If I were the parent of a child diagnosed with bipolar disorder by doctors at Massachusetts General Hospital and prescribed anti-psychotic drugs with serious side effects, how would I feel upon learning that the head honcho of MGH's child psychiatry department not only was on the take from the makers of these powerful drugs but pushed for the establishment of a drug company-funded center at MGH whose stated "rationale" was "to generate and disseminate data supporting use" of these drugs in children?
Betrayed is how I would feel, horribly betrayed.
Moving beyond the issue of betrayal, the actions of Joseph Biederman, as revealed today in The New York Times and The Boston Globe, raise the specter of criminality. By pushing Johnson & Johnson, the maker of Risperdal, to fund a center at MGH whose stated goal was to support the use of Risperdal and "move forward the commercial goals of J&J," the question emerges: did Biederman help Johnson & Johnson illegally market the off-label use of its anti-psychotic drug in children and adolescents?
While it is legal for doctors to prescribe drugs for uses not approved by the FDA, it is illegal for companies to actively market those off-label drugs. As a number of recent books, Side Effects included, show, drug makers routinely got around that restriction by recruiting and paying key opinion leaders to promote the off-label use of their products at medical conferences, company-sponsored meetings and in medical journals. By taking millions of dollars, both personally and to fund his MGH center, Biederman seems to have raised the art of off-label promotion to an entirely new level.
As The New York Times reports, "Biederman's work helped to fuel a 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder and a rapid rise in the use of powerful, risky and expensive anti-psychotic medicines in children... Biederman had a vast influence on the field largely because of his position at one of the most prestigous medical institutions in the world."
Earlier this summer, Congressional investigators led by Senator Charles E. Grassley accused Biederman of failing to disclose at least $1.4 million in personal payments from companies that make anti-psychotic drugs, such as Risperdal, Zyprexa, Abilify and Seroquel (back story). Now comes the news, as revealed in documents unsealed in a lawsuit, that Biederman repeatedly pushed Johnson & Johnson to fund a center at MGH whose stated purpose was to spread the word about Risperdal in treating bipolar disorder in children. Emails unsealed from the multi-state lawsuit also reveal that Biederman was asked to author a study of Risperdal ghost-written by Johnson & Johnson that purported to show the drug was more effective than a placebo in treating children.
In other words, we give you money to fund your center and line your pockets and you spread the word about our wonderful drugs, medical objectivity be damned.
Here is another example of how the tort system that the drug company lawyers are pushing to abolish helps consumers. The reason these documents came to light is because thousands of parents sued J&J, AstraZeneca (the maker Seroquel) and Eli Lilly (the maker of Zypreca), claiming that the companies minimized the risks of the anti-psychotic drugs given to their children. Attorneys representing these families demanded reams of documents from the companies, and while nearly all of these documents remain under seal, a select few that mentioned Biederman became public as part of an effort to compel the MGH psychiatrist to testify under oath as a witness in the legal proceedings. (The plaintiffs won and Biederman is expected to be deposed sometime in January, according to The Boston Globe).
So the question becomes: how long will Mass. General and Harvard Medical School allow such unethical and possibly criminal behavior to tarnish their reputations? Hopefully not long.
Tuesday, November 25, 2008
Wednesday, November 19, 2008
Drug Industry Mantra: If you can't buy them, bully them?
I found a disturbing common thread emerge this week from news coverage of the medical-pharmaceutical industry, a thread that can be summed in these words: If you can't buy them, bully them.
First off, we have reports in The New York Times and Pharmalot that an FDA advisory panel concluded that powerful anti-psychotic drugs are being prescribed much too readily to children; the panel called on the FDA to do more to discourage the use of these drugs in children diagnosed with bipolar disorder. As Gardiner Harris of The New York Times notes, "the leading advocate for the bipolar diagnosis is Dr. Joseph Biederman, a child psychiatrist at Harvard University whose work is under a cloud after a Congressional investigation revealed he had failed to report at least $1.4 million in outside income from the makers of antipsychotic medicines."
Biederman, as this and many other blogs have noted, is just one of many doctors who failed to fully disclose the extent of their earnings from the makers of drugs whom they were, at the same time, studying and touting to colleagues. As I reveal in Side Effects, this is simply the way the drug industry does business: they recruit prominent doctors, called key opinion leaders (KOLs), and pay them lots of money to promote new drugs to other doctors. Such blatant conflicts of interest are only now being widely publicized due to the diligence of Sen. Chuck Grassley's Finance Committee. That's the carrot side of the equation.
Now, we find that the drug industry also used the stick to intimidate doctors who spoke up about the worrisome side effects of some drugs. The Wall Street Journal and Pharmalot today reported that GlaxoSmithKline attempted to intimidate a physician at a Maryland hospital to stop her from voicing concerns about its antidiabetes drug, Avandia. In 2000, Dr. Mary Money and several colleagues at Washington County Hospital in Hagerstown raised concerns with both the company and the FDA that Avandia increased the risk of heart failure. GlaxoSmithKline dismissed their concerns and then wrote a letter to the hospital's chief of staff demanding he take immediate steps to "stop the dissemination of unsubstantiated information by your medical staff."
