LISTSERV mailing list manager LISTSERV 16.5

Help for PED-EM-L Archives


PED-EM-L Archives

PED-EM-L Archives


PED-EM-L@LISTSERV.BROWN.EDU


View:

Message:

[

First

|

Previous

|

Next

|

Last

]

By Topic:

[

First

|

Previous

|

Next

|

Last

]

By Author:

[

First

|

Previous

|

Next

|

Last

]

Font:

Monospaced Font

LISTSERV Archives

LISTSERV Archives

PED-EM-L Home

PED-EM-L Home

PED-EM-L  June 2010

PED-EM-L June 2010

Subject:

BMJ: WHO and the pandemic flu "conspiracies"

From:

marc guttman <[log in to unmask]>

Reply-To:

marc guttman <[log in to unmask]>

Date:

Sun, 6 Jun 2010 18:05:01 -0700

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (399 lines)

http://www.bmj.com/cgi/content/full/340/jun03_4/c2912


Conflic


http://www.bmj.com/cgi/content/full/340/jun03_4/c2912


Conflicts of Interest
WHO and the pandemic flu "conspiracies"
Deborah Cohen, features editor, BMJ, Philip Carter, journalist, The Bureau of
Investigative Journalism, London
[log in to unmask]
Key scientists advising the World Health
Organization on planningfor an influenza pandemic had done
paid work for pharmaceuticalfirms that stood to gain from
the guidance they were preparing.These conflicts of interest have never been publicly disclosedby WHO, and WHO has
dismissed inquiries into its handling ofthe A/H1N1 pandemic
as "conspiracy theories." Deborah Cohenand Philip
Carter investigate

