specifically to study cardiovascular outcomes," it said.
"Until the results of RECORD are in," the Lancet noted, "it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses."
The problem with waiting two years for the results of the RECORD trial is that FDA scientist Dr David Graham reviewed the results of this study thus far and told an FDA advisory panel that the study design is so flawed that the results should not be considered in any risk benefit analysis of Avandia now, or in 2009, in a July 26, 2007 report.
In fact, Dr Graham says the RECORD study is so useless that it's probably unethical to allow it to continue because no possible benefit can be achieved by allowing it to go on and that Avandia should be pulled off the market now because thousands of patients are being injured each month by using the drug.
At the end of his editorial, Dr Gottlieb lists himself as a physician and a resident fellow at the American Enterprise Institute who was Deputy Commissioner of the FDA from 2005 to 2007. However, back on August 24, 2005, the Seattle Times provided a much better picture of his background and highlighted the oddity of the FDA hiring him in the first place in light of his solid alliance with the industry. "Only a month ago," the article states, "Dr Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors."
"Now Gottlieb holds the No. 2 job,"” the Times notes, "at the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted."
"Now, as one of three deputy commissioners," the article said, "Gottlieb will help oversee such major policies as the FDA's fast-track approval process for drug and biotech products, a priority for many Wall Street funds and the pharmaceutical industry."
The Times also noted that a half-dozen current and former FDA officials said they did not know of anyone else from Wall Street ever moving directly into such a high-level job at the agency.
A couple months later, the November 12, 2005, Boston Globe reported that Dr Gottlieb could not participate in formulating the nation's defense plan against the avian flu due to conflicts of interest. He "was recused from key parts of the planning effort because his past consulting work for Manning Selvage & Lee involved companies whose products would be used to combat a flu pandemic," it said.
The article pointed out that Dr Gottlieb's former clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the parent company of the nation's sole flu vaccine maker.
According to the Globe, Manning paid Gottlieb a $12,500 monthly retainer for nine months for projects that included eight companies, and he was also paid $9,000 for private consulting work for VanGen Inc, a firm that won a $878-million contract to supply the US government with 75 million doses of anthrax vaccine.
In communicating with the FDA, lawmakers have mentioned that they found it "troubling" that Mr Arbesfeld might be trying to settle old scores with Dr Nissen because they were on opposite sides regarding the approval of the heart failure drug Natrecor.
However, Dr Nissen and Dr Gottlieb's disputes go way back as well. In fact, on August 2, 2006, they participated in a debate on the topic: "Government Science Panels: Fair and Balanced?" sponsored by the Center for Science in the Public Interest, and reported on by Russell Mokhiber and Robert Weissman in Common Dreams.
Much to his credit, Dr Nissen openly communicated his objections to the industry's infiltration of the FDA. While sitting right next Dr Gottlieb, he candidly described the conflicts of interest which he stated were "evident at the highest levels of the FDA."
"For years," he said of FDA leadership, "we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies."
"Then the administration appointed Andrew von Eschenbach as interim commissioner creating another conflict," he said. "In his role as director of the National Cancer Institute, von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict," he noted.
"But even worse," Dr Nissen stated, "the administration appointed Scott Gottlieb as deputy commissioner."
"He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter," Dr Nissen told the audience.
Dr Gottlieb's response to Dr Nissen's comments was basically that he would not dignify the comments with a response.
Firms that Dr Gottlieb was involved with prior to his gig at the FDA, according to the Globe, also include the Inamed Corp, one of two companies that were seeking to return silicone gel implants to the market and on November 17, 2006, the FDA announced that it would lift restrictions on the sale of the implants.
When Dr Gottlieb left the FDA, he headed right back to greener pastures with the drug giant Novartis. The press release to announce his hiring read: "Bench International Places Eminent Regulatory Advisor Scott Gottlieb, M.D., as Senior Counsel to Novartis."
"Under an exclusive consulting agreement," the release stated, "Scott Gottlieb, M.D., will provide advisory services to Novartis on matters of global regulatory policy and strategy."
The FDA recruited two members of its alumni, Peter Pitts and Robert Goldberg, to take another swipe at Dr Nissen in a June 6, 2007, commentary in the Washington Times, using the same talking points as the anonymous blogger, by referring to Dr Nissen as a "self-appointed and media-anointed Patron Saint of Drug Safety" and "Saint Steven the Pure."
For much of the childish commentary, they poke fun at Dr Nissen because he acknowledged in the NEJM that he consults for many drug companies but said he "requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction."
At the end of the commentary, Mr Pitts says he is a former FDA associate commissioner, and both men list their affiliation with the Center for Medicine in the Public Interest; but as usual, that listing really does not give credit where credit is due.
On its web site, the Center describes itself as "a non-partisan, non-profit educational charity," and Mr Pitts is indeed listed as President, but his bio also says he is the Senior Vice President for Global Health Affairs at none other than Manning, Selvege & Lee.
The Manning firm apparently fills two important roles. It's a breeding ground for industry moles preparing to enter "public service" and serves as an employment hub for industry shills once they finish their on average 2- to 3-year stint inside the Bush Administration.
In his CMPI bio, Mr Pitts describes his duties as the FDA's Associate Commissioner from 2002 to 2004 as serving as the agency's "Chief Messaging Officer."
On June 7, 2007, Mr Pitts had this to say in defense of fellow hit-man Mr Arbesfeld on the Pharmalot web site: "I know Doug Arbesfeld and he is a guy devoted to advancing the public health."
According to Mr Pitts, in sending the derogatory e-mail about Dr Nissen to journalists, Mr Arbesfeld was just standing up for the FDA and that people should know about the sacrifice he made by accepting a job in government.
"He is also a guy," Mr Pitts says, "who took a pretty significant pay cut to put in some time in public service."
Some would no doubt argue that it's difficult to imagine that Mr Arbesfeld will end up in the poor house as a result of serving as the top industry mole inside the FDA.
Mr Pitts' sidekick, Mr Goldberg, is indeed listed as the vice president of CMPI, but Mr Goldberg's bio also says he used to be Director of the Manhattan Institute's Center for Medical Progress and Chairman of its 21st Century FDA Task Force.
In fact, a review of the CMPI web site turned up a whole nest of ex-moles who served the industry in one capacity or another in the Bush Administration's FDA. For instance, Daniel Troy, the former FDA Chief Counsel, also known as the "Godfather of Preemption," sits on this "charity's" Advisory Board.
His bio points out that he "played a principal role in FDA’s generally successful assertion of preemption in selected product liability cases."
This "assertion of preemption" says that, as long as the FDA has approved a drug and its label, private citizens in state courts cannot sue the drug company for failing to warn about a product's serious health risks, even in cases where it can be shown that the company concealed studies that revealed the risk from the public and the FDA.
Now that he's switched back to private practice, Mr Troy's CMPI bio says he currently specializes in constitutional and appellate litigation, as well as strategic counseling with "particular focus" on what else - clients regulated by the FDA.
The Advisory Board also includes, Tomas Philipson, whose bio says he served as the Senior Economic Advisor to the commissioner of FDA during 2003 and 2004 and as the Senior Economic Advisor to the administrator of the Centers for Medicare and Medicaid Services in 2004 and 2005.
That would mean that Mr Philipson served Mark McClellan, and they are now apparently joined at the hip because, as part of a program called "Patient-Centric and Prospective Medicine," CMPI says it has created the Patient-Centric Health Forum and that Mr McClellan, "former Medicare administrator and FDA commissioner, will chair the group."
So, it would appear that anyone looking for the retirement home for industry hit men who served in the Bush Administration's FDA can find it right in the middle of cyberspace on the CMPI web site.
(This article is part of the Avandia Update series sponsored by the Baum Hedlund law firm)
The FDA's latest campaign to protect the profits of a drug company over the safety of Americans is unprecedented, and the organizers include a gang of current and former FDA officials largely credited with turning the nation's regulatory beagle into a lapdog for Big Pharma under the Bush Administration.
FDA spokesman Douglas Arbesfeld, apparently the industry's new inside guy, kicked off the campaign by sending an e-mail to journalists which was intended to discredit Dr Steven Nissen and the Cleveland Clinic. Dr Nissen's study appeared online on May 21, 2007, in the New England Journal of Medicine and warned that GlaxoSmithKline's diabetes drug Avandia increased the risk of heart attacks by 43% and death from cardiovascular events by possibly 64%.
The talking points for the media were obviously agreed upon ahead of time because the stories that appear on the internet refer to Dr Nissen with names like "St Steven", "Patron Saint of Drug Safety" and "Saint Steven the Pure."
In his email to journalists, Mr Arbesfeld pasted portions of an article which appeared on the Heartwire website, containing umpteen critical comments about Dr Nissen and the Avandia study, as well as comments made by an anonymous blogger on the internet which said that business at the Cleveland Clinic is run similar to a Mafia TV series. The full bog states:
"Wake up pharmaceutical companies, this is a call from Dr. Nissen, if you don't hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company."
"The Cleveland Clinic was one of the most respected names in medicine, now they are positioning themselves as candidates to take over for a new series on HBO to replace the Soprano's — the Clinico's 'next week who should we wack ......' — Bata bing bata boon. Comment by Brian A - May 22, 2007."
However, it could just as easily be inferred that Mr Arbesfeld authored the slanderous blog and supplied it to Heartwire with the intention of quoting it later from a “reputable” web site. For its part, Heartwire has since removed what it says are "unsubstantiated remarks about Dr Nissen and the Cleveland Clinic", and states: "In retrospect we regret that we published those sentences, as they do not meet the highest standards of journalistic or scientific integrity or credibility."
The smear campaign has federal lawmakers up in arms. At a June 6, 2007, hearing before the House Oversight and Government Reform Committee, in response to questions about Mr Arbesfeld sending the e-mail under his official title of FDA spokesman, FDA Commissioner Andrew von Eschenbach told the lawmakers, "It was an inappropriate and unfortunate act on the part of an individual which has been addressed through disciplinary procedures."
Dr Nissen is none to happy about the stunt either. "I'm a pretty tough guy," he told ABC News on May 30, 2007, "but I'll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is -- it's an outrage."
As for his part, Mr Arbesfeld told the Boston Globe that the email reflected his own personal views and not the FDA's. Any assertion that the email reflected his own personal views is not quite credible considering that his previous employment was always promoting the views of the industry.
A few articles in the media mentioned that Mr Arbesfeld worked for Johnson & Johnson, but his employment with public relations firm Manning Selvage & Lee was not noted. On December 16, 1999, the Healthcare Marketing & Communications Council reported that Mr Arbesfeld had joined Manning as Senior Vice President in New York.
On January 5, 2001, the firm issued a press release to announce the promotion of Mr Arbesfeld and others and referred to Manning as "one of the largest healthcare practices worldwide and has a broad array of clients including Allergan, Amgen, Eli Lilly and Company, Genentech, Hoffmann La-Roche, Kaiser Permanente, Novartis, Pharmacia and Procter & Gamble."
In reading the press release, Mr Arbesfeld's email expertise is apparently a bi-product of his work for Manning. "In this role," it said, "Arbesfeld will help healthcare clients maximize internet-relations in the marketing and communications mix, and will expand the Practice's strategic e-product offerings."
On August 5, 2002, he identified himself in a Reuters article as representing none other than Glaxo, along with six other drug giants including Bristol-Myers, Aventis, J&J, AstraZeneca, Abbott Labs and Novartis, in a campaign to promote the "Together Rx" prescription drug card program for senior citizens. In 2005, the Reporters Handbook listed him as the contact person for J&J subsidiaries, Janssen Pharmaceutica, Ortho-McNeil Pharmaceutical and Ortho Biotech Products.
Less than a week after Mr Arbesfeld's hatchet job on Dr Nissen, ex-FDA Deputy Commissioner Dr Scott Gottlieb planted an editorial in the May 29, 2007, Wall Street Journal entitled, "Journalist Malpractice," accusing the New England Medical Journal of intentionally publishing the Nissen study to make the FDA look impotent. "The publication was timed," he wrote, "to get ahead of the Food and Drug Administration's more careful evaluation of the same issues."
"The journal seemed bent on beating the FDA to the punch," Dr Gottlieb claimed.
"The goal?" he said, "Painting the FDA as impotent, in order to argue for legislation winding through Congress that would increase regulatory hurdles for drug approvals."
The only problem with the Nissen-NEJM conspiracy theory is that the issue under investigation in Congress right now is why the FDA did not warn the public about Avandia heart risks six months before the Nissen study was ever published.
In the end, when it comes to "Journalistic Malpractice," the larger question would seem to be how was it that so many industry shills were able to get the major media outlets and medical journals to immediately publish commentaries and editorials attacking the NEJM and the Nissen research with headlines splashing all over the internet.
In his editorial, Dr Gottlieb notes that there are "questions" whether Avandia is associated with heart risks, but says they are "so far unsupported by more rigorous, randomized studies and extensive review by the FDA and other authorities around the world."
"When it comes to the issue du jour, drug safety," he wrote, "no description of medical research in a medical journal comes close to the detail level or scrutiny imposed by the FDA on study results before approval."
There is no doubt much truth to this assertion, but the problem is that the industry insiders running the FDA refuse to act on the advice of the agency's top scientists. In a July 26, 2007, speech on the Senate floor, Senator Charles Grassley (R-Iowa), of the Senate Finance Committee, said that, in the case of Avandia, "Not only did the FDA disregard the concerns and recommendations from the office responsible for post-marketing surveillance, but I have found that it also attempted to suppress scientific dissent."
In the past two months, he told his fellow senators, "I've had to write to the FDA regarding the suppression of dissent from not one but two FDA officials involved in the review of Avandia."
The Heartwire website conveniently echoed Dr Gottlieb's sentiments by featuring portions of a May 23, 2007, unsigned editorial from the medical journal The Lancet, which claimed that the verdict on Avandia should await the results of a Glaxo sponsored trial called RECORD, not due out until 2009.
"Taken together," the editorial said of Dr Nissen's findings, "these results, although based on very small numbers of events, certainly raise a signal of concern and indicate the need for more reliable information about rosiglitazone's safety."
"But the FDA, physicians, and patients can reasonably await the results of RECORD, a phase 3 trial designed specifically to study cardiovascular outcomes," it said.
"Until the results of RECORD are in," the Lancet noted, "it would be premature to overinterpret a meta-analysis that the authors and NEJM editorialists all acknowledge contains important weaknesses."
The problem with waiting two years for the results of the RECORD trial is that FDA scientist Dr David Graham reviewed the results of this study thus far and told an FDA advisory panel that the study design is so flawed that the results should not be considered in any risk benefit analysis of Avandia now, or in 2009, in a July 26, 2007 report.
In fact, Dr Graham says the RECORD study is so useless that it's probably unethical to allow it to continue because no possible benefit can be achieved by allowing it to go on and that Avandia should be pulled off the market now because thousands of patients are being injured each month by using the drug.
At the end of his editorial, Dr Gottlieb lists himself as a physician and a resident fellow at the American Enterprise Institute who was Deputy Commissioner of the FDA from 2005 to 2007. However, back on August 24, 2005, the Seattle Times provided a much better picture of his background and highlighted the oddity of the FDA hiring him in the first place in light of his solid alliance with the industry. "Only a month ago," the article states, "Dr Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors."
"Now Gottlieb holds the No. 2 job,"” the Times notes, "at the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted."
"Now, as one of three deputy commissioners," the article said, "Gottlieb will help oversee such major policies as the FDA's fast-track approval process for drug and biotech products, a priority for many Wall Street funds and the pharmaceutical industry."
The Times also noted that a half-dozen current and former FDA officials said they did not know of anyone else from Wall Street ever moving directly into such a high-level job at the agency.
A couple months later, the November 12, 2005, Boston Globe reported that Dr Gottlieb could not participate in formulating the nation's defense plan against the avian flu due to conflicts of interest. He "was recused from key parts of the planning effort because his past consulting work for Manning Selvage & Lee involved companies whose products would be used to combat a flu pandemic," it said.
The article pointed out that Dr Gottlieb's former clients included Roche, the manufacturer of Tamiflu, and Sanofi-Aventis, the parent company of the nation's sole flu vaccine maker.
According to the Globe, Manning paid Gottlieb a $12,500 monthly retainer for nine months for projects that included eight companies, and he was also paid $9,000 for private consulting work for VanGen Inc, a firm that won a $878-million contract to supply the US government with 75 million doses of anthrax vaccine.
In communicating with the FDA, lawmakers have mentioned that they found it "troubling" that Mr Arbesfeld might be trying to settle old scores with Dr Nissen because they were on opposite sides regarding the approval of the heart failure drug Natrecor.
However, Dr Nissen and Dr Gottlieb's disputes go way back as well. In fact, on August 2, 2006, they participated in a debate on the topic: "Government Science Panels: Fair and Balanced?" sponsored by the Center for Science in the Public Interest, and reported on by Russell Mokhiber and Robert Weissman in Common Dreams.
Much to his credit, Dr Nissen openly communicated his objections to the industry's infiltration of the FDA. While sitting right next Dr Gottlieb, he candidly described the conflicts of interest which he stated were "evident at the highest levels of the FDA."
"For years," he said of FDA leadership, "we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies."
"Then the administration appointed Andrew von Eschenbach as interim commissioner creating another conflict," he said. "In his role as director of the National Cancer Institute, von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict," he noted.
