by Deborah Cohen and Philip
February 10, 2014
Key scientists advising the World Health
on planning for an influenza pandemic
had done paid work for
that stood to gain from the
guidance they were preparing.
These conflicts of interest
have never been publicly disclosed by
and WHO has dismissed inquiries into its
of the A/H1N1 pandemic as "conspiracy
Deborah Cohen and Philip Carter
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
The original advisory
opinion was requested by...
(click above image)
Was it appropriate for
WHO (specialized agency of
the United Nations - UN) 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
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.
Next week marks the first anniversary of the official declaration of
influenza A/H1N1 pandemic.
On 11 June 2009 Dr
Margaret Chan, the director
general of the World Health Organization, announced to the world's
"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."
It was the culmination of 10 years of
pandemic preparedness planning for WHO - years of committee meetings
with experts flown in from around the world and reams of draft
documents offering guidance to governments.
But one year on, governments that took
advice from WHO are unwinding their vaccine contracts, and billions
of dollars' worth of stockpiled oseltamivir (Tamiflu)
and zanamivir (Relenza)
- bought from health budgets already under tight constraints - lie
unused in warehouses around the world.
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, and about the transparency of the science
underlying its advice to governments.
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?
And why does the composition of
the emergency committee from which Chan sought guidance
remain a secret known only to those within WHO?
We are left wondering whether major
public health organizations are able to effectively manage the
conflicts of interest that are inherent in medical science.
Already WHO's handling of the pandemic has led to an unprecedented
number of reviews and inquiries by organizations including the
Council of Europe, European Parliament, and WHO itself, following
allegations of industry influence.
Dr Chan has dismissed these as
"conspiracies," and earlier this year, during a speech at the
Centers for Disease Control and Prevention in Atlanta, she said:
"WHO anticipated close scrutiny of
its decisions, but we did not anticipate that we would be
accused, by some European politicians, of having declared a fake
pandemic on the advice of experts with ties to the
pharmaceutical industry and something personal to gain from
increased industry profits."
The inquiry by British MP Paul Flynn
for the Council of Europe Parliamentary Assembly - due to be
published today - will be critical.
It will say that decision making around
the A/H1N1 crisis has been lacking
"Some of the outcomes of the
pandemic, as illustrated in this report, have been dramatic:
distortion of priorities of
public health services all over Europe, waste of huge sums
of public money, provocation of unjustified fear amongst
Europeans, creation of health risks through vaccines and
medications which might not have been sufficiently tested
before being authorized in fast-track procedures, are all
examples of these outcomes.
These results need to be critically
examined by public health authorities at all levels with a view
to rebuilding public confidence in their decisions."
The investigation by the BMJ/The Bureau
reveals a system struggling to manage the inherent conflict between
the pharmaceutical industry, WHO, and the global public health
system, which all draw on the same pool of scientific experts.
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.
Yet these interests have never been
publicly disclosed by WHO and, despite repeated requests from the
BMJ/The Bureau, WHO has failed to provide any details about whether
such conflicts were declared by the relevant experts and what, if
anything, was done about them.
It is this lack of transparency over conflicts of interests -
coupled with a documented changing of the definition of a pandemic
and unanswered questions over the evidence base for therapeutic
interventions1 - that has led to the emergence of these
"Potential conflicts of interest are
inherent in any relationship between a normative and health
development agency, like WHO, and a profit-driven industry.
Similar considerations apply when
experts advising the Organization have professional links with
pharmaceutical companies. Numerous safeguards are in place to
manage possible conflicts of interest or their perception."
Another factor that has fuelled the
conspiracy theories is the manner in which risk has been
No one disputes the difficulty of
communicating an uncertain situation or the concept of risk in a
But one world expert in risk
communication, Gerd Gigerenzer, director of the Centre for
Adaptive Behavior and Cognition at the Max Planck Institute in
Germany, told the BMJ/The Bureau:
"The problem is not so much that
communicating uncertainty is difficult, but that uncertainty was
not communicated. There was no scientific basis for the WHO's
estimate of 2 billion for likely H1N1 cases, and we knew little
about the benefits and harms of the vaccination.
The WHO maintained this 2 billion
estimate even after the winter season in Australia and New
Zealand showed that only about one to two out of 1000 people
were infected. Last but not least, it changed the very
definition of a pandemic."
