Australasian Science: Australia's authority on science since 1938

Effectiveness of Flu Drug Questioned

A Cochrane review of the effectiveness and side-effects of the drug Tamiflu raises critical questions around the future of government stockpiling of such drugs for use in an influenza pandemic.

An earlier paper published in The Lancet Respiratory Medicine suggests that, if patients were NOT on neuraminidase inhibitors (i.e. Tamiflu) there was a 9.2% death rate (959/10,431) but if they were given Tamiflu the death rate was slightly higher at 9.7% (1825/18,803). Yet the conclusion was the opposite of this. They concluded that neuraminidase inhibitors save lives.

Looking at comments on the Lancet paper in the BMJ (http://www.bmj.com/content/348/bmj.g2228/rr/692897), the statistics that were done to reach that conclusion likely have major methodological issues.

In contrast, the new Cochrane review says there is no evidence to show that Tamiflu saves lives based on studying a similar number of patients but with much better methodology, as the patients they included were part of controlled trials (even if Roche did not let the reviewers see all the data).

Professor Peter Collignon is an Infectious Diseases Physician and Microbiologist at Canberra Hospital, Associate Executive Director of ACT Pathology, and Professor of Medicine at the Australian National University.

*****

New data supports the need for greater government investment in influenza vaccine strategies and less investment in stockpiling of anti-influenza drugs such as Tamiflu and Relenza.

Benefits of anti-influenza drugs such as Tamiflu and Relenza are modest at best and most recent data suggests they may not reduce influenza mortality or hospitalisation.

Unlike anti-influenza drugs, influenza vaccines have proven benefits in reducing influenza hospitalisations and deaths.

Next-generation influenza vaccines, such as those being developed by Adelaide company Vaxine Pty Ltd, offer potential for even greater levels of protection, but their development is not currently supported by Australian health funding agencies.

Professor Nikolai Petrovsky is Director of Endocrinology at Flinders Medical Centre with a conjoint position as Professor of Medicine at Flinders University, and Research Director at Vaxine Pty Ltd.

*****

This latest Cochrane review finds (again) that NAIs are associated with only modest benefits in the treatment of mild–moderate seasonal influenza infection among healthy individuals participating in clinical trials. However, the study cannot tell us anything about the effects of Tamiflu in seriously ill patients who are already in hospital. During a pandemic, these are the patients of greatest concern, so we should be careful in our interpretation of this latest Cochrane review.

NAIs are also known to be effective in preventing the spread of symptomatic disease among contacts of infected patients, so they can help stop health services being overwhelmed during a pandemic, although they may still allow asymptomatic infection.

So, are these new findings informative for governments considering the appropriate use of NAIs to reduce clinical cases, health sector burden and death during pandemic events, in which heightened morbidity and mortality are anticipated?

The limitations of the randomised controlled trial are evident from synthesis of “real world” studies conducted during the 2009 H1N1 pandemic, demonstrating that early treatment of hospitalised patients with NAIs significantly reduced ICU admissions and deaths, particularly among those with underlying poor health. In other words, the trial populations studied here just weren’t sick enough to see an effect.

The usefulness of NAIs in prevention of secondary disease when given to household contacts of cases was further supported by observational studies during the 2009 pandemic, such as the UK’s analysis of the “first few hundred” cases. Should we be concerned that asymptomatic secondary infections might occur? Not if our aim is to reduce disease burden on the health care sector and society.

Randomised controlled trials are a “model system” like any other, and necessarily fail to encompass many real world complexities of importance. Caution should be taken in extrapolating their findings without appropriate context.

Associate Professor Jodie McVernon is a Senior Research Fellow in the Melbourne School of Population Health at the University of Melbourne.

Australian Science Media Centre