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Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials

BMJ 2003; 326 doi: (Published 05 June 2003) Cite this as: BMJ 2003;326:1235
  1. Nicola J Cooper (njc21{at}, research fellow1,
  2. Alexander J Sutton, lecturer in medical statistics1,
  3. Keith R Abrams, professor of medical statistics1,
  4. Allan Wailoo, research fellow2,
  5. David Turner, research associate in health economics1,
  6. Karl G Nicholson, professor of infectious diseases3
  1. 1 Department of Epidemiology and Public Health, University of Leicester, Leicester LE1 6TP,
  2. 2 Sheffield Health Economics Group, School of Health and Related Research, University of Sheffield, Sheffield S1 4DA,
  3. 3 Infectious Diseases Unit, Leicester Royal Infirmary, Leicester LE1 5WW
  1. Correspondence to: N J Cooper
  • Accepted 10 April 2003


Objective To review the clinical effectiveness of oseltamivir and zanamivir for the treatment and prevention of influenza A and B.

Design Systematic review and meta-analyses of randomised controlled trials.

Data sources Published studies were retrieved from electronic bibliographic databases; supplementary data were obtained from the manufacturers.

Selection of studies Randomised controlled, double blind trials that were published in English, had data available before 31 December 2001, evaluated treatment or prevention of naturally occurring influenza with zanamivir or oseltamivir (if given using the formulation and dosage licensed for clinical use), and reported at least one end point of relevance.

Review methods The main outcome measures were the median time to the alleviation of symptoms (for treatment trials) and number of flu episodes avoided (for prevention trials). Three population groups were defined: children aged 12 years and under; otherwise healthy individuals aged 12 to 65 years; and “high risk” individuals (those with certain chronic medical conditions or aged 65 years and older).

Results Seventeen treatment trials and seven prevention trials identified met the inclusion criteria. All trials included compared one of the drugs against placebo or standard care. Treatment of children, otherwise healthy individuals, and high risk populations with zanamivir reduced the median duration of symptoms in days respectively by 1.0 (95% confidence interval 0.5 to 1.5), 0.8 (0.3 to 1.3), and 0.9 (−0.1 to 1.9) for the intention to treat population. The corresponding results, in days, for oseltamivir were 0.9 (0.3 to 1.5), 0.9 (0.3 to 1.4), and 0.4 (−0.7 to 1.4). The effect of giving zanamivir and oseltamivir prophylactically resulted in a relative reduction of 70-90% in the odds of developing flu, depending on the strategy adopted and the population studied.

Conclusions Evidence from randomised controlled trials consistently supports the view that both oseltamivir and zanamivir are clinically effective for treating and preventing flu. However, evidence is limited for the treatment of certain populations and for all prevention strategies.


  • Embedded ImageThe full list of trials included in this review is available on Editorial by Stöhr

    We thank GlaxoSmithKline (in particular, Stephen Sharp) and Roche (in particular, Paul Mahoney) for providing additional trial data.

  • Contributors All authors participated in designing the review, checking the data, and revising the manuscript, which was drafted by NJC. NJC, AJS, AW, and DAT decided on trial inclusion or exclusion, extracted data, and assessed study quality. NJC, AJS, and KRA performed the statistical analyses. KRA and KGN were the principal advisers, guiding and interpreting the review. NJC is the guarantor for the paper.

  • Funding This work was commissioned by the NHS Health Technology Assessment programme and the National Institute for Clinical Excellence. NJC is funded by University Hospitals of Leicester NHS Trust. DAT and AW are funded by the Trent Institute for Health Services Research. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.

  • Competing interests KGN has received travel sponsorship and honorariums from GlaxoSmithKline, the manufacturer of zanamivir, and Roche, which makes oseltamivir, for consultancy and speaking at international respiratory and infectious diseases symposiums. His research group has received research funding from GlaxoSmithKline and Roche to participate in multicentre trials of neuraminidase inhibitors; Berna Biotech and Chiron for trials of flu vaccines; and Wyeth for work on the epidemiology of flu in young children. KGN was a founder member and vice chairman of the European Scientific Working Group on Influenza (ESWI), a group of European scientists promoting the study of flu. ESWI is supported by the vaccine manufacturers, Roche and GlaxoSmithKline, but is scientifically independent.

  • Accepted 10 April 2003
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