WHO for years had defined pandemics as
outbreaks causing "enormous numbers of deaths and illness" but in
early May 2009 it removed this phrase - describing a measure of
severity - from the definition.2
The routes to the Council of Europe's criticisms can be traced back
to 1999, a pivotal year in the influenza world.
In April that year WHO - spurred on by
the 1997 chicken flu outbreak in Hong Kong - began to organize
itself for a feared pandemic. It drew up a key document, Influenza
Pandemic Plan: The Role of WHO and Guidelines for National and
WHO's first influenza pandemic preparedness plan was stark in the
scale of the risk the world faced in 1999:
"It is impossible to anticipate when
a pandemic might occur. Should a true influenza pandemic virus
again appear that behaved as in 1918, even taking into account
the advances in medicine since then, unparalleled tolls of
illness and death would be expected."
In the small print of that document it
"R Snacken, J Wood, L R Haaheim, A P
Kendal, G J Ligthart, and D Lavanchy prepared this document for
the World Health Organization (WHO), in collaboration with the
European Scientific Working Group on Influenza (ESWI)."
What this document does not disclose is
that ESWI is funded entirely by Roche and other influenza drug
Nor does it disclose that René
Snacken and Daniel Lavanchy were participating in Roche
sponsored events the previous year, according to marketing material
seen by the BMJ/The Bureau.
Dr Snacken was working for the Belgian ministry of public health
when he wrote about studies involving neuraminidase inhibitors for a
Roche promotional booklet. And Dr Lavanchy, meanwhile, was a WHO
employee when he appeared at a Roche sponsored symposium in 1998.
His role at that time was in the WHO
Division of Viral Diseases. Dr Lavanchy has declined to comment.
In 1999 other members of the European Scientific Working Group on
Influenza included Professor Karl Nicholson of Leicester
University, UK, and Professor Abe Osterhaus of Erasmus
University in the Netherlands.
These two scientists are also identified
in Roche marketing material seen by this investigation which was
produced between 1998 and 2000. Professor Osterhaus told the BMJ
that he had always been transparent about any work he has done with
industry. Professor Nicholson similarly has consistently declared
his connections with pharmaceutical companies, for example, in
papers published in journals such as the BMJ and Lancet.
Both experts were also at that time engaged in a randomized
controlled trial on oseltamivir supported by Roche.
The trial was subsequently published in
the Lancet in 2000.3 It remains one of the main
studies supporting oseltamivir's effectiveness - and one that was
subsequently shown to have employed undeclared industry funded
The influence of the European Scientific Working Group on Influenza
would continue as the decade wore on and the calls for pandemic
planning became more strident.
Founded in 1992, this,
"multidisciplinary group of key
opinion leaders in influenza aims to combat the impact of
epidemic and pandemic influenza",
...and claims links to WHO, the Robert
Koch Institute, and the European Centre for Disease Prevention and
Control, among others.4
Despite the group's claims of scientific
independence its 100% industry funding does present a potential
conflict of interest. One if its roles is to lobby politicians, as
highlighted in a 2009 policy document.5
At a pre-pandemic preparation workshop of the European Scientific
Working Group on Influenza in January last year, Professor Osterhaus
"I can tell you that ESWI is working
on that idea [that is, convincing politicians] quite
intensively. We have contact with MEPs [members of the European
Parliament] and with national politicians.
But it is they who have to decide at
the end of the day, and they will only act at the request of
their constituencies. If the latter are not prompted, nothing
The group's policy plan for 2006-10
specifically stated that government representatives needed to,
"take measures to encourage the
pharmaceutical industry to plan its vaccine/antivirals
production capacity in advance" and also to "encourage and
support research and development of pandemic vaccine" and to
"develop a policy for antiviral stockpiling."
It also added that government
representatives needed to know that,
"influenza vaccination and use of
antivirals is beneficial and safe."
It said that the group provided,
"evidence based, palatable
information"; and also "networking/exchange with other
stakeholders (e.g., with industry in order to establish pandemic
vaccine and antivirals contracts)."
In the meantime, in Roche's own
marketing plan, one goal was to,
"align Roche with credible third
party advocates". They "leveraged these relationships by
enlisting our third-party partners to serve as spokespeople and
increase awareness of Tamiflu and its benefits." 6
Barbara Mintzes, assistant
professor in the Department of Pharmacology and Therapeutics at the
University of British Columbia, is currently part of a group working
with Health Action International and WHO developing model curricula
for medical and pharmaceutical students on drug promotion and
interactions with the industry, including conflicts of interest.
