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Rapid response to:


Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

BMJ 2014; 348 doi: (Published 09 April 2014) Cite this as: BMJ 2014;348:g2545

Rapid Response:

Re: Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

The BMJ and Cochrane Collaboration have revealed serious generic failings in our system of publishing full trial evidence. The lessons in relation to antiviral drugs and future pandemics still need to be properly debated. Service insights from the last pandemic have been little in evidence in the current debate.

Oseltamivir was considered, even in 2009, to be a drug of hope, of weak benefit if given within 48 hours of symptoms, ‘free of side effects’ and ‘ the best we have got’. The limited evidence base around seasonal flu use was the basis for pandemic planning. But even this was sacrificed by Governments, their Departments of Health and the WHO when their ‘expert committees’ encouraged use of the drug, once the pandemic was declared, in people who may have been ill for a week. This led us into massively expensive over reliance on a drug of marginal, if any, benefit during the 2009/10 H1N1 pandemic.

Apologists for Roche are already mounting a rearguard argument that the Cochrane analysis relates to trials undertaken on seasonal flu, not pandemic flu. But this is a bizarre reinterpretation of history given it was precisely the evidence about seasonal flu trials which was used to determine national policy for pandemic stockpiling. The evidence was extrapolated by Departments of Health and governments, advised by experts, paid for by the industry, that said ‘antiviral distribution may be the best we can do’, ‘we don’t have the evidence for these circumstances but we have to make best guesses’, ‘we have to take action in case it becomes a serious infection’. Like Cochrane, like the ALLTrials campaigners we conclude that there would have been even less justification for use in the pandemic, had the limited evidence for its use in seasonal flu been known from the start.

We remain concerned however, that the insights of service providers on the ground during the pandemic have not been given the same level of public consideration. It is well documented that even drugs which may be effective in clinical trials can be inefficient, or fail to deliver the patient benefit predicted by trial results, when subject to limitations of general service use. The lessons from service insights in the pandemic are: the wanton abandonment of first principles such as isolation, basic control of infection measures and clinical assessment in favour of the stubborn insistence on managing ‘England as a single epidemiological unit’ [1]; and the irrational maintenance of the ‘containment’ phase which led directly to perverse and damaging interventions and over-reliance on antivirals in mass prophylaxis exercises particularly in schools. Anti-viral collection centres became loci for the spread of infection as thousands of symptomatic and sub-clinical cases (there is good evidence that flu can be spread by asymptomatic patients [2, 3]) and unaffected contacts convened for a wonder drug with serious potential side effects [4],and which would now appear to be no more effective in pandemic management than paracetamol [5].

It would be irresponsible for these lessons not to underpin current planning for pandemics and any subsequent responses. We believe there is no place for antiviral distribution in a pandemic based on the current evidence of the effectiveness of the drugs, their ineffectiveness for mass prophylaxis and the likely spread of infection brought about by bringing people to a centre for the drugs.

[1] Chambers J, Barker K, Rouse A. Reflections on the UK’s approach to the 2009 swine flu pandemic: Conflicts between national government and the local management of the public health response. Health Place 2012; (18): 737–745.

[2] Centers for Disease control. Additional Information about Vaccination of Specific Populations. Influenza Prevention and Control Recommendations. Published for the 2010-11 Influenza Season; Adapted for the 2012-13 Influenza Season last accessed 13th April 2014.

[3] Chao D-Y, Cheng K-F, Li T-C, Wu T-N, Chen C-Y, et al. Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico. PLoS ONE 2012; 6(1): e14555. doi:10.1371/journal.pone.0014555

[4] Jefferson T, Jones M, Doshi P, Spencer E, Onakpoya I, Heneghan C. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348:g2545

[5] Tamiflu: Millions wasted on flu drug, claims major report. BBC News. Last accessed 13th April 2014.

Competing interests: No competing interests

16 April 2014
Patrick J Saunders
Professor of Public Health
John Middleton
University of Staffordshire
444, Quinton Rd West, Birmingham, B32 1QG