nature

WHO responds to the critics
by the World Health Organization

Background

On Friday 4 June 2010, the BMJ, formerly British Medical Journal, and the Parliamentary Assembly of the Council of Europe (PACE) simultaneously released reports critical of the World Health Organization's handling of the H1N1 pandemic. WHO takes the issues and concerns that were raised seriously and wishes to set the record straight on several points.

Is this a genuine pandemic?

The outbreaks of infection with the new H1N1 virus, which have been confirmed in virtually every country and territory in the world, differ from seasonal influenza in distinct ways. These differences meet the criteria for an influenza pandemic.

1. The first human infections with the new H1N1 virus were confirmed in April 2009. Analysis of laboratory samples showed that the new virus had never before circulated in humans. This is a virus of animal origin with a unique mix of genes from swine, bird, and human influenza viruses. The genetic composition of this virus is distinctly different from that of the older H1N1 virus that has been causing seasonal epidemics since 1977.

2. As the virus spread, it demonstrated epidemiological patterns not seen during seasonal epidemics of influenza. Widespread, high levels of infection with the new virus occurred during the summer in the northern hemisphere in multiple countries, followed by even higher levels during the fall and winter months. In countries with a temperate climate, seasonal epidemics typically taper off in the spring and end before summer.

3. The pattern of illness and death caused by the H1N1 virus differed in striking ways from that seen during seasonal influenza. During seasonal epidemics, more than 90% of deaths occur in the frail elderly. The H1N1 virus affected a younger age group in all categories: those most frequently infected, those requiring hospitalization, those requiring intensive care, and those dying from their infection.

A frequent cause of death was viral pneumonia, caused directly by the virus and difficult to treat. During seasonal epidemics, most cases of pneumonia are caused by secondary bacterial infections, which usually respond well to antibiotics. While many of those who died had underlying medical conditions associated with a higher risk, many others who died were previously in good health.

4. The new H1N1 virus rapidly crowded out other circulating influenza viruses and appears to have displaced the older H1N1 virus. This phenomenon is distinctly seen during pandemics.

5. Early studies showed that antibodies to H1N1 seasonal influenza did not protect people from infection with the new virus. This finding provided critical evidence that the virus was new to the human immune system. Later studies in some countries determined that around one third of people older than 65 years had some immunity to the virus. Younger people, however, had no such protective immunity.

Did WHO remove severity from the definition of a pandemic?

WHO regards severity as an important feature of pandemics and a critical factor when deciding on which actions to take. However, WHO has not required a set level of severity as part of its criteria for declaring a pandemic. Experience shows that all pandemics cause excess deaths, that severity can change over time, and that severity can vary according to location and population.

WHO has published three definitions of an influenza pandemic in the context of phases of pandemic alert. These definitions were contained in broader guidelines for pandemic preparedness issued in 1999, 2005 and 2009. Research on influenza pandemics and pandemic viruses increased considerably following the first human cases of infection with the H5N1 avian influenza virus in 1997. Definitions changed over time in line with this evolving knowledge and the need to increase the precision and practical applicability of phase definitions.

The 2009 guidelines, including definitions of a pandemic and the phases leading to its declaration, were finalized in February 2009. The new H1N1 virus was neither on the horizon at that time nor mentioned in the document.

The media make frequent reference to a 2003 document, available on the WHO web site, stating that an influenza pandemic results in "enormous numbers of deaths and illness." At the time, this was considered a likely scenario should the highly lethal H5N1 avian influenza virus develop an ability to spread readily among humans, but it was never a formal definition.

Did WHO exaggerate the threat?

When WHO Director-General Dr. Margaret Chan announced the start of the pandemic, on 11 June 2009, she expressed the view that the pandemic would be of moderate severity. She further noted the relatively small number of deaths worldwide, and clearly stated that "we do not expect to see a sudden and dramatic jump in the number of severe or fatal infections."

In every assessment of the pandemic, WHO consistently reminded the public that the overwhelming majority of patients experienced mild symptoms and made a rapid and full recovery, even without medical treatment.

WHO also noted, early on, that influenza viruses are unstable and can undergo rapid and significant mutations, making it difficult to predict whether the moderate impact would be sustained. This uncertainty, which persuaded WHO and many national health authorities to err on the side of caution, was further enforced by the behavior of past pandemics, which varied in their severity during first and second waves of international spread.

Were any WHO pandemic decisions made to increase industry profits?

No. Allegations that WHO declared a pandemic to boost the profits of the pharmaceutical industry arise from WHO's use of expert advisers and the way declarations of interest from these experts are handled. No evidence of any specific instance of wrongdoing has emerged from recent enquiries.

