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- guardian.co.uk, Friday 1 May 2009 21.04 BST
- Article history
Look I don't want to freak you out, since Tamiflu is the one thing which everyone believes will save us from Parmageddon, but I've been reading through the published trial data on the drug, and I'm not sure it's all that great.
The Cochrane Library is one of the greatest inventions of modern humankind. It's all very well to do a trial, or lots of little trials, but one trial, simply by chance, might give a false negative, incorrectly missing a true benefit from an effective treatment; or one trial might falsely find a benefit from an ineffective treatment, either by chance, or because the study was designed so badly that it not longer represented a "fair test" of the intervention, against whatever you were comparing it to.
The Cochrane Library is an international non-profit collaboration of academics that brings together all the evidence on a given question, using a predetermined standard method for seeking out information, assessing its quality and combining it into one giant report. They're slightly turgid, and they are considered by medics and academics to be pretty much the best quality evidence available.
Handily, there is a Cochrane review on Tamiflu, and a similar drug called Relenza. In reality the drugs' names are oseltamivir and zanamivir, but for some reason the media always use the original manufacturers' brand names instead of the generic, a bit like calling all ibuprofen tablets Nurofen, or all aspirin tablets Disprin. After a few years all medicines come out of copyright, at which point anyone can manufacture them, but if everyone is used to the brand name rather than the generic then the original company has an advantage.
The review on oseltamivir and zanamivir was done several years ago, but reviews are frequently updated in the Cochrane Library because evidence changes. This review was redone in 2006, and again in May 2008. The reviewers asked two questions: do these drugs treat flu? And do they prevent it?
The time in which flu symptoms were alleviated was assessed by nine trials. The group treated with zanamivir were 24% more likely to have their flu symptoms alleviated than the placebo group, at a given time point. For oseltamivir the figure was 20%. It's alright. I'd take it. It's just not amazing.
Main results
We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza.
Authors' conclusions
Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.
The NICE review from February 2009 looks at similar data, and analyses it in a different way, giving you the absolute time to recovery, which is a little easier to understand. Overall, oseltamivir reduced the average time to alleviation of symptoms by 0.68 days. For zanamivir, the figure was 0.71 days.
The prevention studies are a bit more exciting. Although patients had less of the virus on board, neither drug stopped patients from being infectious. In fact, neither had a protective effect at all against influenza-like illness, or asymptomatic influenza, even at higher doses.
For preventing someone catching symptomatic influenza, the results were more impressive. A 75mg daily dose of oseltamivir was 61% effective compared with a placebo, and 73% effective when the daily dose was 150mg, while Relenza was 62% effective. In trials where researchers were looking at the prevention of influenza in households where someone was already infected, the drugs were also pretty good.
I would take these drugs. Things might be different in a pandemic, and the Cochrane review recommends them in such circumstances. If they make my symptoms less severe then I'm guessing I'm less likely to die, and they might reduce the spread of the disease throughout a whole country.
But they're not a miracle cure, and if this is worrying to you, that just shows how ill-equipped we are to consider the risk. For the question of whether we'll see a pandemic, things are so up in the air that it's not possible to quantify the probability of such an event occurring. We do have numerical risk data which gives an indication of the chances of getting better, but we have to accept that modern medicine is all about cutting the risks and probabilities to achieve the best possible outcome. And after all that, if you got swine flu, you might still die. Which would be seriously rubbish.
Comments - 63
Costs of Treatment: Both oseltamivir and zanamivir cost about £16 for a 5-day course. Source: NICE.org.uk, cf. this is an order of magnitude lower than costs from https://www.onlineclinic.co.uk !!
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