Two years ago, pharmaceutical giant, Roche, promised the BMJ to release key Tamiflu trial data for an independent investigation. However, Roche refuses to provide full access to all its data. According to a new report by the Cochrane Collaboration, Roche’s refusal to provide access leaves critical concerns about how the drug works unresolved.
A BMJ investigation, published at the same time as the report, also voices serious concerns regarding drug data access, the drug approval process and the use of ghostwriters in drug trials.
Because Tamiflu has become a common influenza treatment in the UK, with the World Health Organization also adding the drug onto their list of Essential Medicines, Roche continues to declare that it is supported by influential health agencies.
When Cochrane researchers decided to investigate into Roche’s claim that Tamiflu prevented complications and reduced the number of people in need of hospitalization, they found their investigation to be jeopardized by Roche’s refusal to provide all of its trial data for analysis. They managed to obtain some clinical study reports from the European Medicines Agency (EMA), but discovered that these were inconsistent with published reports and potentially under-reported the drug’s side effects. The BMJ questioned Roche earlier, with Roche admitting that some of its published papers had been written by ghostwriters.
The BMJ study shows how various regulators applied different approaches to the data that was submitted to them, which lead to conflicting messages in terms of the drug’s effectiveness, for example, even though Cochrane obtained a proportion of Tamiflu’s clinical study reports of the trials from the EMA, it admits not asking for the remainder from the manufacturer despite being legally entitled to do so. Since then, the EMA has informed the BMJ of its plans to start publishing reports for all drugs submitted for approval within the next few years.
Dr Fiona Godlee, BMJ Editor-in-Chief declared: “We hope very much that the EMA will indeed take this important step in making the full study reports available. But we are still a long way away from having a full trial history for all drugs in clinical use. Public safety and the proper use of public money demands that we should stop at nothing less than this.”
In the meantime, the US Food and Drug Administration (FDA), decided not to review the largest ever trial of Tamiflu during its drug approval process, even though it reviewed the Tamiflu trial program in probably more detail than anyone outside of Roche. The FDA declares that, “Tamiflu has not been shown to prevent such complications [serious bacterial infections].” In contrast, the US Centers for Disease Control and Prevention (CDC) carries on quoting key published trials of Tamiflu that declare the drug has a lower risk of influenza complications, even after Roche’s confession of using ghostwriters for some of these trials.
Dr Godlee warns: “The discrepancies between the conclusions reached by different regulators around the world highlights the absurd situation we find ourselves in. In a globalized world, regulators should cooperate and pool their limited resources. Otherwise we will continue to waste money and risk people’s health on drugs that don’t work.”
The investigation has also brought questions about Tamiflu’s clinical effects into light. The Cochrane researchers state that after a thorough assessment of trial data Tamiflu seems to affect the production of antibodies, a statement that Roche refutes. The team highlights the importance given that influenza vaccination relies on antibody response to be effective, however when the BMJ questioned Roche, they refused to explain how the drug operates. The Cochrane researchers therefore comment that “until more is known about the mode of action of neuraminidase inhibitors, health professionals, patients and other decision makers need to reflect on the findings of this review before making any decision about the use of the drug.”
Cochrane also disputes claims of Tamiflu’s ability to prevent influenza from spreading, as it has not been proven in trials, however this is one of the main reasons why governments worldwide have spent billions of dollars to stockpile Tamiflu in case of a pandemic.
Roche claims that they have provided the Cochrane team with sufficient information to carry out their investigation, yet according to the Cochrane team this is untrue.
Dr Peter Doshi from Johns Hopkins University School of Medicine declares: “In the BMJ in December 2009, Roche promised full study reports to any legitimate investigators. They have not provided a single full study report to Cochrane, despite our repeated requests.”
Written by: Petra Rattue