Click on image to view video
Watch the BMJ/The Bureau of Investigative Journalism's video on WHO and
disclosure. This video has also appeared on Al Jazeera and
guardian.co.uk.
Next week marks the first anniversary of the official declarationof the influenza A/H1N1 pandemic. On 11 June 2009 Dr MargaretChan, the director general of the World Health Organization,announced to the world’s media: "I have conferred withleading
influenza experts, virologists, and public health officials.In line with procedures set out in the International HealthRegulations, I have sought guidance and advice from an EmergencyCommittee established for this purpose. On the basis of availableevidence, and these expert assessments of the evidence, thescientific criteria for an influenza pandemic have been met...Theworld is now at the start of the 2009 influenza pandemic."
It was the culmination of 10 years of pandemic preparednessplanning for WHO—years of committee meetings with expertsflown in
from around the world and reams of draft documentsoffering
guidance to governments. But one year on, governmentsthat
took advice from WHO are unwinding their vaccine contracts,and billions of dollars’ worth of stockpiled oseltamivir(Tamiflu) and zanamivir (Relenza)—bought from health budgetsalready
under tight constraints—lie unused in warehousesaround the
world.
A joint investigation by the BMJ and the Bureau of InvestigativeJournalism has uncovered evidence that raises troubling questionsabout how WHO managed conflicts of interest among the scientistswho advised its pandemic planning, and about the transparencyof the science underlying its advice to governments. Was itappropriate for WHO to take advice from experts who had declarablefinancial and research ties with pharmaceutical companies producingantivirals and influenza vaccines? Why was key WHO guidanceauthored by an influenza expert who had received payment forother work
from Roche, manufacturers of oseltamivir, and GlaxoSmithKline,manufacturers of zanamivir? And why does the composition ofthe emergency
committee from which Chan sought guidance remaina secret
known only to those within WHO? We are left wonderingwhether major public health organisations are able to effectivelymanage the conflicts of interest that are inherent in medicalscience.
Already WHO’s handling of the pandemic has led to an unprecedentednumber of reviews and inquiries by organisations including theCouncil of Europe, European Parliament, and WHO itself, followingallegations of industry influence. Dr Chan has dismissed theseas
"conspiracies," and earlier this year, during a speech atthe Centers for Disease Control and Prevention in Atlanta, shesaid: "WHO anticipated close scrutiny of its decisions, butwe did not anticipate that we would be accused, by some Europeanpoliticians, of having declared a fake pandemic on the adviceof experts
with ties to the pharmaceutical industry and somethingpersonal to gain from increased industry profits."
The inquiry by British MP Paul Flynn for the Council of EuropeParliamentary Assembly—due to be published today—willbe critical. It will say that decision making around the A/H1N1crisis has been
lacking in transparency. "Some of the outcomesof the
pandemic, as illustrated in this report, have been dramatic:distortion of priorities of public health services all overEurope,
waste of huge sums of public money, provocation of unjustifiedfear amongst Europeans, creation of health risks through vaccinesand medications which might not have been sufficiently testedbefore being authorised in fast-track procedures, are all examplesof these outcomes. These results need to be critically examinedby public health authorities at all levels with a view to rebuildingpublic confidence in their decisions."
The investigation by the BMJ/The Bureau reveals a system
strugglingto manage the inherent conflict between the
pharmaceutical industry,WHO, and the global public health
system, which all draw onthe same pool of scientific
experts. Our investigation has identifiedkey scientists
involved in WHO pandemic planning who had declarableinterests, some of whom are or have been funded by pharmaceuticalfirms that stood to gain from the guidance they were drafting.Yet these interests have never been publicly disclosed by WHOand, despite repeated requests from the BMJ/The Bureau, WHOhas failed to provide any details about whether such conflictswere declared by the relevant experts and what, if anything,was
done about them.
It is this lack of transparency over conflicts of interests—coupledwith a documented changing of the definition of a pandemic andunanswered questions over the evidence base for therapeuticinterventions1—that has led to the emergence of theseconspiracies.
WHO says: "Potential conflicts of interest are inherent in anyrelationship between a normative and health development agency,like WHO, and a profit-driven industry. Similar considerationsapply
when experts advising the Organization have professionallinks with pharmaceutical companies. Numerous safeguards arein
place to manage possible conflicts of interest or their perception."
Another factor that has fuelled the conspiracy theories is themanner in which risk has been communicated. No one disputesthe
difficulty of communicating an uncertain situation or theconcept of risk in a pandemic situation. But one world expertin
risk communication, Gerd Gigerenzer, director of the Centrefor Adaptive Behaviour and Cognition at the Max Planck Institutein Germany, told the BMJ/The Bureau: "The problem is not somuch that communicating uncertainty is difficult, but that uncertaintywas not communicated. There was no scientific basis for theWHO’s estimate of 2 billion for likely H1N1 cases, andwe knew
little about the benefits and harms of the vaccination.The
WHO maintained this 2 billion estimate even after the winterseason in Australia and New Zealand showed that only about oneto
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 "enormousnumbers of deaths and illness" but in early May 2009 it removedthis phrase—describing a measure of severity—fromthe definition.2
The beginnings
The routes to the Council of Europe’s criticisms can betraced back to 1999, a pivotal year in the influenza world.In
April that year WHO—spurred on by the 1997 chickenflu
outbreak in Hong Kong—began to organise itself fora feared
pandemic. It drew up a key document, Influenza PandemicPlan: The Role of WHO and Guidelines for National and RegionalPlanning.
WHO’s first influenza pandemic preparedness plan was starkin the scale of the risk the world faced in 1999: "It is impossibleto anticipate when a pandemic might occur. Should a true influenzapandemic virus again appear that behaved as in 1918, even takinginto account the advances in medicine since then, unparalleledtolls of illness and death would be expected."
In the small print of that document it states: "R Snacken, JWood, L R Haaheim, A P Kendal, G J Ligthart, and D Lavanchyprepared this document for the World Health Organization (WHO),in