She thinks that caution is advised when
working with medical bodies of this sort.
"It is legitimate for WHO to work
with industry at times. But I would have concerns about
involvement with a group that looks like it is for independent
academics that is actually mainly industry funded," she told the
BMJ/The Bureau, adding "the Institute of Medicine has raised
concerns about the need to have a firewall with medical groups.
To me this does not sound like an independent group, as it is
mainly funded by manufacturers."
She also thinks that there is a
difference between the conflict of interest in having a clinical
trial funded by a company and the conflict of interest in being
involved in marketing a drug - for example, on a paid speaker's
bureau or in marketing material.
"Some academic medical departments,
for example Stanford University, have banned staff from being
involved in marketing or being on a paid speakers bureau," she
The presence of leading influenza
scientists at promotional events for oseltamivir reflected not just
the concern of an impending pandemic, but the excitement over the
potential of a new class of drugs - neuraminidase inhibitors - to
offer treatment and protection against seasonal influenza.
In 1999 two new drugs first came to market:
drugs would battle it out over the coming years, with oseltamivir -
aided by its oral administration - trumping its rival in global
sales as the decade wore on.
The potential was quickly grasped. Indeed, that year Professor
Osterhaus published an article proposing the use of neuraminidase
inhibitors in pandemics:
"Finally, during a possible future
influenza pandemic, in view of their broad reactivity against
influenza virus neuraminidase subtypes and the expected lack of
sufficient quantities of vaccine, the new antivirals will
undoubtedly have an essential role to play in reducing the
number of victims." 7
However, he also warned that antivirals
should not be seen as a replacement for vaccinations.
"Close collaboration and
consultation between, on the one hand, companies marketing
influenza vaccines and, on the other, those marketing antivirals
will therefore be absolutely essential. It is important that a
clear and uniform message indicating the complementary roles of
vaccines and antivirals is delivered."
That article appeared in the European
Scientific Working Group on Influenza's bulletin of April 1999;
Professor Osterhaus signs off with the affiliation of WHO National
Influenza Centre Rotterdam, The Netherlands.
Other experts soon followed suit - recommending the role
neuraminidase inhibitors could play in any future pandemic - in both
the academic literature and in the general media.
Food and Drug
While the excitement over these drugs fuelled scientific symposiums,
Food and Drug Administration (FDA) was less than convinced.
The BMJ/The Bureau has since spoken to
people from within the American and European drug regulators, the
FDA and the European Medicines Agency (EMEA), who said that both
regulators struggled with the paucity of the data presented to them
for zanamivir and oseltamivir, respectively, during the licensing
At the end of last year (2009), the BMJ called
for access to raw data for key public health drugs after the
Cochrane Collaboration found the effectiveness of the drugs
impossible to evaluate.8
The group are continuing to negotiate
access to what they say they need to fully assess the effectiveness
In the US, the FDA first approved zanamivir in 1999.9
Michael Elashoff, a former employee of the FDA, was the statistician working
on the zanamivir account. He told the BMJ how the FDA advisory
committee initially rejected zanamivir because the drug lacked
After Dr Elashoff's review (he had access to individual patient data
and summary study reports) the 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
He said that it didn't reduce symptoms
even by a day.
"When I was reviewing the data, I
tried to replicate the analyses in their summary study reports.
The issue was not of data quality, but sensitivity analyses
showed even less efficacy," he said.
"The safety analysis showed there
were safety concerns, but the focus was on if Glaxo had
Dr Elashoff's view was that zanamivir
was no better than placebo - and it had side effects.
And when the FDA medical reviewer made a
presentation, her conclusion was that it could either be approved or
not approved. It was a fairly borderline drug.
There were influenza experts on the FDA's advisory committee and
much of the discussion hinged on why a drug that looked so promising
in earlier studies wasn't working in the largest trials in the US.
One hypothesis was that people in the US were taking other drugs for
symptomatic relief that masked any effect of zanamivir.
So zanamivir might have no impact on
symptoms over and above the baseline medications that people take
when they have influenza.
Two other trials - one in Europe and one in Australia - showed
a bit more promise. But there was a very low rate of people taking
"So in the context of not being
allowed to take anything for symptomatic relief, there might be
some effect of Relenza. But in the context of a typical flu,
where you have to take other things to manage your symptoms, you
wouldn't notice any effect of Relenza over and above those other
things," Dr Elashoff said.
The advisory committee recommended that
the drug should not be approved.
