WHO and the pandemic flu “conspiracies” – The BMJ and the Bureau of Investigative Journalism report that was covered up

Conflicts of Interest

A joint investigation by the BMJ and the Bureau of Investigative Journalism has uncovered evidence that raises troubling questions about how WHO managed conflicts of interest among the scientists who advised its pandemic planning

The secrecy of the committee is also fuelling conspiracy theories, particularly around the activation of dormant pandemic vaccine contracts. A key question will be whether the pharmaceutical companies, which had invested around $4bn (£2.8bn, 3.3bn) in developing the swine flu vaccine, had supporters inside the emergency committee

The original advisory opinion was requested by...

– Was it appropriate for WHO to take advice from experts who had declarable financial and research ties with pharmaceutical companies producing antivirals and influenza vaccines?

– Why was key WHO guidance authored by an influenza expert who had received payment for other work from Roche, manufacturers of oseltamivir, and GlaxoSmithKline, manufacturers of zanamivir?

– Why does the composition of the emergency committee from which Chan sought guidance remain a secret known only to those within WHO?

–  Our investigation has identified key scientists involved in WHO pandemic planning who had declarable interests, some of whom are or have been funded by pharmaceutical firms that stood to gain from the guidance they were drafting

– FDA’s advisory committee voted by 13 to 4 not to approve zanamivir on the grounds that it was no more effective than placebo when the patients were on other drugs such as paracetamol. He said that it didn’t reduce symptoms even by a day.

– conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.”

– the advisory committee decided not to recommend zanamivir, the FDA’s management reassigned the oseltamivir review to someone else. Dr Elashoff believes that the approval of zanamivir paved the way for oseltamivir, which was approved by the FDA later that year.

– “WHO never publishes individual DOIs [declaration of interest], except after consultation with the Office of the Director-General.

Deborah Cohen, features editor, BMJ, Philip Carter, journalist, The Bureau of Investigative Journalism, London

dcohen@bmj.com

Key scientists advising the World Health Organization on planning for an influenza pandemic had done paid work for pharmaceutical firms that stood to gain from the guidance they were preparing. These conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.” Deborah Cohen and Philip Carter investigate

Next week marks the first anniversary of the official declaration of the influenza A/H1N1 pandemic. On 11 June 2009 Dr Margaret Chan, the director general of the World Health Organization, announced to the world’s media: “I have conferred with leading influenza experts, virologists, and public health officials. In line with procedures set out in the International Health Regulations, I have sought guidance and advice from an Emergency Committee established for this purpose. On the basis of available evidence, and these expert assessments of the evidence, the scientific criteria for an influenza pandemic have been met…The world is now at the start of the 2009 influenza pandemic.” Continue reading “WHO and the pandemic flu “conspiracies” – The BMJ and the Bureau of Investigative Journalism report that was covered up”

Half of Tamiflu prescriptions went unused during 2009 H1N1 swine flu pandemic, sewage study concludes

Press release 2013/03 – Issued  by the  Centre for Ecology & Hydrology, UK

 

A new study concludes that  approximately half of the prescriptions of Tamiflu during the 2009-10 influenza  pandemic went unused in England. The unused medication represents approximately  600,000 courses of Tamiflu at a cost of around £7.8 million to the UK taxpayer.  The novel scientific method used in the study could help measure and improve  the effectiveness of future pandemic flu strategies.

The finding, published online in  the open access scientific journal PLOS ONE, comes from the first study of its  kind to use sewage water to estimate drug compliance rates, the degree to which  a patient correctly follows medical advice to take medication. The study  estimated usage of pharmaceuticals from large populations by sampling sewage  and recovering the active component of Tamiflu thus measuring drugs that were  actually consumed by patients, rather than those that were flushed away without  being consumed.

The work was led by scientists at  the UK’s Centre for Ecology & Hydrology working with colleagues at Uppsala,  Linnaeus and Umeå Universities, Sweden, and the  University of South Bohemia, Czech Republic.