collaboration with the European Scientific Working Groupon
Influenza (ESWI)." What this document does not disclose isthat ESWI is funded entirely by Roche and other influenza drugmanufacturers. Nor does it disclose that René Snackenand Daniel Lavanchy
were participating in Roche sponsored eventsthe previous
year, according to marketing material seen by theBMJ/The Bureau.
Dr Snacken was working for the Belgian ministry of public healthwhen he wrote about studies involving neuraminidase inhibitorsfor a Roche promotional booklet. And Dr Lavanchy, meanwhile,was a WHO employee when he appeared at a Roche sponsored symposiumin 1998. His role at that time was in the WHO Division of ViralDiseases. Dr Lavanchy has declined to comment.
In 1999 other members of the European Scientific Working Groupon Influenza included Professor Karl Nicholson of LeicesterUniversity, UK, and Professor Abe Osterhaus of Erasmus Universityin the Netherlands. These two scientists are also identifiedin
Roche marketing material seen by this investigation whichwas produced between 1998 and 2000. Professor Osterhaus toldthe BMJ that he had always been transparent about any work hehas done with industry. Professor Nicholson similarly has consistentlydeclared his connections with pharmaceutical companies, forexample, in papers published in journals such as the BMJ andLancet.
Both experts were also at that time engaged in a randomisedcontrolled trial on oseltamivir supported by Roche. The trialwas
subsequently published in the Lancet in 2000.3 It remainsone of the main studies supporting oseltamivir’s
effectiveness—andone that was subsequently shown to have
employed undeclaredindustry funded ghostwriters.1
The influence of the European Scientific Working Group on Influenzawould continue as the decade wore on and the calls for pandemicplanning became more strident. Founded in 1992, this
"multidisciplinarygroup of key opinion leaders in influenza
aims to combat theimpact of epidemic and pandemic influenza" and claims linksto WHO, the Robert Koch Institute, and the
European Centre forDisease Prevention and Control, among
others.4 Despite the group’sclaims of scientific independence its
100% industry fundingdoes present a potential conflict of
interest. One if its rolesis to lobby politicians, as
highlighted in a 2009 policy document.5
At a pre-pandemic preparation workshop of the European ScientificWorking Group on Influenza in January last year, Professor Osterhaussaid: "I can tell you that ESWI is working on that idea [thatis,
convincing politicians] quite intensively. We have contactwith MEPs [members of the European Parliament] and with nationalpoliticians. But it is they who have to decide at the end ofthe day, and they will only act at the request of their constituencies.If the latter are not prompted, nothing will happen."
The group’s policy plan for 2006-10 specifically statedthat
government representatives needed to "take measures toencourage the pharmaceutical industry to plan its vaccine/antiviralsproduction capacity in advance" and also to "encourage and supportresearch and development of pandemic vaccine" and to "developa
policy for antiviral stockpiling." It also added that governmentrepresentatives needed to know that "influenza vaccination anduse of
antivirals is beneficial and safe." It said that thegroup
provided "evidence based, palatable information"; andalso
"networking/exchange with other stakeholders (eg, withindustry in order to establish pandemic vaccine and antiviralscontracts)." In the meantime, in Roche’s own marketingplan, one goal was to "align Roche with credible third partyadvocates". They
"leveraged these relationships by enlistingour third-party
partners to serve as spokespeople and increaseawareness of
Tamiflu and its benefits."6
Barbara Mintzes, assistant professor in the Department of Pharmacologyand Therapeutics at the University of British Columbia, is
currentlypart of a group working with Health Action
International andWHO developing model curricula for medical
and pharmaceuticalstudents on drug promotion and
interactions with the industry,including conflicts of
interest. She thinks that caution isadvised when working
with medical bodies of this sort.
"It is legitimate for WHO to work with industry at times. ButI would have concerns about involvement with a group that lookslike it is for independent academics that is actually mainlyindustry funded," she told the BMJ/The Bureau, adding: "TheInstitute of Medicine has raised concerns about the need tohave a
firewall with medical groups. To me this does not soundlike
an independent group, as it is mainly funded by manufacturers."
She also thinks that there is a difference between the conflictof interest in having a clinical trial funded by a company andthe conflict of interest in being involved in marketing a drug—forexample, 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 beingon a
paid speakers bureau," she said.
The presence of leading influenza scientists at promotionalevents for oseltamivir reflected not just the concern of animpending pandemic, but the excitement over the potential ofa new
class of drugs—neuraminidase inhibitors—tooffer treatment
and protection against seasonal influenza.
In 1999 two new drugs first came to market: oseltamivir, fromRoche; and zanamivir, manufactured by what is now GlaxoSmithKline.The two drugs would battle it out over the coming years, withoseltamivir—aided by its oral administration—trumpingits rival in global
sales as the decade wore on.
The potential was quickly grasped. Indeed, that year ProfessorOsterhaus published an article proposing the use of neuraminidaseinhibitors in pandemics: "Finally, during a possible futureinfluenza
pandemic, in view of their broad reactivity againstinfluenza virus neuraminidase subtypes and the expected lackof
sufficient quantities of vaccine, the new antivirals willundoubtedly have an essential role to play in reducing the numberof
victims."7
However, he also warned that antivirals should not be seen asa replacement for vaccinations. "Close collaboration and consultationbetween, on the one hand, companies marketing influenza vaccinesand, on the other, those marketing antivirals will thereforebe absolutely essential. It is important that a clear and uniformmessage indicating the complementary roles of vaccines and
antiviralsis delivered."
That article appeared in the European Scientific Working Groupon Influenza’s bulletin of April 1999; Professor Osterhaussigns off with the affiliation of WHO National Influenza CentreRotterdam, The Netherlands.
Other experts soon followed suit—recommending the roleneuraminidase inhibitors could play in any future pandemic—inboth the
academic literature and in the general media.
Food and Drug Administration
While the excitement over these drugs fuelled scientific symposiums,the US Food and Drug Administration (FDA) was less than
