Stockpiling in the dark: Tamiflu and the Public Health Agency of Canada

The Government of Canada reported last week that they are working with pharmaceutical manufacturer Roche to release the neuraminidase inhibitor Tamiflu (oseltamivir) from Canadian stockpiles to ensure availability of the drug for a particularly severe flu season in Canada this year. This move was facilitated by the Public Health Agency of Canada (PHAC) and Health Canada in response to higher than expected demand for the drug.

The agency’s Director of Pandemic Preparedness stated that “given that we are still in the midst of influenza season and given that we certainly do not want to have any kind of supply disruption at this point in time, the Public Health Agency Canada ... has elected to work with Roche to ensure that there will be no supply disruption."

The primary maxim of Evidence-Based Medicine- the whole point of EBM, really- is that clinical decisions should be made according to the best available evidence. We don’t profess to know all the evidence behind what should be stockpiled at a national level in Canada or elsewhere. This complex practice requires an enormous amount of evidence review and surveillance data to determine what will (and could) be needed to safeguard a country.

But we do know something about the evidence base for neuraminidase inhibitors, and the recent controversy about Roche’s withholding of clinical trial data on the use of these drugs to treat influenza. Tom Jefferson and colleagues’ 2009 systematic review and meta-analysis of available data is a great starting point, and notes that publicly available studies, taken together, suggest “modest effectiveness of neuraminidase inhibitors against the symptoms of influenza in otherwise healthy adults”. More importantly, though, their study goes on to note that a “paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza” and that “independent randomized trials to resolve these uncertainties are needed.”

When they reviewed the evidence again in 2012, they were unable to access full clinical study reports despite requesting them from the manufacturer. They concluded that "a high risk of publication and reporting biases in the trial programme of oseltamivir" precluded being able to properly assess the evidence of its effectiveness.

Without this data being available, then, the evidence to support using Tamiflu is questionable at best, and certainly not strong enough to justify stockpiling hundreds of millions of dollars of it for national pandemic preparedness.

What has the PHAC done about this? In 2010, the CMAJ reported that the PHAC reviewed the results of the aforementioned systematic review but “the articles published in the BMJ do not change [the] Public Health Agency of Canada’s advice with respect to the use of antivirals with the H1N1 flu virus.”

The BMJ has taken up this issue of missing clinical trial data, and is pressing Roche to release all its data on Tamiflu trials, and clinical epidemiologists are trying to obtain this data to properly analyze it. Only then, will we know if this drug is truly effective, and if the enormous sum spent on stockpiles around the world was worth it.

The Alltrials petition we wrote about last week is another example of an attempt to remove this critical impediment to scientific progress, and ensure all the necessary evidence is available for decision-making.

Ultimately the decision to prescribe is made by a practitioner acting in patient’s best interest. Beyond understanding relevant guidelines and public health recommendations, we encourage individual practitioners to familiarize themselves with the best available evidence to be the best for their patients. As it stands, we’re slightly bewildered as to PHAC’s decision to promote Tamiflu so strongly, and that’s why we encourage individual practitioners to make their own decisions using the best, most recent evidence.