Two months ago, we pointed out in our story on flu in The Atlantic that the antiviral drug Tamiflu might not be as effective or safe as many patients, doctors, and governments think. The drug has been widely prescribed since the first cases of H1N1 flu surfaced last spring, and the U.S. government has spent more than $1.5 billion stockpiling it since 2005 as part of the nation’s pandemic preparedness plan.
Now it looks as if our concerns were correct, and the nation may have put more than a billion dollars into the medical equivalent of a mirage. This week, the British medical journal BMJ published a multi-part investigation that confirms that the scientific evidence just isn’t there to show that Tamiflu prevents serious complications, hospitalization, or death in people that have the flu. The BMJ goes further to suggest that Roche, the Swiss company that manufactures and markets Tamiflu, may have misled governments and physicians. In its defense, Roche stated that the company “has never concealed (or had the intention to conceal) any pertinent data.”
The BMJ’s investigation began innocently enough, with an update of a review by the Cochrane Collaboration, a widely-respected international consortium of researchers who periodically examine the medical literature to assess the safety and effectiveness of various treatments. Roche has claimed that its drug reduces hospital admissions by 61% in patients who were otherwise healthy before they got the flu. It has also said that Tamiflu reduces such complications as bronchitis, pneumonia, and sinusitis by 67%, and lower respiratory tract infections requiring antibiotics by 55%. A 2006 Cochrane review of Tamiflu came to similar conclusions—based largely on a paper that looked at ten studies, all of them funded by the company.
The dog ate my homework
But when the Cochrane team, led by Chris Del Mar, from Bond University in Australia, re-examined the studies they had previously used in 2006, they found some discrepancies. It turned out that only two of the ten studies had ever been published in medical journals, and those two showed the drug had very little effect on complications compared to a dummy pill, or placebo. So the Cochrane reviewers decided to look at the data for themselves.
First they went to the lead authors of the published studies—the researchers who were supposed to have access to all of the data. One author said he had lost track of the data when he moved offices and the files appeared to have been discarded. The other said he’d never actually seen the data himself, and directed the Cochrane team to go directly to the company.
Four months and multiple requests later, the Cochrane researchers had a hodgepodge of data from the company, including two studies that showed the drug was ineffective, but which the company had never published. Roche also provided data from a third study, which involved 1,447 adults and adolescents aged 13-80, the largest study of the drug ever conducted. Yet the company never published that one either. (A summary of this and other studies is available at www.roche-trials.com). But with only partial data, the Cochrane team couldn’t even figure out what the study had been intended to measure.
In the meantime, two former employees of Adis International, a large communications company, came forward with documents showing they had ghostwritten some of the published studies of Tamiflu. One of the ghostwriters told the BMJ, “The Tamiflu accounts had a list of key messages that you had to get in. It was run by the [Roche] marketing department and you were answerable to them. In the introduction . . . I had to say what a big problem influenza is. I’d also have to come to the conclusion that Tamiflu was the answer.”
The Cochrane team eventually concluded that the evidence that Tamiflu reduces complications, hospitalizations, or deaths is weak at best, and if the drug does offer any benefit, it is slight indeed. This is precisely the conclusion of the U.S. Food and Drug Administration (FDA), and the UK’s National Institute for Health and Clinical Excellence (NICE). As we reported in our story in The Atlantic, the FDA directed Roche to state on the drug’s label the following caveat: “Tamiflu has not been proven to have a positive impact on the potential consequences (such as hospitalizations, mortality, or economic impact) of seasonal, avian, or pandemic influenza.” An FDA spokesperson told the BMJ, "The clinical trials . . . failed to demonstrate any significant difference in rates of hospitalization, complications, or mortality in patients receiving either Tamiflu or placebo.” Yet in the wake of the H1N1 pandemic, the FDA gave temporary approval for the drug to be given to hospitalized flu patients, who are at risk of dying.