Study 329 and the fraudulent FDA approval of Paxil for pediatric use

via CrookReport

via Project on Government Oversight

Warning to readers: hold your nose. Study 329 really stinks.

If you’re new to the issue, corporate funded ghostwriting involves a pharmaceutical company that hires a PR firm to write medical studies. The PR firm then presents the manuscript to academic physicians to sign their names on as authors. Sometimes, the authors make only minor changes. The professors get credit for a publication to add to their CVs, and the pharma company gets a study that is "authored" by physicians who are leading researchers in their field and appear to be independent.

The practice of ghostwriting drives up the costs of healthcare, because these studies trick doctors into prescribing drugs that may be more costly, and sometimes less safe. These studies can also be used to seek approval by the FDA and payment from federal healthcare programs.

In the case of Study 329, GlaxoSmithKline used the study as a tool to market Paxil for use on children, until both the FDA and its British counterpart warned doctors to stop prescribing Paxil to children because it could cause them to commit suicide.

Last November, POGO sent a letter to National Institutes of Health (NIH) asking why taxpayers were funding researchers involved in Study 329 when it was ghostwritten and flawed.

Anyways, the retracted article in The Coast detailed some of Study 329's problems and quoted Alison Bass, a former medical writer at The Boston Globe. Ms. Bass wrote an extensively referenced book titled Side Effects on the scandals and corruption involved in Study 329. The book was widely reviewed by media such as The New York Review of Books and The Canadian Medical Association Journal.

But her book isn't the only detailed account of ethically questionable behavior in Study 329.

In January 2007, the BBC ran an investigative report on Study 329, calling it "one of the biggest medical scandals of recent times." Thttp://www.cmaj.ca/cgi/content/full/179/12/1309he BBC released several internal company documents purporting that GlaxoSmithKline knew that Study 329 was flawed years before the results were published. The BBC also quoted Fiona Godlee, editor of the British Medical Journal, who called Study 329 a "problem" in scientific research.

The list of studies and experts critiquing Study 329 goes on and on.

I vote for Paxil!

So with such an extensive public record on corruption in Study 329 (just use Google, for goodness sake!) how did Dr. Kutcher characterize Study 329?

"I don't think that study caused any particular controversy," he said. "There certainly is a group of people who would like to cause a controversy around it, but science is nasty, brutish and long."

Nasty and brutish? No doubt. Especially, when all those documents and reports on Study 329 are splashed across the Internet.

Still, The Coast apparently ran afoul of Canadian law by publishing a negative story so close to the time of an election. After The Coast retracted and apologized, Dr. Kutcher dashed off a press release.

"It comes as a great surprise that The Coast is confusing opinion with science," he wrote. Dr. Kutcher then crowed, "[T]his is something we are more accustomed to hear from the American right wing than the Canadian left wing."

Yep. Right. Uh-huh.

Intrigued, I called the contact person listed at the bottom of the press release, Layton Dorey. When I asked if he had looked into the problems with Study 329, he said that I should contact Dr. Kutcher at his university.

"Did you see the BBC documentary on Study 329?" I asked.

Long pause…more pause…finally… "I'm not in a position to discuss that," Mr. Layton said.

We then agreed that I would email him questions. He never responded.

I also sent questions to Dr. Kutcher. I then called to confirm that he had received them.

Yesterday morning, Dr. Kutcher's attorney sent a terse email, writing that Dr. Kutcher would not be commenting further on The Coast article. I extended another offer for Dr. Kutcher to respond to questions about Study 329.

Nothing.

For the edification of readers, Canadian voters, and parents whose children were prescribed Paxil, we have provided those questions below. Feel free to provide any answers you feel are pertinent in the comment section of POGO's blog.


Questions for Stan Kutcher regarding press release and Study 329

Dr. Kutcher,

I need to ask you some questions regarding the press release on Tom Bosquet's [sic] article and the comments by author and former Boston Globe medical reporter, Alison Bass. I am an investigator at the Project On Government Oversight (POGO) in Washington. I'm working on a deadline for this, so I need your responses by tomorrow 5 p.m. EST.

In case this is the wrong email, or if you are out of town, I am copying the head of your department to ensure you get them before the deadline.

1. In the press release, you note that Alison Bass is "a writer who is among those most frequently cited by the Citizens Commission on Human Rights." What exactly are you implying with this statement?

2. Do you have any information that Alison Bass is a Scientologist and/or is a supporter of Scientology's public campaign against the field of psychiatry?

3. Alison Bass wrote a book alleging corruption in Study 329 titled Side Effects. The book received positive reviews in, among other places, The New Journal of Medicine, The New York Review of Books, The Boston Globe, and the Canadian Medical Association Journal. Were there errors in this book, and if so, could you please explain?

3. Your press release also states: "Dr. Kutcher intends to launch a defamation suit against the publication as a result of its inflammatory innuendo and the potential to damage his personal, professional and political reputation." Does you plan a defamation lawsuit against Alison Bass for the book Side Effects?