"But even worse," Dr Nissen stated, "the administration appointed Scott Gottlieb as deputy commissioner."
"He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter," Dr Nissen told the audience.
Dr Gottlieb's response to Dr Nissen's comments was basically that he would not dignify the comments with a response.
Firms that Dr Gottlieb was involved with prior to his gig at the FDA, according to the Globe, also include the Inamed Corp, one of two companies that were seeking to return silicone gel implants to the market and on November 17, 2006, the FDA announced that it would lift restrictions on the sale of the implants.
When Dr Gottlieb left the FDA, he headed right back to greener pastures with the drug giant Novartis. The press release to announce his hiring read: "Bench International Places Eminent Regulatory Advisor Scott Gottlieb, M.D., as Senior Counsel to Novartis."
"Under an exclusive consulting agreement," the release stated, "Scott Gottlieb, M.D., will provide advisory services to Novartis on matters of global regulatory policy and strategy."
The FDA recruited two members of its alumni, Peter Pitts and Robert Goldberg, to take another swipe at Dr Nissen in a June 6, 2007, commentary in the Washington Times, using the same talking points as the anonymous blogger, by referring to Dr Nissen as a "self-appointed and media-anointed Patron Saint of Drug Safety" and "Saint Steven the Pure."
For much of the childish commentary, they poke fun at Dr Nissen because he acknowledged in the NEJM that he consults for many drug companies but said he "requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction."
At the end of the commentary, Mr Pitts says he is a former FDA associate commissioner, and both men list their affiliation with the Center for Medicine in the Public Interest; but as usual, that listing really does not give credit where credit is due.
On its web site, the Center describes itself as "a non-partisan, non-profit educational charity," and Mr Pitts is indeed listed as President, but his bio also says he is the Senior Vice President for Global Health Affairs at none other than Manning, Selvege & Lee.
The Manning firm apparently fills two important roles. It's a breeding ground for industry moles preparing to enter "public service" and serves as an employment hub for industry shills once they finish their on average 2- to 3-year stint inside the Bush Administration.
In his CMPI bio, Mr Pitts describes his duties as the FDA's Associate Commissioner from 2002 to 2004 as serving as the agency's "Chief Messaging Officer."
On June 7, 2007, Mr Pitts had this to say in defense of fellow hit-man Mr Arbesfeld on the Pharmalot web site: "I know Doug Arbesfeld and he is a guy devoted to advancing the public health."
According to Mr Pitts, in sending the derogatory e-mail about Dr Nissen to journalists, Mr Arbesfeld was just standing up for the FDA and that people should know about the sacrifice he made by accepting a job in government.
"He is also a guy," Mr Pitts says, "who took a pretty significant pay cut to put in some time in public service."
Some would no doubt argue that it's difficult to imagine that Mr Arbesfeld will end up in the poor house as a result of serving as the top industry mole inside the FDA.
Mr Pitts' sidekick, Mr Goldberg, is indeed listed as the vice president of CMPI, but Mr Goldberg's bio also says he used to be Director of the Manhattan Institute's Center for Medical Progress and Chairman of its 21st Century FDA Task Force.
In fact, a review of the CMPI web site turned up a whole nest of ex-moles who served the industry in one capacity or another in the Bush Administration's FDA. For instance, Daniel Troy, the former FDA Chief Counsel, also known as the "Godfather of Preemption," sits on this "charity's" Advisory Board.
His bio points out that he "played a principal role in FDA’s generally successful assertion of preemption in selected product liability cases."
This "assertion of preemption" says that, as long as the FDA has approved a drug and its label, private citizens in state courts cannot sue the drug company for failing to warn about a product's serious health risks, even in cases where it can be shown that the company concealed studies that revealed the risk from the public and the FDA.
Now that he's switched back to private practice, Mr Troy's CMPI bio says he currently specializes in constitutional and appellate litigation, as well as strategic counseling with "particular focus" on what else - clients regulated by the FDA.
The Advisory Board also includes, Tomas Philipson, whose bio says he served as the Senior Economic Advisor to the commissioner of FDA during 2003 and 2004 and as the Senior Economic Advisor to the administrator of the Centers for Medicare and Medicaid Services in 2004 and 2005.
That would mean that Mr Philipson served Mark McClellan, and they are now apparently joined at the hip because, as part of a program called "Patient-Centric and Prospective Medicine," CMPI says it has created the Patient-Centric Health Forum and that Mr McClellan, "former Medicare administrator and FDA commissioner, will chair the group."
So, it would appear that anyone looking for the retirement home for industry hit men who served in the Bush Administration's FDA can find it right in the middle of cyberspace on the CMPI web site.
(This article is part of the Avandia Update series sponsored by the Baum Hedlund law firm)
Saturday, August 7, 2010
Best Kept Secret - SSRIs Do Not Work
Evelyn Pringle March 3, 2007
The medicalization of distress has led to a dramatic rise in the use of antidepressants, however it is questionable whether patients are being told that in controlled clinical trials the drugs barely outperformed a placebo, says Jonathan Leo, Associate Professor of Neuroanatomy, Lincoln Memorial University, DeBusk College of Osteopathic Medicine
Dr Leo also states that patients are not told that in many cases the symptoms of depression will improve within six months even without medication, or that many people have significant physiological problems when they try and get off the drugs. In the interest of informed consent, he notes, patients should be given all the facts before taking an antidepressant.
That said, the fact that the class of antidepressants known as the selective serotonin reuptake inhibitors (SSRIs), are basically useless in treating depression in children and adults is not news to the FDA. Back on September 23, 2004, during testimony at a hearing before the House Oversight and Investigations Committee on Energy and Commerce, Dr Robert Temple, the FDA's Director of the Office of Medical Policy, discussed the agency's review on the efficacy of SSRIs with the children.
He noted that it was important in a risk-benefit equation to understand the benefit side. "Of the seven products studied in pediatric MDD (Prozac, Zoloft, Paxil, Celexa, Effexor, Serzone and Remeron)," he testified, "FDA's reviews of the effectiveness data resulted in only one approval (Prozac) for pediatric MDD."
"Overall," Dr Temple said, "the efficacy results from 15 studies in pediatric MDD do not support the effectiveness of these drugs in pediatric populations."
Also in 2004, a study of previously hidden unpublished data as well as published studies on five SSRIs, was conducted by Tim Kendall, deputy director of the Royal College of Psychiatrists' Research Unit in London, to help analyze research to draw up the clinical guidelines for British regulators, and published in the Lancet.
Following his evaluation, Mr Kendall stated: "This data confirms what we found in adults with mild to moderate depression: SSRIs are no better than placebo, and there is no point in using something that increases the risk of suicide."
In 2005, the British Medical Journal published another study that concluded that SSRIs are no more effective than a placebo and do not reduce depression.
In December 2006, at the most recent FDA advisory committee meeting held to review studies on SSRI use with adults, SSRI expert, Dr David Healy, author of, "The Antidepressant Era," told the panel that the efficacy of SSRIs has been greatly exaggerated, while the actual studies reveal that only one in ten patients responds specifically to an SSRI rather than a nonspecific factor or placebo.
Critics complain that industry funded studies are presented in ways to exaggerate benefits and obscure side effects. "These include failure to publish negative results, the use of multiple outcome measures, and selective presentation of ones that are positive, multiple publication of positive study results, and the exclusion of subjects from the analysis," according to the paper, "Is Psychiatry For Sale," by Joanna Moncrieff, in People's Voice.
Mr Moncrieff says, psychiatry and the industry make a "formidable combination" because psychiatry derives its legitimacy from the view that mental disorders are equivalent to medical diseases. "Drug treatments that are aimed at specific diagnoses," she explains, "help to endorse this view, and the industry has the financial capacity to ensure that this view becomes accepted and respectable."
"In turn," Ms Moncrieff writes, "the authority of psychiatry enables it to define what is considered as mental disorder and what is appropriate treatment, thus creating markets and opportunities for the pharmaceutical industry."
Critics are most concerned about the continued profit driven prescribing to children with full knowledge that SSRIs are dangerous and do not work with kids. "Drug companies have targeted children as a big market likely to boost profits and children are suffering as a result," says SSRI expert, psychiatrist, Dr Peter Breggin, founder of the International Center for the Study of Psychiatry and Psychology, and author of, "Toxic Psychiatry."
Kelly Patricia O'Meara, author of, Psyched Out: How Psychiatry Sells Mental Illness and Pushes Pills That Kill, prescribing SSRIs to kids must stop. "It is unconscionable," she states, "that it even occurs today given the serious warnings recently made mandatory by the FDA."
In the article, "A Prescription for Disaster," pediatrician, Lawrence Diller, author of, "The Last Normal Child," notes that child psychiatrists have long been viewed as the authorities in the evaluation and treatment of children's emotional and behavioral problems. "Today, however," he says, "these doctors appear to be pushing pills exclusive of anything else."
As an example, Dr Diller points to a survey of child psychiatry practices by the Yale Child Study Center, in the Journal of the American Academy of Child and Adolescent Psychiatry, that found that only one in 10 children who visit a child psychiatrist leaves without a prescription.
Child neurologist, Dr Fred Baughman, author of "The ADHD Fraud: How Psychiatry Makes Patients of Normal Children," also says, "pills are invariably prescribed in 91% of the first visits to a child psychiatrist."
According to Dr Baughman, we have 10 million of the 50 million school children in the nation on one or more psychiatric drugs. "This is death by psychiatry," he states.
The FDA approves drugs for uses and with patient populations that have been adequately tested. The term off-label means prescribing a medication for a different patient group, or at a different dose, duration, or combination with another drug, that has not been approved as safe and effective. While doctors may legally prescribe a drug for an unapproved use, drug makers are barred from promoting a drug for off-label uses but it's common knowledge that they do it on a regular basis.
The cost of off-label prescribing has become a major health problem in the US. According to the 2006, report, Preventing Medication Errors, by the Institute of Medicine, each year errors in the way drugs are prescribed, delivered and used, injure 1.5 million people in the hospital setting alone and cost more than $3.5 billion a year to treat.
Medical experts warn that prescribing drugs to children that have been approved only for adults, is extremely dangerous because the correct dosage has not been established for their weight and developing body organs.
According to patient rights activist, Doyle Mills, psychiatry is turning into Russian Roulette. "There is no known safe dose," he says, "for any of these psychiatric drugs in young children."
"They are never tested in the under-five population," Mr Mills says, "yet children can be given these drugs legally."
California Attorney, Ted Chabasinski, who handles cases involving patient rights and exposing the off-label marketing of psychiatric drugs, says, "the drug companies, and their subsidiary, the American psychiatric profession, push drugs for children that have never been shown to be beneficial, but clearly are dangerous and have many life-threatening effects."
According to Vera Sharav, Director of the Alliance for Human Research Protections, "The only way to stop the prescribed assault on America's children is to put health care professionals (mostly psychiatrists) who prescribe toxic psychotropic drugs (and drug cocktails) for children--for whom these drugs have not been approved as either safe or effective--on trial in open court."
"Let the public bear witness," she states, "to the proceedings that will demonstrate the absence of scientific-medical evidence to support the widespread misprescribing of harmful drugs for children."
Evidence from many sources confirm that SSRIs commonly cause or exacerbate a wide range of abnormal mental and behavioral conditions, according to Dr Breggin. "These adverse drug reactions," he states, "include the following overlapping clinical phenomena: a stimulant profile that ranges from mild agitation to manic psychoses, agitated depression, obsessive preoccupations that are alien or uncharacteristic of the individual, and akathisia."
Each of these reactions, he explains, can worsen the individual's mental condition and can result in suicidality, violence, and other forms of extreme abnormal behavior.
SSRIs have been on the market less than 20 years so their long-term effects are still unknown. Barry Tuner, a professor of law and medical ethics in the UK, says mental illness has skyrocketed in the US because drug companies have marketed it and the US is facing a "societal catastrophe" if this is not reined in.
"In twenty years," he warns, "a huge percentage of the population will be damaged by these medications and the recipients will have real mental disorders caused by the drugs."
Studies are being conducted in attempt to assess the long-term damage on kids. Last year, Dr Amir Raz, assistant professor in the Division of Child and Adolescent Psychiatry at Columbia University, and researcher at the New York State Psychiatric Institute, writing in the journal PLoS Medicine, said mouse studies indicate exposure to SSRIs early in life produces abnormal emotional behaviors in adults.
"Some exploratory findings," Dr Raz wrote, "suggest that artificial perturbation of serotonin function in early life may alter the normal development of brain systems related to stress, motor development, and motor control."
Other medical experts warn that the harm caused to the body by psychiatric drugs is not limited to mental disorders. Dr Grace Jackson, author of, "Rethinking Psychiatric Drugs: A Guide for Informed Consent," points out that, "some physicians seem to only think these pills effect everything from the neck up, and they forget that when they give the medications there is an entire human body that may be feeling unanticipated effects of these medications."
Most patients, including parents acting on behalf of their children, know little if anything about off-label prescribing and assume that their doctors are giving them an approved drug for an approved use. But all too often, experts say, through no fault of their own, patients wind up with more serious health problems then they had to begin with due to off-label prescribing.
The medicalization of distress has led to a dramatic rise in the use of antidepressants, however it is questionable whether patients are being told that in controlled clinical trials the drugs barely outperformed a placebo, says Jonathan Leo, Associate Professor of Neuroanatomy, Lincoln Memorial University, DeBusk College of Osteopathic Medicine
Dr Leo also states that patients are not told that in many cases the symptoms of depression will improve within six months even without medication, or that many people have significant physiological problems when they try and get off the drugs. In the interest of informed consent, he notes, patients should be given all the facts before taking an antidepressant.
That said, the fact that the class of antidepressants known as the selective serotonin reuptake inhibitors (SSRIs), are basically useless in treating depression in children and adults is not news to the FDA. Back on September 23, 2004, during testimony at a hearing before the House Oversight and Investigations Committee on Energy and Commerce, Dr Robert Temple, the FDA's Director of the Office of Medical Policy, discussed the agency's review on the efficacy of SSRIs with the children.
He noted that it was important in a risk-benefit equation to understand the benefit side. "Of the seven products studied in pediatric MDD (Prozac, Zoloft, Paxil, Celexa, Effexor, Serzone and Remeron)," he testified, "FDA's reviews of the effectiveness data resulted in only one approval (Prozac) for pediatric MDD."
"Overall," Dr Temple said, "the efficacy results from 15 studies in pediatric MDD do not support the effectiveness of these drugs in pediatric populations."
Also in 2004, a study of previously hidden unpublished data as well as published studies on five SSRIs, was conducted by Tim Kendall, deputy director of the Royal College of Psychiatrists' Research Unit in London, to help analyze research to draw up the clinical guidelines for British regulators, and published in the Lancet.
Following his evaluation, Mr Kendall stated: "This data confirms what we found in adults with mild to moderate depression: SSRIs are no better than placebo, and there is no point in using something that increases the risk of suicide."
In 2005, the British Medical Journal published another study that concluded that SSRIs are no more effective than a placebo and do not reduce depression.
In December 2006, at the most recent FDA advisory committee meeting held to review studies on SSRI use with adults, SSRI expert, Dr David Healy, author of, "The Antidepressant Era," told the panel that the efficacy of SSRIs has been greatly exaggerated, while the actual studies reveal that only one in ten patients responds specifically to an SSRI rather than a nonspecific factor or placebo.
Critics complain that industry funded studies are presented in ways to exaggerate benefits and obscure side effects. "These include failure to publish negative results, the use of multiple outcome measures, and selective presentation of ones that are positive, multiple publication of positive study results, and the exclusion of subjects from the analysis," according to the paper, "Is Psychiatry For Sale," by Joanna Moncrieff, in People's Voice.
Mr Moncrieff says, psychiatry and the industry make a "formidable combination" because psychiatry derives its legitimacy from the view that mental disorders are equivalent to medical diseases. "Drug treatments that are aimed at specific diagnoses," she explains, "help to endorse this view, and the industry has the financial capacity to ensure that this view becomes accepted and respectable."
"In turn," Ms Moncrieff writes, "the authority of psychiatry enables it to define what is considered as mental disorder and what is appropriate treatment, thus creating markets and opportunities for the pharmaceutical industry."
Critics are most concerned about the continued profit driven prescribing to children with full knowledge that SSRIs are dangerous and do not work with kids. "Drug companies have targeted children as a big market likely to boost profits and children are suffering as a result," says SSRI expert, psychiatrist, Dr Peter Breggin, founder of the International Center for the Study of Psychiatry and Psychology, and author of, "Toxic Psychiatry."
Kelly Patricia O'Meara, author of, Psyched Out: How Psychiatry Sells Mental Illness and Pushes Pills That Kill, prescribing SSRIs to kids must stop. "It is unconscionable," she states, "that it even occurs today given the serious warnings recently made mandatory by the FDA."
In the article, "A Prescription for Disaster," pediatrician, Lawrence Diller, author of, "The Last Normal Child," notes that child psychiatrists have long been viewed as the authorities in the evaluation and treatment of children's emotional and behavioral problems. "Today, however," he says, "these doctors appear to be pushing pills exclusive of anything else."
As an example, Dr Diller points to a survey of child psychiatry practices by the Yale Child Study Center, in the Journal of the American Academy of Child and Adolescent Psychiatry, that found that only one in 10 children who visit a child psychiatrist leaves without a prescription.
