1 Boring Old Man

Roche Strikes Back at Study That Criticized Tamiflu Stockpiling

Pharmalot WSJ

By Ed Silverman

July 1, 2014

Three months after a study concluded the widely used Tamiflu® treatment was not proven to reduce the spread of the flu or its complications, Roche has struck back by calling the analysis “seriously flawed” and warns the conclusions could lead to public health risks by confusing patients and physicians. In a letter to the British Medical Journal, which published the study, the drug maker claims the authors made “basic errors” in assessing effectiveness data, “over-interpreted” the “limited” safety data that was evaluated and “wholly ignored” other types of data in reaching their conclusion.

The study authors “have drawn many conclusions that would not be supported by a methodologically robust and comprehensive analysis of all relevant [Tamiflu®] data,” Roche scientists wrote. “Equally important, they have not exhibited the diligence necessary when working with large clinical trial datasets and extensive regulatory documents.”

The missive was made in response to a study by the Cochrane Collaboration, a non-profit, global network of health care academics. They concluded that Tamiflu® was no more effective than aspirin, and one of its authors said governments that stockpiled the drug had thrown money “down the drain.” The study, however, did not question the ability of Tamiflu® to treat flu symptoms.

One of the Cochrane researchers wrote us that the authors stand by their conclusions. “Their response was disappointing window dressing designed for those who do not know the story,” Tom Jefferson, a study co-author, wrote us. He adds that a complete rebuttal will soon be provided in BMJ.

Tamiflu® was approved by the FDA in 1999 and became a big seller several years ago as governments moved to stockpile the treatment in the wake of the H1N1 swine flu pandemic. This prompted the Cochrane researchers to assess the effectiveness. They analyzed results from 46 of 107 trials pertaining to both Tamiflu® and Relenza®, a less widely used flu drug sold by GlaxoSmithKline.

But their study was released only after they battled, sometimes publicly, with Roche over access to Tamiflu data, because most of the trial information was unpublished. The episode, which played out in the pages of BMJ as the researchers often chronicled their efforts to convince Roche to release data, became a linchpin in the wider debate over access to clinical trial data harbored by drug makers.

As a result, the European Parliament recently passed a law requiring drug makers to publish all clinical trials related to a drug, but only those approved since January 2014. Both Roche and Glaxo now say they are committed to publishing all clinical study reports on all their drugs, although some Cochrane researchers have also squabbled with Glaxo about data for its Paxil antidepressant.

• The battle over Tamiflu
• What the Tamiflu saga tells us about drug trials and big pharma
• Complications: tracking down the data on oseltamivir

Re: Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

BMJ: Rapid Response

by Carl Heneghan, Tom Jefferson, and Peter Doshi

6 April 2014

With the publication of our systematic reviews on oseltamivir and zanamivir for influenza in adults and children, we are making all 107 full clinical study reports publicly available. Despite the worldwide stockpiling of antivirals, these reports have never been reviewed by the World Health Organization, the US Centers for Disease Control and Prevention [CDC] and its European counterpart, the ECDC.

It took us four years to obtain the full set of reports. The story relating to the acquisition has been documented at the BMJ’s open data campaign [http://www.bmj.com/tamiflu]. If you disagree with our findings, or if you want to carry out your own analysis or just want to see what around 150,000 pages of data look like, they are one click away [http://dx.doi.org/10.5061/dryad.77471].

20 April 2014

Peter M English

Public Health Physician

The comments colleagues and I made previously still stand: http://www.bmj.com/content/339/bmj.b2728

Early in the "containment phase" of the pandemic the health secretary promised that everybody with flu-like symptoms would be given antivirals. The effect of this was that we were obliged to honour this promise. There were not the resources to do this in a timely fashion: most people, while I was involved, were delivered the antivirals a week after the onset of symptoms. We were unable to prioritise high-risk patients.

The government has claimed that the "containment phase" was effective; that the reduction in viral shedding that may plausibly have been a consequence of antiviral treatment slowed the spread of the pandemic. There is no reason to believe that antivirals given more than 48 hours after the onset of symptoms had any other benefit; although respiratory physicians tell me they believe it may have had some benefit in the most seriously ill patients.

16 April 2014

Patrick J Saunders

Professor of Public Health

John Middleton

University of Staffordshire

… We remain concerned however, that the insights of service providers on the ground during the pandemic have not been given the same level of public consideration. It is well documented that even drugs which may be effective in clinical trials can be inefficient, or fail to deliver the patient benefit predicted by trial results, when subject to limitations of general service use. The lessons from service insights in the pandemic are: the wanton abandonment of first principles such as isolation, basic control of infection measures and clinical assessment in favour of the stubborn insistence on managing ‘England as a single epidemiological unit’; and the irrational maintenance of the ‘containment’ phase which led directly to perverse and damaging interventions and over-reliance on antivirals in mass prophylaxis exercises particularly in schools. Anti-viral collection centres became loci for the spread of infection as thousands of symptomatic and sub-clinical cases [there is good evidence that flu can be spread by asymptomatic patients] and unaffected contacts convened for a wonder drug with serious potential side effects, and which would now appear to be no more effective in pandemic management than paracetamol [US name: acetaminophen or Tylenol].

It would be irresponsible for these lessons not to underpin current planning for pandemics and any subsequent responses. We believe there is no place for antiviral distribution in a pandemic based on the current evidence of the effectiveness of the drugs, their ineffectiveness for mass prophylaxis and the likely spread of infection brought about by bringing people to a centre for the drugs.