convinced.The BMJ/The Bureau has since spoken to
people from within theAmerican and European drug regulators, the FDA and the EuropeanMedicines Agency (EMEA), who said
that both regulators struggledwith the paucity of the data
presented to them for zanamivirand oseltamivir,
respectively, during the licensing process.At the end of
last year, the BMJ called for access to raw datafor
key public health drugs after the Cochrane Collaborationfound the effectiveness of the drugs impossible to evaluate.8 The group are continuing to negotiate access to what theysay they need to fully assess the effectiveness of antivirals.
In the US, the FDA first approved zanamivir in 1999.9 MichaelElashoff, a former employee of the FDA, was the
statisticianworking on the zanamivir account. He told the BMJ how the FDAadvisory committee initially rejected zanamivir
because thedrug lacked efficacy.
After Dr Elashoff’s review (he had access to individualpatient data and summary study reports) the FDA’s advisorycommittee voted by 13 to 4 not to approve zanamivir on the groundsthat it was no more effective than placebo when the patientswere on other drugs such as paracetamol. He said that it didn’treduce symptoms even by a day.
"When I was reviewing the data, I tried to replicate the analysesin 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, butthe
focus was on if Glaxo had demonstrated efficacy." Dr Elashoff’sview was that zanamivir was no better than placebo—andit had
side effects. And when the FDA medical reviewer madea
presentation, her conclusion was that it could either be approvedor not approved. It was a fairly borderline drug.
There were influenza experts on the FDA’s advisory committeeand much of the discussion hinged on why a drug that lookedso
promising in earlier studies wasn’t working in thelargest
trials in the US. One hypothesis was that people inthe US
were taking other drugs for symptomatic relief that maskedany effect of zanamivir. So zanamivir might have no impact onsymptoms over and above the baseline medications that peopletake
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 ofpeople
taking other medications. "So in the context of not beingallowed to take anything for symptomatic relief, there mightbe 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 abovethose
other things," Dr Elashoff said. The advisory committeerecommended that the drug should not be approved.
Nevertheless, FDA management decided to overturn the committee’srecommendation.
"They would feel better if there was something on the marketin case of a pandemic. It wasn’t a scientific decision,"Dr
Elashoff said.
While Dr Elashoff was working on the zanamivir review, he wasassigned the oseltamivir application. But when the review andthe
advisory committee decided not to recommend zanamivir, theFDA’s management reassigned the oseltamivir review tosomeone
else. Dr Elashoff believes that the approval of zanamivirpaved the way for oseltamivir, which was approved by the FDAlater that year.
European Medicines Agency
In Europe the EMEA was similarly troubled by the evidence foroseltamivir. By early 2002 Roche had sought a European Union-widelicence from the EMEA. It was a lengthy process, taking threemeetings of the Committee for Medicinal Products for Human Useas
well as expert panels, according to one of the two rapporteurs,Pekka Kurki of the Finnish Medicines Agency. Echoing the CochraneCollaborations’s 2009 findings6 Kurki told us: "We discussedthe same issues that are still
discussed today: does it showclinically significant benefits in treatment and prophylaxisof flu and what was the
magnitude of the benefits presentedin the RCTs? Our
assessment and Cochrane’s in 2009 arevery similar with
regard to the effect size in RCTs. The datashow that the
effects of Tamiflu were clear but not very impressive.
"What was unclear and is still unclear is what is the impactof Tamiflu on serious complications. Circulating influenza wasvery mild when Tamiflu was developed and therefore it is verydifficult to say anything about serious complications. The datadid
not clearly show an effect on serious complications—itwas
not demonstrated by the RCTs."
In documents obtained under the freedom of information legislation,two of the experts who provided opinions during the EMEA
licensingprocess have also featured in Roche marketing
material: AnnikeLinde and Rene Snacken. In Dr Snacken’s EMEA presentationdated 18 February 2002, he discussed the need
for chemoprophylaxisand called for the use of oseltamivir
during a pandemic. Hemade his presentation as a
representative of the Belgian Ministryof Public Health. At
the time Dr Snacken was also "liaison officer"for the
European Scientific Working Group on Influenza. He alsoplayed a key role in the Belgian government during its pandemicplanning, and he later became a senior expert at the Preparednessand
Response Unit, European Centre for Disease Prevention andControl. We do not know what, if anything, he declared to theEMEA
about his relationship with Roche.
Annike Linde has confirmed in an email that she has had connectionswith Roche over a number of years. She made a presentation tothe EMEA on "influenza surveillance" in her capacity as a
representativeof the Swedish Institute for Infectious
Disease. Again, it isnot clear what, if anything, she
declared to the EMEA concerningher previous relationship
with Roche.
Dr Linde, now the Swedish state epidemiologist, has told theBMJ/The Bureau that she received payments from Roche Internationalin respect of various pieces of work she did for the companyuntil 2002. She has subsequently given occasional lectures forRoche Sweden. All money she has received from Roche was given,Dr
Linde says, to the Swedish Institute for Infectious DiseaseControl.
We asked the scientists whether they declared their relationshipwith Roche at the time to the EMEA. Neither has answered thatquestion entirely satisfactorily. Dr Snacken has not repliedto
repeated emails posing this question. Dr Linde respondedby
telling the BMJ/The Bureau: "We contribute with our expertiseto the regulatory agencies when asked. When we do so, a
declarationof interest, where e.g. participation at advisory meetings atRoche, is given and evaluated by the regulatory
agency." TheBMJ/The Bureau requested Linde and
Snacken’s declarationof interest statements for the 2002
meeting from the EMEA underthe freedom of information act.
The EMEA was unable to providestatements for those
particular people at that time.
Developing the guidelines
In October 2002 WHO convened a meeting of influenza expertsat its Geneva headquarters. Their purpose was to develop WHO’sguidelines for the use of vaccines and antivirals during aninfluenza
pandemic.
Included at this meeting were representatives from Roche andAventis Pasteur and three experts who had lent their name tooseltamivir’s marketing material (Professors Karl Nicholson,Ab Osterhaus, and Fred Hayden).
