Report | Doc. 12283 | 07 June 2010
The handling of the H1N1 pandemic: more transparency needed
(Former) Social, Health and Family Affairs Committee
Summary
On 11 June 2009, the World Health Organization (WHO) officially declared “Pandemic (H1N1) 2009”. The way in which the H1N1 influenza pandemic has been handled, not only by WHO, but also by the competent health authorities at the level of the European Union and at national level, gives rise to alarm. Some of the consequences of decisions taken and advice given are particularly troubling, as they led to distortion of priorities of public health services across Europe, waste of large sums of public money and also unjustified scares and fears about health risks faced by the European public at large.
Grave shortcomings have been identified regarding the transparency of decision-making processes relating to the pandemic which have generated concerns about the possible influence of the pharmaceutical industry on some of the major decisions relating to the pandemic. It must be feared that this lack of transparency and accountability will result in a plummet in confidence in the advice given by major public health institutions.
The Parliamentary Assembly has shed light on the handling of the H1N1 pandemic in the most comprehensive manner possible and through an open dialogue with WHO and other players. It welcomes the review processes that have been initiated by various public health authorities, including WHO, and urges all stakeholders concerned to share the results in order to learn from experience and ensure that responsibility is taken for any errors made. The Assembly considers that a thorough review of existing governance systems and the immediate communication of essential information not yet published are of utmost importance in order to re-establish confidence in major public health decisions and advice with a view to ensuring that they be followed in the case of the next infectious disease of global scope, which may well be more severe.
A. Draft resolution 
(open)B. Draft recommendation
(open)C. Explanatory memorandum by Mr Flynn, rapporteur
(open)1. Introduction
“The United Nations and business need each other. We need your innovation, your initiative, your technological prowess. But business also needs the United Nations. In a very real sense, the work of the United Nations can be viewed as seeking to create the ideal enabling environment within which business can thrive.”
United Nations Secretary-General Ban Ki-moon
“We are supposed to be prepared for a pandemic of some kind of influenza because the flu watchers, the people who make a living out of studying the virus and who need to attract continued grant funding to keep studying it, must persuade the funding agencies of the urgency of fighting a coming plague.”
Professor Philip Alcabes in Dread
The committee held an exchange
of views with Dr Fiona Godlee (Editor-in-Chief of the British Medical Journal – BMJ) on
4 June 2010 in Paris before the adoption of the report. 2. Global response to the H1N1 pandemic – Basic facts and perception
Declaration of a pandemic
On 11 June 2009, the
pandemic was thus officially declared by designating the situation
as pandemic influenza Phase 6. This declaration
at a very early stage of the event and shortly after the detection
of first infections in Mexico in April 2009 was, according to some
experts, only possible because the description of pandemic alert
phases was modified by WHO in May 2009, and notably the criteria
relating to the severity of the disease removed as a precondition
for passing on to the highest alert level. Numbers of infections and deaths
Firm conclusions on the outbreak
of the pandemic were to be reached after April 2010, the month when
a normal influenza season usually ends; however, these have not
as yet been published by WHO. Reliable estimates of the number of
deaths and the mortality rate during the current pandemic will only
be possible, according to WHO, one or two years after the pandemic
has ended. At the time of preparation of
this report, rates of influenza in Europe had gone down and the
pandemic virus was only being detected sporadically. The Global
Influenza Surveillance Network (GISN) continues monitoring the global
circulation of influenza viruses, including pandemic, seasonal and
other influenza viruses infecting, or with the potential to infect,
humans. Vaccination strategies
Some countries
followed recommendations by pharmaceutical groups that the vaccination
should be given twice in order to ensure full protection against
the virus and had therefore purchased corresponding quantities of
vaccines. Some of the far-reaching approaches followed were justified
by “pessimistic” predictions of numbers of infections and deaths
to be expected as a result of the pandemic. Differing perceptions
It
was precisely these warnings which drew the Parliamentary Assembly’s
attention to the issue and prompted it to take up the topic and
ask for the preparation of the current report.3. Handling the H1N1 pandemic – Transparency and accountability of public health action?
