Tamiflu takedown

Researchers ask Canada’s public health agency the tough questions, and the answers aren’t very reassuring

by Julia Belluz

kanonn/Flickr

Unpredictable, wily, erratic: If the seasonal flu were a person, he would be Charlie Sheen. In any given year, the U.S. Centers for Disease Control and Prevention estimates influenza-associated deaths range from a modest 3,000 to the population of a small city, or 48,000. To confront this annual onset, public health agencies ready themselves with preventative measures (flu vaccine) and treatments (such as Tamiflu).

Last month, during peak flu hysteria, the Public Health Agency of Canada made an announcement: that it would release a bunch of the influenza drug Tamiflu from the emergency national stockpile to ensure all Canadians who needed the medication had access. The release was suspect for one key reason: it did not reflect any of the doubts and questions that have been raised by the international research community about Tamiflu, namely, recent high-quality studies that show the medicine may not be as effective as the drug-maker claims.

At the time, PHAC pointed to data that was nearly a decade old to explain its decision. Not exactly ideal evidence-informed policy-making. So Science-ish asked officials at PHAC to elaborate on the research behind their decision.

Four weeks later, on Tuesday, a trio of high-ranking officials were assembled to explain the agency’s reasoning. Dr. Barbara Raymond, director of pandemic preparedness, explained PHAC’s position this way: “We continue to feel that the balance of the evidence supports the use of these antivirals, particularly in high-risk individuals and for pandemic purposes.”

That’s because, she said, even though the best-available research—systematic reviews and randomized trials, which Science-ish explained here—may not show confidence-inducing results for Tamiflu, newer observational studies do. (See this friendly footnote on the difference between observational and experimental science*.) In particular, Raymond cited this recent review of the observational literature on antivirals for influenza, which found the drugs “may provide a net benefit over no treatment of influenza.”

Science-ish read the study, and it wasn’t very reassuring. The investigators set out to review observational science on treating influenza with antivirals. They took together 74 studies, and concluded that “as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low.”

Researchers who have looked at Tamiflu’s effectiveness and pandemic planning weren’t very impressed with PHAC’s position, either. “Does PHAC endorse making these types of decisions on the basis of very partial evidence when more complete evidence is potentially available?” York University drug regulatory expert, Dr. Joel Lexchin, asked.

Braden O’Neill, a University of Oxford scholar who has been following Canada’s pandemic planning, said in an email to Science-ish, “In this situation, it’s unethical to promote (Tamiflu) on the basis of low quality evidence while ignoring higher quality evidence that calls into question its effectiveness.”

He asked why, if PHAC only considers Tamiflu effective for people with high-risk conditions, they stockpile enough antivirals to treat nearly one-fifth of the population. “Are they saying that 17.5% of the population of Canada is going to: A. develop influenza, B. seek treatment, and C. have a ‘high-risk condition?’”

No doubt, public health decisions are not easy to arrive at. As Dr. Greg Taylor, PHAC’s deputy chief public health officer, explained, “It’s a net balance (of the evidence). Science is not black and white.” That is certainly true. So the researchers asked PHAC to reveal exactly what studies they feel tilt the evidence in favour of supporting the use of Tamiflu.

For now, PHAC said that it is in the process of reviewing and revising its national pandemic influenza plan, but could not say when the process would be complete. Since the last revision, in 2009, four years’ worth of research has accumulated. “There have been fundamental changes in the evidence base for Tamiflu,” O’Neill said, “yet PHAC has no timeline or clear procedure for when to update a plan that involves stockpiling hundreds of millions of dollars worth of a drug based on seven- to ten-year old evidence.”

*In a well-designed randomized controlled trial, one group of participants receives a medical treatment, and another gets nothing or a placebo, and since the only difference between the two groups is the treatment, researchers can usually conclude that any difference in outcome was the result of the treatment. Unlike trials, observational research is non-experimental. In observational studies, researchers are looking at “free-living people”—not trial participants—and how their exposure to something (ie. coffee) is associated with a certain health outcome (ie. risk of death). Since these studies are not experiments, researchers can never control for all confounding factors, or the unmeasurable and random things that may influence the outcomes of the study. (Ie. People who drink coffee may be healthier because sick people tend to avoid coffee, so they may live longer, but that’s because they are already healthier to begin with, not because of the coffee.) For this reason, observational studies can only tell about the associations between treatments and effects—and not causitive links—so they tend to rank lower on the evidence hierarchy.

Science-ish is a joint project of Maclean’s, the Medical Post and the McMaster Health Forum. Julia Belluz is the senior editor at the Medical Post. Got a tip? Seen something that’s Science-ish? Message her at julia.belluz@medicalpost.rogers.com or on Twitter @juliaoftoronto




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Tamiflu takedown

  1. Great article – thanks Julia.

    • Macleans is refreshing, good journalism. Its why I just subscribed to the print version. Or votes with money and subscriptions is better than democracy.

  2. I am always suspicious of supposedly “science” (understanding it is only science-ish) and “fact based” based columns where the writer’s “opinion” on how evidence is weighted serves as the basis for “proving” one side (the side she does not favour?) has made the wrong decision, especially such a complex decision.

    The column is also tainted by the opinion provided by York’s “drug regulatory expert”, Dr. Joel Lexchin who speaks of “very partial evidence” and “more complete evidence”. Given the complexity of analyzing the available data, it is difficult to believe an “expert” such as Dr. Lexchin, who apparently does not realize that there are no degrees of partiality or who feels that an item may be “more complete” (sort of like the 150% that coaches strive for from their players…) can understand the interplay of proof and data that must exist on this important topic.

    Overall, the column comes across as sophomoric and facile. Clearly intended to undermine the government department in question, rather than inform the public (stated purpose?) and increase understanding, allowing intelligent readers to draw their own conclusions.

  3. Maybe PHAC released their stockpile of Tamiflu to get rid of it in advance of a new policy that will acknowledge high-quality evidence that it is not as effective as the drug maker claims. Maybe they just don’t want to be left holding millions of dollars’ worth of a dud drug.

  4. A valid article in that the Public Health Agency of Canada (PHAC) spends millions and millions of dollars and are never called ‘to task for’ in many cases a waste of our tax dollars.
    This Tamiflu article is an excellent example of stockpiling so much of a drug that may or may not be of significant benefit based on good science.
    Another prime example is ‘salt 101′. where millions are spent to make the sodium in salt being equated to a poison when in fact for 80% of the population sodium and/or salt is not an issue and in fact is normally excreted.
    The huge numbers of medical specialists in the PHAC, the management and the government should be taken to task from time to time in justifying significant amounts of tax dollars spent by this agency.

  5. Enlightening article. Thank you.

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