Since 2002, governments around the world have spent billions of dollars stockpiling neuraminidase inhibitors (NIs) such as Tamiflu® (oseltamivir) and Relenza® (zanamivir) in anticipation of an influenza pandemic. This trend increased dramatically following the outbreak of the H1N1 virus (swine flu) in April 2009. It was initially believed that NIs would reduce hospital admissions and complications of influenza, such as pneumonia, during influenza pandemics. However, the original evidence presented to government agencies around the world was incomplete, raising questions about the accuracy of these claims and the efficacy of both preparations. An international team of researchers, based in Australia, Italy, Japan, the UK, and the US, working with the Cochrane Acute Respiratory Infections Group, expanded their research beyond the typical systematic review analysis, which focused on using published trial reports available in scientific journals. These reported on only a small percentage of the research carried out on the effectiveness of NIs. Over the last six years, following publication of the first Cochrane Reviews of oseltamivir and zanamivir, the Cochrane NI Research Group has accessed and reviewed more than 160,000 pages of regulatory documents in order to examine the full evidence picture.
The latest updated Cochrane Review, published on 10 April 2014, is based on full internal reports of 20 Tamiflu and 26 Relenza trials. These trials involved more than 24,000 people and the findings challenge the historical assumption that NIs are effective in combating influenza. The review confirms small benefits on symptom relief, namely shortening duration of symptoms by half a day on average. However, there is little evidence to support any belief that use of NIs reduces hospital admission or the risk of developing confirmed pneumonia. The evidence also suggests that there are insufficient grounds to support the use of NIs in preventing the person-to-person spread of influenza.
This latest Cochrane Review has benefited from access to more complete reports of the original research, now made available by the manufacturers, Roche and GlaxoSmithKline. Along with documenting evidence of harms from use of NIs, the review raises the question of whether global stockpiling of the drugs is still justifiable given the lack of reliable evidence to support the original claims of its benefits.
Dr David Tovey, Editor-in-Chief of The Cochrane Library, commenting on the release of the updated Cochrane Review, said: “We now have the most robust, comprehensive review on neuraminidase inhibitors that exists. Initially thought to reduce hospitalisations and serious complications from influenza, the review highlights that [NIs are] not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications. This shows the importance of ensuring that trial data are transparent and accessible.”
The publication of this review has generated widespread attention from media worldwide, leading the health news agenda in the UK on the day of its release and receiving national coverage in Australia, Canada, the US, and various countries in Africa, Asia, and Europe. A selection of news stories is available here, with some key pieces highlighted in the ‘Related resources’ section below.
Tamiflu & Relenza: how effective are they? Cochrane/BMJ press release, 10 April 2014
What the Tamiflu saga tells us about drug trials and big pharma by Ben Goldacre, The Guardian, 10 April 2014
The Tamiflu Timeline, by Holly Millward, UK Cochrane Centre, Storify
Drug data shouldn't be secret by Peter Doshi and Tom Jefferson,The New York Times, 10 April 2012
Clinical trial data for all drugs in current use, by Fiona Godlee, BMJ, 29 October 2012
Tamiflu open data campaign