Millions of young people were prescribed a common anti-depressant on the basis of a notorious medical trial that actually showed the drug was neither safe nor effective in children and adolescents, a major review has confirmed.
The new analysis of tens of thousands of pages of GlaxoSmithKline’s ‘study 329’, including documents that were previously confidential, starkly contradicts the original report’s claims about the drug paroxetine.
It is the first study to be reassessed under a pioneering initiative aimed at over-turning the findings of potentially misleading studies, often funded by drug companies.
While the dangers of paroxetin, which can lead to suicidal behaviour and aggression in children and adolescents, are now well established, the reassessment of study 329 marks a milestone in the medical community’s campaign to open up clinical trial data held by pharmaceutical companies to independent scientific scrutiny.
The original trial report, funded by what was then SmithKline Beecham in 2001, was not written by any of the 22 named experts, but by a medical writer hired by the drug company. It concluded that the drug was “generally well tolerated and effective” and led to a marketing campaign that boasted of “remarkable efficacy and safety”.
In fact, according to researchers from the University of Adelaide, writing in the BMJ, an assessment of all the data from the trial supports the opposite conclusion in young people.
Within a year of the original report, the US Food and Drug Administration branded study 239 a “failed trial”. However, in 2002 alone, over two million prescriptions for paroxetine were written for children and adolescents in the USA.
A review by NICE in the UK, in 2004, concluded that the study had made claims of efficacy for paroxetine – sold in the UK as Seroxat - that were not supported, even in the documents then publicly available. Seroxat is still available in the UK, but NICE guidelines state it should not be used for the treatment of depression in children and young people.
GlaxoSmithKline (GSK), which was created in 2000 from the merger of SmithKline Beecham with Glaxo Wellcome, was eventually fined a record $3bn (£2bn) in 2012, in part for the fraudulent marketing of paroxetine.
Despite serious questions over the influence of the drug company on the eventual findings, study 329 has never been withdrawn by the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) where it was first published.
The new assessment in the BMJ is the result of the Restoring Invisible and Abandoned Trials (RIAT) initiative – part of wider movement to force pharmaceutical companies to release all of their data to independent scientific scrutiny. GSK is the only pharmaceutical company signed up to the All Trials campaign, a group co-founded by the BMJ, which is calling for all trials to be registered and all results made public.
Dr Fiona Godlee, editor of the BMJ, said that the review of study 329 meant that an “iconic and infamous paper has now been brought to book”.
She called for legislation to ensure results of all clinical trials, including individual patient data, were made available for “legitimate third party scrutiny”, with criminal convictions for non-compliance, adding that clinical trials should be not be directly paid for or managed by industry.
Responding to the BMJ study a GSK spokesperson said: “We were able to help this team to carry out their reanalysis by providing access to the detailed data from the original trial. This reflects our commitment to data transparency – we publish the results of all our studies regardless of whether they are positive or negative.”
A spokesperson for JAACAP said: “The statements and opinions expressed in JAACAP articles are those of the authors, and not necessarily those of AACAP, the editors, or the publisher.”
The 'open data' movement
The BMJ’s final judgement on the infamous “Study 329” represents a symbolic victory for the burgeoning “open data” movement in health.
Spearheaded by the writer Ben Goldacre, whose 2012 book Bad Pharma accused drug companies of burying unhelpful trial results, the AllTrials campaign, which calls for the open publication of all results from all clinical trials, now has the backing of 615 medical and research organisations, including the Wellcome Trust and the Medical Research Council.
The need for light to be cast upon the clinical trial data held by drug companies was revealed by a recent review in the Journal of the American Medical Association, which found that of 37 reassessments of old trial data, a third led to new interpretations of the data.
GSK is the first pharmaceutical company to join the initiative, and made once-confidential documents available for the new assessment of Study 329.
Earlier this year, the World Health Organisation backed the campaign in principle, saying that researchers have an ethical imperative to make results publicly available, and in July the initiative received a welcome boost when an influential group of drug company investors called for greater transparency.
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