Child neurologist, Dr Fred Baughman, author of "The ADHD Fraud: How Psychiatry Makes Patients of Normal Children," also says, "pills are invariably prescribed in 91% of the first visits to a child psychiatrist."
According to Dr Baughman, we have 10 million of the 50 million school children in the nation on one or more psychiatric drugs. "This is death by psychiatry," he states.
The FDA approves drugs for uses and with patient populations that have been adequately tested. The term off-label means prescribing a medication for a different patient group, or at a different dose, duration, or combination with another drug, that has not been approved as safe and effective. While doctors may legally prescribe a drug for an unapproved use, drug makers are barred from promoting a drug for off-label uses but it's common knowledge that they do it on a regular basis.
The cost of off-label prescribing has become a major health problem in the US. According to the 2006, report, Preventing Medication Errors, by the Institute of Medicine, each year errors in the way drugs are prescribed, delivered and used, injure 1.5 million people in the hospital setting alone and cost more than $3.5 billion a year to treat.
Medical experts warn that prescribing drugs to children that have been approved only for adults, is extremely dangerous because the correct dosage has not been established for their weight and developing body organs.
According to patient rights activist, Doyle Mills, psychiatry is turning into Russian Roulette. "There is no known safe dose," he says, "for any of these psychiatric drugs in young children."
"They are never tested in the under-five population," Mr Mills says, "yet children can be given these drugs legally."
California Attorney, Ted Chabasinski, who handles cases involving patient rights and exposing the off-label marketing of psychiatric drugs, says, "the drug companies, and their subsidiary, the American psychiatric profession, push drugs for children that have never been shown to be beneficial, but clearly are dangerous and have many life-threatening effects."
According to Vera Sharav, Director of the Alliance for Human Research Protections, "The only way to stop the prescribed assault on America's children is to put health care professionals (mostly psychiatrists) who prescribe toxic psychotropic drugs (and drug cocktails) for children--for whom these drugs have not been approved as either safe or effective--on trial in open court."
"Let the public bear witness," she states, "to the proceedings that will demonstrate the absence of scientific-medical evidence to support the widespread misprescribing of harmful drugs for children."
Evidence from many sources confirm that SSRIs commonly cause or exacerbate a wide range of abnormal mental and behavioral conditions, according to Dr Breggin. "These adverse drug reactions," he states, "include the following overlapping clinical phenomena: a stimulant profile that ranges from mild agitation to manic psychoses, agitated depression, obsessive preoccupations that are alien or uncharacteristic of the individual, and akathisia."
Each of these reactions, he explains, can worsen the individual's mental condition and can result in suicidality, violence, and other forms of extreme abnormal behavior.
SSRIs have been on the market less than 20 years so their long-term effects are still unknown. Barry Tuner, a professor of law and medical ethics in the UK, says mental illness has skyrocketed in the US because drug companies have marketed it and the US is facing a "societal catastrophe" if this is not reined in.
"In twenty years," he warns, "a huge percentage of the population will be damaged by these medications and the recipients will have real mental disorders caused by the drugs."
Studies are being conducted in attempt to assess the long-term damage on kids. Last year, Dr Amir Raz, assistant professor in the Division of Child and Adolescent Psychiatry at Columbia University, and researcher at the New York State Psychiatric Institute, writing in the journal PLoS Medicine, said mouse studies indicate exposure to SSRIs early in life produces abnormal emotional behaviors in adults.
"Some exploratory findings," Dr Raz wrote, "suggest that artificial perturbation of serotonin function in early life may alter the normal development of brain systems related to stress, motor development, and motor control."
Other medical experts warn that the harm caused to the body by psychiatric drugs is not limited to mental disorders. Dr Grace Jackson, author of, "Rethinking Psychiatric Drugs: A Guide for Informed Consent," points out that, "some physicians seem to only think these pills effect everything from the neck up, and they forget that when they give the medications there is an entire human body that may be feeling unanticipated effects of these medications."
Most patients, including parents acting on behalf of their children, know little if anything about off-label prescribing and assume that their doctors are giving them an approved drug for an approved use. But all too often, experts say, through no fault of their own, patients wind up with more serious health problems then they had to begin with due to off-label prescribing.
GlaxoSmithKline Defamed With Truth About Paxil
Evelyn Pringle January 31, 2007
GlaxoSmithKline has labeled the allegations made in a Panorama television program that said the company had suppressed the results of clinical trials that showed Paxil was ineffective and caused children to become suicidal "defamatory."
According to the January 30, 2007, Guardian, an official at the company said Glaxo had looked into taking legal action, "but that there wouldn't be much to gain from taking action against the BBC".
The Guardian also reported that Glaxo "utterly rejects any suggestion that it has improperly withheld drug trial information."
This is not news. Glaxo has falsely denied these assertions probably 100 times in the past from one end of the globe to the other. If Glaxo files a lawsuit against the BBC, it might as well file a worldwide class action against all the other "defamers" who for some reason or another repeated the exact same allegations.
The BBC has broadcast several Panorama programs on Glaxo's marketing of Paxil for children even after the company's own research showed the drug to be ineffective and dangerous with children. The latest program titled, "Secrets of the Drug Trials," was broadcast on January 29, 2007.
Glaxo's worn-out declarations of innocence can only be adequately responded to by highlighting a few of the historical moments in Paxil's never-ending trail of misery.
A good place to start is Wyoming in the year 2000, with the trial involving the case of Donald Schell, who had been on Paxil just two days when he killed his wife, daughter and infant granddaughter before killing himself.
His surviving son-in-law, Tim Tobin, brought a wrongful death lawsuit against Glaxo.
Prior to the trial, an expert for the plaintiff, Dr David Healy, a well-recognized expert on selective seratonin reuptake inhibitor antidepressants (SSRIs), was given access to Glaxo's files on the Paxil studies.
He spent two days reviewing several hundred thousand documents looking for reports on the trials conducted on "healthy volunteers." Healthy volunteer refers to study participants who were not depressed or mentally ill to begin with before taking a drug. If it was shown that suicidality was evident in health volunteers it would disprove Glaxo's theory that suicide was caused by the underlying illness of depression.
Dr Healy was interested in these trials because he knew of recent studies that had surfaced on another SSRI, Pfizer's Zoloft, that showed the drugs could trigger suicidality in healthy volunteers. When he finally found the right files, Dr Healy told the BBC:
"It seemed clear that some people that went on the drugs had no major problems, but equally clear that others who went on the drug ended up more restless, in a state of mental turmoil, complaining about dreams, nightmares and a range of things like this. These don't seem to have been explored further in any great detail."
Dr Healy discovered that one in 4 healthy volunteers suffered this mental turmoil even when they were on normal doses of Paxil and had only been taking it for a few days.
In addition, he found the agitation was worse when the dose was increased and cleared up when Paxil was stopped, only to reemerge when it was started again. There had also been a suicide in the program, and in one healthy volunteer study, Paxil was linked to withdrawal effects in around 85% of subjects.
After hearing the testimony of Dr Healy, the Wyoming jury awarded Mr Tobin more than $6 million in damages in the first jury verdict against a drug maker for the psychiatric side effects caused by an SSRI.
Going up against SSRI makers on behalf of SSRI victims has cost Dr Healy plenty. In 2000, he accepted a position at the University of Toronto, but in the wake of a lecture at the University in November 2000, in which he mentioned that there had been an almost complete lack of research on the risk of suicide associated with SSRIs, Dr Healy was informed that he had lost his job before it even began.
The next historical moment worth noting in the Paxil saga took place in June 2004, when New York's attorney general, Elliot Spitzer, filed charges of consumer fraud against Glaxo and alleged that the company had "repeatedly" concealed damaging information in Paxil studies conducted on children.
The complaint stated that, "starting in 1998, GSK engaged in a concerted effort to withhold negative information concerning Paxil and misrepresented data concerning Paxil's safety and efficacy when prescribed for depression in children and adolescents."
It also alleged an internal 1999, document showed that the company intended to "manage the dissemination of data in order to minimize any potential negative commercial impact.''
The lawsuit charged that Glaxo conducted at least 5 studies on Paxil with children, but only published one. A study referred to as Study 377, noted that some children exhibited suicidal behaviors and attempts to commit suicide. Referring to that study, and also Study 329, the complaint alleged, an internal Glaxo memo acknowledged that Paxil "failed to demonstrate a statistically significant difference from placebo on the primary efficacy measures."
Glaxo might want to add Mr Spitzer as a defendant in the worldwide class action for his "defamatory" remarks, made in print no less. According to a June 2, 2004, press release by Mr Spitzer, by concealing negative studies, Glaxo made out like a bandit in 2002, with more than 2 million pediatric prescriptions for Paxil written in the US. "Prescriptions for Paxil to treat mood disorders in children and adolescents," Mr Spitzer said, "translated into US sales for GSK of approximately $55 million in 2002 alone."
The lawsuit also alleged that Glaxo misrepresented the results of the company's own research to its sales representatives who promoted Paxil to physicians and portrayed the drug as having "remarkable efficacy and safety in the treatment of adolescent depression," when in fact, the studies did not demonstrate that Paxil was effective in treating children and showed the possibility of increased risk of suicidal thoughts and acts in adolescents.
The suit further alleged that Glaxo failed to disclose this information in "Medical Information Letters" that it sent to physicians, and thus deprived physicians of the information needed to evaluate the risks and benefits of prescribing Paxil for children and deprived children of the benefit of their doctor's professional judgment.
In August 2004, to settle the charges that were based on the same allegations made during the Panorama program that Glaxo now claims are "defamatory," Glaxo agreed to pay $2.5 million and to publicly disclose all clinical studies.
Glaxo's largest clinical trial on the use of Paxil with children was conducted in the US in the 1990s, and was called Study 329. Child psychiatrist, Dr Neal Ryan, of the University of Pittsburgh, was paid by Glaxo and was listed as co-author of the study.
In 2002, Dr Ryan also gave a talk on childhood depression at a medical conference sponsored by Glaxo and said that Paxil would be a suitable treatment for children. He later told Panorama reporter, Shelley Jofre, that Paxil had probably lowered rather than raised suicide rates.
But an internal company email penned by a public relations executive working for Glaxo describes Study 329 differently. "Originally we had planned to do extensive media relations surrounding this study," it said, "until we actually viewed the results."
"Essentially the study did not really show it was effective in treating adolescent depression," the email stated, "which is not something we want to publicise."
However, the manipulated results from Study 329 were in fact published in the Journal of American Child Adolescent Psychiatry in 2001, with the positive spin stating, "Paxil is generally well tolerated and effective for major depression in adolescents."
Another publication that Glaxo might want to add as a defendant in its class action against the world would be the Canadian Medical Association Journal. In March 2004, the Journal printed excerpts from an internal Glaxo memo to illustrate how the company had withheld studies from regulatory agencies that showed the ineffectiveness of Paxil with children which stated in part: "It would be unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine".
A television program in the US could be added to the list of "defamers" as well. Back in December 2004, ABC's "Primetime Live," also said it had obtained hidden Glaxo studies and reported that some children in the studies showed the same types of suicidal thoughts and behaviors that parents had for years claimed their children were exhibiting.
According to these documents, Primetime said, internal studies showed Paxil had little or no effect in treating depression in children and adolescents and as far back as 1997, the company was aware of suicide related behaviors in young patients taking the drug.
In spite of this information, Primetime reported, Glaxo distributed a memo to its sales force in 2001 touting the drug's "remarkable efficacy and safety in the treatment of adolescent depression."
And last but not least, another "defamer" would appear to be the US Congress. It too claimed that Glaxo hid negative studies in the name of profits. "This is about money," said Representative, Henry Waxman (D-CA), who was on a congressional committee investigating SSRI makers at the time.
"This is not about science," he stated, "because what they're doing is withholding the scientific information, suppressing the studies that could have a negative impact on their sales and their profits."
GlaxoSmithKline has labeled the allegations made in a Panorama television program that said the company had suppressed the results of clinical trials that showed Paxil was ineffective and caused children to become suicidal "defamatory."
According to the January 30, 2007, Guardian, an official at the company said Glaxo had looked into taking legal action, "but that there wouldn't be much to gain from taking action against the BBC".
The Guardian also reported that Glaxo "utterly rejects any suggestion that it has improperly withheld drug trial information."
This is not news. Glaxo has falsely denied these assertions probably 100 times in the past from one end of the globe to the other. If Glaxo files a lawsuit against the BBC, it might as well file a worldwide class action against all the other "defamers" who for some reason or another repeated the exact same allegations.
The BBC has broadcast several Panorama programs on Glaxo's marketing of Paxil for children even after the company's own research showed the drug to be ineffective and dangerous with children. The latest program titled, "Secrets of the Drug Trials," was broadcast on January 29, 2007.
Glaxo's worn-out declarations of innocence can only be adequately responded to by highlighting a few of the historical moments in Paxil's never-ending trail of misery.
A good place to start is Wyoming in the year 2000, with the trial involving the case of Donald Schell, who had been on Paxil just two days when he killed his wife, daughter and infant granddaughter before killing himself.
His surviving son-in-law, Tim Tobin, brought a wrongful death lawsuit against Glaxo.
Prior to the trial, an expert for the plaintiff, Dr David Healy, a well-recognized expert on selective seratonin reuptake inhibitor antidepressants (SSRIs), was given access to Glaxo's files on the Paxil studies.
He spent two days reviewing several hundred thousand documents looking for reports on the trials conducted on "healthy volunteers." Healthy volunteer refers to study participants who were not depressed or mentally ill to begin with before taking a drug. If it was shown that suicidality was evident in health volunteers it would disprove Glaxo's theory that suicide was caused by the underlying illness of depression.
Dr Healy was interested in these trials because he knew of recent studies that had surfaced on another SSRI, Pfizer's Zoloft, that showed the drugs could trigger suicidality in healthy volunteers. When he finally found the right files, Dr Healy told the BBC:
"It seemed clear that some people that went on the drugs had no major problems, but equally clear that others who went on the drug ended up more restless, in a state of mental turmoil, complaining about dreams, nightmares and a range of things like this. These don't seem to have been explored further in any great detail."
Dr Healy discovered that one in 4 healthy volunteers suffered this mental turmoil even when they were on normal doses of Paxil and had only been taking it for a few days.
In addition, he found the agitation was worse when the dose was increased and cleared up when Paxil was stopped, only to reemerge when it was started again. There had also been a suicide in the program, and in one healthy volunteer study, Paxil was linked to withdrawal effects in around 85% of subjects.
After hearing the testimony of Dr Healy, the Wyoming jury awarded Mr Tobin more than $6 million in damages in the first jury verdict against a drug maker for the psychiatric side effects caused by an SSRI.
Going up against SSRI makers on behalf of SSRI victims has cost Dr Healy plenty. In 2000, he accepted a position at the University of Toronto, but in the wake of a lecture at the University in November 2000, in which he mentioned that there had been an almost complete lack of research on the risk of suicide associated with SSRIs, Dr Healy was informed that he had lost his job before it even began.
The next historical moment worth noting in the Paxil saga took place in June 2004, when New York's attorney general, Elliot Spitzer, filed charges of consumer fraud against Glaxo and alleged that the company had "repeatedly" concealed damaging information in Paxil studies conducted on children.
The complaint stated that, "starting in 1998, GSK engaged in a concerted effort to withhold negative information concerning Paxil and misrepresented data concerning Paxil's safety and efficacy when prescribed for depression in children and adolescents."
It also alleged an internal 1999, document showed that the company intended to "manage the dissemination of data in order to minimize any potential negative commercial impact.''
The lawsuit charged that Glaxo conducted at least 5 studies on Paxil with children, but only published one. A study referred to as Study 377, noted that some children exhibited suicidal behaviors and attempts to commit suicide. Referring to that study, and also Study 329, the complaint alleged, an internal Glaxo memo acknowledged that Paxil "failed to demonstrate a statistically significant difference from placebo on the primary efficacy measures."
Glaxo might want to add Mr Spitzer as a defendant in the worldwide class action for his "defamatory" remarks, made in print no less. According to a June 2, 2004, press release by Mr Spitzer, by concealing negative studies, Glaxo made out like a bandit in 2002, with more than 2 million pediatric prescriptions for Paxil written in the US. "Prescriptions for Paxil to treat mood disorders in children and adolescents," Mr Spitzer said, "translated into US sales for GSK of approximately $55 million in 2002 alone."
The lawsuit also alleged that Glaxo misrepresented the results of the company's own research to its sales representatives who promoted Paxil to physicians and portrayed the drug as having "remarkable efficacy and safety in the treatment of adolescent depression," when in fact, the studies did not demonstrate that Paxil was effective in treating children and showed the possibility of increased risk of suicidal thoughts and acts in adolescents.
The suit further alleged that Glaxo failed to disclose this information in "Medical Information Letters" that it sent to physicians, and thus deprived physicians of the information needed to evaluate the risks and benefits of prescribing Paxil for children and deprived children of the benefit of their doctor's professional judgment.
In August 2004, to settle the charges that were based on the same allegations made during the Panorama program that Glaxo now claims are "defamatory," Glaxo agreed to pay $2.5 million and to publicly disclose all clinical studies.
