In January 2011 the BMJ published a searching critique of the evidence concerning the effects of neuraminidase inhibitors. This deserves comment because it brings into question the way in which we assess medicines at a public policy level and an individual prescribing level and the evidence that we accept when making decisions about the use of medicines.
In 2009 an updated Cochrane review concluded that there was insufficient evidence to say one way or the other whether oseltamivir reduced the risk of complications in influenza. Moreover, evidence on serious side effects was lacking. This year Jefferson and colleagues commented that, “US regulators today still require that oseltamivir’s label clearly states that it has not been shown to reduce complications whereas the opposite is stated on European and Australian labels.” How is it that the same data can apparently support two opposing conclusions? Where does the truth lie? And what are pharmacists to make of this?
The great benefit of evidence-based medicine is that it enabled us to pool data from small trials and identify (true) effects that might not have been obvious in individual small trials. However, this is based on the assumption that all the trials were of suitable quality (in design, execution and reporting) and all were published, and therefore subject to the peer review process. Systematic reviewers are encouraged to search for publications in the ‘grey literature’ but not to include items that have not been published at all. The inclusion of unpublished data is problematic because others are unable to scrutinise the data and check the quality against the established criteria.
In this case a key meta-analysis of 10 trials contained eight that had not been published and the raw data were not available for general scrutiny. Moreover, one large study was missing altogether. As the reviewers probed deeper they formed the view that evidence from the whole trial programme was required to permit assessment of the integrity of the whole trial programme. Accordingly they have now designed and published a protocol for just such a study. However, it comes as something of a disapppointment to realise that systematic reviews with meta-analyses of questionable quality had made it through all the hurdles and been published in prestigious journals. The Cochrane reviewers call for a change in the way information is identified, appraised, and synthesised and suggest that any industry-sponsored trial published in journals be regarded as marketing, unless proved otherwise.
What does this mean for pharmacists? This episode and the recent rosiglitazone farrago will reinforce pharmacists’ natural scepticism about the processes for registration of new products. Pharmacists need to process this information for themselves but they also need to be able to explain its implications to health policy planners and to the public at large. All of this is best done in a calm and rational atmosphere before the next pandemic. When flu strikes decisions can be heavily influenced by the mass media and public opinion.
Pharmacists should support the call for access to data of sufficient detail to allow for the independent exploration and re-analysis of trials. Only in this way can we have robust information on which to base decisions about how medcines should be used. After all, as the Cochrane reviewers argue, “If you swallow a medication, you need to know how it works – for real.”