Two years later the WHO published a key report from that meeting,WHO Guidelines on the Use of Vaccines and Antivirals duringInfluenza Pandemics 2004. The specific guidance on antivirals,Considerations for the Use of Antivirals During an InfluenzaPandemic,
was written by Fred Hayden. Professor Hayden has confirmedto the BMJ/The Bureau in an email that he was being paid byRoche for lectures and consultancy work for the company at thetime the guidance was produced and published. He also told usin
an email that he had received payments from GlaxoSmithKlinefor consultancy and lecturing until 2002. According to ProfHayden: "DOI [declaration of interest] forms were filled outfor the 2002 consultation."
The WHO guidance concluded that: "Based on their pandemic responsegoals and resources, countries should consider developing plansfor ensuring the availability of antivirals. Countries thatare
considering the use of antivirals as part of their pandemicresponse will need to stockpile in advance, given that currentsupplies are very limited." Many countries around the worldwould
adopt this guidance.
The previous year Professor Hayden was also one of the mainauthors of a Roche sponsored study that claimed what was tobecome
one of oseltamivir’s main selling points—aclaimed 60%
reduction in hospitalisations from flu, which theCochrane
Collaboration was later unable to verify.8
Our investigation has also identified relevant and declarableinterests relating to the two other named authors of annexesto WHO’s
2004 guidelines. Arnold Monto was the authorof the annexe
dealing with vaccine usage in pandemics. Between2000 and
2004—and at the time of writing the annexe—DrMonto has
consistently and openly declared honorariums, consultancyfees, and research support from Roche, 10 11 12 consultancyfees 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 annexhe wrote for WHO. When asked if he had signed a declarationof
interest form for WHO, Dr Monto told the BMJ/The Bureau:"Conflict of Interest forms are requested before participationin any
WHO meeting".
Professor Karl Nicholson is the author of the third annex, PandemicInfluenza. According to declarations made by Professor
Nicholsonin the BMJ16and Lancet in 2003,17 he had received travel sponsorshipand honorariums from
GlaxoSmithKline and Roche for consultancywork and speaking
at international respiratory and infectiousdiseases
symposiums. Before writing the annexe, he had alsobeen paid
and declared ad hoc consultancy fees by Wyeth, Chiron,and
Berna Biotech.
Even though the previous year these declarations had been openlymade in the Lancet and the BMJ, no conflict of interest
statementwas included in the annex he wrote for WHO.
Professor Nicholsontold the BMJ/The Bureau that he
last had "financial relations"with Roche in 2001. When asked if he had signed a declarationof interest form for WHO,
Prof Nicholson replied: "The WHO doesrequire attendees of
meetings, such as those held in 2002 and2004, to complete
declarations of interest."
Leaving aside the question of what declarations experts madeto WHO, one simple fact remains: WHO itself did not publiclydisclose any of these conflicts of interest when it publishedthe
2004 guidance. It is not known whether information aboutthese conflicts of interest was relayed privately to governmentsaround the world when they were considering the advice containedin the guidelines.
The year before WHO issued the 2004 guidance, it published aset of rules on how WHO guidelines should be developed and howany conflicts of interest should be handled. This guidance includedrecommendations that people who had a conflict of interest shouldnot take
part in the discussion or the piece of work affectedby that
interest or, in certain circumstances, that the personwith
the conflict should not participate in the relevant discussionor work at all. The WHO rules make provision for the directorgeneral’s office to allow declarations of interest tobe seen if the
objectivity of a meeting has been called intoquestion.18
The BMJ/The Bureau has asked WHO for the conflict of interestdeclarations for the Geneva 2002 meeting and those related tothe guidance document itself. WHO told us that the query wentdirectly up to Margaret Chan’s office. "WHO never publishesindividual DOIs [declaration of interest], except after consultationwith the Office of the Director-General. In this case, we putin a request on your behalf but it was not granted. In morerecent years, many WHO committees have published summaries ofrelevant interests with their meeting reports."
In a BMJ interview (see film on bmj.com),
WHO spokesperson GregoryHartl reiterated the fact that Dr
Margaret Chan, "is very committedpersonally to
transparency." Yet her office has turned downrepeated
requests for declaration of interest statements anddeclines
to comment on the allegations that authors of the guidelineshad declarable interests.
Nevertheless, Prof Hayden told the BMJ/The Bureau: "I stronglysupport transparency in declarations of interest, in part becausethis allows those reading documents, particularly ones authoredby specific individuals (eg, Annex 5) [the part he wrote], tomake their own judgments about the possible relevance of anypotential conflicts."
While experts need to work with industry to develop the bestpossible drugs for illnesses, questions remain about what levelof
involvement experts with industry ties should have in theformulation of public health policy decisions and guidelines.Professor
Nicholson told the BMJ/The Bureau: "The WHO and decisionmakers must be informed of ongoing developments and researchfindings to ensure that they are as up to date as possible.Some of
the most relevant expertise and information are heldby
companies or individuals with conflicts of interest. I understandthe view that experts with conflicts of interest should notadvise governments or organisations such as the WHO. But toexclude such people from discussions could deprive WHO and decisionmakers of important new information."
But not everyone agrees. Barbara Mintzes is unequivocal aboutwhat role they should play. "No one should be on a committeedeveloping guidelines if they have links to companies that eitherproduce a product—vaccine or drug—or a medical deviceor test for a
disease. It would be preferable that there areno financial
ties when it comes to making big decisions on publichealth—for example, stockpiling a drug—and thatincludes if they have a currently funded clinical trial," shesaid.
"Ideally, what you want are independent experts who are in thepublic sector to provide expertise on drugs and vaccines. Butthey
can be hard to find. One solution is consult with the expertswho are involved in industry, but not put them on any decisionmaking committee. You need a firewall," she added.
Indeed, Professor Harvey Fineberg, president of the Instituteof Medicine and chairman of the panel reviewing WHO’smanagement of the pandemic, takes a similarly hard line. Hisown