Glaxo's largest clinical trial on the use of Paxil with children was conducted in the US in the 1990s, and was called Study 329. Child psychiatrist, Dr Neal Ryan, of the University of Pittsburgh, was paid by Glaxo and was listed as co-author of the study.
In 2002, Dr Ryan also gave a talk on childhood depression at a medical conference sponsored by Glaxo and said that Paxil would be a suitable treatment for children. He later told Panorama reporter, Shelley Jofre, that Paxil had probably lowered rather than raised suicide rates.
But an internal company email penned by a public relations executive working for Glaxo describes Study 329 differently. "Originally we had planned to do extensive media relations surrounding this study," it said, "until we actually viewed the results."
"Essentially the study did not really show it was effective in treating adolescent depression," the email stated, "which is not something we want to publicise."
However, the manipulated results from Study 329 were in fact published in the Journal of American Child Adolescent Psychiatry in 2001, with the positive spin stating, "Paxil is generally well tolerated and effective for major depression in adolescents."
Another publication that Glaxo might want to add as a defendant in its class action against the world would be the Canadian Medical Association Journal. In March 2004, the Journal printed excerpts from an internal Glaxo memo to illustrate how the company had withheld studies from regulatory agencies that showed the ineffectiveness of Paxil with children which stated in part: "It would be unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine".
A television program in the US could be added to the list of "defamers" as well. Back in December 2004, ABC's "Primetime Live," also said it had obtained hidden Glaxo studies and reported that some children in the studies showed the same types of suicidal thoughts and behaviors that parents had for years claimed their children were exhibiting.
According to these documents, Primetime said, internal studies showed Paxil had little or no effect in treating depression in children and adolescents and as far back as 1997, the company was aware of suicide related behaviors in young patients taking the drug.
In spite of this information, Primetime reported, Glaxo distributed a memo to its sales force in 2001 touting the drug's "remarkable efficacy and safety in the treatment of adolescent depression."
And last but not least, another "defamer" would appear to be the US Congress. It too claimed that Glaxo hid negative studies in the name of profits. "This is about money," said Representative, Henry Waxman (D-CA), who was on a congressional committee investigating SSRI makers at the time.
"This is not about science," he stated, "because what they're doing is withholding the scientific information, suppressing the studies that could have a negative impact on their sales and their profits."
Drug Eluting Stent Patients Beware
Evelyn Pringle January 24, 2007
Drug eluting stents were promoted as working so much better than the old bare metal stents that 6 million people worldwide have received them in the few years since the arrived on the market.
"It was a modern record for any medical device," the Boston Globe reported on December 4, 2006. Some 2 to 3 million people in the US now carry one of these devices in an artery, according to FDA estimates, with new implants topping 900,000 per year.
Only two brands of DES are sold in the US, the Taxus, by Boston Scientific, and the Cypher, by Johnson & Johnson's Cordis Division.
The trials submitted by the DES makers to obtain FDA approval for use in limited procedures with non-complex patients with single-vessel heart disease, involved a low risk population. However, off-label DES use for procedures not approved by the FDA has become rampant and according to the agency:
"It is estimated that a majority of DES are implanted in lesions outside of their current indications for use, such as in-stent restenosis lesions, bifurcation lesions, coronary artery bypass grafts, acute myocardial infarction, chronic total occlusions, overlapping and multiple stents per vessel and in patients with multivessel disease and chronic renal insufficiency."
Surgeons have been implanting the new devices in every kind of heart patient. And for good reason. The stenting business represents maga bucks to device makers, hospitals and surgeons alike. In the US, the implant procedure itself costs $38,203, according to a report by the Associated Press on December 26, 2006.
But as has been the case with so many pharmaceutical products in recent years, after being massively promoted, and implanted in millions of patients for indications not approved, DES are proving to be no better than the bare metal stents, and in fact research has shown them to worse because they come with more adverse reactions.
In early December 2006, the FDA's Circulatory System Devices Advisory Committee held a public meeting to review data on thrombosis both when DES were used according to their label and when they are implanted off-label for unapproved uses, and to address the appropriate duration for the use of the blood-thinning drug, Plavix, with DES patients.
In the briefing provided to the Committee before the hearing, the FDA informed the panel that recent presentations at scientific meetings had indicated a small but significant increase in the rates of death or myocardial infarction, and non-cardiac mortality, in DES patients when compared to patients who received bare metal stents.
The briefing included a specific discussion of presentations made at the Transcatheter Cardiovascular Therapeutics meeting, in October 2006, where doctors, Martin Leon and Gregg Stone, presented a meta-analyses of patient data from the Cypher and Taxus clinical trails.
Based on these analyses, Dr Stuart Pocock reported that after one year, five Cypher patients, compared to no bare metal patients, had experienced late thrombosis, and with the Taxus, thrombosis occurred in nine patients after one year compared with two bare metal stent patients.
Last year, the Swiss government commissioned a study to determine whether the DES were worth their price of between $2,200 and $2,700, when compared to the $600 to $800 for bare metal stents, and also to test how long Plavix should be prescribed to patients after the implantation of a DES to prevent blood clots from developing.
The study appeared in the December 19, 2006, Journal of the American College of Cardiology, and reported that patients with DES had double the risk of cardiac problems after stopping Plavix compared to patients with bare metal stents.
The Swiss researchers, led by Dr Matthias Pfisterer, found that when patients stop taking Plavix, they had a small but serious risk of blood clots leading to death or heart attack.
The lead author noted that the majority of DES implants in the study were off-label. "About two-thirds of our patients were really treated with off-label use of drug-eluting stents," Dr Pfisterer told WebMD on December 5, 2006.
"The FDA label says these are only for stable patients with limited disease," he notes. "But, in fact," he told WebMD, "most doctors who use drug-eluting stents use them in unstable patients and in more complex disease."
In an editorial accompanying the Pfisterer study, Dr Robert Califf and Dr Robert Harrington, warned that research on DES has not kept up with clinical realities. "As is frequently seen with new cardiac devices," they wrote, "rapid increase in clinical adoption quickly outstripped what is known about the device from limited clinical trials."
Medical professionals say an important point to keep in mind when considering the risks associated with the DES is that these devices have only been on the market in the US for less than four years and that many more unknown risks could surface in years to come.
More problems may have already surfaced according to Dr Joseph Muhlestein, a professor at the University of Utah. He told ABC New's Healthday reporter on December 4, 2006, that his research group has followed patients receiving DES implants very carefully and has found "something we don't understand."
As expected, he said, the DES did reduce artery closure at the site where they were implanted, but the incidence of artery problems at other sites occurred "significantly more often than when we used bare-metal stents," he told Healthday.
So, the overall incidence of artery problems ended up being the same, regardless of which type of stent was implanted, Dr Muhlestein said.
It is possible that the problem occurred because DES were used on more high-risk patients, he noted. But it's also possible, he said, that the DES interfered with the endothelium, the delicate tissue that lines the arteries.
These doubts have caused some doctors to cut back on DES use. "We used to use them in 90 percent of cases," Dr Muhlestein told Healthday. "Now, it's about 40 percent."
Finally, experts are warning that if unexpected health problems do develop in patients already implanted with the DES, removal of the stent is not possible because once it is placed in the body, the tissue in the artery grows over the stent.
Drug eluting stents were promoted as working so much better than the old bare metal stents that 6 million people worldwide have received them in the few years since the arrived on the market.
"It was a modern record for any medical device," the Boston Globe reported on December 4, 2006. Some 2 to 3 million people in the US now carry one of these devices in an artery, according to FDA estimates, with new implants topping 900,000 per year.
Only two brands of DES are sold in the US, the Taxus, by Boston Scientific, and the Cypher, by Johnson & Johnson's Cordis Division.
The trials submitted by the DES makers to obtain FDA approval for use in limited procedures with non-complex patients with single-vessel heart disease, involved a low risk population. However, off-label DES use for procedures not approved by the FDA has become rampant and according to the agency:
"It is estimated that a majority of DES are implanted in lesions outside of their current indications for use, such as in-stent restenosis lesions, bifurcation lesions, coronary artery bypass grafts, acute myocardial infarction, chronic total occlusions, overlapping and multiple stents per vessel and in patients with multivessel disease and chronic renal insufficiency."
Surgeons have been implanting the new devices in every kind of heart patient. And for good reason. The stenting business represents maga bucks to device makers, hospitals and surgeons alike. In the US, the implant procedure itself costs $38,203, according to a report by the Associated Press on December 26, 2006.
But as has been the case with so many pharmaceutical products in recent years, after being massively promoted, and implanted in millions of patients for indications not approved, DES are proving to be no better than the bare metal stents, and in fact research has shown them to worse because they come with more adverse reactions.
In early December 2006, the FDA's Circulatory System Devices Advisory Committee held a public meeting to review data on thrombosis both when DES were used according to their label and when they are implanted off-label for unapproved uses, and to address the appropriate duration for the use of the blood-thinning drug, Plavix, with DES patients.
In the briefing provided to the Committee before the hearing, the FDA informed the panel that recent presentations at scientific meetings had indicated a small but significant increase in the rates of death or myocardial infarction, and non-cardiac mortality, in DES patients when compared to patients who received bare metal stents.
The briefing included a specific discussion of presentations made at the Transcatheter Cardiovascular Therapeutics meeting, in October 2006, where doctors, Martin Leon and Gregg Stone, presented a meta-analyses of patient data from the Cypher and Taxus clinical trails.
Based on these analyses, Dr Stuart Pocock reported that after one year, five Cypher patients, compared to no bare metal patients, had experienced late thrombosis, and with the Taxus, thrombosis occurred in nine patients after one year compared with two bare metal stent patients.
Last year, the Swiss government commissioned a study to determine whether the DES were worth their price of between $2,200 and $2,700, when compared to the $600 to $800 for bare metal stents, and also to test how long Plavix should be prescribed to patients after the implantation of a DES to prevent blood clots from developing.
The study appeared in the December 19, 2006, Journal of the American College of Cardiology, and reported that patients with DES had double the risk of cardiac problems after stopping Plavix compared to patients with bare metal stents.
The Swiss researchers, led by Dr Matthias Pfisterer, found that when patients stop taking Plavix, they had a small but serious risk of blood clots leading to death or heart attack.
The lead author noted that the majority of DES implants in the study were off-label. "About two-thirds of our patients were really treated with off-label use of drug-eluting stents," Dr Pfisterer told WebMD on December 5, 2006.
"The FDA label says these are only for stable patients with limited disease," he notes. "But, in fact," he told WebMD, "most doctors who use drug-eluting stents use them in unstable patients and in more complex disease."
In an editorial accompanying the Pfisterer study, Dr Robert Califf and Dr Robert Harrington, warned that research on DES has not kept up with clinical realities. "As is frequently seen with new cardiac devices," they wrote, "rapid increase in clinical adoption quickly outstripped what is known about the device from limited clinical trials."
Medical professionals say an important point to keep in mind when considering the risks associated with the DES is that these devices have only been on the market in the US for less than four years and that many more unknown risks could surface in years to come.
More problems may have already surfaced according to Dr Joseph Muhlestein, a professor at the University of Utah. He told ABC New's Healthday reporter on December 4, 2006, that his research group has followed patients receiving DES implants very carefully and has found "something we don't understand."
As expected, he said, the DES did reduce artery closure at the site where they were implanted, but the incidence of artery problems at other sites occurred "significantly more often than when we used bare-metal stents," he told Healthday.
So, the overall incidence of artery problems ended up being the same, regardless of which type of stent was implanted, Dr Muhlestein said.
It is possible that the problem occurred because DES were used on more high-risk patients, he noted. But it's also possible, he said, that the DES interfered with the endothelium, the delicate tissue that lines the arteries.
These doubts have caused some doctors to cut back on DES use. "We used to use them in 90 percent of cases," Dr Muhlestein told Healthday. "Now, it's about 40 percent."
Finally, experts are warning that if unexpected health problems do develop in patients already implanted with the DES, removal of the stent is not possible because once it is placed in the body, the tissue in the artery grows over the stent.
Business Booming for SSRI Makers
Evelyn Pringle January 8, 2007
The market for antidepressants is the largest segment of the Central Nervous System drug sector with global sales of $16.2 billion in 2005. Depression costs the US economy an estimated $44 billion a year and the World Health Organization predicts depression will be the leading cause of disability by 2020, according to a report by Research and Markets.
Currently, depression seems to have reached epidemic proportions in the US only. In 2005, the US market for antidepressants accounted for 66% of the global market, compared to 23% in Europe, and 11% for the rest of world, largely Japan, according to R&M's December 18, 2006, press release.
Since the new class of selective serotonin reuptake inhibitor antidepressants, or SSRIs, arrived in the late-1980s, the market has exploded. In 1985, sales of antidepressants in the US totaled roughly $240 million, but from September 1, 2003 to August 30, 2004, sales rose to $11.2 billion, according to IMS, a health care tracking firm.
The most commonly prescribed SSRIs in the US include Prozac, by Eli Lilly, Paxil by GlaxoSmithKline, Zoloft by Pfizer, and Celexa and Lexapro by Forest Laboratories.
Award winning journalist and author, Robert Whitaker, reports that no coincidently, during the same time-frame, the "number of Americans disabled by mental illness has nearly doubled since 1987, when Prozac-the first in a second generation of wonder drugs for mental illness-was introduced."
There are now nearly 6 million Americans disabled by mental illness, and this number increases by more than 400 people each day, according to Mr Whitaker's report in the Spring 2005, issue of Ethical Human Psychology and Psychiatry, Volume 7, Number I.
In 1955, the number of people disabled by mental illness in the US was 3.38 per 1,000, but during the past 50 years, when psychiatric drugs have become the cornerstone of care, Mr Whitaker reports, "the disability rate has climbed steadily, and has now reached around 20 people per 1,000."
"A review of the scientific literature," he notes, "reveals that it is our drug-based paradigm of care that is fueling this epidemic."
"The drugs," he states, "induce new and more severe psychiatric symptoms in a significant percentage of patients."
"In Prozac's first 2 years on the market," Mr Whitaker says, "the FDA's Medwatch program received more adverse-event reports about this new "wonder drug" than it had received for the leading tricyclic in the previous 20 years."
In terms of adding to the number of people disabled by mentally ill, Mr Whitaker says, "the propensity of Prozac and other SSRIs to trigger mania or psychosis is undoubtedly the biggest problem with these drugs."
According to Harvard trained psychiatrist, Dr Stefan Kruszewski, "due to predictable neurochemical changes in the human central nervous system, SSRIs can also increase the risk of violence and aggressive acting out."
And experts say, when that happens, instead of recognizing the side effects of SSRIs, doctors change the diagnosis to schizophrenia or bipolor disorder and prescribe more drugs which pretty much guarantees that disability due to mental illness is right around the corner.
It is at this junction that the tax payers become completely responsible for the injuries caused by the drug makers, and must pay not only for the patient's medical care and drugs, but for the person's very existence.
Dr Kruszewski says that because SSRI makers have concealed the research that identified the adverse effects, doctors who prescribe SSRIs have not been adequately warned about the risks. "Neither patients nor physicians," he explains, "can accurately assess the risks and benefits of any medicine unless the manufacturers and the FDA work together to ensure that all information is transparent and readily available."
Regulatory agencies have focused most of their attention on the link between suicidality and SSRIs. In October 2004, the FDA directed SSRI makers to change their labeling to include a black box warning about an increased risk of suicide and suicidal thoughts in children and adolescents. The FDA strengthened the warnings after assessments showed that at least 13 of the 15 studies on SSRI use with children failed to show efficacy and there appeared to be an activation syndrome associated with the drugs.
In July 2005, the FDA issued a public health advisory saying the possibility of a risk of suicidality should also be applied to adults taking SSRIs. And last month, the FDA's Psychopharmacologic Drugs Advisory Committee held a public hearing to review the suicidality data on adults and SSRIs, and recommended a widening of the black box warning to include adults.
The data presented to the Committee by the FDA showed that SSRIs double the risk of suicidal behavior in young adults, from around three cases per thousand to 7, and for the first time, the FDA publicly acknowledged that SSRIs are linked to suicidality among persons over the age of 18.
Many of the world's leading experts on SSRIs traveled to Washington to testify at the hearing, as did many family members who lost love ones to suicide. In many cases family members testified that the deceased patients were not depressed to begin with and that the SSRIs were prescribed for conditions other than depression.
The day before the hearing, the Alliance for Human Research Protection, together with WoodyMatters.com, arranged two press conferences, one at the National Press Club and the other at the Silver Springs Hilton in Maryland, to provide a forum for the experts to brief the public and media on the issues.
At the press conferences, presentations were made by Kim Witczak and Eric Swann, Vera Hassner Sharav, Dr Joseph Glenmullen, Dr David Healy, Dr John Abramson, Dr David Cohen, and Attorney, Karen Barth Menzies.
Kim Witczac and Eric Swann described their personal experience of living through the tragic suicide of Kim's husband, Woody, a happy, healthy 37-year-old man who committed suicide after being prescribed Zoloft off-label for insomnia.
Vera Sharav, president of the Alliance for Human Research Protection, discussed how SSRIs have been marketed as "magic bullets," but compared them to "snake oil." She went over a long list of conditions for which the drugs are approved, followed by an even longer list of conditions for which doctors are prescribing SSRIs off-label.
