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Volume 22, Number 6—June 2016

Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

Aeron C. HurtComments to Author  and Heath Kelly
Author affiliations: World Health Organization Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia (A.C. Hurt); University of Melbourne, Parkville, Victoria, Australia (A.C. Hurt); The Peter Doherty Institute for Infection and Immunity, Melbourne (H. Kelly); Australian National University, Canberra, Australian Capital Territory, Australia (H. Kelly)

Main Article


Conclusions of study evaluating the use of oseltamivir for seasonal and pandemic influenza and wisdom of stockpiling*

Summary conclusions
1. Although debate continues, there is general agreement from meta-analyses of RCTs that oseltamivir reduces symptoms in healthy adults and adolescents with influenza by up to 1 day. There is disagreement on the mechanism. On 1 side of the debate, the Cochrane group maintains that there is a nonspecific effect of oseltamivir, whereas, on the other side, investigators sponsored by Roche maintain that oseltamivir has a specific anti–influenza virus effect.
2. There have been no RCTs that can be meta-analyzed to summarize the effect of oseltamivir on severe outcomes of influenza virus infection. Evidence derived from observational studies of serious outcomes consistently suggests that oseltamivir reduces the risk for death in severely ill patients with documented influenza infection.
3. The apparent discrepancy between a modest drug effect for healthy persons and a substantial effect on number of deaths remains unexplained. Currently, oseltamivir is the only licensed drug available for all ages.
4. Based on available evidence, oseltamivir should be used for treatment of hospitalized patients with laboratory-confirmed seasonal influenza and stockpiled for the treatment of patients with severe laboratory-confirmed pandemic influenza, whether hospitalized or not. These stockpiles should be widely distributed to facilitate rapid use when needed.
5. Without a mechanism for rapid distribution of the drug in an emergency, any potential benefit of such large-scale stockpiling will not be realized. Rapid distribution in an emergency is only likely if a mechanism exists for routine rapid distribution. In countries where such a mechanism does not exist, we see no place for stockpiling oseltamivir for widespread community use during a pandemic.
6. It is unlikely that conventional RCT-level evidence to support antiviral treatment of severe laboratory-confirmed influenza in hospitalized patients will appear within the next decade due to the ethical constraints of evaluating oseltamivir vs placebo, when oseltamivir is the current standard of care for the treatment of severe influenza infection. New studies should be pragmatic trials or high-quality prospective multisite observational studies and employ methods to minimize bias to the greatest extent possible.
7. Studies designed for assessing interventions for seasonal influenza should be readily adaptable to studies of pandemic influenza on very short notice. Because of the ethical and design constraints of RCTs, prospective observational studies are more feasible than RCTs in an emergency response situation. In addition to data on outcome, such as risk of ICU admission and death among adults, or length of stay among children, these observational studies should also record time from disease onset to treatment and time from treatment to outcome to minimize bias. Sequential data on markers of immune function in at least a subset of recruited patients would also be valuable.

*RCT, randomized controlled trial; ICU, intensive care unit.

Main Article

Page created: May 16, 2016
Page updated: May 16, 2016
Page reviewed: May 16, 2016
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