3.1. The role of the World Health Organization (WHO)
the
objective of WHO shall be the attainment by all peoples of the highest possible
level of health. It co-ordinates and directs international health
work, provides technical assistance and aid in emergencies. It develops
an informed public opinion on health matters and seeks to eradicate
epidemic, endemic and other diseases. WHO is therefore the international
authority on public health recommendations for the 193 member states
of the organisation. In the light of its overwhelming success regarding
the eradication of major human diseases (such as smallpox) and the
control of others, WHO rightly benefits from its member states’
highest respect and active support and collaboration through specially
designed governance structures.Governance system of WHO and bodies concerned by pandemic situations
Proportionality and appropriateness of the response
For
those, however, in favour of far-reaching measures, these considered
them justified by the “precautionary principle”. It would appear
that numerous scientists had expected the outbreak of a new worldwide
pandemic for a long time and were therefore extremely sensitive
to the possible dramatic consequences of any new viruses. Moreover,
the possible mutation of the swine flu virus was considered as its
greatest danger as this could have made both existing flu medication
and vaccines ineffective, and could have increased the severity
of the disease, as well. at
a Parliamentary Assembly hearing held in Paris on 29 March 2010,
stated that “few (if any) national and international surveillance
systems make the distinction between influenza and influenza-like
illness, either because they do not believe the question is important,
because the ‘system’ is not geared up for it or for other still
unclear reasons”. He further noted that only 7% to 15% of people
with flu symptoms truly have influenza. In other words, vaccination
programmes are directed against what surveillance systems worldwide
call “influenza”, but in reality are influenza-like illness or flu.
In advancing this data, he expressed the concern of certain critical experts
as to whether the response to the H1N1 situation was appropriate.
Furthermore, many countries have had difficulties in clearly distinguishing
between patients dying with swine flu (that is, showing symptoms
of swine flu whilst having died of other pathologies) and patients
dying of swine flu (that is, swine flu being the main lethal cause),
which might have “falsified” some of the statistics on which later
public health decisions were founded. Very recently, Dr Klaus Stoehr,
who was until 2007 in charge of WHO's pandemic preparedness, reinforced
doubts about the appropriateness of the response given to H1N1 influenza
by saying: "The pandemic planning I was involved with was always
based on a severe public health event. … Moving to Phase 6 meant
that we wanted governments … to kick in their plans whether they
thought it was urgent or not". He then further expressed his belief that
moving to Phase 6 that early was, in hindsight, not needed, and
that WHO, over the course of summer 2009, had failed to read the
signs about swine flu coming from the southern hemisphere. In his statement
made in January 2010, he further added that it was too early to
say whether the pandemic was over and that another significant wave
could still be expected across Europe in the winter or spring. In the view
of the rapporteur, it is therefore of utmost importance that vital
decisions regarding public health threats, notably when placed in
a context of uncertainty, are taken in a fully transparent way. Furthermore,
complete information needs to be provided to the public in a manner
which allows even those with little scientific knowledge to follow
the arguments in a dispassionate manner. In this respect, the rapporteur recognises
that assessing and communicating the impact of a virus is difficult
and that only in retrospect can one say what is a severe or mild
to moderate level of pandemic. However, in order to avoid what has
been called the “concern bias”, in which anxiety drives reactions
to a greater extent than the disease itself, some commentators have
recently called for a more calibrated approach to emerging infections
and the need to reassess both the risk assessment and risk management
strategies. Changing the definition of a pandemic
In other words, the pandemic could
be declared without the need to show that it was likely to be severe
in terms of its impact on the population (for example, regarding
severity of illness and death). The definition before 4 May 2009
was worded as follows: “An influenza pandemic occurs when a new
influenza virus appears against which the human population has no
immunity, resulting in epidemics worldwide with enormous numbers
of deaths and illness. With the increase in global transport, as
well as urbanization and overcrowded conditions, epidemics due to
the new influenza virus are likely to quickly take hold around the world”,
whilst the same definition became the following on WHO’s website
after this date: “A disease epidemic occurs when there are more
cases of that disease than normal. A pandemic is a worldwide epidemic
of a disease. An influenza pandemic may occur when a new influenza
virus appears against which the human population has no immunity
…. Pandemics can be either mild or severe in the illness and death
they cause, and the severity of a pandemic can change over the course
of that pandemic”. These subsequent definitions and comments
presented at a time when the pandemic was imminent were confusing
for both public health professionals involved and attentive observers
amongst the European public at large.Public-private partnership under scrutiny
Amongst
the factors leading to the suspicion of undue influence were the early
measures taken on contractual arrangements for vaccine delivery
between member states and pharmaceutical companies, as well as the
enormous profits that companies were able to make as a result of the
pandemic. The main suspicion, however, arises with regard to the
issue of whether members of WHO advisory bodies have professional
links to pharmaceutical groups, bringing into question the neutrality
of their advice. Unfortunately, due to WHO’s refusal to release
the names and declarations of interest of persons concerned, any
current research on the matter depends entirely on the results of
investigative journalism. have on several occasions called
for the list of experts and their respective declarations of interest
to be published, WHO has failed to provide this information. The
organisation continues to hold back on releasing further information
on the interests of experts, justifying this position by the need
to protect experts’ privacy and to prevent them from coming under
extreme pressure from certain private companies or interest groups.