Ms Sharav also pointed out the disparity between reports by the FDA and UK regulators when analyzing the same data. She noted that the UK found 16 suicides and 177 attempts in 40,000 patients, compared to the FDA's report of 8 suicides and 133 attempts in 100,000 patients.
UK psychiatrist, Dr David Healy, a professor at North Wales Department of Psychological Medicine, at Cardiff University, and author of, The Antidepressant Era, and The Creation of Psychopharmacology, also discussed how data obtained from British regulators contradicts the data released by the FDA. He questioned the overall validity of the information used by the FDA to draw conclusions about SSRI induced suicidality.
Dr Healy explained how the effectiveness of SSRIs has been misconstrued, when in fact, the data reveals that only one in 10 patients on the drugs can be shown to respond specifically to the SSRI rather than a nonspecific factor or a placebo.
He discussed the manipulation of trial data and showed how suicide related events in previous trials were arbitrarily switched from drug treated groups to placebo treated groups and gave several examples of ghostwritten reports professing to validate safety and efficacy of SSRIs in clinical trials.
In his presentation, Dr David Cohen, co-author with Dr Peter Breggin of, "Your Drug May Be Your Problem," explained why clinical trials used by the FDA to determine whether there is a link between SSRIs and suicidality are completely unsuited for that purpose.
He pointed out that these trials were conducted by drug companies as a means of testing a drug's superiority over a placebo or its equivalency to an existing drug, and not to determine how a drug might be psychologically influencing patients who take the drug for a long period of time.
Dr John Abramson, a clinical faculty member at Harvard Medical School, and author of, Overdosed America, gave an overview of the overwhelming industry influence inside what experts say should be the most scientific and evidence-based forums of general and primary care physicians.
He presented slides illustrating the presence of the industry in every location at an annual convention for a professional organization, including drug ads at each registration desk, ads on the cards given to doctors to record attendance of specific courses for continuing education credits, and how ads were even placed in the bathrooms.
Dr Joe Glenmullen, an instructor at Harvard Medical School, and the author of, Prozac Backlash, and The Antidepressant Solution, gave a brief review of the literature related to antidepressant induced suicidality.
He explained that the difference between SSRI suicidality and ordinary suicidality can be easily distinguished due to an activation syndrome that usually accompanies SSRI suicidality which includes akathisia and mania.
According to Dr Glenmullen, the FDA has systematically swept the suicide issue under the carpet even though the agency has possessed ample research linking SSRIs to suicidality for many years.
Attorney, Karen Barth Menzies, a partner at the Baum Hedlund law firm, who has battled the SSRI makers in the legal arena for a decade, summarized the numerous instances where data on suicidality was suppressed by the drug companies for years and finally made public only after it surfaced in litigation.
Its not as if more studies are necessary to link SSRIs to suicide, but a recent study in the December 2006, issue of Archives of General Psychiatry, analyzed the data on 15,390 people, from age 10 to 100-years-old, who had been hospitalized after attempting suicide, and determined that 602 of these people went on to commit suicide, and 7,136 attempted suicide again, over the following 3 years.
In making their comparisons, the researchers found that although people who took antidepressants were slightly, or 9%, less likely to successfully commit suicide than people who took no drugs, antidepressant users were 36% more likely to attempt suicide than people who were not taking the drugs, and the risk was slightly higher for persons between 10 and 19-years-old.
The market for antidepressants is the largest segment of the Central Nervous System drug sector with global sales of $16.2 billion in 2005. Depression costs the US economy an estimated $44 billion a year and the World Health Organization predicts depression will be the leading cause of disability by 2020, according to a report by Research and Markets.
Currently, depression seems to have reached epidemic proportions in the US only. In 2005, the US market for antidepressants accounted for 66% of the global market, compared to 23% in Europe, and 11% for the rest of world, largely Japan, according to R&M's December 18, 2006, press release.
Since the new class of selective serotonin reuptake inhibitor antidepressants, or SSRIs, arrived in the late-1980s, the market has exploded. In 1985, sales of antidepressants in the US totaled roughly $240 million, but from September 1, 2003 to August 30, 2004, sales rose to $11.2 billion, according to IMS, a health care tracking firm.
The most commonly prescribed SSRIs in the US include Prozac, by Eli Lilly, Paxil by GlaxoSmithKline, Zoloft by Pfizer, and Celexa and Lexapro by Forest Laboratories.
Award winning journalist and author, Robert Whitaker, reports that no coincidently, during the same time-frame, the "number of Americans disabled by mental illness has nearly doubled since 1987, when Prozac-the first in a second generation of wonder drugs for mental illness-was introduced."
There are now nearly 6 million Americans disabled by mental illness, and this number increases by more than 400 people each day, according to Mr Whitaker's report in the Spring 2005, issue of Ethical Human Psychology and Psychiatry, Volume 7, Number I.
In 1955, the number of people disabled by mental illness in the US was 3.38 per 1,000, but during the past 50 years, when psychiatric drugs have become the cornerstone of care, Mr Whitaker reports, "the disability rate has climbed steadily, and has now reached around 20 people per 1,000."
"A review of the scientific literature," he notes, "reveals that it is our drug-based paradigm of care that is fueling this epidemic."
"The drugs," he states, "induce new and more severe psychiatric symptoms in a significant percentage of patients."
"In Prozac's first 2 years on the market," Mr Whitaker says, "the FDA's Medwatch program received more adverse-event reports about this new "wonder drug" than it had received for the leading tricyclic in the previous 20 years."
In terms of adding to the number of people disabled by mentally ill, Mr Whitaker says, "the propensity of Prozac and other SSRIs to trigger mania or psychosis is undoubtedly the biggest problem with these drugs."
According to Harvard trained psychiatrist, Dr Stefan Kruszewski, "due to predictable neurochemical changes in the human central nervous system, SSRIs can also increase the risk of violence and aggressive acting out."
And experts say, when that happens, instead of recognizing the side effects of SSRIs, doctors change the diagnosis to schizophrenia or bipolor disorder and prescribe more drugs which pretty much guarantees that disability due to mental illness is right around the corner.
It is at this junction that the tax payers become completely responsible for the injuries caused by the drug makers, and must pay not only for the patient's medical care and drugs, but for the person's very existence.
Dr Kruszewski says that because SSRI makers have concealed the research that identified the adverse effects, doctors who prescribe SSRIs have not been adequately warned about the risks. "Neither patients nor physicians," he explains, "can accurately assess the risks and benefits of any medicine unless the manufacturers and the FDA work together to ensure that all information is transparent and readily available."
Regulatory agencies have focused most of their attention on the link between suicidality and SSRIs. In October 2004, the FDA directed SSRI makers to change their labeling to include a black box warning about an increased risk of suicide and suicidal thoughts in children and adolescents. The FDA strengthened the warnings after assessments showed that at least 13 of the 15 studies on SSRI use with children failed to show efficacy and there appeared to be an activation syndrome associated with the drugs.
In July 2005, the FDA issued a public health advisory saying the possibility of a risk of suicidality should also be applied to adults taking SSRIs. And last month, the FDA's Psychopharmacologic Drugs Advisory Committee held a public hearing to review the suicidality data on adults and SSRIs, and recommended a widening of the black box warning to include adults.
The data presented to the Committee by the FDA showed that SSRIs double the risk of suicidal behavior in young adults, from around three cases per thousand to 7, and for the first time, the FDA publicly acknowledged that SSRIs are linked to suicidality among persons over the age of 18.
Many of the world's leading experts on SSRIs traveled to Washington to testify at the hearing, as did many family members who lost love ones to suicide. In many cases family members testified that the deceased patients were not depressed to begin with and that the SSRIs were prescribed for conditions other than depression.
The day before the hearing, the Alliance for Human Research Protection, together with WoodyMatters.com, arranged two press conferences, one at the National Press Club and the other at the Silver Springs Hilton in Maryland, to provide a forum for the experts to brief the public and media on the issues.
At the press conferences, presentations were made by Kim Witczak and Eric Swann, Vera Hassner Sharav, Dr Joseph Glenmullen, Dr David Healy, Dr John Abramson, Dr David Cohen, and Attorney, Karen Barth Menzies.
Kim Witczac and Eric Swann described their personal experience of living through the tragic suicide of Kim's husband, Woody, a happy, healthy 37-year-old man who committed suicide after being prescribed Zoloft off-label for insomnia.
Vera Sharav, president of the Alliance for Human Research Protection, discussed how SSRIs have been marketed as "magic bullets," but compared them to "snake oil." She went over a long list of conditions for which the drugs are approved, followed by an even longer list of conditions for which doctors are prescribing SSRIs off-label.
Ms Sharav also pointed out the disparity between reports by the FDA and UK regulators when analyzing the same data. She noted that the UK found 16 suicides and 177 attempts in 40,000 patients, compared to the FDA's report of 8 suicides and 133 attempts in 100,000 patients.
UK psychiatrist, Dr David Healy, a professor at North Wales Department of Psychological Medicine, at Cardiff University, and author of, The Antidepressant Era, and The Creation of Psychopharmacology, also discussed how data obtained from British regulators contradicts the data released by the FDA. He questioned the overall validity of the information used by the FDA to draw conclusions about SSRI induced suicidality.
Dr Healy explained how the effectiveness of SSRIs has been misconstrued, when in fact, the data reveals that only one in 10 patients on the drugs can be shown to respond specifically to the SSRI rather than a nonspecific factor or a placebo.
He discussed the manipulation of trial data and showed how suicide related events in previous trials were arbitrarily switched from drug treated groups to placebo treated groups and gave several examples of ghostwritten reports professing to validate safety and efficacy of SSRIs in clinical trials.
In his presentation, Dr David Cohen, co-author with Dr Peter Breggin of, "Your Drug May Be Your Problem," explained why clinical trials used by the FDA to determine whether there is a link between SSRIs and suicidality are completely unsuited for that purpose.
He pointed out that these trials were conducted by drug companies as a means of testing a drug's superiority over a placebo or its equivalency to an existing drug, and not to determine how a drug might be psychologically influencing patients who take the drug for a long period of time.
Dr John Abramson, a clinical faculty member at Harvard Medical School, and author of, Overdosed America, gave an overview of the overwhelming industry influence inside what experts say should be the most scientific and evidence-based forums of general and primary care physicians.
He presented slides illustrating the presence of the industry in every location at an annual convention for a professional organization, including drug ads at each registration desk, ads on the cards given to doctors to record attendance of specific courses for continuing education credits, and how ads were even placed in the bathrooms.
Dr Joe Glenmullen, an instructor at Harvard Medical School, and the author of, Prozac Backlash, and The Antidepressant Solution, gave a brief review of the literature related to antidepressant induced suicidality.
He explained that the difference between SSRI suicidality and ordinary suicidality can be easily distinguished due to an activation syndrome that usually accompanies SSRI suicidality which includes akathisia and mania.
According to Dr Glenmullen, the FDA has systematically swept the suicide issue under the carpet even though the agency has possessed ample research linking SSRIs to suicidality for many years.
Attorney, Karen Barth Menzies, a partner at the Baum Hedlund law firm, who has battled the SSRI makers in the legal arena for a decade, summarized the numerous instances where data on suicidality was suppressed by the drug companies for years and finally made public only after it surfaced in litigation.
Its not as if more studies are necessary to link SSRIs to suicide, but a recent study in the December 2006, issue of Archives of General Psychiatry, analyzed the data on 15,390 people, from age 10 to 100-years-old, who had been hospitalized after attempting suicide, and determined that 602 of these people went on to commit suicide, and 7,136 attempted suicide again, over the following 3 years.
In making their comparisons, the researchers found that although people who took antidepressants were slightly, or 9%, less likely to successfully commit suicide than people who took no drugs, antidepressant users were 36% more likely to attempt suicide than people who were not taking the drugs, and the risk was slightly higher for persons between 10 and 19-years-old.
FDA Advisory Committee Schedules Hearing on SSRIs and Suicide
Evelyn Pringle December 5, 2006
The FDA's Psychopharmacologic Drugs Advisory Committee will hold a public hearing on December 13, 2006, to review the adult selective serotonin reuptake inhibitor (SSRI) studies on the increased risk of suicide associated with the antidepressants.
The panel is expected to vote on whether the risk of suicidality in adults should be included in a Black Box warning on all SSRI labels, including Paxil, Prozac, Zoloft, Lexapro, and Celexa.
The fact is, the FDA has known about the increased suicide risk associated with SSRIs for over 15 years as evidenced at a September 20, 1991, hearing, at which FDA official Dr Robert Temple stated:
"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."
Yet here it is nearing the end of 2006, and the FDA is still refusing to provide a logical answer to explain why people who were not depressed before taking SSRIs would all of a sudden commit suicide after taking the drugs.
Top experts from all over the US and abroad will be testifying at the hearing and for many it will be a repeat performance. For instance, Baum Hedlund attorney, Karen Barth-Menzies, will be testifying again. She has been battling SSRI makers for over a decade and as a result, she has obtained internal company documents that show the SSRI makers were fully aware of the increased suicide risks associated with SSRIs but instead of warning the public, they continued to promote SSRIs as safe and effective with children and adults.
"Through our Paxil litigation," Ms Menzies says, "we obtained documents that show a seriously troubling mentality of profit over safety and a callous disregard for the welfare of children."
"That's about as reprehensible as you can get," Ms Menzies says.
"The manufacturers of the SSRIs," she states, "have continuously and adamantly denied even the possibility of a causal connection between the SSRIs and suicide, and, instead, have blamed the victim and the 'disease.'"
"This is notwithstanding clear evidence," Ms Menzies says, "very early on in the clinical trials of these drugs that they can cause these problems."
"We have documents," she notes, "obtained through discovery in our litigation showing that there was an awareness of the problem as far back as the late 1970s, long before the first SSRI, Prozac, was approved for marketing in this country."
Over the past 10 years, in addition to representing thousands of clients in SSRI lawsuits, Ms Menzies has been a tireless advocate working to increase public awareness about the host of health risks now known to be associated with SSRIs.
After listening to her testimony before the FDA Advisory Committee in 2004, a California state Senator invited Ms Menzies to work on legislation designed to inform California healthcare providers and parents about the increased risk of suicidality in children and adolescents taking SSRIs.
She also testified at a hearing in August 2004, before the California State Senate and called for better patient informed consent on the risks associated with SSRIs.
Ms Menzies has given presentations at medical conferences in the US and other countries to warn healthcare professionals about the dangers of SSRIs.
In fact, she gave one presentation that directly addressed the FDA's mishandling of the SSRI matter titled, "Federal Preemption - How the U.S. Food & Drug Administration Has Become an Advocate for the Drug Industry Against the Consumers It Has a Duty to Protect" - SSRIs and Collisions Between Medical, Legal and Regulatory Worlds, at the 29th International Congress On Law and Mental Health, in Paris, France, on July 2-8, 2005.
Another one of the world's most highly respected experts on SSRIs, Dr David Healy, a professor at the Department of Psychological Medicine, at Cardiff University in North Wales, will be traveling from the UK to testify. His appearance will also be a repeat performance.
Dr Healy states that he will testify about the manipulation of the scientific data on SSRIs. "We have here," he says, "the greatest divide in medicine between the raw data on an issue on the one side and the published accounts purporting to represent those data on the other."
"The divide," he says, "it is important to note, only came to light as a result of the efforts of journalists and lawyers."
"No clinician or scientist had a hand in questioning the validity of the 'science'," he points out.
The most famous fraudulent study involving SSRIs is GlaxoSmithKline's study 329, involving Paxil. The study stated that Paxil was safe, well-tolerated and effective in children, but noted that some children became emotionally "labile" while taking the drug.
"In the published version of 329," Dr Healy points out, "suicidality vanishes under a carpet of emotional lability."
Few readers of this paper, academic or lay, he says, would have realized what lay behind this term as it appeared in the paper. "The question of what was happening to children," Dr Healy says, "deemed to have become emotionally labile, was picked up by journalists and lawyers rather than scientists or regulators."
As a result of Glaxo's application for a license for the use of Paxil to treat children with nervous disorders, he explains, the raw data from clinical trials were lodged with a number of national regulators.
"Within a fortnight of seeing the raw data in May 2003," Dr Healy says, "after the events lying behind the term emotional lability had been clarified, the regulators in the UK issued a warning against the use of Paxil for minors."
A few weeks later, he notes, Glaxo wrote to all doctors warning that Paxil was linked to suicidality and that withdrawal from the drug was also linked to an apparent doubling of the rate of suicidality.
"This reassessment of the data does not however represent a triumph of scientific method," Dr Healy says, "it indicates rather a crisis triggered by media concerns."
The final nail in the coffin as far as selling SSRIs to kids in the UK, came in December 2003, when British regulators issued a position statement that said none of the SSRIs had demonstrated efficacy in treating depression in children.
By far the most damning revelations about what SSRI makers knew about the link between SSRIs and suicide came when the British Medical Journal received internal company documents from an anonymous source that left no doubt that Eli Lilly knew about the suicide risks with Prozac years before the drug was FDA approved.
After receiving the documents, the BMJ sent them to officials at the FDA, and to US Congressman, Maurice Hinchey, who in turn sent them to psychiatrist, Dr Peter Breggin, a court-certified expert on SSRIs, and author of, "Talking Back to Prozac," and "The Anti-Depressant Fact Book."
After examining the documents, Dr Breggin confirmed their authenticity as those that he had evaluated in the early 1990s when he served as an expert witness in Prozac litigation and discussed when testifying during a trial in 1994.