institution went through a detailed review of how they interactwith industry and experts with conflicts of interests last year.19 "Sometimes publication of conflict of interests is enough—forexample with a journal. But if you are giving expert judgmentto
influence policy, revealing is not enough," he told the BMJ,referring to the Institute of Medicine’s policy.
WHO also says that it takes conflicts of interests seriouslyand has the mechanisms in place to deal with them. But whataction does it take when a scientist declares a conflict ofinterest, and when does it judge a scientist to be too conflictedto
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 forWHO, according to Professor Chris Del Mar, a Cochrane Reviewauthor and expert on WHO’s Strategic Advisory Group ofExperts on
Immunization group. "If it proves to be the casethat authors of WHO guidance which promoted the use of certaindrugs were being paid at the same time by the makers of thosedrugs for other work they were doing for these companies thatis
reprehensible and should be condemned in the strongest possibleterms."
WHO’s endorsement of oseltamivir was not lost on Roche.In an advert placed by the company for the drug in the mainconference programme of the European Scientific Working Groupon
Influenza’s 2005 conference in Malta, it says: "Antiviralswill initially be the principal medical intervention in a pandemicsituation and Roche is working as a responsible partner withgovernments to assist in their pandemic planning." The sourcereference
for this is the WHO Global Influenza PreparednessPlan.
Throughout the following years, WHO would appear to have beeninconsistent in how it treated conflicts of interest. Updatedpandemic
plans would continue to be prepared by experts whoopenly had work funded and acted as consultants to manufacturersof
vaccines and antivirals. WHO produced its global influenzapreparedness plan in 2005, and in 2006 it constituted an interimInfluenza Pandemic Task Force. No public declarations of interesthave been made and to date no details have been provided byWHO
in response to our requests.
WHO’s stance that it does not publish declarations ofinterest from its experts is far from consistent. It is undermined,for example, by the position WHO adopts in relation to the StrategicAdvisory Group of Experts on Immunization, its standing vaccineadvisory body. Here, contrary to its approach to pandemic planningadvisers, WHO does publish summaries of declarations of interest.
Emergency Committee
These seeming inconsistencies in WHO’s approach to transparencyand its handling of conflicts of interest extend into the workingsof the Emergency Committee formed last year to advise the directorgeneral on the pandemic. The identities of its 16 members areunknown outside WHO. This secret committee has guided WHO pandemicpolicy since then—including deciding when to judge thatthe
pandemic is over.
WHO says it has to keep the identities secret to protect thescientists from being influenced or targeted by industry. Ina phone
call to the BMJ/The Bureau in March, WHO spokespersonGregory Hartl explained: "Our general principle is we want toprotect the committee from outside influences."
The committee advised the WHO director general on phase changesas well as temporary recommendations. According to WHO, Whenthe Emergency Committee met to discuss a possible move to adeclaration of a pandemic, the meeting additionally includedmembers who represented Australia, Canada, Chile, Japan, Mexico,Spain,
the UK, and the US, eight countries that experiencedwidespread outbreaks at the time. These national representativeswere
present to ensure full consideration of the views and possiblereservations of the countries expected to bear the initial bruntof
economic and social repercussions.
WHO says all members of the Emergency Committee sign a confidentialityagreement, provide a declaration of interests, and agree togive their consultative time freely, without compensation. However,only one member of the committee has been publicly named: ProfessorJohn MacKenzie, who chairs it.
This is a troubling stance: it suggests that WHO considers otheradvisory groups whose members are not anonymous —suchas the
Strategic Advisory Group of Experts on Immunization—tobe
potentially subject to outside influences, and it allowsno
scrutiny of the scientists selected to advise WHO and globalgovernments on a major public health emergency.
Under the International Health Regulations framework, the membershipof the Emergency Committee is drawn from a roster of about 160experts covering a range of public health areas. This frameworkprovides guidelines about how WHO deals with acute public healthrisks. The BMJ/The Bureau has identified approximately 15
scientistsfrom the International Health Regulations roster
with influenzaexpertise and has emailed them to ask if they
were on the EmergencyCommittee. Under the framework at least some of these scientistsare members of the Emergency
Committee. Yet because of the confidentialityagreements they have signed, these scientists cannot acknowledgetheir
membership of the committee, putting them in an invidiousposition.
David Salisbury, chair of WHO’s Strategic Advisory Groupof
Experts on Immunization (SAGE) committee at the time of thepandemic and a member of the International Health Regulations,says
the secrecy has caused problems for his group. "It certainlycaused problems for SAGE. Since all of the details of SAGE arein
the public domain, there was a perception that it had beenSAGE that had given advice about the changing of definitionsor
the pandemic levels—when we had not done so. SAGE memberscame in for unfair personal abuse by journalists," he told theBMJ/The Bureau.
"Given the importance of the advice, the transparency of thesource of the advice was important. I believe it is necessaryto
keep confidential the source of advice if revealing detailsmight put individuals at risk, for example when bioterrorismis
being discussed. This does not seem to be the case for pandemicflu," he added.
The secrecy of the committee is also fuelling conspiracy theories,particularly around the activation of dormant pandemic vaccinecontracts. A key question will be whether the pharmaceuticalcompanies, which had invested around $4bn (£2.8bn, 3.3bn)in developing the swine flu vaccine, had supporters inside theemergency committee, who then put pressure on WHO to declarea pandemic. It was the declaring of the pandemic that triggeredthe contracts.
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, hisInfectious Disease Society of America biography states thathe is a
member.20
Last year, according to figures made public in the US by
GlaxoSmithKline,Professor Monto received $3000 speakers fees from the companyin the period between the second quarter
and the last quarterof 2009. As a national official of the
Japanese government,Dr Tashiro says that he must "have
nothing concerning conflictof interest with private
companies". Dr John Wood works forthe UK National Institute