The rapporteur is very concerned by this attitude and remains convinced
that it is entirely justified to require full transparency with regard
to the profiles of experts whose recommendations have far-reaching
consequences for the public health sector and the health and well-being
of Europeans. At
the same time, WHO stated more than once that it considered existing
mechanisms to be satisfactory, but declared its intention to respond
to allegations of undeclared conflicts of interest, which it claimed
to take very seriously. As early as January 2010, WHO announced
its intention to launch a review of the way in which the ongoing
pandemic was handled, including an evaluation of its own performance,
with the participation of external experts and with a view to reviewing
existing International Health Regulations (IHR). an internal review process was
launched by WHO through the Review Committee on the Functioning
of the International Health Regulations (2005) in relation to Pandemic
(H1N1) 2009. It met for the first time from 12 to 14 April 2010
in Geneva. According to its first report, the committee pursued
a threefold objective: (1) to assess the IHR in relation to the
current pandemic, (2) to review the scope, appropriateness, effectiveness
and responsiveness of global action as well as the role of the WHO
Secretariat, and (3) to identify and review the major lessons learnt
from the global response to the current pandemic. However,
the rapporteur is very concerned that it appears that some of the
members of the Review Committee are also members of the Emergency
Committee whose actions they are meant to review (in particular
the chair of the latter). Communication and dialogue on sensitive health issues
Most people, however, expected more dramatic
consequences, not least because in spring 2009, the approaching
swine flu was repeatedly compared to previous infectious diseases,
notably the avian flu and SARS in more recent years, but also the
Spanish flu of 1918. For some experts, such as Professor Keil, epidemiologist
and Director of WHO Collaborating Centre on Epidemiology of the
University of Münster (Germany), who was heard at the public hearing
of 26 January 2010, the comparison with the Spanish flu of 1918
was generally inappropriate given that empirical figures were far
from comparable. The Spanish flu took place in the historical context
of the First World War where infections were easily transmitted
by soldiers, many of whom were undernourished and without medication
considered as basic today, such as penicillin. In reacting to this,
WHO stated that reference to former health events should be taken
as a positive sign: the organisation for example pointed to the
success in limiting the spread of SARS as a major public health
victory. 3.2. The role of the pharmaceutical industry
At
European level the vaccines – Focetria of Novartis, Pandemrix of
GlaxoSmithKline, Celvapan of Baxter International as well as Panenza
of Sanofi-Pasteur – were used during the H1N1 pandemic. These companies
are organised in the European Vaccine Manufacturers Group (EVM)
belonging to the European Federation of Pharmaceutical Industries
and Associations (EFPIA). In its official statements, the agency
asserted that, despite the short delays within which vaccines were
authorised, they had been sufficiently tested, along with the adjuvants used. Whether
or not there was sufficient testing remains highly controversial
within the medical community. There is, however, evidence that at
least one vaccine without adjuvants made by Sanofi-Pasteur (Panenza) was
treated differently and was able to receive national authorisation
in some countries, such as France, without passing through some
of the rigid European procedures. Without wishing to take a definitive
stance on this highly specific question here, the rapporteur considers
it entirely justified to ask whether scientific evidence was sufficient
to remove any remaining doubts about the relevant products. A few months after the declaration
of the pandemic, even the European Medicines Agency pointed out
that “only limited data on the safety and immunogenicity of influenza
A(H1N1)v vaccines will be available when member states start to
use the vaccines. In addition, due to the possible mutation of the virus,
the effectiveness of the vaccines will need to be followed.” Whilst this anticipation of a major
public health event by governments and pharmaceutical groups could
be generally welcomed, the rapporteur would like to point out that
there is evidence of doubtful commercial practices followed by some industrial
groups. The rapporteur refers in particular to pressure exerted
on national governments to activate “sleeping contracts” after very
short delays of reflection (using the argument of “first come –
first served”) and the attempt to transfer the main responsibility
for side effects of vaccines to the governments themselves (see the
experience of Poland described later). Following these suspicions,
and in light of the major impacts on public health budgets all over
Europe, the rapporteur welcomes the willingness of pharmaceutical
groups to step back from contractual arrangements made with national
governments and allow them to opt out of some of the orders not
yet delivered. As such,
and from the point of view of the market economy, justified commercial
interests cannot be generally criticised. The rapporteur would,
however, like to raise the question as to whether it was justified
to sell H1N1 vaccines to national governments at prices seemingly
up to two to three times higher than those for the usual seasonal
influenza by primarily using patented adjuvants, and thus making