Evidence of the hidden studies showing the suicide risk can be found in a May 1984 document presented at trial which states regarding Prozac: "During the treatment with the preparation 16 suicide attempts were made, 2 of these with success."
"As patients with a risk of suicide were excluded from the studies," the document says, "it is probable that this high proportion can be attributed to an action of the preparation."
In fact, a March 29, 1985 document says that the rate of suicide with Prozac was 5.6 times higher than with the other medication imipramine and went on to state:
"The benefits vs. risks considerations for fluoxetine currently does not fall clearly in favor of the benefits. Therefore, it is of the greatest importance that it be determined whether there is a particular subgroup of patients who respond better to fluoxetine than to imipramine, so that the higher incidence of suicide attempts may be tolerable."
On November 13, 1990, a memo from a Lilly employee in Germany, Claude Bouchy, to another Lilly employee, Leigh Thompson, regarding the adverse drug event reporting of suicide and Prozac written in response to Lilly's request that he change the event "suicidal ideation" to "depression," Mr Bouchy writes:
"Hans (Lilly employee) has medical problems with these directions and I have great concerns about it.
"I do not think I could explain to the BGA, a judge, to a reporter or even to my family why we would do this especially on the sensitive issue of suicide and suicidal ideation."
A second memo dated November 14, 1990, from Mr Bouchy to Leigh Thompson about adverse drug event reporting states: "I personally wonder whether we are really helping the credibility of an excellent ADE system by calling overdose what a physician reports as suicide attempt and by calling depression what a physician is reporting as suicide ideation."
The documents also reveal how worried Lilly was about the commercial impact to the company if the truth about the Prozac-induced suicides got out. A February 7, 1990 Leigh Thompson Memo, says, "Anything that happens in the UK can threaten this drug in the US and worldwide. We are now expending enormous efforts fending off attacks because of (1) relationship to murder and (2) inducing suicidal ideation."
On February 7, 1990, a Leigh Thompson memo also says, "I hope Patrick (a Lilly employee) realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that."
Dr Breggin says that after he testified in the trial in 1994, these documents seemed to just disappear, until they were handed over to the BMJ.
The FDA's Psychopharmacologic Drugs Advisory Committee will hold a public hearing on December 13, 2006, to review the adult selective serotonin reuptake inhibitor (SSRI) studies on the increased risk of suicide associated with the antidepressants.
The panel is expected to vote on whether the risk of suicidality in adults should be included in a Black Box warning on all SSRI labels, including Paxil, Prozac, Zoloft, Lexapro, and Celexa.
The fact is, the FDA has known about the increased suicide risk associated with SSRIs for over 15 years as evidenced at a September 20, 1991, hearing, at which FDA official Dr Robert Temple stated:
"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."
Yet here it is nearing the end of 2006, and the FDA is still refusing to provide a logical answer to explain why people who were not depressed before taking SSRIs would all of a sudden commit suicide after taking the drugs.
Top experts from all over the US and abroad will be testifying at the hearing and for many it will be a repeat performance. For instance, Baum Hedlund attorney, Karen Barth-Menzies, will be testifying again. She has been battling SSRI makers for over a decade and as a result, she has obtained internal company documents that show the SSRI makers were fully aware of the increased suicide risks associated with SSRIs but instead of warning the public, they continued to promote SSRIs as safe and effective with children and adults.
"Through our Paxil litigation," Ms Menzies says, "we obtained documents that show a seriously troubling mentality of profit over safety and a callous disregard for the welfare of children."
"That's about as reprehensible as you can get," Ms Menzies says.
"The manufacturers of the SSRIs," she states, "have continuously and adamantly denied even the possibility of a causal connection between the SSRIs and suicide, and, instead, have blamed the victim and the 'disease.'"
"This is notwithstanding clear evidence," Ms Menzies says, "very early on in the clinical trials of these drugs that they can cause these problems."
"We have documents," she notes, "obtained through discovery in our litigation showing that there was an awareness of the problem as far back as the late 1970s, long before the first SSRI, Prozac, was approved for marketing in this country."
Over the past 10 years, in addition to representing thousands of clients in SSRI lawsuits, Ms Menzies has been a tireless advocate working to increase public awareness about the host of health risks now known to be associated with SSRIs.
After listening to her testimony before the FDA Advisory Committee in 2004, a California state Senator invited Ms Menzies to work on legislation designed to inform California healthcare providers and parents about the increased risk of suicidality in children and adolescents taking SSRIs.
She also testified at a hearing in August 2004, before the California State Senate and called for better patient informed consent on the risks associated with SSRIs.
Ms Menzies has given presentations at medical conferences in the US and other countries to warn healthcare professionals about the dangers of SSRIs.
In fact, she gave one presentation that directly addressed the FDA's mishandling of the SSRI matter titled, "Federal Preemption - How the U.S. Food & Drug Administration Has Become an Advocate for the Drug Industry Against the Consumers It Has a Duty to Protect" - SSRIs and Collisions Between Medical, Legal and Regulatory Worlds, at the 29th International Congress On Law and Mental Health, in Paris, France, on July 2-8, 2005.
Another one of the world's most highly respected experts on SSRIs, Dr David Healy, a professor at the Department of Psychological Medicine, at Cardiff University in North Wales, will be traveling from the UK to testify. His appearance will also be a repeat performance.
Dr Healy states that he will testify about the manipulation of the scientific data on SSRIs. "We have here," he says, "the greatest divide in medicine between the raw data on an issue on the one side and the published accounts purporting to represent those data on the other."
"The divide," he says, "it is important to note, only came to light as a result of the efforts of journalists and lawyers."
"No clinician or scientist had a hand in questioning the validity of the 'science'," he points out.
The most famous fraudulent study involving SSRIs is GlaxoSmithKline's study 329, involving Paxil. The study stated that Paxil was safe, well-tolerated and effective in children, but noted that some children became emotionally "labile" while taking the drug.
"In the published version of 329," Dr Healy points out, "suicidality vanishes under a carpet of emotional lability."
Few readers of this paper, academic or lay, he says, would have realized what lay behind this term as it appeared in the paper. "The question of what was happening to children," Dr Healy says, "deemed to have become emotionally labile, was picked up by journalists and lawyers rather than scientists or regulators."
As a result of Glaxo's application for a license for the use of Paxil to treat children with nervous disorders, he explains, the raw data from clinical trials were lodged with a number of national regulators.
"Within a fortnight of seeing the raw data in May 2003," Dr Healy says, "after the events lying behind the term emotional lability had been clarified, the regulators in the UK issued a warning against the use of Paxil for minors."
A few weeks later, he notes, Glaxo wrote to all doctors warning that Paxil was linked to suicidality and that withdrawal from the drug was also linked to an apparent doubling of the rate of suicidality.
"This reassessment of the data does not however represent a triumph of scientific method," Dr Healy says, "it indicates rather a crisis triggered by media concerns."
The final nail in the coffin as far as selling SSRIs to kids in the UK, came in December 2003, when British regulators issued a position statement that said none of the SSRIs had demonstrated efficacy in treating depression in children.
By far the most damning revelations about what SSRI makers knew about the link between SSRIs and suicide came when the British Medical Journal received internal company documents from an anonymous source that left no doubt that Eli Lilly knew about the suicide risks with Prozac years before the drug was FDA approved.
After receiving the documents, the BMJ sent them to officials at the FDA, and to US Congressman, Maurice Hinchey, who in turn sent them to psychiatrist, Dr Peter Breggin, a court-certified expert on SSRIs, and author of, "Talking Back to Prozac," and "The Anti-Depressant Fact Book."
After examining the documents, Dr Breggin confirmed their authenticity as those that he had evaluated in the early 1990s when he served as an expert witness in Prozac litigation and discussed when testifying during a trial in 1994.
Evidence of the hidden studies showing the suicide risk can be found in a May 1984 document presented at trial which states regarding Prozac: "During the treatment with the preparation 16 suicide attempts were made, 2 of these with success."
"As patients with a risk of suicide were excluded from the studies," the document says, "it is probable that this high proportion can be attributed to an action of the preparation."
In fact, a March 29, 1985 document says that the rate of suicide with Prozac was 5.6 times higher than with the other medication imipramine and went on to state:
"The benefits vs. risks considerations for fluoxetine currently does not fall clearly in favor of the benefits. Therefore, it is of the greatest importance that it be determined whether there is a particular subgroup of patients who respond better to fluoxetine than to imipramine, so that the higher incidence of suicide attempts may be tolerable."
On November 13, 1990, a memo from a Lilly employee in Germany, Claude Bouchy, to another Lilly employee, Leigh Thompson, regarding the adverse drug event reporting of suicide and Prozac written in response to Lilly's request that he change the event "suicidal ideation" to "depression," Mr Bouchy writes:
"Hans (Lilly employee) has medical problems with these directions and I have great concerns about it.
"I do not think I could explain to the BGA, a judge, to a reporter or even to my family why we would do this especially on the sensitive issue of suicide and suicidal ideation."
A second memo dated November 14, 1990, from Mr Bouchy to Leigh Thompson about adverse drug event reporting states: "I personally wonder whether we are really helping the credibility of an excellent ADE system by calling overdose what a physician reports as suicide attempt and by calling depression what a physician is reporting as suicide ideation."
The documents also reveal how worried Lilly was about the commercial impact to the company if the truth about the Prozac-induced suicides got out. A February 7, 1990 Leigh Thompson Memo, says, "Anything that happens in the UK can threaten this drug in the US and worldwide. We are now expending enormous efforts fending off attacks because of (1) relationship to murder and (2) inducing suicidal ideation."
On February 7, 1990, a Leigh Thompson memo also says, "I hope Patrick (a Lilly employee) realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that."
Dr Breggin says that after he testified in the trial in 1994, these documents seemed to just disappear, until they were handed over to the BMJ.
Thursday, August 5, 2010
Accutane still a Top Seller for Hoffman-LaRoche
Evelyn Pringle August 25, 2006
Accutane, manufactured by Hoffman-LaRoche, was FDA approved in 1982, only to treat the most severe form of acne. Yet by 1998, the medication was the company's second-largest-selling drug, with about $800 million in sales.
Accutane (Isotretinoin) entered the market in the US in 1982, and has been at the center of one firestorm after another ever since. It was never intended to treat a large number of patients. The FDA approved the drug for the treatment of severe nodular cystic acne, a type of acne that is painful, disfiguring, and will not respond to other forms of treatment.
The FDA approved labeling specifically points out that the drug is not to be considered a treatment of first choice:
"Because of significant adverse effects associated with its use, Accutane should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics."
The original labeling issued in 1982, designated the drug as Category X, meaning it was to be avoided by all pregnant women. Yet by 1983, babies were being born with birth defects to mothers who used the drug during pregnancy.
Alarmed by these reports, in September 1983, the non-profit consumer advocacy group, Public Citizen, submitted a petition to the FDA requesting patient package inserts and a black box warning label be added to Accutane describing the risk of birth defects and mental retardation.
Looking back, Public Citizen has been warning the FDA about the risks of serious harm to fetuses exposed to Accutane for more than 20 years. In 1984 the group sent a letter to the FDA advocating for improved pregnancy surveillance and lower dosing regimens.
During an FDA Advisory Committee meeting in 1988, the group described isotretinoin as an imminent public health hazard and urged the panel to remove the drug from the market unless tighter and effective restrictions were implemented.
The next year the group testified again and asked the FDA to withdraw isotretinoin from the market unless the previously proposed restrictions were adopted immediately.
In 1989, the CDC testified before an FDA Advisory Committee, and stated that the birth of babies with defects caused by fetal exposure to Accutane was unnecessary and called the FDA's decision to allow the marketing of Accutane, a "failed regulatory experiment."
At a December 11, 2002 House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, internal documents from the nation's regulatory agencies were placed in the record that showed public health officials had been expressing serious concerns about Accutane and birth defects for well over a decade.
For instance, a 1990 internal FDA memo stated, "Accutane poses an imminent hazard to public health, and as such should be withdrawn immediately from the market."
A 1990 report by the FDA said, "The magnitude of fetal injury and death has been great and permanent, with 11,000 to 13,000 Accutane-related abortions and 900 to 1,100 Accutane birth defects."
In August 1997, the FDA issued a warning letter to Roche for failing to submit serious adverse event reports in a timely manner and Roche claimed its computer systems were responsible for delays of up to eight years in complying with the law.
A February 1998 FDA memo stated that Roche "had not acted in good faith to truly and accurately answer questions relating to Accutane use in women and pregnancy exposure."
The memo goes on to recommend "active consideration of removal of Accutane from the market."
A 1998 letter to the FDA from an official at the Centers For Disease Control compared Accutane to the infamous cancer and leprosy drug, Thalidomide, known for causing of birth defects, and stated, "we simply need to remove the drug from the market."
In response to calls for the withdrawal of Accutane, Roche proposed a patient education program on the risk of birth defects, that included patient materials and informed consent forms for women to sign before receiving the drug.
In September, 2000, because the number of prescriptions to women of child-bearing age had tripled from 70,000 a year in 1989, to almost 210,000 in 1999, there was more concern over the increasing number of pregnant women exposed to the drug so FDA's Dermatologic and Ophthalmic Drugs Advisory Committee held a meeting to discuss what measures might help prevent further fetal exposure.
Public Citizen once again testified at the hearing and recommended that a Patient Medication Guide be issued and again urged the FDA to remove Accutane from the market unless restrictions were implemented and proven to be effective.
As a result of recommendations made by the Advisory Committee following the hearing, Roche agreed to develop a program designed to prevent pregnancies in women using Accutane.
The "System to Manage Accutane Related Teratogenicity," or SMART program, was implemented in April 2002, and required women to have 2 pregnancy tests before starting on Accutane, to get a pregnancy test each month before refilling a prescription, to receive counseling on birth control, and to agree to use two forms of birth control simultaneously while using Accutane.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events for all approved drugs, designed to support the FDA's post-marketing safety surveillance program.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
During the December 11, 2002 hearing, Roche claimed that only 2,300 pregnancies had occurred among Accutane users since its introduction in 1982. However, Congressman Bart Stupak (D-MI), refuted that assertion, by citing a 1999 company report indicating that in a single 3 month period that year, 93 unwanted pregnancies were reported and 42 abortions occurred.
According to Dr Janet Woodcock, Director of the CDER at the hearing, AERS contained almost 23,000 adverse event reports for Accutane from the time of its approval in 1982 to December 2002.
For 2002 thus far, she said, AERS contains just over 1,100 adverse event reports. During 2002, she told the panel, the five most frequently reported reactions are, in descending order, depression, pregnancy, induced abortion, suicidal ideation, and headache.
Dr Woodcock explained that the Office of Drug Safety (ODS) within CDER maintains a quarterly cumulative count of reports of Accutane-exposed pregnancies and outcome, if known, based on Roche's quarterly submission.
The latest update as of June 2002, she said, "shows a total of 2,350 Accutane-exposed pregnancies and 172 babies born with a congenital defect or anomaly in the U.S. since the product was approved in 1982."
According to testimony by Dr Nancy Green, medical director of the March of Dimes Birth Defects Foundation, Associate Professor of Pediatrics and Cell Biology at the Albert Einstein College of Medicine, the major birth defects include a syndrome that includes mental retardation, hydrocephalus, microcephaly, cleft lip and palate, cardiovascular anomalies, and ear and limb abnormalities.
Lynn Martinez, Manager of the Organization of Teratology Information Services (OTIS), a national group that tracks prenatal birth defects exposure, informed the committee that OTIS was still receiving reports from women who had become pregnant while taking Accutane, despite the SMART program.
To measure compliance with the SMART program, researchers surveyed 34 women who had called a member service of the OTIS between April 2002 and September 2004 because they had become pregnant while taking isotretinoin.
The survey revealed that only 24% of the women received contraception counseling and while SMART required women to use two forms of birth control simultaneously while taking Accutane, only 62% of the women reported using any birth control and only 29% of those women reported using two forms.
According to the rules, women were required to have two negative pregnancy tests before receiving a prescription, but 76% said they did not have a second pregnancy test
When asked about the requirement of receiving a pregnancy test each month before refilling a prescription, 35% of the women surveyed said they did not have monthly pregnancy tests.
In addition, only 53% of the women reported signing the informed consent required by SMART prior to taking the drug.
Julia Robertson, coordinator of the Birth Defects and Genetics Program at the Utah Department of Health in Salt Lake City, and lead author of the study, said the failure to avoid pregnancy had resulted in a high rate of abortions and at least one baby born with severe birth defects.
The survey confirmed that the SMART program was not being followed by women or doctors, mainly because the program was not mandatory. The results of the study appeared online on October 14, 2005, in the journal Birth Defects Research (Part A): Clinical and Molecular Teratology.
The survey also revealed that the majority of women were prescribed Accutane off-label for less severe acne than is recommended by the SMART program.
At the December 11, 2002, hearing, the subcommittee discussed the problem of "off-label" prescribing to patients without severe cystic acne and some experts estimated it to be as high as 90% among women.
During the hearing, Roche's North American president and CEO, George Abercrombie, denied promoting Accutane for patients not suffering from severe acne. When confronted with print advertisements that featured teenage models with little or no visible acne, Mr Abercrombie pointed out that the ads did not specifically mention Accutane and said they were intended to make consumers aware that there were treatments for severe acne.