Nevertheless, FDA management decided to overturn the committee's
"They would feel better if there was
something on the market in case of a pandemic. It wasn't a
scientific decision," Dr Elashoff said.
While Dr Elashoff was working on the
zanamivir review, he was assigned the oseltamivir application.
But when the review and 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.
In Europe the EMEA was similarly troubled by the evidence for
By early 2002 Roche had sought a
European Union-wide licence from the EMEA. It was a lengthy process,
taking three meetings of the Committee for Medicinal Products for
Human Use as well as expert panels, according to one of the two
rapporteurs, Pekka Kurki of the Finnish Medicines Agency.
Echoing the Cochrane Collaborations's
2009 findings 6 Kurki told us:
"We discussed the same issues that
are still discussed today: does it show clinically significant
benefits in treatment and prophylaxis of flu and what was the
magnitude of the benefits presented in the RCTs?
Our assessment and Cochrane's in
2009 are very similar with regard to the effect size in RCTs.
The data show that the effects of Tamiflu were clear but not
"What was unclear and is still unclear is what is the impact of
Tamiflu on serious complications. Circulating influenza was very
mild when Tamiflu was developed and therefore it is very
difficult to say anything about serious complications.
The data did not clearly show an
effect on serious complications - it was not demonstrated by the
In documents obtained under the freedom
of information legislation, two of the experts who provided opinions
during the EMEA licensing process have also featured in Roche
marketing material: Annike Linde and Rene Snacken.
In Dr Snacken's EMEA presentation dated
18 February 2002, he discussed the need for chemoprophylaxis and
called for the use of oseltamivir during a pandemic.
He made his presentation as a
representative of the Belgian Ministry of Public Health.
At the time
Dr Snacken was also "liaison officer" for the European Scientific
Working Group on Influenza. He also played a key role in the Belgian
government during its pandemic planning, and he later became a
senior expert at the Preparedness and Response Unit, European Centre
for Disease Prevention and Control.
We do not know what, if anything, he
declared to the EMEA about his relationship with Roche.
Annike Linde has confirmed in an email that she has had connections
with Roche over a number of years. She made a presentation to the
EMEA on "influenza surveillance" in her capacity as a representative
of the Swedish Institute for Infectious Disease.
Again, it is not clear what, if
anything, she declared to the EMEA concerning her previous
relationship with Roche.
Dr Linde, now the Swedish state epidemiologist, has told the BMJ/The
Bureau that she received payments from Roche International in
respect of various pieces of work she did for the company until
2002. She has subsequently given occasional lectures for Roche
All money she has received from Roche
was given, Dr Linde says, to the Swedish Institute for Infectious
We asked the scientists whether they declared their relationship
with Roche at the time to the EMEA. Neither has answered that
question entirely satisfactorily. Dr Snacken has not replied to
repeated emails posing this question.
Dr Linde responded by telling the BMJ/The
"We contribute with our expertise to
the regulatory agencies when asked. When we do so, a declaration
of interest, where e.g. participation at advisory meetings at
Roche, is given and evaluated by the regulatory agency."
The BMJ/The Bureau requested Linde and
Snacken's declaration of interest statements for the 2002 meeting
from the EMEA under the freedom of information act.
The EMEA was unable to provide
statements for those particular people at that time.
In October 2002 WHO convened a meeting of influenza experts at its
Geneva headquarters. Their purpose was to develop WHO's guidelines
for the use of vaccines and antivirals during an influenza pandemic.
Included at this meeting were representatives from Roche and Aventis
Pasteur and three experts who had lent their name to oseltamivir's
marketing material (Professors Karl Nicholson, Ab Osterhaus, and
Two years later the WHO published a key report from that meeting,
WHO Guidelines on the Use of Vaccines and Antivirals during
Influenza Pandemics 2004.
The specific guidance on antivirals,
Considerations for the Use of Antivirals During an Influenza
Pandemic, was written by Fred Hayden.
Professor Hayden has confirmed to the
BMJ/The Bureau in an email that he was being paid by Roche for
lectures and consultancy work for the company at the time the
guidance was produced and published. He also told us in an email
that he had received payments from GlaxoSmithKline for consultancy
and lecturing until 2002.
According to Prof Hayden:
"DOI [declaration of interest] forms
were filled out for the 2002 consultation."