Lead author Dr Andrew Singer, a  Chemical Ecologist from the Centre for Ecology & Hydrology, says,  “Influenza pandemics are rare, making a study such as this a unique and  important window into how people behave during a public health emergency such  as a pandemic. This study sheds new light on people’s willingness to follow  medical advice on antiviral usage. Importantly, this method could be used to  monitor how many people take certain kinds of medicine in real time and alert  national health authorities to the need for stronger public information  campaigns during pandemic emergencies.”

The research highlights that  despite the central role of antivirals in many nations’ influenza pandemic  preparedness plans, there remains considerable uncertainty regarding antiviral  compliance rates. Poor compliance drains resources by diverting limited  antiviral stocks from those who may need it most. Mis-used antivirals can lead  to antiviral resistance and represents a significant financial cost and health  risk. Previous research on antiviral compliance had focused on small  populations, typically fewer than 200, and used survey-based analyses of drug  compliance, which can be unreliable.

Dr Singer adds, “Our study was the  first compliance study to utilise waste water as an evidence base for whether a  population consumed Tamiflu or not. Because of this unique study design, we  were able to examine populations orders of magnitude larger than previous  studies. One population was just over 6,000 people and the second population  was 208,000. Tamiflu gets transformed into the active antiviral only after  being consumed, and is released into the sewage with every visit to the toilet.  This waste water epidemiology approach is particularly robust for drugs such as  Tamiflu and potentially more reliable than some survey based methods of  assessing compliance.”

Predictions of oseltamivir  consumption from Tamiflu recovered in sewage were compared with two sources of  national government statistics to derive compliance rates. Scenario and  sensitivity analysis indicated an estimated compliance rate between 45-60%,  (between 45 to 60 people out of every 100 people who received Tamiflu completed  the antiviral course, as prescribed).

Dr Singer says, “With  approximately half the collected antivirals going unused, there is a clear need  to improve public health messages so that less antiviral is wasted and that the  duration and severity of infection is reduced. Furthermore, we feel the waste  water epidemiology approach undertaken can potentially help shape future public  health messages, making them more timely, targeted, and population sensitive,  while potentially leading to less mis- and un-used antiviral, less wastage and  ultimately a more robust and efficacious pandemic preparedness strategy.”

Notes to Editors

For further information, or to request interviews with Dr Andrew Singer, please contact the CEH press office.

This research was supported by the  Swedish Research Council Formas, the Natural Environment Research  Council–Knowledge Transfer (PREPARE) Initiative contract NE/F009216/1 to  A.C.S., and the Ministry of Education, Youth and Sports of the Czech Republic  CENAKVA No. CZ.1.05/2.1.00/01.0024 and the Grant Agency of the University of  South Bohemia No. 047/2010/Z to R.G. and G.F.F. Hoffman – La Roche Ltd. donated  deuterated OC.

Full paper reference: Andrew C.  Singer, Josef D. Järhult, Roman Grabic, Ghazanfar A. Khan, Ganna Fedorova,  Jerker Fick, Richard H. Lindberg, Michael J. Bowes, Björn Olsen and Hanna  Söderström. ‘Compliance to oseltamivir among two populations in Oxfordshire,  United Kingdom affected by influenza A(H1N1)pdm09, November 2009 – a waste  water epidemiology study’ is published in PLOS ONE. The paper will be available from: http://dx.plos.org/10.1371/journal.pone.0060221.

Staff page of Dr Andrew Singer

 

 

Release all Tamiflu data as promised, argue researchers

Contact: Emma Dickinson edickinson@bmjgroup.com 44-020-738-36529 BMJ-British Medical Journal

Company plans to set up review board, but researchers want it to keep its promise

The latest correspondence is posted online today as part of the BMJ‘s open data campaign, aimed at persuading Roche to honour the promise it made almost three years ago to make key Tamiflu trial data available for independent scrutiny.

Last week, Donald MacLean, Life Cycle Leader for Tamiflu, wrote to Professor Chris Del Mar in his capacity as coordinating editor of the Cochrane Acute Respiratory Infections Group, concerning “our debate on Tamiflu data.”