That statement went over like a lead balloon. "What you just said is not a truthful statement," Congressman Peter Deutsch (D-FL), told him. "You're beyond the straight-face test, I'm sorry."
Due to the failure of the SMART program, and the continuation of babies born with birth defects, in March 2006, the FDA implemented the iPledge program, which basically follows the same rules as the SMART program, but doctors and patients are no longer on the honor system.
IPledge requires a woman to have two pregnancy tests before the initial prescription for Accutane is written, and to have a monthly pregnancy testing before each refill. But now, the prescribing doctor is required to register the test results in the computerized iPledge system, and the woman must fill her prescription within seven days.
In addition, the woman must agree to use two forms of birth control while using the drug and she must also register with the iPledge system to certify that she is using two forms of contraception.
It could be said that Roche has between 300 and 450 good reasons to keep selling Accutane off-label to as many women as possible each month, because according to an August 21, 2006 article by the Associated Press, the daily pill costs between $10 to $15 a pop.
Accutane, manufactured by Hoffman-LaRoche, was FDA approved in 1982, only to treat the most severe form of acne. Yet by 1998, the medication was the company's second-largest-selling drug, with about $800 million in sales.
Accutane (Isotretinoin) entered the market in the US in 1982, and has been at the center of one firestorm after another ever since. It was never intended to treat a large number of patients. The FDA approved the drug for the treatment of severe nodular cystic acne, a type of acne that is painful, disfiguring, and will not respond to other forms of treatment.
The FDA approved labeling specifically points out that the drug is not to be considered a treatment of first choice:
"Because of significant adverse effects associated with its use, Accutane should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics."
The original labeling issued in 1982, designated the drug as Category X, meaning it was to be avoided by all pregnant women. Yet by 1983, babies were being born with birth defects to mothers who used the drug during pregnancy.
Alarmed by these reports, in September 1983, the non-profit consumer advocacy group, Public Citizen, submitted a petition to the FDA requesting patient package inserts and a black box warning label be added to Accutane describing the risk of birth defects and mental retardation.
Looking back, Public Citizen has been warning the FDA about the risks of serious harm to fetuses exposed to Accutane for more than 20 years. In 1984 the group sent a letter to the FDA advocating for improved pregnancy surveillance and lower dosing regimens.
During an FDA Advisory Committee meeting in 1988, the group described isotretinoin as an imminent public health hazard and urged the panel to remove the drug from the market unless tighter and effective restrictions were implemented.
The next year the group testified again and asked the FDA to withdraw isotretinoin from the market unless the previously proposed restrictions were adopted immediately.
In 1989, the CDC testified before an FDA Advisory Committee, and stated that the birth of babies with defects caused by fetal exposure to Accutane was unnecessary and called the FDA's decision to allow the marketing of Accutane, a "failed regulatory experiment."
At a December 11, 2002 House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, internal documents from the nation's regulatory agencies were placed in the record that showed public health officials had been expressing serious concerns about Accutane and birth defects for well over a decade.
For instance, a 1990 internal FDA memo stated, "Accutane poses an imminent hazard to public health, and as such should be withdrawn immediately from the market."
A 1990 report by the FDA said, "The magnitude of fetal injury and death has been great and permanent, with 11,000 to 13,000 Accutane-related abortions and 900 to 1,100 Accutane birth defects."
In August 1997, the FDA issued a warning letter to Roche for failing to submit serious adverse event reports in a timely manner and Roche claimed its computer systems were responsible for delays of up to eight years in complying with the law.
A February 1998 FDA memo stated that Roche "had not acted in good faith to truly and accurately answer questions relating to Accutane use in women and pregnancy exposure."
The memo goes on to recommend "active consideration of removal of Accutane from the market."
A 1998 letter to the FDA from an official at the Centers For Disease Control compared Accutane to the infamous cancer and leprosy drug, Thalidomide, known for causing of birth defects, and stated, "we simply need to remove the drug from the market."
In response to calls for the withdrawal of Accutane, Roche proposed a patient education program on the risk of birth defects, that included patient materials and informed consent forms for women to sign before receiving the drug.
In September, 2000, because the number of prescriptions to women of child-bearing age had tripled from 70,000 a year in 1989, to almost 210,000 in 1999, there was more concern over the increasing number of pregnant women exposed to the drug so FDA's Dermatologic and Ophthalmic Drugs Advisory Committee held a meeting to discuss what measures might help prevent further fetal exposure.
Public Citizen once again testified at the hearing and recommended that a Patient Medication Guide be issued and again urged the FDA to remove Accutane from the market unless restrictions were implemented and proven to be effective.
As a result of recommendations made by the Advisory Committee following the hearing, Roche agreed to develop a program designed to prevent pregnancies in women using Accutane.
The "System to Manage Accutane Related Teratogenicity," or SMART program, was implemented in April 2002, and required women to have 2 pregnancy tests before starting on Accutane, to get a pregnancy test each month before refilling a prescription, to receive counseling on birth control, and to agree to use two forms of birth control simultaneously while using Accutane.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events for all approved drugs, designed to support the FDA's post-marketing safety surveillance program.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
During the December 11, 2002 hearing, Roche claimed that only 2,300 pregnancies had occurred among Accutane users since its introduction in 1982. However, Congressman Bart Stupak (D-MI), refuted that assertion, by citing a 1999 company report indicating that in a single 3 month period that year, 93 unwanted pregnancies were reported and 42 abortions occurred.
According to Dr Janet Woodcock, Director of the CDER at the hearing, AERS contained almost 23,000 adverse event reports for Accutane from the time of its approval in 1982 to December 2002.
For 2002 thus far, she said, AERS contains just over 1,100 adverse event reports. During 2002, she told the panel, the five most frequently reported reactions are, in descending order, depression, pregnancy, induced abortion, suicidal ideation, and headache.
Dr Woodcock explained that the Office of Drug Safety (ODS) within CDER maintains a quarterly cumulative count of reports of Accutane-exposed pregnancies and outcome, if known, based on Roche's quarterly submission.
The latest update as of June 2002, she said, "shows a total of 2,350 Accutane-exposed pregnancies and 172 babies born with a congenital defect or anomaly in the U.S. since the product was approved in 1982."
According to testimony by Dr Nancy Green, medical director of the March of Dimes Birth Defects Foundation, Associate Professor of Pediatrics and Cell Biology at the Albert Einstein College of Medicine, the major birth defects include a syndrome that includes mental retardation, hydrocephalus, microcephaly, cleft lip and palate, cardiovascular anomalies, and ear and limb abnormalities.
Lynn Martinez, Manager of the Organization of Teratology Information Services (OTIS), a national group that tracks prenatal birth defects exposure, informed the committee that OTIS was still receiving reports from women who had become pregnant while taking Accutane, despite the SMART program.
To measure compliance with the SMART program, researchers surveyed 34 women who had called a member service of the OTIS between April 2002 and September 2004 because they had become pregnant while taking isotretinoin.
The survey revealed that only 24% of the women received contraception counseling and while SMART required women to use two forms of birth control simultaneously while taking Accutane, only 62% of the women reported using any birth control and only 29% of those women reported using two forms.
According to the rules, women were required to have two negative pregnancy tests before receiving a prescription, but 76% said they did not have a second pregnancy test
When asked about the requirement of receiving a pregnancy test each month before refilling a prescription, 35% of the women surveyed said they did not have monthly pregnancy tests.
In addition, only 53% of the women reported signing the informed consent required by SMART prior to taking the drug.
Julia Robertson, coordinator of the Birth Defects and Genetics Program at the Utah Department of Health in Salt Lake City, and lead author of the study, said the failure to avoid pregnancy had resulted in a high rate of abortions and at least one baby born with severe birth defects.
The survey confirmed that the SMART program was not being followed by women or doctors, mainly because the program was not mandatory. The results of the study appeared online on October 14, 2005, in the journal Birth Defects Research (Part A): Clinical and Molecular Teratology.
The survey also revealed that the majority of women were prescribed Accutane off-label for less severe acne than is recommended by the SMART program.
At the December 11, 2002, hearing, the subcommittee discussed the problem of "off-label" prescribing to patients without severe cystic acne and some experts estimated it to be as high as 90% among women.
During the hearing, Roche's North American president and CEO, George Abercrombie, denied promoting Accutane for patients not suffering from severe acne. When confronted with print advertisements that featured teenage models with little or no visible acne, Mr Abercrombie pointed out that the ads did not specifically mention Accutane and said they were intended to make consumers aware that there were treatments for severe acne.
That statement went over like a lead balloon. "What you just said is not a truthful statement," Congressman Peter Deutsch (D-FL), told him. "You're beyond the straight-face test, I'm sorry."
Due to the failure of the SMART program, and the continuation of babies born with birth defects, in March 2006, the FDA implemented the iPledge program, which basically follows the same rules as the SMART program, but doctors and patients are no longer on the honor system.
IPledge requires a woman to have two pregnancy tests before the initial prescription for Accutane is written, and to have a monthly pregnancy testing before each refill. But now, the prescribing doctor is required to register the test results in the computerized iPledge system, and the woman must fill her prescription within seven days.
In addition, the woman must agree to use two forms of birth control while using the drug and she must also register with the iPledge system to certify that she is using two forms of contraception.
It could be said that Roche has between 300 and 450 good reasons to keep selling Accutane off-label to as many women as possible each month, because according to an August 21, 2006 article by the Associated Press, the daily pill costs between $10 to $15 a pop.
Merck Legal Team Makes Killing Off losing Vioxx Strategy
Evelyn Pringle June 5, 2006
Not much has changed at Merck since Vioxx was pulled off the market. The only difference for shareholders is that instead of spending hundreds of millions of dollars a year to promote Vioxx, the attorney's fees are now costing hundreds of millions of dollars a year.
As of December 31, 2004, Merck had established a reserve of $675 million solely for legal defense costs related to Vioxx, according to the company's 2005 annual report.
During 2005, the report said, Merck spent "$285 million in the aggregate in legal defense costs worldwide" related to Vioxx.
In the fourth quarter of 2005, Merck recorded a charge of $295 million to increase the reserve solely for its future legal defense costs related to Vioxx, the report said, to $685 million as of December 31, 2005.
"This reserve is based on certain assumptions," Merck told shareholders, "and is the best estimate of the amount that the Company believes, at this time, it can reasonably estimate will be spent through 2007."
That said, the company has not set aside one dime for potential damage awards in Vioxx trials through 2007. Which means the only good news to report as far as Merck's legal strategy of a case by case defense of thousands of lawsuits in the years ahead, is that the company's legal team will keep raking in dough while Merck slowly goes under.
We now know that tens of thousands of people died, and many more were injured, because Merck concealed the information about the adverse effects of Vioxx. But to date, Merck has not paid one red cent in damages. And the appeals process initiated by Merck attorneys, guarantees that that money awarded to any plaintiff so far will be years away. And even then, experts say, the close to $300 million in damages awarded will be reduced to $48 million by caps on punitive damages.
In addition to the thousands of personal injury and wrongful death claims, Merck also faces class actions, filed on behalf of prescription drug plans and insurance carriers seeking treble damages, that experts say could expose Merck to multi-billion dollar verdicts.
The plaintiffs in the class actions allege that Merck misrepresented the safety profile of Vioxx, ignoring clear and early warning signs of its risks in order to continue its sale, and that had they known the truth, they would not have included Vioxx as an approved drug or agreed to reimburse plan members for its high cost. They also contend that Vioxx was no more effective than over-the-counter painkillers already on the market.
In seeking reimbursement, these plaintiffs will not have to prove that Vioxx caused any injuries or deaths. All they will have to show is that Merck continued to push Vioxx after it knew about the drug's increased risks.
And on top of the class action monsters, there is the pesky little matter of lawsuits filed on behalf of the individual states that also have the potential to expose Merck to billion dollar damage awards. The state actions are similar to the class actions and seek repayment for money paid for Vioxx by state run health care programs like Medicaid.
The damages sought are huge. For instance, Texas Attorney General, Gregg Abbott, is seeking $168 million and says he can prove total damages in excess of $250 million over five years in payments for Vioxx.
According to Merck's 2005 annual report, "The Company has received a Civil Investigative Demand from a group of the Attorneys General of 31 states and the District of Columbia who are investigating whether the Company violated state consumer protection laws when marketing Vioxx. The Company is cooperating with the Attorneys General in responding to the Civil Investigative Demand."
The state of New York's Controller, Alan Hevesi, claims his state's retirement fund lost $171 million when Merck's stock value dropped and that teachers, policemen, and firefighters have lost $287 million all total from their retirement funds.
The NY suit alleges that Merck violated federal securities laws by failing to disclose information about the safety risks of Vioxx. "The New York State Common Retirement Fund is exactly the kind of sophisticated and knowledgeable financial institution that the Congress, in the 1995 Private Securities Litigation Reform Act, intended to lead such class action suits," Mr Hevesi said in a press release.
The NYSCRF is reportedly the second largest public pension fund in the US, in terms of membership and assets, with more than 970,000 retirees, beneficiaries and members and over $120 billion in assets.
"Merck must be held legally responsible for its actions," Mr Hevesi noted in his press release. "These actions have put lives at risk and cost shareholders billions of dollars."
Experts say that for Merck's "no pay" strategy to work, the company would have to win virtually every one of the of individual lawsuits and then hope that such success would help defeat the claims by state health care programs, and the insurance and healthcare plans. Which they say is absolutely impossible because Merck has already admitted that consumers who used Vioxx over 18 months were exposed to an increased risk.
Billion dollar awards could easily drain Merck's insurance coverage and punitive damages based on evidence that shows the company withheld, manipulated, and misrepresented the results of clinical studies, and therefore willfully marketed Vioxx, are not covered by insurance and must be paid by Merck directly.
According to attorney, Barry Turner, "Merck may be holding its own at the moment but the fact is that the lying and deceit cannot continue indefinitely without some major blow to stockholder funds."
"I do think that Merck will get burned over this one," he says, "if their lawyers are dumb enough to fight each personal injury case."
Even though insurance does not cover punitive damages, Mr Turner says, "personal injury litigation costs are factored into so called R&D and marketing costs and the end user price covers all of this money."
"But the securities actions are different," he says. "Anyone who thinks this strategy is going to help the stockholders is crazy," he warns.
He predicts that Merck will soon start trying to settle PI cases with confidentiality clauses. "This would mean less payouts," he says, "and less knock on effect as other plaintiffs and their lawyers stand by to watch the action before running their own cases."
The fact is, that in every new trial, the lawyers for the plaintiffs introduce more embarrassing evidence. For instance, in a California trial that began last week, a former Merck employee, testified that the company did not inform federal authorities about two clinical trials in which users of Vioxx were found to be more likely to die than people given a placebo.
Dr Edward Scolnick, the former head of Merck's research laboratories, said in a videotaped deposition played for the jury, that he did not believe the numbers were coincidental. "It's not likely due to chance," he said.
Dr Scolnick testified that people on Vioxx died at a rate 4 times higher than those who didn't receive the drug in one trial, and the rate was 2 1/2 times higher in the other. Both studies were done in 2001 to see if Vioxx could help Alzheimer patients.
He said Merck did not turn over results to the FDA when company officials met with an FDA representatives in April of that year and that he was not aware of the trial results at the time.
The juries have also viewed internal documents that show Merck training its sales reps to avoid answering tough questions from doctors about the adverse effects of Vioxx on the heart. In one training manual, each of the last four pages of potential questions that doctors might ask, the manual said "DODGE!" to avoid answering.
In the first trial in Texas, the plaintiff's attorney, Mark Lanier, presented documents showing that Vioxx sales reps at one time received a $ 2,000 bonus if one of the doctors they met with prescribed Vioxx more than 55% of the time, and that the rep was paid another $2,000 if the rate exceeded 61%.
Mr Lanier also showed the jurors a Merck SEC filing that said Merck's CEO Gilmartin was making about $3 million in salary and bonuses in 2000, when the company received the results of the clinical study in which Vioxx users suffered 5 times as many heart attacks as those taking naproxen.
In March 2006, Merck lost a major legal battle that had the company's attorneys kicking and screaming, when US District Judge Eldon Fallon ordered FDA scientist, Dr David Graham to testify in a deposition in response to a subpoena from attorneys for Vioxx plaintiffs.
A major part of Merck's legal strategy has been to continuously point out that Vioxx had been approved by the FDA. Experts say, Dr Graham's testimony will throw a monkey-wrench into that strategy because it will reveal the long-fought battles over the deliberate concealment of the safety risks of Vioxx within the FDA itself.
Judge Fallon said the deposition would be limited to material relevant to the up-coming federal trial in July 2006, and Dr Graham's previous public statements. In the deposition, Dr Graham alleged that Merck dragged its feet about changing the label on Vioxx to warn of the increased risk of heart attacks.
So now in their latest run-up-the-costs tactic, Merck attorneys have filed a motion to limit the use of Dr Graham's deposition claiming it goes beyond anything Dr Graham previously said and therefore portions of it should not be heard by a jury.
Merck's memorandum filed with the motion, asks the court to exclude the following: "The two-year period for coming up with the revised label for a problem as serious as high risk of heart attacks with Vioxx, this is an extraordinary long period of time, and the only explanation based on my long experience at FDA is that there was foot dragging by the company."