What safeguards are in place to guard against conflicts of interest?

Potential conflicts of interest are inherent in any relationship between a normative and health development agency, like WHO, and profit-driven industry. Advice from top experts is sought by industry as well as by agencies like WHO that need to issue guidance based on the best expertise. Many experts who advise WHO have ties with industry, and these ties can range from funding to conduct research, to paid consultancies, to participation in conferences sponsored by industry.

WHO has systems in place to protect the Organization from advice biased by commercial interests. WHO requires all expert advisers to declare their professional and financial interests when they participate in advisory groups and consultations. WHO assesses declared interests to determine whether a potential conflict or a potential perception of conflict exists. Where necessary, WHO requests more detailed information and then decides on the appropriate action to be taken.

The publication of summaries of relevant interests following meetings is inconsistent and needs to be made routine. WHO further acknowledges that safeguards surrounding engagement with industry need to be tightened, and is doing so.

What is the function of the Emergency Committee and why have the names of its members not been disclosed?

The International Health Regulations (IHR) contain a set of requirements that are legally binding for WHO and the 194 States Parties of the IHR. The IHR call upon the WHO Director-General to convene an Emergency Committee, drawn from a standing roster of IHR experts, to provide WHO with independent guidance during public health emergencies of international concern, such as an influenza pandemic. The IHR came into force in 2007.

The emergence of the new H1N1 virus prompted the first convening of an Emergency Committee under the IHR. At that time, WHO debated whether or not to publicly disclose the names of members, and faced a dilemma. On one hand, the names of members of other advisory groups are made public after they meet; the identification of persons offering guidance adds transparency to their advice and subsequent WHO decisions. On the other hand, experiences during the SARS outbreak demonstrated the considerable economic and social disruption caused by some public health emergencies, meaning that experts could well be lobbied or pressured for commercial or political reasons, potentially compromising the objectivity of their advice.

After considering these issues, WHO decided to apply its usual practice of disclosing the names of experts after an advisory body has completed its work. The members themselves welcomed this decision as a protective measure, and not as an attempt to veil their deliberations and decisions in secrecy. However, given the duration of the pandemic, the Emergency Committee has held a number of meetings over more than a year, rather than a single meeting like most advisory groups, thus delaying even further the release of the names of its members.

WHO is now fully aware that this decision has fostered suspicion that the Committee might be providing guidance shaped by commercial interests or pressures. Names of members and a summary of relevant declarations of interest will be made public when the Committee advises that the pandemic has ended. Procedures for revealing names of members of future Emergency Committees are under review.

What evidence supports a role for antiviral drugs during an influenza pandemic?

Given widespread population vulnerability to infection, an influenza pandemic presents health authorities with a significant challenge in finding ways to protect populations. From the outset, WHO has recommended a wide range of measures, including hand washing, respiratory hygiene, and not traveling or going to work when ill, and has offered advice on the clinical care of patients and the use of antiviral drugs and vaccines.

At the start of the pandemic, data from the Centers for Disease Control and Prevention (USA) showed that the new virus was sensitive to oseltamivir and zanamivir. Prior to the pandemic, WHO had developed guidelines for the treatment of severe influenza infections caused by the avian H5N1 influenza virus. These two factors allowed WHO to rapidly issue guidelines for use of antivirals in the context of H1N1 pandemic influenza, with emphasis on the treatment and prevention of severe illness.

Over the course of the pandemic, an increasing volume of clinical data has been published in peer-reviewed medical journals. These studies confirm that prompt use of antivirals correlates with improved recovery from illness and fewer deaths. Evidence shows that antivirals have been especially effective for treating patients at increased risk of developing complications from H1N1[1].

Was a WHO meeting held in 2002 on influenza vaccines and antiviral drugs influenced by industry?

In 2002, WHO convened a consultation with experts to develop a document, WHO guidelines on the use of vaccines and antivirals during influenza pandemics, which was published in 2004. Some critics have alleged that certain experts who participated in the meeting and the drafting of the guidelines had ties with industry interpreted as conflicts of interest. In line with WHO policy, all experts who participated in this meeting were required to submit a declaration of interest form and all such forms were duly reviewed by WHO. However, a summary of relevant interests was not issued together with the publication. WHO regrets this oversight.

Since that time, a number of administrative and legal changes have been implemented to strengthen procedures for addressing potential conflicts of interest that might influence the advice provided to WHO. WHO is committed to tightening these procedures further and ensuring their more consistent application.