WhatFinger


"Paxil turned me into a monster:" The still-unfolding story of GlaxoSmithKline's Study 329

The ghost writer



On 29 January 2007, the BBC news program Panorama aired the documentary, "Secrets of the drug trials." This episode, presented by BBC reporter Shelley Jofre, detailed the behind-the-scenes attempts to spin the results of SmithKline Beecham's Study 329 of Paxil, which was published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry. (In 2000, SmithKline Beecham merged with Glaxo Wellcome to form GlaxoSmithKline, at the time the biggest drug company in the world.) This was the fourth documentary about Paxil produced by Panorama, which had never before repeated a subject. The episode revealed internal GSK documents, made available by the law firm of Baum Hedlund, which acknowledged that GSK's own studies had shown the drug was either safe or effective for treating depression in adolescents:
  • "The possibility of obtaining a safety statement from this data was considered but rejected."
  • "The best which could have been achieved was a statement that although safety data was reassuring, efficacy had not been demonstrated."
  • "Consultation of the marketing teams confirmed that this would be unacceptable commercially."
Series: Part 1: “I tried killing myself thirty times” Part 2: “Remarkable efficacy and safety” Part 3: “An effective drug treatment” Part 4: The Ghost Writer Part 5: It's shameful" Karin Barth Menzies, a partner at Baum Hedlund, told Panorama "They figured out ways that they could downplay the risks, blow up out of proportion the supposed benefits or the good sides of the study and really downplay the negative findings." This task fell to Sally K Laden of Scientific Therapeutics Information, Inc. She had not taken part in the study design nor the collection of data, but it was to her that GlaxoSmithKline gave the task of presenting the data from Study 329 in the best light possible. The manuscript she produced became the JAACAP paper, which listed as first author Doctor Martin B Keller, from the Department of Psychiatry and Human Behavior at Brown University, along with 21 others. A 1999 article in the Boston Globe by reporter Alison Bass revealed that in a two-year period, Dr. Keller had taken a million dollars from the pharmaceutical industry, and that he had not disclosed the full extent of his financial ties to the drugmakers, either to the medical journals that published his research, or to the American Psychiatric Association, which sponsored meeting where Dr. Keller presented his findings. Ms. Laden was not listed as an author of the JAACP paper, although a note in fine print at the bottom states "Editorial assistance was provided by Sally K Laden, M.S." In a memo to Dr. Keller, Ms. Laden states that all the materials necessary for submitting Study 329 are enclosed, right down to the cover letter. "Please re-type on your own letterhead," the memo helpfully advises. "Revise if you wish." The term "ghost writer" has often been used to describe Ms. Laden's role. In a telephone interview, Dr. Healy explained "Most medical articles--when I say ‚Äòmost,' I mean over ninety percent--that are done on patent drugs--that's drugs that are recently released, that the company is in the business of marketing--will be ghostwritten." He went on to argue that the term "ghost writer" has been misapplied. "The ghosting actually applies to the fact that you've got a bunch of workers there who haven't ever seen the data. Their names are there on the authorship line, but they're ghostly presences. They're not real, if you see what I mean."