4. In January 2007, the BBC ran an investigative report on Study 329, calling it "one of the biggest medical scandals of recent times." Do you feel that the BBC, like The Coast, is guilty of "inflammatory innuendo"? If not, why not? Please be as expansive as you wish, in your response.

5. Dr. Fiona Godlee, editor of the British Medical Journal, told the BBC that Study 329 is an example of a "problem" in scientific research. "[W]e have to work very hard not only to uncover cases such as this but to work out how to prevent things like this happening in the future," she said. How do you respond to Dr. Godlee's charges against your study?

6. Jon Jureidini, associate professor of psychiatry at the University of Adelaide, and Leemon McHenry, lecturer in philosophy at California State University Northridge, published a study in 2008 that examined Study 329 and charged that the authors selectively reported results that favored GlaxoSmithKline. They have called for Study 329 to be retracted. How do you respond to their charges?

7. Drs. Jeffrey Lacasse and Jonathan Leo published a study in PLOS Medicine last year charging that Study 329 was ghostwritten by a company paid by GlaxoSmithKline and misrepresented data. How do you respond to their charges and do you plan to write a letter to PLOS Medicine to set the record straight?

8. Last November, POGO sent a letter to the National Institutes of Health charging that Study 329 was ghostwritten and "clearly flawed." We attached several document to our letter to support the claims of ghostwriting. Do you have documents to counter our claims? If so, will you make them part of the public record?

9. Are you required to disclose your financial conflicts to your university as is required here in the United States? If so, what was your financial relationship with GlaxoSmithKline at the time of Study 329's publication? How much money have you received from pharmaceutical companies in the last two years?

10. Within two years of Study 329's publication that found efficacy for Paxil in adolescents, the United Kingdom government warned British physicians to not prescribe Paxil for children due to fears of potential suicide. In May 2004, our own FDA issued a similar warning. Why do you think these two regulatory bodies came to dramatically different conclusions from your own published research?

Thank you so much for your time. I really appreciate it. Again, I need a response to our questions by tomorrow at 5 pm EST. If you have any other questions, please feel free to give me a call.

Sincerely,

Paul

UPDATE: Ed Silverman over at Pharmalot got a response from Stan Kutcher's chairman, Nicholas Delva. Dr. Delva toldPharmalot, "I have no concerns about Dr. Kutcher or his participation in Trial 329, and we will, therefore, not be conducting any investigation of his participation in this study."

I'm a little nonplussed by this response. Three years ago, a couple of reporters at Brown University did some digging and found plenty of concerns about the study. As I told Pharmalot, "It's pretty pathetic that a couple of college students can figure out the problems with the study, but Dr. Delva still remains confused."

For goodness, sake. The only thing Dr. Delva needs to do for an investigation is search the internet. Doesn't the man know how to use Google?

Paul Thacker is a POGO Investigator.

Conflicts of Interest are Real

The following is from the Alliance for Human Research Protection, whose mission statement on their website states:

"The Alliance for Human Research Protection (AHRP) is a national network of lay people and professionals dedicated to advancing responsible and ethical medical research practices, to minimizing the risks associated with such endeavors and to ensuring that the human rights, dignity and welfare of human subjects are protected" 

Conflicts of Interest in Clinical Trials

Presented by Vera Hassner Sharav
14th Tri-Service Clinical Investigation Symposium
Sponsored by
The U.S. Army Medical Department
and
The Henry M. Jackson Foundation for the Advancement of Military Medicine
May 5-7, 2002

Case 7: Children exposed to risks in psychotropic drug trials:

Psychotropic drugs are being tested in children despite the acknowledged risks of harm. Psychotropic drugs are advertised as normalizing a "chemical imbalance" in the brain. In fact, they do the opposite: they induce profound changes in the central nervous system with demonstrable physical and neurological impairments.[48] Dr. Steven Hyman, former director of NIMH, an expert on the mechanisms by which psychoactive drugs work, explained that, whether abused or prescribed, the mechanisms by which psychoactive drugs work are the same.[49] Hyman stated that antidepressants, psychostimulants, and anti-psychotics created "perturbations in neurotransmitter function."[50] The drugs' severe adverse side effects are symptoms of the drugs' disruptive effect on the neurotransmitter system and on brain function.

In 2001 Dr. Benedetto Vitiello, NIMH's director of Child and Adolescent Treatment and Preventive Interventions Branch acknowledged the impact of FDAMA: "pediatric psychopharmacology has recently seen an unprecedented expansionclinical trials in youths has more than doubled in the last few years."[51] Indeed, children as young as three are being recruited to test mind-altering drugs that may affect their developing brain. Parents are being offered financial inducements to volunteer their children for drug trials. The foremost problem with prescribing or testing psychotropic drugs for children is the absence of any objective criteria for diagnosing children with pathological behavioral problems to justify pharmacologic intervention. Vitiello acknowledged "diagnostic uncertainty surrounding most manifestations of psychopathology in early childhood."[52] Vitiello also acknowledged the possibility of long-term harm: "The impact of psychotropics on the developing brain is largely unknown, and possible long-term effects of early exposure to these drugs have not been investigated."