for Biological Standards and Control(NIBSC). Dr Wood, like
Dr Tashiro, has no personal conflictof interests but he told the BMJ/The Bureau that as part ofits statutory role in developing standards for measurement ofbiological
medicines to ensure accurate dosing and carryingout
independent control testing to assure their safety and efficacy,the institute must work closely with the pharmaceutical industry.This is made clear on their website.
"The International Federation of Pharmaceutical Manufacturersand Associations has also made publicly available the natureof
their close interaction with NIBSC and similar organisationsin order to develop influenza vaccines," he said.21
Those who said that they were not on the committee include DavidSalisbury, Alan Hampson, Albert Osterhaus, Donato Greco, andHoward
Njoo. Maria Zambon, from the UK’s Health ProtectionAgency
told the BMJ: "I undertake various advisory roles toWHO. Declaration of interest statements are prepared beforeundertaking such roles.
"The HPA Centre for Infection, as part of its role in nationalinfectious disease surveillance, provision of specialist andreference
microbiology and vaccine efficacy monitoring, worksclosely
with vaccine manufacturers and biotechnology companies."
International Health Regulations review
WHO’s own review into the operation of the InternationalHealth Regulations and WHO’s handling of the pandemicis now being
conducted by Harvey Feinberg, president of theUS Institute
of Medicine, and will report its findings nextyear. Dr Chan
and Professor Feinberg have both made clear theneed for a
thorough investigation. But questions are alreadyarising
about how independent the review will turn out to be.According to the International Health Regulations list in ourpossession, some 13 of the 29 members of the review panel aremembers of the International Health Regulations itself and oneis the
chair of the Emergency Committee. To critics that mightsuggest a somewhat incestuous approach.
Professor Mintzes does not agree with WHO’s explanationthat
secrecy was needed to protect against the influence ofoutside interest on decision making. "I can’t understandwhy the WHO kept this secret. It should be public in terms ofaccountability like the expert advisory committees. If the rationaleof
secret membership is not to be unduly influenced, there areother ways of dealing with this through strong conflict of interestprovisions," she said.
She also believes that the very nature of allowing a triggerpoint for vaccine contracts opens the system up unnecessarilyto
exploitation. "It seems a problem that this declaration mighttrigger contracts to be realised. There should be safeguardsin
place to make sure those with an interest in vaccine manufacturerscan’t exploit the situation. The WHO will have to looklong and
hard at this in future," she said.
The number of victims of H1N1 fell far short of even the moreconservative predictions by the WHO. It could, of course, havebeen far
worse.. Planning for the worst while hoping for thebest
remains a sensible approach. But our investigation hasrevealed damaging issues. If these are not addressed, H1N1 mayyet
claim its biggest victim—the credibility of the WHOand the
trust in the global public health system.
Cite this as: BMJ 2010;340:c2912
________________________________
Competing interests: PC declares no competing interests. DChas been paid expenses by WHO for giving talks at two conferences.
References
1. Cohen D.
Complications: tracking down the data on oseltamivir. BMJ 2009;339:b5387.[Free Full Text]
2. Doshi P. Calibrated response to emerging infections. BMJ 2009;339:b3471.[Free Full Text]
3. Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, et al.
Efficacy and safety of oseltamivir in treatment of acute influenza: a
randomised controlled trial. Lancet 2000;355:1845-50.[CrossRef][Web of Science][Medline]
4. European Scientific Working Group on Influenza. About ESWI. www.eswi.org/who-are-we/about-eswi.
5. European Scientific Working Group on Influenza. Revised policy plan 2006-2010. www.eswi.org/userfiles/files/ESWI%20policy%20plan%202006-2010.doc.
6. Holmes Report. Tamiflu launch media campaign. www.holmesreport.com/story.cfm?edit_id=71&typeid=4.
7. Osterhaus A, de Jong J. Prophylactic role. www.eswi.org/modulefiles/publications/pdfs/no-10-december-1998.pdf.
8. Jefferson T, Jones M, Doshi P, Del Mar C. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and
meta-analysis. BMJ 2009;339:b5106.[Abstract/Free Full Text]
9. US Food and Drug Administration. FDA approved drugs for influenza. www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm100228.htm#ApprovedDrugs.
10. Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Clinical signs and symptoms predicting influenza infection. Arch Intern Med 2000;160:3243-7[Abstract/Free Full Text]
11. Monto AS, Rotthoff J, Teich E, Herlocher ML, Truscon R, Yen HL, et al.
Detection and control of influenza outbreaks in well-vaccinated nursing
home populations. Clin Infect Dis 2004;39:459-64.[CrossRef][Web of Science][Medline]
12. Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, et al. Influenza
viruses resistant to the antiviral drug oseltamivir: transmission
studies in ferrets. J Infect Dis 2004;190:1627-30.[CrossRef][Web of Science][Medline]
13. Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM,
et al. Zanamivir prophylaxis: an effective strategy for the prevention
of influenza types A and B within households. J Infect Dis 2002;186:1582-8.[CrossRef][Web of Science][Medline]
14. Herlocher ML, Truscon R, Fenton R, Klimov A, Elias S, Ohmit SE, et al. Assessment of development of resistance to antivirals in the ferret model of
influenza virus infection. J Infect Dis 2003;188:1355-61[CrossRef][Web of Science][Medline]
15. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of
non-influenza-related viral respiratory tract infection in the United
States. Arch Intern Med 2003;163:487-94.[Abstract/Free Full Text]
16. Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG.
Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised
controlled trials. BMJ 2003;326:1235.[Abstract/Free Full Text]
17. Nicholson KG, Wood JM, Zambon M. Influenza. Lancet 2003;362:1733-45.[CrossRef][Web of Science][Medline]
18. World Health Organization. Guidelines for WHO guidelines. World Health
Organization, 2003.
19. National Academies. Policy and procedures on committee composition and balance
and conflicts of interest for committees used in the development of
reports. www.nationalacademies.org/coi/index.html.
20. Infectious Disease Society of America. Congratulations to the 2009 Society Award
Recipients. www.idsociety.org/Content.aspx?id=15497.
21. International Federation of Pharmaceutical Manufacturers and Associations Influenza
Vaccine Supply International Task Force. WHO influenza virus
surveillance system and influenza vaccine production. 2008. www.ifpma.org/Influenza/content/pdfs/WHO_IGM/06_2008_WHO_Influenza_Virus_Surveillance_System.pdf.