The WHO guidance concluded that:
"Based on their pandemic response
goals and resources, countries should consider developing plans
for ensuring the availability of antivirals. Countries that are
considering the use of antivirals as part of their pandemic
response will need to stockpile in advance, given that current
supplies are very limited."
Many countries around the world would
adopt this guidance.
The previous year Professor Hayden was also one of the main authors
of a Roche sponsored study that claimed what was to become one of
oseltamivir's main selling points - a claimed 60% reduction in
hospitalizations from flu, which the Cochrane Collaboration was
later unable to verify.8
Our investigation has also identified relevant and declarable
interests relating to the two other named authors of annexes to
WHO's 2004 guidelines. Arnold Monto was the author of the
annex dealing with vaccine usage in pandemics.
Between 2000 and 2004 - and at the time
of writing the annexe - Dr Monto has consistently and openly
declared honorariums, consultancy fees, and research support from
Roche, 10 11 12 consultancy fees and research
support from GlaxoSmithKline 10 12 13 14; and also
research funding from ViroPharma.15
No conflict of interest statement was included in the annex he wrote
When asked if he had signed a
declaration of interest form for WHO, Dr Monto told the BMJ/The
"Conflict of Interest forms are
requested before participation in any WHO meeting".
Professor Karl Nicholson is the
author of the third annex, Pandemic Influenza.
According to declarations made by
Professor Nicholson in the BMJ16and Lancet in 2003,17 he had
received travel sponsorship and honorariums from GlaxoSmithKline and
Roche for consultancy work and speaking at international respiratory
and infectious diseases symposiums.
Before writing the annex, he had
also been paid and declared ad hoc consultancy fees by Wyeth,
Chiron, and Berna Biotech.
Even though the previous year these declarations had been openly
made in the Lancet and the BMJ, no conflict of interest statement
was included in the annex he wrote for WHO.
Professor Nicholson told the BMJ/The
Bureau that he last had "financial relations" with Roche in 2001.
When asked if he had signed a
declaration of interest form for WHO, Prof Nicholson replied:
"The WHO does require attendees of
meetings, such as those held in 2002 and 2004, to complete
declarations of interest."
Leaving aside the question of what
declarations experts made to WHO, one simple fact remains:
WHO itself did not publicly disclose
any of these conflicts of interest when it published the 2004
It is not known whether information
about these conflicts of interest was relayed privately to
governments around the world when they were considering the advice
contained in the guidelines.
The year before WHO issued the 2004 guidance, it published a set of
rules on how WHO guidelines should be developed and how any
conflicts of interest should be handled. This guidance included
recommendations that people who had a conflict of interest should
not take part in the discussion or the piece of work affected by
that interest or, in certain circumstances, that the person with the
conflict should not participate in the relevant discussion or work
The WHO rules make provision for the
director general's office to allow declarations of interest to be
seen if the objectivity of a meeting has been called into question.18
The BMJ/The Bureau has asked WHO for the conflict of interest
declarations for the Geneva 2002 meeting and those related to the
guidance document itself.
WHO told us that the query went directly
up to Margaret Chan's office.
"WHO never publishes individual DOIs
[declaration of interest], except after consultation with the
Office of the Director-General. In this case, we put in a
request on your behalf but it was not granted. In more recent
years, many WHO committees have published summaries of relevant
interests with their meeting reports."
In a BMJ interview (see film on
WHO spokesperson Gregory Hartl reiterated the fact that Dr Margaret
"is very committed personally to
Yet her office has turned down repeated
requests for declaration of interest statements and declines to
comment on the allegations that authors of the guidelines had
Nevertheless, Prof Hayden told the BMJ/The Bureau:
"I strongly support transparency in
declarations of interest, in part because this allows those
reading documents, particularly ones authored by specific
individuals (e.g., Annex 5) [the part he wrote], to make their
own judgments about the possible relevance of any potential
While experts need to work with industry
to develop the best possible drugs for illnesses, questions remain
about what level of involvement experts with industry ties should
have in the formulation of public health policy decisions and
Professor Nicholson told the BMJ/The
"The WHO and decision makers must be
informed of ongoing developments and research findings to ensure
that they are as up to date as possible. Some of the most
relevant expertise and information are held by companies or
individuals with conflicts of interest.
I understand the view that experts
with conflicts of interest should not advise governments or
organizations such as the WHO. But to exclude such people from
discussions could deprive WHO and decision makers of important
But not everyone agrees.
Barbara Mintzes is unequivocal
about what role they should play.