exaggeratedly high profits from a declared public health emergency?3.3. The role of member states and their health authorities
The rapporteur considers that
with hindsight it can be concluded that France is not in an enviable
position. France, however, is not alone in this situation. The National Assembly and the
Senate have taken a proactive approach by organising a public hearing
on the possible action by researchers and public authorities with regard
to the H1N1 influenza through the parliamentary office for the evaluation
of scientific and technological choices. The French
Senate launched an inquiry committee into the role of pharmaceutical
companies in the handling of the H1N1 influenza by the French Government,
which started its investigations in February 2010 with a view to
presenting a report in August 2010. The National Assembly has launched
a parallel procedure through its “Investigation committee on the
way in which the vaccination campaign against Influenza A (H1N1) was
planned, explained and handled”. The committee is due to present
its report on 13 July 2010. 3.4. The role of European Union bodies
The
mission of the ECDC, established in 2005 and seated in Stockholm/Sweden,
is to identify, assess and communicate current and emerging threats
to human health posed by infectious diseases in partnership with
national health protection bodies across Europe and by associating
health experts throughout Europe. As with WHO, the ECDC relies on
internal advisory bodies. The names and declarations of interest
of experts on these bodies have still not been released either.4. Conclusions – Recommendations
Appendix – Visit to WHO, Geneva, 15 April 2010
(open)Written responses by WHO to the questions presented by the rapporteur
A. SEASONAL AND PANDEMIC INFLUENZA: THE H1N1 INFLUENZA OUTBREAK
1. Please provide an overview of the definition of "influenza pandemic" and any changes in the definition over the last five years? What was the reason for the change of the pandemic influenza definition (May 2009) and who was responsible for changing this?
A pandemic of disease refers to the worldwide spread of an
epidemic disease. An
example of a pandemic that is not related to influenza is the emergence
and spread of HIV. A pandemic of influenza refers specifically to
the emergence and worldwide spread of an influenza virus that is
"new" in the sense that it is immunologically "novel" for much of
the world's population.
In 1999, WHO produced its first pandemic preparedness guideline for countries based on the input from global experts. This document was updated in 2005 and 2009 to incorporate ongoing changes in scientific knowledge and concepts and public health experience. These are the guidelines that contain WHO's pandemic phase definitions provided to countries to assist them in national planning efforts.
The 1999 document is entitled: “Influenza Pandemic Preparedness Plan: The role of WHO and guidelines for national and regional planning” (WHO/CDS/CSR/EDC/99.1). On page 14, this document indicates "The Pandemic will be declared when the new virus sub-type has been shown to cause several outbreaks in at least one country, and to have spread to other countries, with consistent disease patterns indicating that serious morbidity and mortality is likely in at least one segment of the population. Onset shall be defined as that point in time when WHO has confirmed that a virus with a new haemagglutinin sub-type compared to recent epidemic strains is beginning to spread from one or more initial foci. Depending on the amount of early warning, this phase may or may not have been preceded by the above-described series of increasing levels of preparedness." The same wording is used in Table 1 on page 19. Explicitly, severity is not stated as a requirement.
The 2005 document is entitled: "WHO global influenza preparedness plan: The role of WHO and recommendations for national measures before and during pandemics”. On page 1, in the Executive Summary, some reasons for the update are articulated – "This new plan addresses the possibility of a prolonged existence of an influenza virus of pandemic potential, such as the H5N1 influenza virus subtype in poultry flocks in Asia which persisted from 2003 onwards." On page 2, in the Table of New Phases, it states that the pandemic phase is defined by: "increased and sustained transmission in general population". In footnote "b", which pertain to Phases 3, 4, and 5, it states that these phases are "based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal strain), and/or other scientific parameters." In other words, many potential factors may be considered. Explicitly severity was not stated as a requirement.
The 2009 document is entitled "Pandemic influenza preparedness and response: A WHO guidance document." In the acknowledgements, this work is ascribed to more than 135 experts along with more than 90 WHO staff. On page 3, the Foreword states "The information and recommendations in this guidance is the product of expert opinion, derived from several international consultations which included examination of available information and modelling studies, input from public health experts on lessons learned from SARS and both animal and human influenza responses, and consolidation of recommendations in existing WHO guidance. This guidance was subject to an extensive public review." On page 8, the Executive Summary covers reasons for the update including to "more accurately reflect pandemic risk and the epidemiological situation based upon observable phenomena". On page 11, Table 1 states that Phase 6 is described by: "in addition to the criteria defined in Phase 5, the same virus has caused sustained community level outbreaks in at least one other country in another WHO region."