For more information, send mail to [log in to unmask] with the message: info PED-EM-L
The URL for the PED-EM-L Web Page is:
                 http://listserv.brown.edu/ped-em-l.html

Top of Message | Previous Page | Permalink

Advanced Options


Options

Log In

Log In

Get Password

Get Password


Search Archives

Search Archives


Subscribe or Unsubscribe

Subscribe or Unsubscribe


Archives

June 2019
May 2019
April 2019
March 2019
February 2019
January 2019
December 2018
November 2018
October 2018
September 2018
August 2018
July 2018
June 2018
May 2018
April 2018
March 2018
February 2018
January 2018
December 2017
November 2017
October 2017
September 2017
August 2017
July 2017
June 2017
May 2017
April 2017
March 2017
February 2017
January 2017
December 2016
November 2016
October 2016
September 2016
August 2016
July 2016
June 2016
May 2016
April 2016
March 2016
February 2016
January 2016
December 2015
November 2015
October 2015
September 2015
August 2015
July 2015
June 2015
May 2015
April 2015
March 2015
February 2015
January 2015
December 2014
November 2014
October 2014
September 2014
August 2014
July 2014
June 2014
May 2014
April 2014
March 2014
February 2014
January 2014
December 2013
November 2013
October 2013
September 2013
August 2013
July 2013
June 2013
May 2013
April 2013
March 2013
February 2013
January 2013
December 2012
November 2012
October 2012
September 2012
August 2012
July 2012
June 2012
May 2012
April 2012
March 2012
February 2012
January 2012
December 2011
November 2011
October 2011
September 2011
August 2011
July 2011
June 2011
May 2011
April 2011
March 2011
February 2011
January 2011
December 2010
November 2010
October 2010
September 2010
August 2010
July 2010
June 2010
May 2010
April 2010
March 2010
February 2010
January 2010
December 2009
November 2009
October 2009
September 2009
August 2009
July 2009
June 2009
May 2009
April 2009
March 2009
February 2009
January 2009
December 2008
November 2008
October 2008
September 2008
August 2008
July 2008
June 2008
May 2008
April 2008
March 2008
February 2008
January 2008
December 2007
November 2007
October 2007
September 2007
August 2007
July 2007
June 2007
May 2007
April 2007
March 2007
February 2007
January 2007
December 2006
November 2006
October 2006
September 2006
August 2006
July 2006
June 2006
May 2006
April 2006
March 2006
February 2006
January 2006
December 2005
November 2005
October 2005
September 2005
August 2005
July 2005
June 2005
May 2005
April 2005
March 2005
February 2005
January 2005
December 2004
November 2004
October 2004
September 2004
August 2004
July 2004
June 2004
May 2004
April 2004
March 2004
February 2004
January 2004
December 2003
November 2003
October 2003
September 2003
August 2003
July 2003
June 2003
May 2003
April 2003
March 2003
February 2003
January 2003
December 2002
November 2002
October 2002
September 2002
August 2002
July 2002
June 2002
May 2002
April 2002
March 2002
February 2002
January 2002
December 2001
November 2001
October 2001
September 2001
August 2001
July 2001
June 2001
May 2001
April 2001
March 2001
February 2001
January 2001
December 2000
November 2000
October 2000
September 2000
August 2000
July 2000
June 2000
May 2000
April 2000
March 2000
February 2000
January 2000
December 1999
November 1999
October 1999
September 1999
August 1999
July 1999
June 1999
May 1999
April 1999
March 1999
February 1999
January 1999
December 1998
November 1998
October 1998
September 1998
August 1998
July 1998
June 1998
May 1998
April 1998
March 1998
February 1998
January 1998
December 1997
November 1997
October 1997
September 1997
August 1997
July 1997
June 1997
May 1997
April 1997
March 1997
February 1997
January 1997
December 1996
November 1996
October 1996
September 1996
August 1996
July 1996
June 1996
May 1996
April 1996
March 1996
February 1996
January 1996
December 1995
November 1995
October 1995
September 1995
August 1995
July 1995
June 1995
May 1995
April 1995
March 1995
February 1995
January 1995
December 1994
November 1994
October 1994
September 1994

ATOM RSS1 RSS2



LISTSERV.BROWN.EDU

CataList Email List Search Powered by the LISTSERV Email List Manager