But this statement is not new. Dr Graham publicly discussed the failure by Merck and the FDA to warn the public and add a new label to Vioxx while testifying at a congressional hearing a couple years ago on November 18, 2004.
In regard to the death and injuries caused by those failures, he in fact said: "I strongly believe that this should have been, and largely could have been, avoided."
Maybe Merck would rather have the jury listen to how Dr Graham put the number of people injured by Vioxx into perspective, when he told members of the Senate committee that instead of side-effects from Vioxx, to picture the number of people as if it were airline crashes.
"If there were an average of 150 to 200 people on an aircraft," he told the panel, "this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky."
"This translates to 2-4 aircraft every week," he noted, "week in and week out, for the past 5 years."
Merck also does not want the jury to hear Dr Graham say that Vioxx should not have been approved to begin with and that after learning the results of the VIGOR study in 2000, that Merck should have done a large study to determine whether Vioxx damaged the heart or blood vessels; and that an FDA official had recommended "at least" a warning label for the drug.
There is nothing new about these allegations either. Dr Graham made basically the same charges when he told the committee that the FDA "views the pharmaceutical industry it is supposed to regulate, as its client, over-values the benefits of the drugs it approves and seriously under-values, disregards and disrespects drug safety."
Dr Graham also pointed out that even when the FDA did try to take measures to limit harm, the agency lacked the enforcement authority to make companies comply. In the case of Vioxx, he said it took more than 2 years to get Merck to add the increased risk of heart attack and stroke to its label.
In their memorandum, Merck attorneys complained because: "Much of Dr Graham's testimony is an elaboration of why and how he believes the FDA is 'broken.'"
"However," they wrote, "Congress (not the jury) is the only body that can address Dr Graham's concerns."
Well then perhaps Merck should call members of congress to testify at future Vioxx trials to explain how Merck got top FDA officials to protect Vioxx profits by concealing the health risks associated with Vioxx that were revealed in damaging studies as far back as 2000.
In a statement following the verdict in first trial, Senator Grassley was quick to point out the FDA's involvement in the Vioxx disaster. "Those running the nation's public safety agency repeatedly dismissed the concerns of their own scientists and seemed to do everything possible to keep the public in the dark about emerging problems with Vioxx," he said.
"The Food and Drug Administration was also negligent in the Vioxx case," Senator Grassley declared.
A hearing on Merck's motion is scheduled for July 5, 2006, to decide what parts of Dr Graham's deposition will be allowed in during the trial of a suit brought by retired FBI agent, Gerald Barnett, who had a heart attack in September 2002.
Sooner rather than later, the steady stream of multi-million dollar judgments is bound to enrage Merck shareholders who have already suffered massive losses in their investments since October of 2004.
When Vioxx was pulled off the market in September 2004, the drug's $2.5 billion in annual sales equaled 11% of Merck's revenues. When news of the recall broke, Merck shares plunged $12 to $33, wiping out $28 billion of stock value in one day for investors, pension funds and mutual funds.
Stock value dropped another $2.35 per share, or 7.7%, following the first jury's verdict for the plaintiff in Texas on August 19, 2005.
Up until then, analysts had estimated Vioxx liability to be as high as $18 billion. But by the following Monday morning after the verdict, analyst, David Moskowitz, from Friedman, Billings, Ramsey & Co, told CNBC that he had raised his forecast for Merck's total tab from $11 billion to $50 billion.
Critics says, Merck is misleading investors by not making any provision whatsoever for the Vioxx liabilities in financial statements. In its annual report, regarding Vioxx litigation for 2006, Merck said:
"The Company has not established any reserves for any potential liability relating to the VIOXX Litigation. Unfavorable outcomes in the VIOXX Lawsuits or resulting from the VIOXX Investigations could have a material adverse effect on the Company's financial position, liquidity and results of operations."
Overall, there appears to be no good news out there for Merck shareholders. According to the January 27, 2006, Business Week Online, research from Morgan Stanley and Danish investment bank, Jyske Bank, estimates that patent expirations this year will equal 25% of Merck's 2005 sales as major medicines face generic competition.
And in the meantime, more and more angry consumers are saying civil damage awards are not a enough punishment for Merck and that top management people who allowed the Vioxx disaster to happen should be in jail.
Although unbeknownst to most people, criminal charges are being considered that could lead some of the culprits in that direction.
In New Jersey, the $9 million punitive damage award against Merck in April 2006, resulted in the case being referred to the state's Attorney General. Under the New Jersey Punitive Damage Act, any time there is a punitive damage award there must be an investigation "as to whether a criminal act has been committed by the defendant."
By now, there's certainly plenty of evidence in the public domain to prove that criminal acts were committed. For starters, the Attorney General can review the victims revealed in a 2004 study, lead by FDA scientist, Dr Graham, that says Vioxx caused as many as 140,000 heart attacks and strokes and killed as many as 55,000 people.
Not much has changed at Merck since Vioxx was pulled off the market. The only difference for shareholders is that instead of spending hundreds of millions of dollars a year to promote Vioxx, the attorney's fees are now costing hundreds of millions of dollars a year.
As of December 31, 2004, Merck had established a reserve of $675 million solely for legal defense costs related to Vioxx, according to the company's 2005 annual report.
During 2005, the report said, Merck spent "$285 million in the aggregate in legal defense costs worldwide" related to Vioxx.
In the fourth quarter of 2005, Merck recorded a charge of $295 million to increase the reserve solely for its future legal defense costs related to Vioxx, the report said, to $685 million as of December 31, 2005.
"This reserve is based on certain assumptions," Merck told shareholders, "and is the best estimate of the amount that the Company believes, at this time, it can reasonably estimate will be spent through 2007."
That said, the company has not set aside one dime for potential damage awards in Vioxx trials through 2007. Which means the only good news to report as far as Merck's legal strategy of a case by case defense of thousands of lawsuits in the years ahead, is that the company's legal team will keep raking in dough while Merck slowly goes under.
We now know that tens of thousands of people died, and many more were injured, because Merck concealed the information about the adverse effects of Vioxx. But to date, Merck has not paid one red cent in damages. And the appeals process initiated by Merck attorneys, guarantees that that money awarded to any plaintiff so far will be years away. And even then, experts say, the close to $300 million in damages awarded will be reduced to $48 million by caps on punitive damages.
In addition to the thousands of personal injury and wrongful death claims, Merck also faces class actions, filed on behalf of prescription drug plans and insurance carriers seeking treble damages, that experts say could expose Merck to multi-billion dollar verdicts.
The plaintiffs in the class actions allege that Merck misrepresented the safety profile of Vioxx, ignoring clear and early warning signs of its risks in order to continue its sale, and that had they known the truth, they would not have included Vioxx as an approved drug or agreed to reimburse plan members for its high cost. They also contend that Vioxx was no more effective than over-the-counter painkillers already on the market.
In seeking reimbursement, these plaintiffs will not have to prove that Vioxx caused any injuries or deaths. All they will have to show is that Merck continued to push Vioxx after it knew about the drug's increased risks.
And on top of the class action monsters, there is the pesky little matter of lawsuits filed on behalf of the individual states that also have the potential to expose Merck to billion dollar damage awards. The state actions are similar to the class actions and seek repayment for money paid for Vioxx by state run health care programs like Medicaid.
The damages sought are huge. For instance, Texas Attorney General, Gregg Abbott, is seeking $168 million and says he can prove total damages in excess of $250 million over five years in payments for Vioxx.
According to Merck's 2005 annual report, "The Company has received a Civil Investigative Demand from a group of the Attorneys General of 31 states and the District of Columbia who are investigating whether the Company violated state consumer protection laws when marketing Vioxx. The Company is cooperating with the Attorneys General in responding to the Civil Investigative Demand."
The state of New York's Controller, Alan Hevesi, claims his state's retirement fund lost $171 million when Merck's stock value dropped and that teachers, policemen, and firefighters have lost $287 million all total from their retirement funds.
The NY suit alleges that Merck violated federal securities laws by failing to disclose information about the safety risks of Vioxx. "The New York State Common Retirement Fund is exactly the kind of sophisticated and knowledgeable financial institution that the Congress, in the 1995 Private Securities Litigation Reform Act, intended to lead such class action suits," Mr Hevesi said in a press release.
The NYSCRF is reportedly the second largest public pension fund in the US, in terms of membership and assets, with more than 970,000 retirees, beneficiaries and members and over $120 billion in assets.
"Merck must be held legally responsible for its actions," Mr Hevesi noted in his press release. "These actions have put lives at risk and cost shareholders billions of dollars."
Experts say that for Merck's "no pay" strategy to work, the company would have to win virtually every one of the of individual lawsuits and then hope that such success would help defeat the claims by state health care programs, and the insurance and healthcare plans. Which they say is absolutely impossible because Merck has already admitted that consumers who used Vioxx over 18 months were exposed to an increased risk.
Billion dollar awards could easily drain Merck's insurance coverage and punitive damages based on evidence that shows the company withheld, manipulated, and misrepresented the results of clinical studies, and therefore willfully marketed Vioxx, are not covered by insurance and must be paid by Merck directly.
According to attorney, Barry Turner, "Merck may be holding its own at the moment but the fact is that the lying and deceit cannot continue indefinitely without some major blow to stockholder funds."
"I do think that Merck will get burned over this one," he says, "if their lawyers are dumb enough to fight each personal injury case."
Even though insurance does not cover punitive damages, Mr Turner says, "personal injury litigation costs are factored into so called R&D and marketing costs and the end user price covers all of this money."
"But the securities actions are different," he says. "Anyone who thinks this strategy is going to help the stockholders is crazy," he warns.
He predicts that Merck will soon start trying to settle PI cases with confidentiality clauses. "This would mean less payouts," he says, "and less knock on effect as other plaintiffs and their lawyers stand by to watch the action before running their own cases."
The fact is, that in every new trial, the lawyers for the plaintiffs introduce more embarrassing evidence. For instance, in a California trial that began last week, a former Merck employee, testified that the company did not inform federal authorities about two clinical trials in which users of Vioxx were found to be more likely to die than people given a placebo.
Dr Edward Scolnick, the former head of Merck's research laboratories, said in a videotaped deposition played for the jury, that he did not believe the numbers were coincidental. "It's not likely due to chance," he said.
Dr Scolnick testified that people on Vioxx died at a rate 4 times higher than those who didn't receive the drug in one trial, and the rate was 2 1/2 times higher in the other. Both studies were done in 2001 to see if Vioxx could help Alzheimer patients.
He said Merck did not turn over results to the FDA when company officials met with an FDA representatives in April of that year and that he was not aware of the trial results at the time.
The juries have also viewed internal documents that show Merck training its sales reps to avoid answering tough questions from doctors about the adverse effects of Vioxx on the heart. In one training manual, each of the last four pages of potential questions that doctors might ask, the manual said "DODGE!" to avoid answering.
In the first trial in Texas, the plaintiff's attorney, Mark Lanier, presented documents showing that Vioxx sales reps at one time received a $ 2,000 bonus if one of the doctors they met with prescribed Vioxx more than 55% of the time, and that the rep was paid another $2,000 if the rate exceeded 61%.
Mr Lanier also showed the jurors a Merck SEC filing that said Merck's CEO Gilmartin was making about $3 million in salary and bonuses in 2000, when the company received the results of the clinical study in which Vioxx users suffered 5 times as many heart attacks as those taking naproxen.
In March 2006, Merck lost a major legal battle that had the company's attorneys kicking and screaming, when US District Judge Eldon Fallon ordered FDA scientist, Dr David Graham to testify in a deposition in response to a subpoena from attorneys for Vioxx plaintiffs.
A major part of Merck's legal strategy has been to continuously point out that Vioxx had been approved by the FDA. Experts say, Dr Graham's testimony will throw a monkey-wrench into that strategy because it will reveal the long-fought battles over the deliberate concealment of the safety risks of Vioxx within the FDA itself.
Judge Fallon said the deposition would be limited to material relevant to the up-coming federal trial in July 2006, and Dr Graham's previous public statements. In the deposition, Dr Graham alleged that Merck dragged its feet about changing the label on Vioxx to warn of the increased risk of heart attacks.
So now in their latest run-up-the-costs tactic, Merck attorneys have filed a motion to limit the use of Dr Graham's deposition claiming it goes beyond anything Dr Graham previously said and therefore portions of it should not be heard by a jury.
Merck's memorandum filed with the motion, asks the court to exclude the following: "The two-year period for coming up with the revised label for a problem as serious as high risk of heart attacks with Vioxx, this is an extraordinary long period of time, and the only explanation based on my long experience at FDA is that there was foot dragging by the company."
But this statement is not new. Dr Graham publicly discussed the failure by Merck and the FDA to warn the public and add a new label to Vioxx while testifying at a congressional hearing a couple years ago on November 18, 2004.
In regard to the death and injuries caused by those failures, he in fact said: "I strongly believe that this should have been, and largely could have been, avoided."
Maybe Merck would rather have the jury listen to how Dr Graham put the number of people injured by Vioxx into perspective, when he told members of the Senate committee that instead of side-effects from Vioxx, to picture the number of people as if it were airline crashes.
"If there were an average of 150 to 200 people on an aircraft," he told the panel, "this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky."
"This translates to 2-4 aircraft every week," he noted, "week in and week out, for the past 5 years."
Merck also does not want the jury to hear Dr Graham say that Vioxx should not have been approved to begin with and that after learning the results of the VIGOR study in 2000, that Merck should have done a large study to determine whether Vioxx damaged the heart or blood vessels; and that an FDA official had recommended "at least" a warning label for the drug.
There is nothing new about these allegations either. Dr Graham made basically the same charges when he told the committee that the FDA "views the pharmaceutical industry it is supposed to regulate, as its client, over-values the benefits of the drugs it approves and seriously under-values, disregards and disrespects drug safety."
Dr Graham also pointed out that even when the FDA did try to take measures to limit harm, the agency lacked the enforcement authority to make companies comply. In the case of Vioxx, he said it took more than 2 years to get Merck to add the increased risk of heart attack and stroke to its label.
In their memorandum, Merck attorneys complained because: "Much of Dr Graham's testimony is an elaboration of why and how he believes the FDA is 'broken.'"
"However," they wrote, "Congress (not the jury) is the only body that can address Dr Graham's concerns."
Well then perhaps Merck should call members of congress to testify at future Vioxx trials to explain how Merck got top FDA officials to protect Vioxx profits by concealing the health risks associated with Vioxx that were revealed in damaging studies as far back as 2000.
In a statement following the verdict in first trial, Senator Grassley was quick to point out the FDA's involvement in the Vioxx disaster. "Those running the nation's public safety agency repeatedly dismissed the concerns of their own scientists and seemed to do everything possible to keep the public in the dark about emerging problems with Vioxx," he said.
"The Food and Drug Administration was also negligent in the Vioxx case," Senator Grassley declared.
A hearing on Merck's motion is scheduled for July 5, 2006, to decide what parts of Dr Graham's deposition will be allowed in during the trial of a suit brought by retired FBI agent, Gerald Barnett, who had a heart attack in September 2002.
Sooner rather than later, the steady stream of multi-million dollar judgments is bound to enrage Merck shareholders who have already suffered massive losses in their investments since October of 2004.
When Vioxx was pulled off the market in September 2004, the drug's $2.5 billion in annual sales equaled 11% of Merck's revenues. When news of the recall broke, Merck shares plunged $12 to $33, wiping out $28 billion of stock value in one day for investors, pension funds and mutual funds.
Stock value dropped another $2.35 per share, or 7.7%, following the first jury's verdict for the plaintiff in Texas on August 19, 2005.
Up until then, analysts had estimated Vioxx liability to be as high as $18 billion. But by the following Monday morning after the verdict, analyst, David Moskowitz, from Friedman, Billings, Ramsey & Co, told CNBC that he had raised his forecast for Merck's total tab from $11 billion to $50 billion.
Critics says, Merck is misleading investors by not making any provision whatsoever for the Vioxx liabilities in financial statements. In its annual report, regarding Vioxx litigation for 2006, Merck said:
"The Company has not established any reserves for any potential liability relating to the VIOXX Litigation. Unfavorable outcomes in the VIOXX Lawsuits or resulting from the VIOXX Investigations could have a material adverse effect on the Company's financial position, liquidity and results of operations."
Overall, there appears to be no good news out there for Merck shareholders. According to the January 27, 2006, Business Week Online, research from Morgan Stanley and Danish investment bank, Jyske Bank, estimates that patent expirations this year will equal 25% of Merck's 2005 sales as major medicines face generic competition.
And in the meantime, more and more angry consumers are saying civil damage awards are not a enough punishment for Merck and that top management people who allowed the Vioxx disaster to happen should be in jail.
Although unbeknownst to most people, criminal charges are being considered that could lead some of the culprits in that direction.
In New Jersey, the $9 million punitive damage award against Merck in April 2006, resulted in the case being referred to the state's Attorney General. Under the New Jersey Punitive Damage Act, any time there is a punitive damage award there must be an investigation "as to whether a criminal act has been committed by the defendant."
By now, there's certainly plenty of evidence in the public domain to prove that criminal acts were committed. For starters, the Attorney General can review the victims revealed in a 2004 study, lead by FDA scientist, Dr Graham, that says Vioxx caused as many as 140,000 heart attacks and strokes and killed as many as 55,000 people.
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