TORONTO – A British medical journal, a U.K.-based TV network and researchers from the Cochrane Review are calling into question the science behind the flu drug Tamiflu, suggesting among other things that too few data are publicly available to judge whether the drug is worth what governments have spent to stockpile it.
There are no new findings in the package of reviews, commentaries and point-counterpoints between the researchers and drug maker Roche.
The conclusion of the main review is that Tamiflu and Relenza, another drug in the same class, have only a modest effect when given to otherwise healthy adults who come down with a bout of seasonal flu – a point that is not in dispute.
“That’s entirely consistent with our views and our guidelines,” said Charles Penn, an antiviral expert with the World Health Organization.
“Because what we say – even with the pandemic virus – for otherwise healthy people presenting with an uncomplicated normal influenza, they need not be treated (with the drugs).”
The review is about how much benefit the drugs confer to otherwise healthy people who catch seasonal flu, not how useful the drugs are in patients at high risk from pandemic flu or hospitalized with severe cases of the H1N1 virus.
But Penn and several academic researchers who have studied the drug are concerned the timing of the publication may confuse the public and doctors about whether Tamiflu ought to be used in the treatment of the H1N1 virus.
“If clinicians misinterpret it because of the subtleties involved in looking at seasonal disease versus pandemic H1N1 and that results in delays to treatment in those who really do benefit from treatment, that would be potentially harmful,” said Dr. Frederick Hayden, an antiviral expert at the University of Virginia.
Hayden has done studies on the drug that were funded by Roche. And he is a co-author of a meta-analysis of studies on the drug that is at the heart of this dispute.
That meta-analysis was used in an earlier examination of flu antivirals published by the Cochrane Collaboration in 2006.
The Cochrane Collaboration is an international network of scientists who work to advance evidence-based medicine by periodically amalgamating and re-analyzing the highest-calibre evidence available on a drug or a medical procedure.
Prompted by a reader’s queries about the fact that several of the studies in Hayden’s meta-analysis remain unpublished, lead researcher Tom Jefferson set out to update the document – as required under the collaboration’s rules.
Meanwhile, Channel 4 was investigating Tamiflu. And both parties were having trouble getting their hands on the data from the unpublished studies in the meta-analysis.
They joined forces with the BMJ. In an editorial, editor-in-chief Fiona Godlee used the case to question the way drugs are regulated.
Roche, which says it has to protect the anonymity of patients in its trials, asked Jefferson to sign a confidentiality agreement to access the data. A standoff ensued.
The company now says it will put the data on a password-protected website which will be accessible to researchers who agree to some ground rules on responsible use of the data. But it’s unclear whether that will allay the criticism or the Cochrane Review’s queries about the value of these drugs.
Under Cochrane rules, only certain types of evidence can be considered. Studies in which volunteers are randomly assigned to get a treatment or a placebo are considered the gold standard of evidence and they qualify. Studies that observe outcomes in people who receive a treatment don’t make the cut.
But sometimes it isn’t possible to conduct randomized controlled trials. Sometimes observational data are the best evidence available.
For instance, it’s unlikely any researchers could get permission to test Tamiflu against a placebo in people severely ill with H1N1. It would be considered unethical to withhold the drug from severely ill H1N1 patients if observational data suggested the drug might help.
And observational data on these drugs’ usefulness in patients hospitalized with severe cases of flu – seasonal and H1N1 – points toward benefit, Dr. Tim Uyeki of the U.S. Centers for Disease Control recently reported in the New England Journal of Medicine.
“We don’t want people to stop using the antivirals in the way that we’re recommending they’re used because we believe they are having a beneficial effect on hospitalization, on severity of illness and indeed (preventing) death,” Penn said Tuesday from WHO headquarters in Geneva.
“And if people stop using them, then the consequences of that will be an increased burden on the health-care system and worse outcomes.”