Throughout, WHO has not sought to define or redefine "pandemic". WHO has provided descriptions of pandemics based on historical observations. WHO has however set out a phased approach to pandemic response, which has included definitions of pandemic phases
2. Please explain how the 2009 outbreak of H1N1 meets the definition of a pandemic, while the annual worldwide circulation and mutation of seasonal influenza viruses do not?
The pandemic H1N1 virus was considered "new" because it contained a constellation of genes derived from animal influenza viruses, and because antigenic testing indicated that antibodies to existing human influenza H1N1 viruses did not react with the new virus, indicating the virus would be immunologically novel for most or many people. This constellation of genes had never been seen before in an influenza virus infectious for humans. The rapid and well-documented global spread of this virus was associated with unusual epidemiological disease patterns such as extensive disease activity in many countries during summer months. Infection was also associated with an unusual disease pattern with higher levels of death and serious illness observed in young people, many of whom were healthy.
By contrast, seasonal human influenza epidemics are characterised by variants of well known viruses that generally have epidemiological and disease patterns different from those associated with the H1N1 pandemic virus.
More recent analyses have shown that the haemagglutinin of this H1N1 virus (the key determinant of immunogenicity) is probably derived from that in the 1918 pandemic virus. Thus, the vast majority of the human population will not have pre-existing immunity to this virus, and will therefore be susceptible to infection.
The spread of the pandemic (H1N1) 2009 virus clearly has caused a global influenza pandemic.
3. Please explain why the number of deaths is no longer taken into account in the definition of an "influenza pandemic" and whether this might change again?
WHO never specified any number of deaths as part of any "pandemic phase definitions" – see above documentation. But WHO has pointed out that the impact of pandemics is variable and has been very high in some past pandemics.
4. WHO has in the past said that pandemics cause "enormous numbers of deaths and illness". However, the last two influenza pandemics are said to have occurred in 1957 and 1968, but among those people who lived through them, few people even knew they occurred. Even fewer recall the outbreak of novel "Russian flu" virus in 1977. Similarly, SARS infected less than 8 000 people in a world of 6 billion. It would therefore appear that pandemics can be mild or strong. In what ways did the WHO's pandemic plan anticipate and prepare for the possibility of both mild and serious forms of pandemics?
In all WHO pandemic preparedness and response documents it was anticipated that the next pandemic could be of varying levels of severity. The estimated mortality of individual influenza pandemics in the 20th century has ranged from approximately one million in 1968-69 to over 40 million in 1918 to 1919. The limitation of SARS is considered a major public health victory and one of the watershed events in modern public health that demonstrated that global co-ordination can halt the spread of a newly emerging disease. All versions (1999, 2005, 2009) of the WHO pandemic preparedness guidelines anticipated the possibility that the range of impact could be wide.
5. Following laboratory tests, researchers in Mexico reported that only 11% of "swine flu" cases in that country's outbreak were found to be influenza. This proportion is the same as in normal seasons, where the vast majority of influenza-like illnesses cannot be linked to influenza. Given this, why has WHO emphasised vaccines and antivirals, which only work for influenza, to combat epidemics which seem to be caused by a large cocktail of all sorts of viruses?
In responding to the H1N1 pandemic, WHO has emphasised the use of effective methods to reduce pandemic infections and disease including communications, so called non-pharmacological interventions and pharmacological methods such as vaccines and antiviral drugs. This is in keeping with how many other infectious diseases are approached. Vaccines are used to reduce the number of infections or serious disease. Antiviral drugs are used to treat infections, but can also be used for prophylaxis against infection in certain situations. Among cases of influenza-like illness, the percentage of such cases attributable to influenza, or other pathogens, will vary depending on the time of year and circumstances. This is a very basic characteristic of the epidemiology of respiratory diseases and influenza. Other surveillance data from elsewhere indicate that the proportion of pandemic (H1N1) 2009 viruses isolated from patients suffering from influenza-like illness was up to 70%.
WHO recommended use of influenza antiviral drugs and vaccines to reduce serious illnesses and to save lives. Thus, WHO recommended vaccination for individuals at higher risk of serious disease, and health care workers, as a priority. Similarly, antiviral treatment is recommended for treatment of seriously ill patients, and those at higher risk of progressing to serious disease, but in the context of local epidemiological information. This latter point in particular allows for the fact that the likelihood of influenza-like illness being due to pandemic H1N1 will vary with seasons.
Influenza vaccines are one of the most effective ways to protect people from contracting illness during influenza epidemics and pandemics. This is especially important for those persons at higher risk of severe or complicated illness, and in these situations vaccination helps to prevent such severe illness and death. Similarly, antivirals have been proved to reduce or prevent severe illness and prevent death, especially in persons already at higher risk of developing severe influenza illness. WHO's guidelines for use of vaccines and antivirals are consistent with the above proven benefits.