Support Canada Free Press


After Panorama began its investigation of Paxil, emails archived by GSK revealed that Doctor Neal Ryan of the University of Pittsburgh, one of the notional authors of JAACAP paper, had consulted GSK for advice to respond to questions from BBC reporter Shelley Jofre. "This supposedly independent academic was asking the company that sponsored his research how to respond to me," Ms. Jofre told viewers. In 2008, a year after "Secrets of the drug trials" aired, the International Journal of Risk and Safety in Medicine published a paper by Doctor Jon Jureidini and two others which re-analyzed the data from Study 329, using secret documents obtained by Baum Hedlund. They found the original study protocol, as designed by Dr. Keller, listed two primary outcome measures along with six secondary outcomes. There was no significant difference between Paxil and placebo for any of these eight measures. Investigators looked at at least 19 other outcomes; for four of these, Paxil performed significantly better than placebo, while for the remaining 15 it did not. In plain English, Paxil did better than placebo for four out of 27 outcome variables that were looked at, or fifteen percent of them. The final paper reported on all four outcome measures for which paroxetine outperformed placebo, and only four out of 23 for which it did not. In addition, four of the eight originally specified outcome measures were dropped from the final paper, and replaced by the four for which investigators actually found a significant difference between Paxil and placebo. The practice of switching of study endpoints has a name: Hypothesizing After Results are Known. In a telephone interview, Dr. Jureidini explained: "When you do a study like this, people tend to measure a lot of things. You might end up with certainly tens or maybe a hundred different things you're measuring. If researchers have discretion to use any of those hundred outcomes that suit them best then the temptation is, obviously, that they use the ones that make the drug look most positive." In addition, while the JAACAP paper reported that five youths given Paxil had displayed serious "emotional lability" (all five had self-harmed or reported emergent suicidal ideas), Jureidini and his colleagues found that the company's final internal report listed an additional three such cases. In other words, eight of 93 youths given Paxil experienced self-harm or emergent suicidal ideas, as opposed to one out of 87 given placebo. While the original JAACAP paper had claimed "[Paxil] is generally well-tolerated and effective for major depression in adolescents," Jureidini and his colleagues concluded ‘Study 329 was negative for efficacy and positive for harm.'" The years that followed brought more bad news to GSK in particular and the drug companies in general. Doctor Irving Kirsch and his colleagues used a Freedom of Information Act request to obtain data for all clinical trials submitted to the FDA for four antidepressants, including Paxil. A meta-analysis of these data showed these drugs were not significantly better than a placebo in treating depression. All but one of the studies Kirsch and his colleagues looked at were for patients with "very severe depression," and omission of that one study did not change the results. Kirsch's 2010 book, The Emperor's New Drugs: Exploding the Antidepressant Myth, was a devastating indictment of biological psychiatry. That same year, a study published by Thomas J Moore of the Institute for Safe Medication Practices and his colleagues tabulated violence case reports as a percentage of all serous adverse event reports submitted to the FDA for a five-year period. A total of 484 drugs, including eleven antidepressants, were included in their analysis. The eleven antidepressants, including Paxil, stood out from the pack with a whopping 578 violence case reports, or 30 percent of the total. Only the stop-smoking drug Chantix had a stronger violence signal. The following year, an even more devastating indictment of biological psychiatry, Anatomy of an Epidemic, was published by author Robert Whitaker, who showed that the proportion of Americans disabled by depression had skyrocketed since so-called "antidepressants" were introduced. That makes no sense if you believe these drugs are curing depression. It makes perfect sense if you accept that these drugs cause depression. On 2 July 2012, the United States Department of Justice announced that GlaxoSmithKline had agreed to pay $3 billion to settle claims of illegal marketing of its products, including Paxil as well as the anti-diabetes drug Avandia. This was the largest settlement of its kind in history. The morning the settlement was announced, shares of GSK stock rose 1.3%. In a telephone interview, Dr. Healy noted "The harms that these drugs cause are built into the price industry charges for the drugs, as a cost of doing business." Meanwhile, the saga of Study 329 was still not over. Next: Part 5: "It's shameful"

List of Sources

  1. Jon Jureidini, telephone interview, 23 September 2015.
  2. David Healy, telephone interview, 24 September 2015.
  3. Bass, A. 1999. Drug companies enrich Brown professor. Boston Globe October 4 1999.
  4. Jureidini, J. et al. 2008. Clinical trials and drug promotion: Selective reporting of Study 329. International Journal of Risk and Safety in Medicine 20:73-81.
  5. Kirsch, I. 2010. The Emperor's New Drugs: Exploding the Antidepressant Myth. Basic Books.
  6. Moore, T.J. et al. 2010. Prescription drugs associated with reports of violence towards others. Retrieved 13 September 2015.
  7. Whitaker, R. 2011. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Broadway Books.
  8. United States Department of Justice 2012. GlaxoSmithKline to plead guilty and pay $3 billion to resolve fraud allegations and failure to report safety data. Retrieved 7 September 2015.
  9. Riley, C. and E.J. Fox 2012. GlaxoSmithKline in $3 billion fraud settlement. Retrieved 7 September 2015.


View Comments

Patrick D Hahn -- Bio and Archives

Patrick D Hahn is the author of Prescription for Sorrow: Antidepressants, Suicide, and Violence (Samizdat Health Writer’s Cooperative) and Madness and Genetic Determinism: Is Mental Illness in Our Genes? (Palgrave MacMillan). Dr. Hahn is an Affiliate Professor of Biology at Loyola University Maryland.



Sponsored