The Truth About Tamiflu"

" 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."

The Truth About Tamiflu"

The Atlantic (December 10, 2009)
http://www.theatlantic.com/doc/200912u/tamiflu

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."

Stockpiling

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.

Another big unknown is just how safe-or dangerous-Tamiflu may be. According
to an FDA spokesperson, side effects may include potentially fatal heart
problems. If the drug is going to be used to prevent death, it seems
reasonable to ask whether or not its potentially deadly side effects are
outweighed by potential benefits. We asked the FDA whether it had required
Roche to conduct an additional trial or trials looking at whether or not, on
balance, the drug reduces more serious complications than it causes. This
week, a spokesperson reported back that there has been no such request made
to Roche.

All of which leaves open the question of why governments around the world
have invested so much-on the order of $3 billion since the emergence of H1N1
last spring, according to investment bank, JP Morgan-in a drug that appears
to do so little.

The answer may lie in the politics of disease. Far from a commercial success
when it was initially approved by the FDA in 1999, Tamiflu's fortunes began
to look up in 2003, after the SARS outbreak and the emergence of bird flu.
Then Hurricane Katrina hit. In the wake of criticism over its handling of
the disaster in New Orleans, the Bush Administration announced a
multi-billion-dollar pandemic and bioterrorism preparedness strategy, which
included stockpiling millions of doses of Tamiflu.

As the nation's lead public health agency, the Centers for Disease Control
and Prevention appears to be operating in some alternative universe, where
valid science no longer matters to public policy. The agency's flu
recommendations are in lockstep with Roche's claims that the drug can be
life-saving-despite the FDA's findings and despite the lack of studies to
prove such a claim. What's more, neither the CDC nor the FDA has demanded
the types of scientific studies that could definitively determine whether or
not the company's claims are true: that Tamiflu reduces the risk of serious
complications and saves lives. Nancy Cox, who heads the CDC's flu program,
told us earlier this year she opposes a placebo-controlled study (in which
one half of patients would be given Tamiflu and the other half would be
given placebo), because the drug's benefits are already proven.

There are a couple of take-home messages here. One is pretty obvious:
Tamiflu may not be doing much good for patients with the flu who take it,
and it might be causing harm. The more important issue, however, involves
the need for trust in science and medicine. Governments, public health
agencies, and international bodies such as the World Health Organization,
have all based their decisions to recommend and stockpile Tamiflu on studies
that had seemed independent, but had in fact been funded by the company and
were authored almost entirely by Roche employees or paid academic
consultants. So did the Cochrane Collaboration, at least in its earlier
assessments of Tamiflu. Millions of flu patients have taken the drug as a
result.

That trust appears to have been misplaced, and a drug touted as beneficial
on the basis of flimsy evidence has by now become so entrenched that no one
appears willing to conduct the sort of study needed to prove whether or not
it can, in fact, save lives.

Shannon Brownlee is a senior research fellow at the New America Foundation
and the author of Overtreated (2007). Jeanne Lenzer is an investigative
journalist and a frequent contributor to the British medical journal BMJ.