Tamiflu takedown

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

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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 [email protected] or on Twitter @juliaoftoronto