Tamiflu dissed by Cochrane

Only Ireland went mad buying and distributing Iodine tablets in 2002 against a nuclear disaster.  But five years later governments across the West bought and stockpiled millions of units of Tamiflu (oseltamivir, Roche) and Relenza (zanamivir, GlaxoSmithKline) at about €10 a pop. That's about 20x more than the ould Iodine tabs.  These drugs are a class of anti-neuraminidase, and they were claimed at the time to reduce the time for which people experienced 'flu-like symptoms if and when they caught influenza. Neuraminidase - the N in H7N9 or H1N4 - is a destructive enzyme produced by flu-virus. Epidemiologists have been quaking in their boots about the Next Great Pandemic ever since HIV-AIDS swept out of Africa in the 1980s and started to infect white folks. Bird-flu, swine-flu, SARS, have all come and gone and most recently Ebola hemorrhagic fever scythed through Guinea a month ago. Anyone have any idea where's Ebola at now - it's not in the news any more!  The British government lashed out more than half a £billion on the drugs (the Irish were pro-rata quite as flaithulach). In short order HMG had to write down about £75m of this because some of the drugs were not stored properly and so had to be thrown away.  It requires something like 2500cu.m to store all those drugs or about 10x the volume of our modest home.  That's a lot of fridge, if that's what is required.

And while we're at it, why do these drugs have two names?  The trade-name is what appears on the tin and that, for marketing purposes has to be at least pronouncable by the doctor or health bureaucrat who's going to order some up from the drug company. But why does anyone bother with oseltamivir, infliximab and other SciFi warlords?  wuggawuggamab is a monoclonal antibody, didgeridoovir is an anti-viral so that part is handily informative.  I have no idea whether there there is a Committee for Nomenclature in Big Pharma

Someone - it might as well be me - has to ask a) what is the cost of stemming an outbreak of some deadly pandemic [BIG] b) what is the likelihood that such a pandemic will occur [small] and multiply the two numbers together to get an idea of bangs for bucks. If the drug of choice is merely going to ameliorate the symptoms or shorten the time of distress, then the bangs need to be appropriately down-graded.

The Cochrane Index, no relation to Nellie Bly, is The Gold Standard for assessing the efficacy of drugs, treatments and protocols in medicine.  It is based in London and it takes on particular claims which have been widely studied and which have led to contradictory results. They direct a group of competent professionals to carry out a meta-analysis of all the available data and summarise the evidence so that the rest of us can make an informed decision about which, if any, of the claims to believe.  A meta-analysis throws all the previous analyses into a big statistical hopper and stirs and shakes them until something approaching truth and reliability emerges. Claims of big effect based on small sample-size are, for example, downplayed.

According to Nature 24/04/14, Cochrane has just released its considered opinion on neuraminidase inhibitors and their usefulness in combatting epidemic influenza.  The answer is Not A Lot.  Cochrane and the British Medical Journal also report that they've been trying for half a decade to get Glaxo and GSK to release the data on which they made their claims for efficacy of the drug.  If it costs half €billion to bring a novel drug to market (and it does), then there is a little pressure to downplay any adverse reactions or negative/equivocal trials at least until the first warehouseful of  drugs has been shipped and paid for. At the inevitable press conference Fiona Godlee the BMJ's Editor summarised the drugs as having had their "effectiveness overplayed and their harms underplayed" which the headline writers of the red-tops summarisummarised as "Tamiflu useless and ineffective".  I tell ya, twitter has a lot to answer for in eroding the quality and subtlety of debate in matters of social and medical importance.

Everyone agrees that neuraminidase inhibitors are effective in helping deal with severe cases of influenza - the people who are fluttering on the abyss in Intensive Care. And they also acknowledge that the duration of feeling crap is shortened by a day or 17 hours or half a day on average.  In the Nature article, their staffer Declan Butler tries to make a story out of flu-workers dissing the Cochrane report. It reads a bit like the flu-workers want Cochrane to take into account their many anecdotes of miraculous Tamiflu cures. But that's not what Cochrane does. It does science. The other take-home is that many of the reports that Cochrane incorporated into its meta-analysis were badly under-powered. If, for example,  you set up a study to answer a scientific question and you opt for a sample size so small that it cannot give an unequivocal answer - positive or negative according as the chips fall - then you have wasted somebody's money just as surely as the people who left £75million worth of Tamiflu out in the bike shed. If, for other example, participants in the trial are all fit young college students, or recruited in a home for the elderly then the findings may well not be universally applicable.

And one final thought, there is evidence now emerging from China that some people with H7N9 influenza are harboring viruses which are resistant to Tamiflu and Relenza!  If we hand out millions of doses of one of the few drugs effective against severe life-threatening influenza to healthy people who have mild influenza (and that effectively includes people who have the (bad) dose of the common cold called man-flu) then we are squandering a valuable resource just like we've done with Augmentin and other antibiotics. But Big Pharma is only going to recoup their investment if they shift a lot of units.