Tuesday, December 08, 2009

BMJ: A Review Of Tamiflu’s Efficacy Against Seasonal Influenza



# 4136



Today the BMJ (British Medical Journal) tackles a controversial, and oft times contentious, subject.  Whether Tamiflu is of sufficient benefit to warrant its widespread use against seasonal influenza.


This is part of an ongoing review of the existing literature.


This review is of Oseltamivir’s use against seasonal influenza in otherwise healthy adults.  The use of Tamiflu against pandemic strains of influenza, or in patients with underlying conditions, isn’t directly addressed here.


You’ll find, after reading this research, that there remain many unresolved questions regarding the efficacy of Tamiflu. Hence the use of a question mark (?) in the BMJ title below.  


This review raises more questions than it answers.   Some excerpts below (reparagraphed for readability).



Pandemic influenza

The truth about Tamiflu?


This Cochrane group's update of a 2005 review of oseltamivir in pandemic influenza concludes:


"Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective.


Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza.

Independent randomised trials to resolve these uncertainties are needed."



A cluster of articles on bmj.com seeks to elucidate problems with the data that have underpinned the use of oseltamivir in healthy adults with pandemic influenza.


Deborah Cohen retraces the steps of the Cochrane reviewers as they tried to obtain all the relevant data and finds that commitments to transparency are still in doubt.


Peter Doshi explains that the public evidence base for this global public health drug is fragmented and inconsistent.


And Nick Freemantle and Mel Calvert find that observational studies of oseltamivir's efficacy show minimal benefit. In an accompanying editorial, Fiona Godlee and Mike Clarke say that the full data from drug trials must be available for scrutiny by the scientific community.


Read also:




Published 8 December 2009, doi:10.1136/bmj.b5106
Cite this as: BMJ 2009;339:b5106

Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis


While the entire study is worth reading, the bottom line is there is insufficient evidence, according to the authors, to conclude either for or against Tamiflu for use in healthy adults with seasonal influenza.


In other words, more studies are needed.


Regarding its use against pandemic strains, the authors state:


Role of neuraminidase inhibitors in pandemic influenza

We identified no direct comparative evidence of the role of neuraminidase inhibitors in avian influenza A/H5N1 or in the current novel influenza A/H1N1 pandemic. This means that we have to generalise from the trials, and this seems reasonable given that the pandemic influenza A/H1N1 virus will likely be acted on in the same biological manner as previously circulating influenza viruses, such as seasonal A/H1N1.


Neuraminidase inhibitors do not, however, prevent infection or stop nasal viral excretion, so they may be a suboptimal means of interrupting viral spread in a pandemic. If used to contain a severe pandemic outbreak, neuraminidase inhibitors should be considered only part of a package of measures to interrupt spread, including physical measures.


You’ll find Roche’s response to this research, and to questions raised by the BMJ, along with an editorial statement, but some of these items will require a subscription to the BMJ to access. 


The research, however, is freely available.


MSNBC quotes the World Health Organization:

They said data from countries around the world show that when given early, Tamiflu can reduce the severity of swine flu symptoms, though the agency recommends the drug be saved for people at risk of complications, like pregnant women, the elderly, children, and those with underlying medical problems.


"This will not change our (Tamiflu) guidelines," said Charles Penn, a WHO antivirals expert. Penn said that while past studies show Tamiflu only has a modest benefit, when patients with severe illness or at risk of complications are treated early, there are fewer hospitalizations and deaths.