We also learn that another physician from Duke University testified before Congress that he too had been attacked as a liar and threatened with a lawsuit by the drug company when he raised concerns about Avandia. It was not until 2007, after The New England Journal of Medicine published a meta-analysis showing an increased risk of heart failure among patients taking Avandia, that the FDA put black box warnings on the drug. (It's worth noting that researchers would never have been able to do this meta-analysis if not for the New York State Attorney General's lawsuit against GlaxoSmithKline for deceiving physicians and consumers about another of its drugs, the antidepressant Paxil; as part of settling that lawsuit, Glaxo agreed to post the findings of all its clinical trials, including those about Avandia).
So what's the common theme in all of this? If the drug industry can't buy doctors to promote their new drugs, then they will do what they can to bully them into silence. For shame.
First off, we have reports in The New York Times and Pharmalot that an FDA advisory panel concluded that powerful anti-psychotic drugs are being prescribed much too readily to children; the panel called on the FDA to do more to discourage the use of these drugs in children diagnosed with bipolar disorder. As Gardiner Harris of The New York Times notes, "the leading advocate for the bipolar diagnosis is Dr. Joseph Biederman, a child psychiatrist at Harvard University whose work is under a cloud after a Congressional investigation revealed he had failed to report at least $1.4 million in outside income from the makers of antipsychotic medicines."
Biederman, as this and many other blogs have noted, is just one of many doctors who failed to fully disclose the extent of their earnings from the makers of drugs whom they were, at the same time, studying and touting to colleagues. As I reveal in Side Effects, this is simply the way the drug industry does business: they recruit prominent doctors, called key opinion leaders (KOLs), and pay them lots of money to promote new drugs to other doctors. Such blatant conflicts of interest are only now being widely publicized due to the diligence of Sen. Chuck Grassley's Finance Committee. That's the carrot side of the equation.
Now, we find that the drug industry also used the stick to intimidate doctors who spoke up about the worrisome side effects of some drugs. The Wall Street Journal and Pharmalot today reported that GlaxoSmithKline attempted to intimidate a physician at a Maryland hospital to stop her from voicing concerns about its antidiabetes drug, Avandia. In 2000, Dr. Mary Money and several colleagues at Washington County Hospital in Hagerstown raised concerns with both the company and the FDA that Avandia increased the risk of heart failure. GlaxoSmithKline dismissed their concerns and then wrote a letter to the hospital's chief of staff demanding he take immediate steps to "stop the dissemination of unsubstantiated information by your medical staff."
We also learn that another physician from Duke University testified before Congress that he too had been attacked as a liar and threatened with a lawsuit by the drug company when he raised concerns about Avandia. It was not until 2007, after The New England Journal of Medicine published a meta-analysis showing an increased risk of heart failure among patients taking Avandia, that the FDA put black box warnings on the drug. (It's worth noting that researchers would never have been able to do this meta-analysis if not for the New York State Attorney General's lawsuit against GlaxoSmithKline for deceiving physicians and consumers about another of its drugs, the antidepressant Paxil; as part of settling that lawsuit, Glaxo agreed to post the findings of all its clinical trials, including those about Avandia).
So what's the common theme in all of this? If the drug industry can't buy doctors to promote their new drugs, then they will do what they can to bully them into silence. For shame.
Thursday, November 6, 2008
New Zoloft study: an eerie case of deja vu
Between teaching journalism and working on my master's thesis, I have only now found the time to scrutinize the much-heralded Zoloft study published last Friday in the online version of The New England Journal of Medicine. And I have a few bones to pick with it, some of which have already been picked by commentators on Pharmalot.
The study found that a combined regimen of Zoloft and cognitive behavior therapy was more effective than either the drug or therapy alone in treating anxiety in children (age 7 to 17). It also concluded that Zoloft and CBT by themselves were more effective than placebo. News accounts of the study trumpeted the fact that none of the children in this trial committed suicide and that there was no significant increase in suicidal thoughts among those taking Zoloft. By highlighting these findings, the study's researchers no doubt intended to add weight to the argument that the FDA acted too hastily back in 2004 in putting black box warnings on Zoloft and other antidepressants.
Not so fast please. If you look closely at the data in this study, there are indications that a number of children taking Zoloft did have adverse reactions to the drug and experienced "a worsening" of psychiatric behaviors, in one case so severe that the child required hospitalization. Indeed of the three children in thte study who had serious adverse effects, two of them were in the Zoloft only arm of the study and one in the combination arm. Yet the study researchers dismiss the case requiring psychiatric hospitalization as being "unrelated to the study treatment."