The Cochrane researchers say they object to Roche’s suggestion that there is a debate on Tamiflu data. “There is no debate nor can there be any debate about the data whilst you do not honour your promise,” they say. “The only reason we keep asking Roche to keep its promise, rather than simply getting the data from the European Medicines Agency directly, is because Roche has not supplied all of the data to the European regulator.”

Roche’s letter also mentions “disagreements” over the type of analyses the Cochrane team wish to do, but the researchers point out that their methods and analyses have been public for nearly two years and “follow Cochrane procedure” and state that they are not aware of any specific concerns from Roche.

Roche’s letter goes on to say that, in order to reach “an amicable resolution” Roche plans to set up “a multi-party advisory board to review the totality of Tamiflu data” …. which they believe is “a sensible, fair and transparent way of addressing this public debate.”

But the Cochrane team argue that Roche’s offer is merely a belated attempt at turning the clock back, and call on the company to expand its data sharing pledges “to become compatible with current regulatory norms.”

They say: “The European Medicines Agency and the EU Ombudsman have made abundantly clear that there is no reason for anonymised clinical data to be withheld from public scrutiny once a marketing authorisation has been obtained for a pharmaceutical.  Why should Roche not – at the minimum – meet this standard?”

In summary, they say, “we ask to you to honour your promise of three years ago and make public full clinical study reports in your possession.”

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Tamiflu survives sewage treatment ( oseltamivir )

Contact: Jerker Fick jerker.fick@chem.umu.se 46-480-446-225 Public Library of Science

Swedish researchers have discovered that oseltamivir (Tamiflu); an antiviral drug used to prevent and mitigate influenza infections is not removed or degraded during normal sewage treatment. Consequently, in countries where Tamiflu is used at a high frequency, there is a risk that its concentration in natural waters can reach levels where influenza viruses in nature will develop resistance to it. Widespread resistance of viruses in nature to Tamiflu increases the risk that influenza viruses infecting humans will become resistant to one of the few medicines currently available for treating influenza.

”Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it,” advises Björn Olsen, Professor of Infectious Diseases with the Uppsala University and the University of Kalmar. “Otherwise there is a risk that they will be ineffective when most needed, such as during the next influenza pandemic.”

The Swedish research group demonstrated that oseltamivir, the active substance in Tamiflu, passes virtually unchanged through sewage treatment.

“That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters,” says Jerker Fick, Doctor in Chemistry at Umeå University and the leader of this study.

The Swedish research group also revealed that the level of oseltamivir discharged through sewage outlets in certain countries may be so high that influenza viruses in nature can potentially develop resistance to the drug.

“Use of Tamiflu is low in most countries, but there are some exceptions such as Japan, where a third of all influenza patients are treated with Tamiflu,” explains Jerker Fick.

Influenza viruses are common among waterfowl, especially dabbling ducks such as mallards. These ducks often forage for food in water near sewage outlets. Here they can potentially encounter oseltamivir in concentrations high enough to develop resistance in the viruses they carry.

“The biggest threat is that resistance will become common among low pathogenic influenza viruses carried by wild ducks.” adds Björn Olsen.  These viruses could then recombinate with viruses that make humans sick to create new viruses that are resistant to the antiviral drugs currently available.

The Swedish researchers advise that this problem must be taken seriously so that humanity’s future health will not be endangered by too frequent and unnecessary prescription of the drug today.

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Disclaimer

This press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions.  Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.

