Published: Dec 11, 2014
By Andrew Buelt, DO
Action Points
The author discusses his reasons for a belief that there is no clinical benefit associated with the use of Tamiflu.
Pointless Prescribing
I think there comes a time when everyone realizes that the easy, well-worn path is not always the best option.
For physicians, this metaphor can be seen in the daily struggle of whether to champion the conversation on how antibiotics are not indicated, or to just go ahead and write for the Z-Pak to get the patient out of the office. Whether we’re talking about screening for prostate cancer, breast cancer, cholesterol levels, or low vitamin D, the beaten path is rarely good for all patients.
The first time I realized that the dangers at the end of the path even existed was a little over 2 years ago. That cliff was the discussion of our first podcast — Tamiflu.
With flu season upon us, I see no better time than the present to bring this discussion to the forefront, and, ultimately, question medicine.
Background
Oseltamivir, brand name Tamiflu, was released onto the market in 1999 for the treatment of influenza. As they clearly state on their drug information card, “There is no evidence for efficacy of TAMIFLU in any illness caused by agents other than influenza viruses types A and B.”
What a perfect drug! After all the “CDC estimates that from the 1976-1977 season to the 2006-2007 flu season, flu-associated deaths ranged from a low of about 3,000 to a high of about 49,000 people.” According to the World Health Organization, “Worldwide, these annual epidemics are estimated to result in about 3 to 5 million cases of severe illness, and about 250,000 to 500,000 deaths.”
Sounds too good to be true that a drug has come to market to quell the tides of this yearly doom. We have an illness that affects so many, and yet, we have a treatment for it! With these numbers, no wonder the WHO “recommends neuraminidase inhibitors as the first-line treatment for people requiring antiviral therapy.”
With the average cost of this drug for a 5-day treatment course roughly $135 (prices vary based on location and pharmacy), it’s not surprising that there are so many reports stating the U.S. Department of Health and Human Services stockpiled over $1 billion worth of this little pill. A report from The Cochrane Collaboration in partnership with The BMJ mentions it. And USA Today reported on it, too.
It’s easy to see why everyone thought this was a wonder drug. A meta-analysis of 10 randomized controlled trials — with data from 3,564 patients — published in the Archives of Internal Medicine in 2003, even concluded that “Oseltamivir treatment of influenza illness reduces LRTCs [lower respiratory tract complications], antibiotic use, and hospitalization in both healthy and ‘at-risk’ adults.”
However, the same authors (Kaiser L, et al) also said acute bronchitis requires antibiotic use, which we know it doesn’t, and that eight of the 10 trials were unpublished or published only in abstract form. Finally, 68% of the randomized patients tested positive for influenza when, on average, only about 14% of those in a given flu season test positive, according to U.S. virological surveillance data.
When Tom Jefferson, MD, of the Cochrane Review, asked for the clinical studies and full research, he was turned away. This started a 4-year stall by Roche, makers of Tamiflu. For those of you who are interested in the exchange, youshould follow the paper trail on The BMJ website.
Why stall, Roche? Why keep as much as 60% of your data from being published? If the product is that good, why not show how good it is to the entire world?
The largest Tamiflu trial, known as M76001, enrolled 1,400 adults. A 9,800 word manuscript describes the study, but until recently, the only published mention was an abstract.
The Big Picture
Finally, Roche started to release the clinical studies.
First, a report with access to some of the full clinical data concluded “there is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia, or combined outcome of pneumonia.” And what was more shocking was that this trial, WV15912, which took 401 adults with at least one cardiac or respiratory condition, had an end result of a nonsignificant 1-hour reduction in symptoms. I repeat only 1 hour, only 60 minutes, only 3,600 seconds.
When the Cochrane reviewers were finally able to look at and sort through the body of information, and not just the abstract data, they came to similar conclusions, and reported that there were no differences for hospital admissions, reductions in confirmed pneumonia, or other complications.
However, I don’t want to say the drug did nothing, as there were increases in symptoms of nausea (NNH 28), vomiting (NNH 22), and headaches (NNH 32).
Yes, Tamiflu is too good to be true. Patients who have the flu feel bad, they want a drug to help them feel any amount of relief. Sadly, we have nothing for them. We can encourage hydration and rest, but that’s about it.
The easy path is to write a prescription for Tamiflu and move to the next patient. The hard path is to discuss why you are not going to write the script to someone who doesn’t want to hear it.
As with most things in medicine, we should do our best till we know better, and when we know better we should do better.
It’s safe to say with Tamiflu, as well as with the medical topics in previous posts, we know better!