6. How many cases of influenza, as a proportion of influenza-like illness, were there in the last five years and related hospitalisations and deaths (exact numbers verified by laboratory tests)? How was it calculated? If it is not possible to quantify seasonal (ordinary) influenza, how is it possible to know what is extraordinary (pandemic) influenza?
At a global level, some countries have adequate surveillance systems and data to monitor influenza epidemics. Based on such data and systems, studies and models have estimated the burden of influenza and have shown that the proportion of illnesses and hospitalisations attributable to influenza is highly variable. For example, patterns in the tropics differ from those in temperate zones – and over time – proportions are usually higher in the winter than the summer in temperate climate zones.
As described in the responses to Questions 1 and 2, the differences between seasonal and pandemic influenza relate to a combination of epidemiological, virological and clinical features. In contrast to seasonal influenza epidemics, the H1N1 pandemic has differed in several important respects. These include:
- A higher incidence of severe illness and hospitalisation in children and young adults than is usual with seasonal influenza
- The occurrence of epidemics in several regions of the world outside the normal seasonal periods for influenza
- A higher incidence than usual of viral pneumonia, which has been observed in previous pandemics, and which is difficult to treat, than in seasonal influenza
- Lack of pre-existing immunity from either natural infection by current seasonal influenza viruses or by vaccination
- The almost complete displacement of the previous seasonal H1 virus, and a significant displacement of the other seasonal A strain (H3N2), as was seen for previous pandemics.
7. WHO states that 250 000 to 500 000 deaths from seasonal influenza occur on average each year. What are WHO’s estimates of the annual number of deaths attributable to non-influenza virus caused influenza-like illnesses (ILI), and what is WHO doing to address this problem?
The influenza estimate was made in 2002 based on well-accepted studies done in temperate industrialised countries and extrapolated to estimate the worldwide impact of seasonal influenza. At a global level the proportion of pneumonia-related deaths due to non-influenza viral infections is not known.
WHO has a broad-based approach to the reduction of such deaths including support to countries in developing critical health capacities, information and guidance in several areas, advocacy, co-ordination of global surveillance, biannual updating of influenza candidate vaccine strains and assistance with outbreaks.
8. Were WHO pandemic planning assumptions and guidance to states based on the assumption that avian influenza H5N1 would cause the next pandemic?
The revisions of the guidelines were based on a broad assessment of new scientific knowledge and public health experience as well as study of past pandemics (1918, 1957, 1968). Contemporary experience took into account H5N1 infections, and several human influenza infections due to other animal viruses (H3, H9, H7). The revisions also reflected work of modelling groups that helped delineate the range of outcomes that might be expected.
9. Can you please provide the most recent estimates for H1N1 – persons contracting the disease, numbers died, numbers inoculated, vaccines ordered (and not used)? Can you also explain why the number of deaths from H1N1 has fallen far short of the self-described “relatively conservative estimate – from 2 million to 7.4 million deaths” that WHO said would occur in a future pandemic?
As of 7 May 2010, worldwide more than 214 countries and overseas territories or communities have reported laboratory-confirmed cases of pandemic influenza H1N1 2009, and over 18 000 laboratory confirmed deaths. This number is, fortunately, well below the figures quoted for previous pandemics and this may be attributable to two factors:
- Pandemic H1N1 has had a relatively low infection rate in the elderly. Since the elderly are particularly vulnerable to influenza, and account for the majority of deaths due to seasonal influenza epidemics, this low "attack rate" in older age-groups may have contributed to a lower than anticipated mortality
- Even in groups that have experienced high rates of infection, the death rate ("case fatality rate") has been lower than observed in previous pandemics, an observation which could not have been predicted at the start of the pandemic. This is likely to be due to the properties of the virus itself, but advances in medical care (such as intensive care, newer antivirals) will have made some contribution to this.
Other considerations are also important when considering the mortality data currently available:
- The current numbers of deaths reported for the H1N1 pandemic reflect deaths that were laboratory tested and individually confirmed. Estimates for previous pandemics and seasonal influenza epidemics are determined by retrospective statistical estimation of "excess deaths" during the period of an epidemic or pandemic. This gives a better estimate of the actual impact of the pandemic. A more accurate and complete assessment of mortality from this pandemic, using statistical models, will take about one to two years after the pandemic has ended and complete national mortality data are available.
- Most of the deaths that have been recorded for this pandemic have occurred in younger age-groups. The impact of the pandemic in terms of "years of life lost" is therefore higher than indicated by the absolute numbers.