Their study was published in the high-ranked journal PLoS ONE. The entire article is available free online, and can be read at the following address: http://www.plosone.org/doi/pone.0000986

Citation: Fick J, Lindberg RH, Tysklind M, Haemig PD, Waldenstro¨m J, et al (2007) Antiviral Oseltamivir Is not Removed or Degraded in Normal Sewage Water Treatment: Implications for Development of Resistance by Influenza A Virus. PLoS ONE 2(10): e986. doi:10.1371/journal.pone.0000986

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (URL live from October 2): http://www.plosone.org/doi/pone.0000986

* Requested Repost

Effects of Tamiflu still uncertain, warn experts, as Roche continues to withhold key trial data

2 years after pharmaceutical giant Roche promised the BMJ it would release key Tamiflu trial data for independent scrutiny, the safety and effectiveness of this anti-influenza drug remains uncertain, warn experts today

Two years after pharmaceutical giant Roche promised the BMJ it would release key Tamiflu trial data for independent scrutiny, the safety and effectiveness of this anti-influenza drug remains uncertain, warn experts today.

A new report by the Cochrane Collaboration says Roche’s refusal to provide full access to all its data leaves critical questions about how well the drug works unresolved.

A BMJ investigation, published to coincide with today’s report, also raises serious concerns about access to drug data, the use of ghost writers in drug trials, and the drug approval process.

Meanwhile, Tamiflu has become the mainstay of influenza treatment in the UK. It has also made it onto the World Health Organisation’s list of Essential Medicines and Roche’s claims continue to be supported by influential health agencies.

The Cochrane researchers set out to test Roche’s claim that Tamiflu prevented complications and reduced the number of people needing hospital treatment. But their investigation was hampered by Roche’s refusal to provide all of its trial data for analysis. The team obtained some clinical study reports from the European Medicines Agency (EMA), but found inconsistencies with published reports and possible under-reporting of side effects.

When previously questioned by the BMJ, Roche also admitted that some of the published papers had been ghost written.

The BMJ investigation reveals how different regulators took different approaches to the data submitted to them, leading to conflicting messages about it effectiveness.

For example, the EMA released a proportion of the clinical study reports relating to the Tamiflu trials to Cochrane, but it admits that it did not ask for the remainder from the manufacturer, although it was legally entitled to do so. The EMA has since told the BMJ that it plans to start publishing reports for all drugs submitted for approval in the next few years.

Dr Fiona Godlee, BMJ Editor-in-Chief says: “We hope very much that the EMA will indeed take this important step in making the full study reports available. But we are still a long way away from having a full trial history for all drugs in clinical use. Public safety and the proper use of public money demands that we should stop at nothing less than this.”

Meanwhile, the US Food and Drug Administration (FDA), which has reviewed the Tamiflu trial programme in perhaps more detail than anyone outside of Roche, chose not to review the largest ever trial of Tamiflu when considering the drug for approval. It states that “Tamiflu has not been shown to prevent such complications [serious bacterial infections].”

However, the US Centers for Disease Control and Prevention (CDC) continue to cite key published trials of Tamiflu, claiming a reduced risk of influenza complications, even after Roche admitted that some of these trials have been ghost written.

Dr Godlee says: “The discrepancies between the conclusions reached by different regulators around the world highlights the absurd situation we find ourselves in. In a globalised world, regulators should cooperate and pool their limited resources. Otherwise we will continue to waste money and risk people’s health on drugs that don’t work.”

The investigation also raises questions about Tamiflu’s clinical effects. After careful evaluation of trial data, the Cochrane group say that Tamiflu appears to affect antibody production – a claim that Roche refutes. This is important, say Cochrane, because influenza vaccination relies on an antibody response to be effective. But when asked by the BMJ, Roche refused to explain how the drug works.

As such, the Cochrane group say that “until more is known about the mode of action of neuraminidase inhibitors, health professionals, patients and other decision makers need to reflect on the findings of this review before making any decision about the use of the drug.”

Cochrane also argue that Tamiflu’s ability to prevent the spread of influenza has not been demonstrated in trials. Yet this is one of the main reasons governments around the world have spent billions of dollars stockpiling Tamiflu in case of a pandemic.

Roche maintain they provided the Cochrane team with enough information to conduct their evaluation, but the Cochrane team say this is not the case. Dr Peter Doshi from Johns Hopkins University School of Medicine says: “In the BMJ in December 2009, Roche promised full study reports to any legitimate investigators.  They have not provided a single full study report to Cochrane, despite our repeated requests.”