"No one should be on a committee
developing guidelines if they have links to companies that
either produce a product - vaccine or drug - or a medical device
or test for a disease.
It would be preferable that there
are no financial ties when it comes to making big decisions on
public health - for example, stockpiling a drug - and that
includes if they have a currently funded clinical trial," she
"Ideally, what you want are independent experts who are in the
public sector to provide expertise on drugs and vaccines. But
they can be hard to find. One solution is consult with the
experts who are involved in industry, but not put them on any
decision making committee.
You need a firewall," she added.
Indeed, Professor Harvey Fineberg,
president of the Institute of Medicine and chairman of the panel
reviewing WHO's management of the pandemic, takes a similarly hard
line. His own institution went through a detailed review of how they
interact with industry and experts with conflicts of interests last
"Sometimes publication of conflict
of interests is enough - for example with a journal. But if you
are giving expert judgment to influence policy, revealing is not
enough," he told the BMJ, referring to the Institute of
WHO also says that it takes conflicts of
interests seriously and has the mechanisms in place to deal with
But what action does it take when a
scientist declares a conflict of interest, and when does it judge a
scientist to be too conflicted to play a leading role in the
formulation of global health policy? Since WHO has not provided us
with an answer to this question, we are left to guess.
As it stands, this situation is the worst possible outcome for WHO,
according to Professor Chris Del Mar, a Cochrane Review
author and expert on WHO's Strategic Advisory Group of Experts on
"If it proves to be the case that
authors of WHO guidance which promoted the use of certain drugs
were being paid at the same time by the makers of those drugs
for other work they were doing for these companies that is
reprehensible and should be condemned in the strongest possible
WHO's endorsement of oseltamivir was not
lost on Roche. In an advert placed by the company for the drug in
the main conference program of the European Scientific Working Group
on Influenza's 2005 conference in Malta, it says:
"Antivirals will initially be the
principal medical intervention in a pandemic situation and Roche
is working as a responsible partner with governments to assist
in their pandemic planning."
The source reference for this is the WHO
Global Influenza Preparedness Plan.
Throughout the following years, WHO would appear to have been
inconsistent in how it treated conflicts of interest. Updated
pandemic plans would continue to be prepared by experts who openly
had work funded and acted as consultants to manufacturers of
vaccines and antivirals.
WHO produced its global influenza
preparedness plan in 2005, and in 2006 it constituted an interim
Influenza Pandemic Task Force. No public declarations of interest
have been made and to date no details have been provided by WHO in
response to our requests.
WHO's stance that it does not publish declarations of interest from
its experts is far from consistent. It is undermined, for example,
by the position WHO adopts in relation to the Strategic Advisory
Group of Experts on Immunization, its standing vaccine advisory
Here, contrary to its approach to
pandemic planning advisers, WHO does publish summaries of
declarations of interest.
These seeming inconsistencies in WHO's approach to transparency and
its handling of conflicts of interest extend into the workings of
the Emergency Committee formed last year to advise the director
general on the pandemic.
The identities of its 16 members are
unknown outside WHO. This secret committee has guided WHO pandemic
policy since then - including deciding when to judge that the
pandemic is over.
WHO says it has to keep the identities secret to protect the
scientists from being influenced or targeted by industry. In a phone
call to the BMJ/The Bureau in March, WHO spokesperson Gregory Hartl
"Our general principle is we want to
protect the committee from outside influences."
The committee advised the WHO director
general on phase changes as well as temporary recommendations.
According to WHO, When the Emergency
Committee met to discuss a possible move to a declaration of a
pandemic, the meeting additionally included members who represented
Australia, Canada, Chile, Japan, Mexico, Spain, the UK, and the US,
eight countries that experienced widespread outbreaks at the time.
These national representatives were
present to ensure full consideration of the views and possible
reservations of the countries expected to bear the initial brunt of
economic and social repercussions.
WHO says all members of the Emergency Committee sign a
confidentiality agreement, provide a declaration of interests, and
agree to give their consultative time freely, without compensation.
However, only one member of the
committee has been publicly named: Professor John MacKenzie, who
This is a troubling stance: it suggests that WHO considers other
advisory groups whose members are not anonymous - such as the
Strategic Advisory Group of Experts on Immunization - to be
potentially subject to outside influences, and it allows no scrutiny
of the scientists selected to advise WHO and global governments on a
major public health emergency.
Under the International Health Regulations framework, the membership
of the Emergency Committee is drawn from a roster of about 160
experts covering a range of public health areas.