This language of blithe dismissal is eerily reminscient of another antidepressant trial: Paxil study 329, which is currently under investigation by the U.S. Department of Justice back story. In study 329, researchers not only dismissed some adverse effects as being unrelated to Paxil, but they also concluded that Paxil was more effective than placebo, when in fact the data showed it was not. (As I reveal in my book, Side Effects, Brown University researchers also misrepresented data in the trial, coding teenagers who were suicidal as being "noncompliant."
Indeed, as Doug Bremner, professor of psychiatry at Emory University, points out on Pharmalot, the results of this study are not that different from the non-statistically significant results in the Paxil study. In that study, Paxil was found to be no more effective than placebo on the two primary outcome measures. In the more recent Zoloft study, Bremner notes that when you look at the actual data on one of the primary outcomes, the Pediatric Anxiety scale, the difference in improvement between the patients in the Zoloft only arm and the patients in the placebo group are also not statistically significant. Bremner dissects problems with the Zoloft study in greater depth on his blog.
There's more. The Zoloft study also minimizes the fact that of the 14 patients who withdrew from either treatment or the study due to adverse side effects, most of them were in the Zoloft only group. While its authors make much of the finding that there were no patients with suicidal thoughts in the Zoloft only group, they gloss over the fact that there were five patients who expressed suicidal ideation in the combined Zoloft/CBT group.
The researchers also ignore the finding that overall, there were many fewer side effects among the children in the cognitive behavior therapy group alone; patients in the latter group reported fewer cases of insomnia, fatigue, sedation, restlessness and fidgeting than those in the Zoloft study. That makes a lot of sense given the research showing that there is an increased risk of akathasia (agitation and restlessness) among patients who take SSRI antidepressants like Zoloft, Prozac and Paxil.
Finally, the Zoloft trial shares another disturbing similarity with Paxil study 329: in the fine print at the end of the NEJM report, its researchers disclose a myriad of financial ties to the pharmaceutical industry, including extensive consulting and speaking fees from companies that make SSRI antidepressants. So as several of the Pharmalot commentators ask, why should we trust the conclusions of this study? Why indeed.
The study found that a combined regimen of Zoloft and cognitive behavior therapy was more effective than either the drug or therapy alone in treating anxiety in children (age 7 to 17). It also concluded that Zoloft and CBT by themselves were more effective than placebo. News accounts of the study trumpeted the fact that none of the children in this trial committed suicide and that there was no significant increase in suicidal thoughts among those taking Zoloft. By highlighting these findings, the study's researchers no doubt intended to add weight to the argument that the FDA acted too hastily back in 2004 in putting black box warnings on Zoloft and other antidepressants.
Not so fast please. If you look closely at the data in this study, there are indications that a number of children taking Zoloft did have adverse reactions to the drug and experienced "a worsening" of psychiatric behaviors, in one case so severe that the child required hospitalization. Indeed of the three children in thte study who had serious adverse effects, two of them were in the Zoloft only arm of the study and one in the combination arm. Yet the study researchers dismiss the case requiring psychiatric hospitalization as being "unrelated to the study treatment."
This language of blithe dismissal is eerily reminscient of another antidepressant trial: Paxil study 329, which is currently under investigation by the U.S. Department of Justice back story. In study 329, researchers not only dismissed some adverse effects as being unrelated to Paxil, but they also concluded that Paxil was more effective than placebo, when in fact the data showed it was not. (As I reveal in my book, Side Effects, Brown University researchers also misrepresented data in the trial, coding teenagers who were suicidal as being "noncompliant."
Indeed, as Doug Bremner, professor of psychiatry at Emory University, points out on Pharmalot, the results of this study are not that different from the non-statistically significant results in the Paxil study. In that study, Paxil was found to be no more effective than placebo on the two primary outcome measures. In the more recent Zoloft study, Bremner notes that when you look at the actual data on one of the primary outcomes, the Pediatric Anxiety scale, the difference in improvement between the patients in the Zoloft only arm and the patients in the placebo group are also not statistically significant. Bremner dissects problems with the Zoloft study in greater depth on his blog.
There's more. The Zoloft study also minimizes the fact that of the 14 patients who withdrew from either treatment or the study due to adverse side effects, most of them were in the Zoloft only group. While its authors make much of the finding that there were no patients with suicidal thoughts in the Zoloft only group, they gloss over the fact that there were five patients who expressed suicidal ideation in the combined Zoloft/CBT group.
The researchers also ignore the finding that overall, there were many fewer side effects among the children in the cognitive behavior therapy group alone; patients in the latter group reported fewer cases of insomnia, fatigue, sedation, restlessness and fidgeting than those in the Zoloft study. That makes a lot of sense given the research showing that there is an increased risk of akathasia (agitation and restlessness) among patients who take SSRI antidepressants like Zoloft, Prozac and Paxil.
Finally, the Zoloft trial shares another disturbing similarity with Paxil study 329: in the fine print at the end of the NEJM report, its researchers disclose a myriad of financial ties to the pharmaceutical industry, including extensive consulting and speaking fees from companies that make SSRI antidepressants. So as several of the Pharmalot commentators ask, why should we trust the conclusions of this study? Why indeed.
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