WHO provided potential numbers of pandemic deaths to help national planners develop preparedness plans. Effective planning is difficult if not impossible to conduct without some range of figures.
10. Can you please provide a definition of "new influenza virus"?
See answer to question 2. In terms of the potential for the virus to cause a pandemic of influenza, the most important determinants of whether an influenza virus should be considered a pandemic candidate is whether it is infectious for humans, where it can spread sustainably among humans, and whether there is no or little pre-existing immunity to this virus.
11. If classical aspects of pandemics, such as high attack rates and severity, are not taken into consideration, what is the remaining public health rationale for treating pandemics any differently than we treat seasonal influenza?
The future course of a pandemic cannot be predicted at its onset, or even through much of its course. Pandemics are treated differently than seasonal influenza because they have a potential to cause more severe disease and death among more people than seasonal influenza. They also have the potential to cause significant social disruption. Since manufacturing capacity and supplies of influenza vaccines and antiviral drugs are geared to seasonal incidence and demand, they may not be available during high levels of pandemic disease. As was seen with the current H1N1 pandemic, population groups not normally considered at risk for complications of severe influenza disease may be at high risk, requiring changes to public health policy.
B. WHO’S STANCE ON VACCINES
12. What concerns did WHO have about the vaccines and their suitability/risks? Has the position changed? What view did WHO have on pharmaceutical companies declining responsibility for the vaccines and seeking to transfer this responsibility on to governments ordering the vaccines?
Pandemic influenza vaccines underwent the same testing methods as seasonal influenza vaccines. The increased timeliness was achieved not by any compromise in quality assurance or testing rigor but due to a collaborative effort by countries and officials to review and approve the vaccine in the most timely manner possible in a time of great uncertainty and public health concern. This shows what can be achieved through international collaboration in a public health emergency.
Outcomes of studies completed to date show that pandemic vaccines have a similar safety record as seasonal influenza vaccines
WHO is not involved in country-level decisions regarding the purchase of vaccines.
13. Could the viral infection have been prevented with vaccines in stock? If not, why not?
No. Studies on human immune responses have confirmed that an immune response to the seasonal H1 will not protect against pandemic H1 virus and therefore the seasonal influenza vaccines could not confer protection against the pandemic virus.
14. Has WHO done any head-to-head studies to compare behavioural interventions such as hand washing versus vaccines?
WHO has not commissioned or conducted any such studies. Moreover, such interventions are complementary rather than competitive options.
C. RELATIONS WITH INDUSTRY, EXPERTS AND CONFLICT OF INTEREST
15. What steps are being taken by WHO to be more transparent and to avoid conflicts of interest with pharmaceutical companies?
Whenever WHO utilises outside expertise for a particular activity, the experts concerned are required to complete a WHO Declaration of Interest form (DOI) in advance of their participation in that activity (generally an expert meeting or other work, aimed at providing expert advice to WHO).
Through the DOI, each expert is asked to declare any interests that could constitute a real, potential or apparent conflict of interest with respect to his/her involvement in the meeting or work.
Conflict of interest means that the expert, or his/her partner, or the administrative unit with which the expert has an employment relationship, has a financial or other interest in a commercial entity that could unduly influence the expert’s position with respect to the subject matter being considered. An apparent conflict of interest exists when an interest would not necessarily influence the expert but could result in the expert’s objectivity being questioned by others. A potential conflict of interest exists with an interest which any reasonable person could be uncertain whether or not should be reported.
The information submitted by the expert is assessed by the WHO Secretariat and may, depending on the situation, result in a number of measures to curtail any real or perceived conflicts. Such measures may range from total to partial exclusion from the activity, and/or public disclosure of the interest (that is, at the start of the meeting and in the report of activity). As reports of expert meetings are generally published by WHO, information on experts' disclosed interests are generally available to the public.
Regarding WHO staff, in addition to general rules which apply to all staff, certain categories of staff must file declarations of interest each year to identify potential conflicts of interest that could affect their objectivity and independence.
16. How does WHO define an inappropriate conflict of interest?
Information disclosed in the WHO DOI for experts is used to determine whether the declared interests constitute an appreciable real, potential or apparent conflict of interest. An appreciable real conflict of interest is defined as the expert having a financial or other interest that could unduly influence the expert’s position with respect to the subject matter being considered. An apparent conflict of interest is defined as an interest that would not necessarily influence the expert but could result in the expert’s objectivity being questioned by others. A potential conflict of interest is defined as an interest which any reasonable person could be uncertain whether or not should be reported.
17. Please provide more details on the “public-private partnerships for health” system in relation to the pandemic influenza preparedness, and in particular the development of “benefit sharing arrangements with influenza vaccine manufacturers”?