Eli Lilly's highly touted new anti-psychotic, Zyprexa,[53] reveals much about the collision between corporate interests and the health and safety of children. In clinical trials averaging 6 weeks, Zyprexa was tested in 2,500 adults. The drug was linked to serious, in some cases life-threatening side effects requiring hospitalization in 22% of those tested.[24]Acute weight gain of 50 to 70 lbs is usual, and with it the increased risk of diabetes. FDA data (under FOIA) reveals a 65% drop out rate, and only 26% favorable response. During those 6 week clinical trials there were 20 deaths, of which 12 were suicides.[54] David Healy, who found a suicidal link to antidepressants (Selective Serotonin Re-uptake Inhibitors) in his research says, as far as he can establish, the data from these trials "demonstrate a higher death rate on Zyprexa than on any other antipsychotic ever recorded." [55] In 2000, FDA approved Zyprexa for short- term use only, in bi-polar patients. [56]

Yet, children aged six to eleven were recruited for clinical trials to test the drug. According to their published report, UCLA investigators tested Zyprexa on children who were not even diagnosed as having schizophrenia. The children were diagnosed as having a variety of questionable psychiatric disorders, including ADHD.[57] According to the published report, all the children in the trial experienced adverse effects, including sedation, acute weight gain, and akathisia (restless agitation). The trial was terminated less than six weeks after it had begun.

Controversy surrounds a Zyprexa trial at Yale University. In that experiment, 31 youngsters aged 12 to 25 who have not been diagnosed with any psychiatric illness are being exposed to the drug for one year. The stated rationale given by the researchers (who are under contract with the sponsor) is their speculation that these children may be "at risk" for schizophrenia. Since there are, as yet, no objective tests or biological markers for the illness - they hypothesize without evidence, merely on the basis of conjecture. The shaky basis for their conjecture is that assumption that the children may develop schizophrenia because one of their siblings has been diagnosed with the disorder.

The risk of schizophrenia for the general population is 1%. For siblings the risk increases from 2% to 15% - in other words there is 85% likelihood that these children will never develop schizophrenia.

Given the absence of scientifically accurate tools for interpreting psychiatric symptoms, psychiatrists cannot as yet accurately diagnose schizophrenia much less predict which children will get it. Is it ethical to expose healthy children to risks of drug- induced pathology on such speculation? The Wall Street Journal aptly noted that such a study "raises the question of whether the drug companies are mainly interested in "creating" a new illness that requires drug treatment." Read the entire report here

Here is another Report from Alliance for Human Research Protection:

State Medicaid agencies began to question "off label" use of antipsychotics after the December 2006 death of Rebecca Riley, a four-year-old Massachusetts girl whose family received Medicaid benefits. After being diagnosed with bipolar disorder at age two, she was prescribed a cocktail of drugs, including an antipsychotic, court records show.

Some states began moving to require special approval before they would cover a claim for an antipsychotic. A group of 16 states started studying the use of psychiatric medication in children in 2007 in an effort they dubbed "too many, too much, too young," says Jeffrey Thompson, the medical director of the Washington state Medicaid program.

In California, the number of children six and under using psychiatric medications has fallen to 4,200 from 5,686 since a 2006 prior-authorization plan was put in place, the state's top Medicaid official says.

Florida's state Medicaid agency says the number of prescriptions for atypical antipsychotics written for children under age six in the second half of last year dropped to 1,137 from 3,167 a year earlier.

The agency says the decline was the result of a state program started last year under which prescriptions for children under six are reviewed for appropriateness by state-hired psychiatric consultants before Medicaid will cover them. 

Washington has created a system to flag the use of psychiatric drugs that may contain too high a dose for young children or have side effects that it regards as particularly dangerous. From May 2006 to April 2008, the system flagged 1,032 cases for review by outside consultants.

Write to David Armstrong at david.armstrong@wsj.com

Printed in The Wall Street Journal, page B1                                                    Complete article here

Copyright 2009 Dow Jones & Company, Inc. All Rights Reserved

It is obvious to me the informed consent guidelines for foster kids in Washington State primarily protect the State of Washington; not the children in State care.  Let's be real, who in their right mind would believe that it is in the "best interests" of the children and teenagers in Washington State to lower the legal age of consent for psychiatric treatment to thirteen?  Human's brains are not fully fully mature,until we are in our early 20's. Couple this reality with the dishonesty, abuse of authority and of "Medical" privilege that psychiatry is known to rely upon in standard clinical practice; we have in effect, "legally" placed kids in harm's way.