Pharmaceutical companies should make full data from their clinical trials publicly available so the risks and benefits of the drugs can be independently analysed, researchers say.
The researchers have documented a number of cases in which access to full trial data “radically changed public knowledge of safety and efficacy” of widely used drugs, including Vioxx and Tamiflu.
Professor Chris Del Mar points to insufficient evidence that Tamiflu – stockpiled by the Australian Government in 2009 to quarantine swine flu – had any preventative effect.
Professor Del Mar, from the Centre for Research in Evidence-Based Practice at Bond University, and colleagues presented their argument today in the peer-reviewed Public Library of Science Medicine journal.
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“It is the public who take and pay for approved drugs, and therefore the public should have access to complete information about those drugs,” the researchers said.
Earlier this year Professor Del Mar was involved in a review of Tamiflu, which concluded that although it does reduce symptoms, there is no reliable evidence the drug reduces the complications of influenza and hospitalisations.
He says governments around the world rushed to stockpile Tamiflu largely on the basis of these claims.
“All the data we’ve seen so far suggests it’s no better than aspirin. It could be, but we don’t have the data to say so,” Professor Del Mar said.
He adds the available evidence is insufficient to tell whether Tamiflu is successful in preventing influenza and stopping its transmission.
Professor Del Mar says there is far better evidence available for physical barriers such as handwashing, masks, gloves and quarantining.
Turned on its head
Professor Del Mar says the evidence for Tamiflu reducing hospitalisation came from a publication which summarised data from a number of trials by drug manufacturer Roche.
“It wasn’t until you scratched it a bit that you realised there was a problem,” he said.
In 2009, the professor and his research group sought to verify the conclusions of the published study by checking lengthy clinical study reports, which describe in detail what happened in the trials.
When the first author of that study did not have the full data, Professor Del Mar and his team turned to Roche, but after two years of “extensive correspondence” they only received a fraction of the reports from the company.
Professor Del Mar’s group then supplemented the incomplete data from Roche with reports obtained from regulators under freedom of information requests, along with leaked documents.
“This information has turned our understanding of the drug’s effects on its head,” the researchers said.
“Our review has led to the detection of numerous reporting biases and fundamental problems in trial design, and we have concluded that previous effectiveness claims were not supported by the available evidence.”
The researchers also found evidence that serious adverse events were not reported in published papers.
“The drug companies are not publishing some of the experiments they’ve done,” Professor Del Mar said.
“Suspicious people around the world say, ‘well, it’s because those data don’t say what the drug company wants to show and will affect their shareholders’ interest’.”
In a statement to ABC Science Online, Roche said it stood by the efficacy and safety of Tamiflu.
It said it provided the Cochrane research group that analysed Tamiflu with access to 3,200 pages of very detailed information, and says more information was made available on a password-protected site.
“Roche has made full clinical study data available to global health authorities, including the Therapeutic Goods Administration (TGA), for their review as part of the licensing process,” the statement says.
“It is the role of global health authorities to review detailed information on medicines when assessing benefit and risk.”
But Professor Del Mar says the TGA is not resourced to properly review the vast amount of information it is sent.
He says the better-equipped US Food and Drug Administration (FDA) has rejected some claims made by Roche, including that Tamiflu reduces the complications of influenza and hospitalisations.
A spokeswoman for the TGA says the Australian Government stockpiled $179 million worth of Tamiflu and the related antiviral Relenza.
She says TGA approves Tamiflu in Australia for the treatment and prevention of influenza but is yet to see the full data on the drug’s effect on influenza complications and transmission.
“The TGA expects full study reports containing study protocol, reporting analysis plan, statistical analysis plan and individual patient data to clarify outstanding issues. These full clinical study reports are at present unavailable to us.”
And those reports in the TGA’s possession so far are being kept secret.
“At the current time the TGA does not make full clinical study reports publicly available as they are provided to the TGA as commercial-in-confidence information at the time of an application,” the TGA spokeswoman said.
The TGA is currently developing a policy on the disclosure of commercially confidential information.
Meanwhile, European regulators agree financial conflicts of interest can distort research findings and that clinical trial data should not be kept secret.
But they challenge the idea that independent academics are free from conflicts of interest.
“Personal advancement in academia, confirmation of previously defended positions, or simply raising one’s own visibility within the scientific community may be powerful motivators,” write representatives from a number of European regulators in a response to Professor Del Mar, appearing in the same issue of PLoS Medicine.
“More often than not, ego trumps money.”
Professor Del Mar disagrees, saying while professional conflicts of interest exist, “a few crackpot academics at a few tin-pot universities” would be no match for the huge financial interests of big pharmaceutical companies.