Thursday, October 08, 2015

Wellcome Trust/AMS Report On Antivirals For Influenza


Photo Credit – Wikipedia




Last year many headlines in the UK, and around the world, screamed `Tamiflu: Millions wasted on flu drug, claims major report’.  While many would argue these media reports were based on incomplete information – they seriously undermined the public’s (and probably some doctor’s) confidence in using antiviral drugs for influenza.  


Fueling this controversy was a Cochrane group analyses that found insufficient evidence that the drug reduces seasonal influenza complications in healthy adults. Their analyses was limited to RCTs (Randomized Controlled Trials) of which relatively few exist for this drug. 


Observational studies – of which there are many supporting its use (see Revisiting Tamiflu Efficacy (Again)) – were not included.  And unlike the RCTs, they often looked at the benefits of using antivirals for severe or pandemic flu.


Granted, the evidence for using influenza antivirals (like Tamiflu ® or Relenza ®) for uncomplicated seasonal flu in healthy adults has always been fairly weak, with most recipients only seeing a reduced duration of symptoms by a few hours. .


But as we saw in The CDC Responds To The Cochrane Group’s Tamiflu Study) and the UK’s PHE (see Revisiting Influenza Antiviral Recommendations), and a meta-analysis in The Lancet, the evidence of their benefit in the treatment of severe influenza, or at risk individuals, is far more compelling. 

Last month, in The Conversation: The Rise & Fall Of The Challenge To Tamiflu, we looked at additional evidence of the benefits of Tamiflu in treating severe, or pandemic, influenza.  Other blogs in this vein include:


CID Journal: Outcomes Of Prompt Influenza Antiviral Treatment Of Older Adults
CDC Expert Commentary (Video) On Use Of Neuraminidase Antiviral Drugs

CID Journal: Under Utilization Of Antivirals For At Risk Flu Patients

Overnight two well respected, independent organizations in the UK (The Wellcome Trust  &The Academy of Medical Sciences) released a report on the use of these NAI (neuraminidase inhibitor) antivirals for influenza – that while calling for more research – acknowledges their value in the treatment of severe influenza.

Among their conclusions:

  • They did not support the routine use of NAIs in healthy individuals with uncomplicated seasonal flu
  • However, they found antivirals significantly reduced deaths in hospitalized patients, and they support their use for severely ill or hospitalized patients
  • They acknowledge their use could be critical in a flu epidemic situation
  • And the more severe the epidemic or pandemic, the greater the likelihood the population will benefit from the use of NAIs. 


Currently the link to the full report appears to be inoperative.  But the Wellcome Trust press release below provides a good summary of their findings.  (Updated: This PDF LINK works)


Prepare to conduct flu trials in hospitals now, urge experts

8 October 2015

Flu - SM

When the next influenza pandemic hits our shores, UK hospitals must be prepared to conduct trials into the effectiveness of available antiviral drugs, according to the conclusions of a leading panel of experts.

Today, the Academy of Medical Sciences and the Wellcome Trust publish a report into the use of antiviral drugs called neuraminidase inhibitors (NAIs) – specifically oseltamivir (trade name: Tamiflu) and zanamivir (trade name: Relenza). The report draws on recent reviews of the evidence for the treatment and prevention of influenza using these drugs, considers possible future treatments and defines research priorities.

An influenza pandemic tops the UK’s risk register, but although there has been much research into how to prevent and treat flu during seasonal outbreaks, there is very limited evidence from flu epidemics, which are significantly different due to the increased severity of symptoms and numbers of people infected. In particular, the failure to conduct trials in the 2009 H1N1 pandemic has contributed to the current weaknesses in the evidence base.

This lack of evidence has led to recent controversies about the efficacy and effectiveness of NAIs, particularly whether or not the UK government is justified in stockpiling these drugs.

The authors of today’s report conclude that antivirals can lead to a reduction in duration of symptoms by between 14 and 17 hours for seasonal flu. However, they do not support the routine use of antivirals in patients with seasonal flu as, unless the flu strain is particularly severe or the individual is very ill, the benefits are unlikely to outweigh the risks of side-effects.

The steering group also concluded that antivirals did significantly reduce deaths in hospitalised patients, particularly if they started treatment within 48 hours of first onset of symptoms. This could be critical in a flu epidemic situation, and the report supports the use of antivirals to treat patients who require hospitalisation.

The group stresses that if future outbreaks of flu are more virulent or show greater incidence of complications and death than during the period when the current evidence was collected (i.e. mainly during seasonal flu outbreaks) then the treatment of larger numbers of the population may be justified. In other words, the more severe the epidemic or pandemic, the greater the likelihood the population will benefit from the use of NAIs.

Importantly, the steering group recommend that plans are put in place to make sure that we can learn from any future outbreak. Conducting randomised control trials of NAIs use in hospitalised patients and in high-risk groups is a high priority. It is essential that steps are taken now to put in place pre-agreed protocols and research infrastructure so that trials can begin as soon as a pandemic begins.

The report doesn’t make any recommendation on whether the government should or shouldn’t stockpile antivirals. It presents the state of the scientific evidence which should be used alongside economic, political and ethical factors when making any decisions.

Professor Sir Patrick SissonsFMedSci, Chair of the report's steering group said: “Given the huge impact an influenza pandemic could have on the nation, we want to be sure we have access to the best available options for treating influenza and preventing its spread.

"After reviewing the recent major analyses of the evidence for the impact of the two most commonly used antivirals, we can conclude that the current treatments do reduce deaths from flu in seriously ill patients requiring hospitalisation. There is evidence of some benefit in patients with seasonal influenza who are not severely ill, however this benefit is modest and may not support the routine use of antivirals in this setting. There is some, but as yet limited, evidence to support the use of antivirals for prophylaxis of influenza.

"However we emphasise that decisions about the widespread use of antivirals in a new pandemic setting must take into account factors such as the virulence of the circulating strain, cost-effectiveness, distribution and the risk of resistance. Since these may be different from previous situations, it can be difficult to apply evidence collected in one outbreak to another, and very important to learn as much as possible from any new outbreak.

"We hope that our conclusions will inform the Department of Health, Public Health England and other policymakers who are deciding how to best prepare for a possible influenza pandemic."

Dr Jeremy Farrar, Director of the Wellcome Trust and member of the steering group said: "The failure to conduct research during the last influenza pandemic has contributed to the current weaknesses in the evidence base and the uncertainty facing clinicians.

"Research on the use of antivirals – in hospitalised patients and in high-risk groups in a serious epidemic or pandemic – is a priority. It could help health professionals take the best course of action, which could mean fewer hospitalisations and deaths.

"The research protocols and infrastructure need to be put in place now - in 'peace time' - so we can start collecting new evidence immediately at the start of a new epidemic or pandemic. An assessment of the ability to do this research must be included in any scenario planning exercises for future pandemics.”

The report was developed by a steering group of experts after a request from the Department of Health for an evidence-based report to inform future policy decisions. The steering group was informed by a one day workshop held in February 2015 and attended by the authors of recent studies as well as a range of individuals from clinical disciplines, public health, virology, industry and research funders.

A full copy of the report, 'Use of neuraminidase inhibitors in influenza', is available here.

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