This framework provides guidelines about
how WHO deals with acute public health risks. The BMJ/The Bureau has
identified approximately 15 scientists from the International Health
Regulations roster with influenza expertise and has emailed them to
ask if they were on the Emergency Committee.
Under the framework at least some of
these scientists are members of the Emergency Committee.
Yet because of the confidentiality
agreements they have signed, these scientists cannot acknowledge
their membership of the committee, putting them in an invidious
David Salisbury, chair of WHO's Strategic Advisory Group
of Experts on Immunization (SAGE) committee at the time of the
pandemic and a member of the International Health Regulations, says
the secrecy has caused problems for his group.
"It certainly caused problems for
SAGE. Since all of the details of SAGE are in the public domain,
there was a perception that it had been SAGE that had given
advice about the changing of definitions or the pandemic levels
- when we had not done so.
SAGE members came in for unfair
personal abuse by journalists," he told the BMJ/The Bureau.
"Given the importance of the advice, the transparency of the
source of the advice was important. I believe it is necessary to
keep confidential the source of advice if revealing details
might put individuals at risk, for example when bioterrorism is
This does not seem to be the case
for pandemic flu," he added.
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, who then put pressure on WHO to declare a
pandemic. It was the declaring of the pandemic that triggered the
The BMJ/The Bureau can confirm that Dr Monto, Dr John Wood, and Dr
Masato Tashiro are members of the Emergency Committee.
Although Dr Monto did not answer the question directly, his
Infectious Disease Society of America biography states that he
is a member.20
Last year, according to figures made public in the US by
GlaxoSmithKline, Professor Monto received $3000 speakers fees from
the company in the period between the second quarter and the last
quarter of 2009.
As a national official of the Japanese
government, Dr Tashiro says that he must,
"have nothing concerning conflict of
interest with private companies".
Dr John Wood works for the UK
National Institute for Biological Standards and Control (NIBSC).
Dr Wood, like Dr Tashiro, has no
personal conflict of interests but he told the BMJ/The Bureau that
as part of its statutory role in developing standards for
measurement of biological medicines to ensure accurate dosing and
carrying out independent control testing to assure their safety and
efficacy, the institute must work closely with the pharmaceutical
This is made clear on their website.
"The International Federation of
Pharmaceutical Manufacturers and Associations has also made
publicly available the nature of their close interaction with
NIBSC and similar organisations in order to develop influenza
vaccines," he said.21
Those who said that they were not on the
Maria Zambon, from the UK's
Health Protection Agency told the BMJ:
"I undertake various advisory roles
to WHO. Declaration of interest statements are prepared before
undertaking such roles.
The HPA Centre for Infection, as
part of its role in national infectious disease surveillance,
provision of specialist and reference microbiology and vaccine
efficacy monitoring, works closely with vaccine manufacturers
and biotechnology companies."
Health Regulations review
WHO's own review into the operation of the International Health
Regulations and WHO's handling of the pandemic is now being
conducted by Harvey Feinberg, president of the US Institute
of Medicine, and will report its findings next year.
Dr Chan and Professor Feinberg have both
made clear the need for a thorough investigation. But questions are
already arising about how independent the review will turn out to
According to the International Health
Regulations list in our possession, some 13 of the 29 members of the
review panel are members of the International Health Regulations
itself and one is the chair of the Emergency Committee.
To critics that might suggest a somewhat
Professor Mintzes does not agree with WHO's explanation that secrecy
was needed to protect against the influence of outside interest on
"I can't understand why the WHO kept
this secret. It should be public in terms of accountability like
the expert advisory committees.
If the rationale of secret
membership is not to be unduly influenced, there are other ways
of dealing with this through strong conflict of interest
provisions," she said.
She also believes that the very nature
of allowing a trigger point for vaccine contracts opens the system
up unnecessarily to exploitation.
"It seems a problem that this
declaration might trigger contracts to be realized.
There should be safeguards in place
to make sure those with an interest in vaccine manufacturers
can't exploit the situation. The WHO will have to look long and
hard at this in future," she said.
The number of victims of H1N1 fell far
short of even the more conservative predictions by the WHO. It
could, of course, have been far worse. Planning for the worst while
hoping for the best remains a sensible approach. But our
investigation has revealed damaging issues.
If these are not addressed, H1N1 may yet
claim its biggest victim - the credibility of the WHO and the trust
in the global public health system.
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