WHO works with government, civil society and private sector partners to advance public health, including for risk assessment and control as stipulated under the International Health Regulations. Concerning benefits sharing arrangements for influenza, this remains an area of negotiation by the member states of WHO. The latest framework containing a number of agreed sections is available publicly in the World Health Assembly Document WHA A62/5Add.1 (http://apps.who.int/gb/ebwha/pdf_files/A62/A62_5Add1-en.pdf). Additional information on the intergovernmental process is available at http://apps.who.int/gb/pip.
Financing and in-kind support have been secured both multilaterally and bilaterally during recent years; these include options to stockpile H5N1 and H1N1 vaccines and antiviral agents through donations from governments and industry, and agreements for technology transfer. In addition support has been received for capacity building for laboratory surveillance and pandemic response, as required under the International Health Regulations (2005)
With the onset of pandemic A(H1N1), WHO worked closely with member states and the pharmaceutical industry to identify means to obtain required vaccines and antiviral drugs. WHO reported to its Executive Board at its 126th session in January 2010 with information on the pharmaceutical industry's donations of pandemic vaccine and antiviral medicines, as well as funding to WHO to support its response activities.
18. Please provide more details on the selection methods of experts to WHO advisory bodies and expert committees (including the “Review Committee”);
The selection of experts to WHO expert committees (including the Review Committee) is governed by the Regulations for Expert Advisory Panels and Committees (and the International Health Regulations, in the case of the Review Committee). Experts to WHO expert committees, including the Review Committee, are selected from WHO expert advisory panels on the basis of the principles of equitable geographical representation, gender balance, a balance of experts from developed and developing countries, representation of different trends of thought, approaches and practical experience in various parts of the world, and an appropriate interdisciplinary balance. Selection of members of WHO expert advisory panels is based primarily on their technical ability and experience. Efforts are also to be made to ensure that the panels have the broadest possible international representation in terms of diversity of knowledge, experience and approaches in the fields for which the panels are established.
19. Please provide more details on the system in place to prevent or curb conflicts of interest: is there a questionnaire? Are declarations of interest filed and consultable, and if so by whom (member states)? If there are consultations with the experts on these issues, are reports drafted afterwards and are these available and consultable and if so by whom?
See the answer to question 15 above. The completed WHO DOIs are filed by the WHO Secretariat. As noted above, the reports of WHO expert meetings generally contain information on appreciable conflicts of interest which were declared by the participating experts. Since such reports are generally published, the information is as such available to the public.
20. Dr Keiji Fukuda told the Council of Europe on 26 January 2010: "Providing independent advice to member states is a very important function of WHO that is taken seriously. WHO guards against the influence of any improper interests." In that light, what evidence did WHO base itself on in recommending the use and stockpiling of TAMIFLU (for example, to reduce complications of influenza). Did WHO do an analysis of the drug independent of that done by the manufacturer of the drug?
WHO published guidelines for the use of antivirals in August 2009, subsequently revised and republished March 2010.
These guidelines were based on an independent review of the available evidence conducted for WHO by independent consultants. The evidence review was then used by an expert panel in the formulation of specific treatment recommendations.
In the published guidelines, WHO has ensured full transparency both in the process followed, and in the basis for the recommendations. The documentation includes:
- statement on the quality of clinical evidence that supports each recommendation
- details of the methods for evidence review, the published studies that were considered, and the assessment grading
- Full list of members of the expert panel, and disclosure of their relevant interests
21. In their review of the 1976 “swine flu fiasco”, Neustadt and Fineberg write: “In a swine flu case when evidence is thin … it is not only the assumptions but appraisal of their scientific quality that top decision makers need. Panels tend toward ‘group think’ and over-selling, tendencies nurtured by long-standing interchanges and intimacy, as in the influenza fraternity. Other competent scientists, who do not share their group identity or vested interests, should be able to appraise the scientific logic applied to available evidence”. What steps did and does WHO take to include experts with diverse or contrary views into its advisory and policy guidance preparation process and to avoid what is being referred to as “group think”?
Please see response to question 18.
22. What systems are in place to analyse WHO recommendations and whether they were appropriate and well founded?
23. What lessons have been learnt from the H1N1 pandemic?
An in-depth review of the global response to the influenza pandemic began in April. An external Review Committee, convened under the International Health Regulations (IHR), will examine how the world and WHO responded to the pandemic H1N1.
The overarching goal is to identify lessons learned and ways to improve how the world can work together to protect global health during a public health emergency.
This rigorous, external review of the global response to pandemic H1N1 is an unprecedented process that will influence public health decision making during the next pandemic, and in other public health emergencies of international concern.