Map of life expectancy at birth from Global Education Project.

Friday, December 11, 2009

Nobody here but us chickens . . .

guarded by the fox. This is a somewhat complicated story, but I'll try to make it simple. I'll try.

In today's BMJ there is a rather unusual Cochrane review of oseltamivir, brand name Tamiflu, which is supposedly an effective treatment for influenza. As co-author Peter Doshi discusses elsewhere in the issue (prescription subscription only), the CDC has stated that oseltamivir reduces the risk of hospitalization and pneumonia; and as part of preparedness for the so-called "pandemic" of H1N1 influenza, spent billions of dollars stockpiling the drug. In the UK, in the midst of the "pandemic" panic, hundreds of thousands of people were given prescriptions for the drug after telephone consultations, without ever seeing a physician.

Oh, wait a minute. What's a Cochrane review, you ask? The Cochrane Collaboration is an international non-profit organization that promotes understanding of evidence based medicine by promoting so-called meta-analyses -- a systematic approach to incorporating results of multiple studies into a stronger overall picture of the effectiveness of drugs and other medical interventions.

So, it turns out that an earlier Cochrane review had found that oseltamivir is effective in reducing complications from influenza in otherwise healthy adults. Roche has claimed that it results in a 67% reduction in complications. Another review by Kaiser et al (not an official Cochrane review) had found that it reduces the risk of hospitalization in both healthy and at-risk subjects. The U.S. Department of Health and Human Services relied on these findings in 2005 to claim that it reduces the risk of hospitalization by 50%, and also reduces mortality. And the Cochrane reviewers had also relied on the review by Kaiser et al

The updated Cochrane review was commissioned as the specter of apocalyptic, civilization destroying H1N1 "pandemic" influenza loomed over humanity. As the review was about to begin, a Japanese physician, Keiji Hayashi, wrote to the Cochrane Collaboration noting that the conclusions about effectiveness were based on the Kaiser review, and that relied on unpublished data held by the manufacturer Roche. Dr. Hayashi found that situation unacceptable, as well he should. So, the new reviewers tried to get that data. Roche gave them an elaborate runaround for several months, during which a vast mist of confusion arose over who had actually conducted the analyses on which the review depended, who had written what articles, what studies even existed, what data existed and what exactly the heck was in it. To this day, it's still a secret, and massively confusing. (Some of the academic physicians who Roche said had overseen the studies claim to have had nothing to do with them.)

So, the new reviewers decided they could only rely on published, peer reviewed data. And, on that basis, while it does appear that oseltamivir shortens the duration of symptoms in otherwise healthy adults, they could not conclude that it reduces the risk of complications or hospitalization. In fact, since most people who have flu-like illnesses do not in fact have influenza (even during the apocalyptic killer H1N1 civilization destroying "pandemic"), it is basically not worth giving it to people in general.

So, based on this sad story, I can only conclude that it is imperative that the pharmaceutical industry be represented on the board of directors of the agency that oversees comparative effectiveness research. Oh wait, that's not what I conclude. I conclude that clinical trials should be done a) independently of drug manufacturers and b) openly and transparently, with all of the data available to anyone, including me. If the drug companies still want to claim that they need a huge markup on their products to finance research and development, fine. They can still put up the money. They just can't be in charge of spending it.

How's that for a compromise?


C. Corax said...

So wait. This Cochrane Review thingie--is it supposed to be the cat's meow of this sort of thing? I'm having trouble wrapping my head around their use of a study that wasn't peer-reviewed.

Anyway, I like your idea of a compromise.

Cervantes said...

Yes the Cochrane Review is the tippity top. What they did actually was use a peer-reviewed review (yup) without stopping to question that the articles reviewed therein were not peer reviewed, if you see what I mean. Much of the research used to evaluate new drugs is proprietary research by drug companies, and they decide what to publish and what not to publish. The standards are changing, obviously.