January 29, 2007, 8:30 p.m. GMT
(In the United States via Internet: 12:30 p.m. PST;
2:30 p.m. CST; 3:30 p.m. EST)
Documents Reveal Academic "Thought Leaders" Hired by Drug Maker Promoted Paxil for Children and Adolescents Despite Clinical Trials
Showing the Drug Was Ineffective and Unsafe
On Monday, January 29, 2007, BBC-One will air " Secrets of the Drug Trials," a program detailing the investigation by reporter Shelley Jofre, which reveals how "one of Britain's biggest drug companies misled doctors into prescribing the antidepressant Seroxat (known as Paxil in the US) to teenagers, even after one of its own clinical trials indicated that they were more likely to become suicidal after taking it." This program is Panorama's fourth in a series involving the selective serotonin reuptake inhibitor (SSRI) Paxil.
The BBC program touches on a number of important issues, such as:
Academics serving as spokespersons for the pharmaceutical industry;
Medical journal articles ghostwritten by PR companies working for industry
and academics lending their names to the process;
Promotion of drugs as more effective than they are, while downplaying side effects
See the British Medical Journal's review of the program: "Inside big pharma's box of tricks"
Ms. Jofre's October 2002 program "The Secrets of Seroxat" launched a firestorm of controversy and generated an unprecedented 65,000 telephone calls and emails to BBC in response. British regulators thereafter appointed a panel of experts to examine Paxil studies for treatment emergent suicidal behavior.
On June 10, 2003, the regulators announced that a review of the Paxil studies showed that the drug failed to demonstrate efficacy and showed "an increase in the risk of harmful outcomes including episodes of self-harm and potentially suicidal behavior in the [Paxil] group compared to placebo." Six months later, on December 10, 2003, U.K. regulators announced they would contra-indicate the use of most antidepressants in children and adolescents in the UK. The US FDA followed suit the following year, in 2004, instructing manufacturers of antidepressants to include a "black box" warning regarding the increased risk of suicidality in children and adolescents.
Many of the documents in the BBC's upcoming program were obtained through a consumer fraud class action lawsuit filed by Baum Hedlund. The lawsuit, which is pending in a California court, was filed on June 21, 2004 against Paxil's maker, GlaxoSmithKline (GSK) alleging the company suppressed evidence of Paxil's failed efficacy and increased risk of suicidality in children and adolescents.
For the past two and a half years, Baum Hedlund has amassed and reviewed hundreds of thousands of pages of documents and taken numerous depositions of GSK employees and academic "thought leaders" hired by GSK to promote Paxil. Although virtually every document produced by GSK is stamped "confidential," Baum Hedlund attorneys were able to get some of the documents out from under confidentiality seal by court order or by getting GSK to concede that the documents were not properly labeled confidential trade secrets to begin with.
articles re ghostwriting, academics and pharmaceutical industry
"The SSRI Trials in Children: Disturbing Implications for Academic Medicine" by Jonathan Leo, PhD
Inside big pharma's box of tricks
Collier BMJ.2007; 334: 209
January 27, 2007Views & reviews
REVIEW OF THE WEEK
Joe Collier, professor of medicines policy and consultant in clinical pharmacology, St George's Hospital and Medical School, London
Joe Collier is impressed by a BBC documentary about the marketing of paroxetine.
The list of examples of big pharma's trickery seems endless (even though many of those employed in it are of the highest calibre and of unquestionable integrity). Indeed, it is as though, in the marketing arm of some drug companies, mischief is institutionalised. But much of this is recognised, and the adverse effects of drug companies could be countered by alert regulators, scientists, prescribers, and the medical press. All too often, however, these checks fail. There is even evidence that, in some cases, these counter-forces collude with industry and so compound its indiscretions. It is this area, the interplay between industry and some of the would-be counter-forces, that Panorama's "The Secrets of Seroxat" seeks to tackle.
Panorama has been investigating drug companies' behaviour for years, and this inquiry is its third involving selective serotonin reuptake inhibitors (SSRIs), and in particular Seroxat (paroxetine), since 2002.
It deals primarily with GlaxoSmithKline's history as it relates to the development of paroxetine for the treatment of children with depression.
Drawn into the frame are opinion formers and medical journals, and the picture painted is one of a conspiracy orchestrated by the company in which doctors have been misled, regulators duped, journals exposed, and children harmed.
The story is said to be based on information gained from "secret" company files made available through court cases and freedom of information regulations. It starts with the company discovering the results of trials it has commissioned to investigate the value of paroxetine in the treatment of adolescent depression: the product was found to be no more effective than placebo and able to cause serious psychological side effects such as self harm, suicidal thoughts, and suicidal attempts.
At the time the company had wanted to license the drug for use in depressed children but privately realised that with such information an application would be unsuccessful. The inquiry then tells of how the company is claimed to have "written up" the trial for publication, bought and manipulated (apparently willingly) opinion formers, worked to promote the product for use in children (although it was not, and never has been, licensed for such use), and distorted information about the safety and efficacy of the drug in letters to prescribers, in advice to their sales force, and in messages to the media.
The programme covers many areas, and claims that there was a failure by the company to reveal material about Seroxat to the regulatory authorities and a failure by the regulatory authorities to recognise and respond to the various problems with due speed. But these are areas in which Panorama has investigated before. It is the pursuit of media manipulation that now gets particular attention. The inquiry claims that the manufacturer, through its agencies, "ghost wrote" the major trial that was subsequently published in the Journal of the American Academy of Child and Adolescent Psychiatry, and how that in the "writing" data were distorted to maximise the known benefits and minimise known harms.
It also reports that key named authors of the paper do not appear to have critically read the report; how the journal editors had failed to spot the distortions (although at least one other medical journal had been concerned enough to reject the article earlier); how key opinion formers "promoting" the product were so close to the company financially and intellectually that they could not possibly offer independent advice; and how drug company spokespeople simply lied to the media when pressed about the product's side effects.
If these claims are well founded, patients deserve better. Panorama has made its contribution by telling this story. It has reminded us again of a social contract involving drug producers, drug prescribers, drug regulators, and information suppliers. In a properly functioning society, openness and honesty should be assumed and certain standards of behaviour expected. Indeed, in an ideal world, drug companies should be trusted. It has to be recognised that not all activities can be controlled through legislation; rather they rely on good practice and honesty and a will not to cheat patients.
It does seem to be the case that regulatory authorities now appear to be more prepared to tackle these issues and prescribers now have greater insights into drug company behaviour and have every reason to be vigilant. For their part, professional bodies must start to look seriously at how their members behave and bring to book those who mislead (or collude in misleading) others about drug properties.
The new players to enter the equation are the medical journals. These provide a crucial conduit between drug companies and society at large as they publish original papers, opinion pieces, and, of course, advertisements for drugs.
Many are suspicious of the media, but as is often the case it is the media (and typically Panorama) that will have been important in prompting much needed change. It seems silly that we should need the media to shame us into altering our ways; surely we should be proactive and get there first.
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