H1N1 Influenza: Not to be Sneezed at

February 1, 2011

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-02-01-2011, Volume 20, Issue 2

Renewed pandemic fears drawn the sting from criticisms of industry and regulators.

A new mid-January influenza warning from the European Region of the World Health Organization (WHO) has cast a new light on the ongoing controversy in Europe over the authorities' response to the H1N1 outbreak.

Peter O'Donnell

Influenza activity is increasing, said WHO, most notably in Northwest Europe, with pandemic (H1N1) 2009 not only among the most prevalent viruses, but also associated with most of the severe and fatal cases reported in some countries.

This reality may take some of the wind out of the sails of the harshest critics of Europe's actions to date. As this column commented last October, both in the Council of Europe and in the European Parliament, accusations have been repeatedly leveled at regulators and at industry for exaggerating the risks, and for resorting too uncritically to medication, regardless both of real need and of potential side effects.

Last year a report for the Council of Europe blamed European Union agencies, WHO, and national governments for wasting large sums of public money, and for "unjustified scares and fears about the health risks faced by the European public." It spoke of "overwhelming evidence that the seriousness of the pandemic was vastly overrated by WHO," resulting in distorted health priorities, and "grave shortcomings" in decision-making. Central to the criticisms were suspicions that advice to the authorities was biased in favor of vaccination by scientists with links to the drug firms that stood to benefit.

European parliament criticisms

To prove that not everything is new in the new year, a draft report for the European parliament's health committee, due for discussion early this year, also makes sharp criticisms of the EU's performance in 2009-2010, revisiting many of the allegations of drug industry manipulation of the regulatory system in pursuit of vaccine sales. The report, and many of the still-more hostile amendments that have been tabled to it, also focuses heavily on what it sees as an inadequate approach to testing.

The tone is set by passages claiming that most efficacy studies "have been conducted by pharmaceutical companies, meaning that no objective proof has been provided of the efficacy of influenza vaccines," and that "differing recommendations made within the EU" reveal "huge uncertainties surrounding the evaluation of the H1N1 vaccines recommended."

The evaluation of the management of H1N1 influenza in the EU has been prepared by French Green MEP Michèle Rivasi, who has already made herself conspicuous with her criticisms of the pharma industry in other areas. The debate in the parliament will attract further attention, with attacks scheduled on "the EU's lack of independence and critical acumen in risk evaluation," "blind faith" in influenza vaccines, and failing to take into account "scientific data that contradict that belief." Calls will be made for screening procedures for experts to be tightened up to exclude pro-industry bias. There will also be criticism of the way that vaccine manufacturers' purchase contracts transferring part of the liability for any side effects to the purchasing countries; pressure will be exerted for full liability for the quality, safety, and effectiveness of a medicine to remain entirely with the manufacturer.

Rivasi's draft report makes the familiar accusation that authorization decisions are made in too much secrecy, and it "reminds the EMA [European Medicines Agency] of the regulatory requirement to give access to all the documents relating to clinical trials, research protocols, and the undesirable effects of the medicinal products evaluated by its experts, including the vaccines and anti-viral drugs recommended as a means of combating H1N1 influenza." It also reiterates "lingering uncertainties" about benefit-risk profiles and urges a review of the EU's accelerated marketing authorization procedures. One of the specific accusations is that "the stock 'pandemic' vaccines given to millions of people in Europe were the subject of extraordinary 'facilitated' authorization procedures, based in fact on old studies and vaccine formula produced at the time of the H5N1 virus, which also dated from the years 2005/2007." The draft report also claims that Zsuzsanna Jakob, a former head of the European Center for Disease Control, said that "no vaccine had ever been authorized on the basis of so little scientific information."

Some of the amendments proposed go further, demanding examination of "the influence exerted on the WHO and the EU by lobbyists working on behalf of international pharmaceuticals companies," and referring to "lawsuits in various member states, alleging corruption and conspiracy on the part of civil servants in relation to contracts signed in summer 2009 between ministries of public health and manufacturers."

If these views go unchecked and unchallenged, the outcome is likely to be further political endorsement of the need for changes in the current healthcare system in the EU so as to diminish the role of pharmaceuticals and limit the influence of the industry. Industry critics have been drawing a contrast with increasing frequency between "public health objectives" and "a purely pharmacological approach," and if criticisms are unanswered, the view will increasingly prevail. The recent shifts toward greater disclosure of drug data by the EMA are also likely to be discounted as insufficient.

WHO reality check

Against this background, the January statement from WHO Europe may come as a salutary reality check. It underlines that—as the WHO Director-General stated in a post-pandemic announcement in August 2010—"the pandemic (H1N1) 2009 virus was expected to continue to circulate and cause local outbreaks and epidemics, as well as severe disease and deaths both in recognized higher-risk groups and in previously healthy people."

It makes clear that on the available evidence, groups identified during the pandemic as at high risk for severe or fatal illness remain at heightened risk, and points out that most of the fatal cases had not been vaccinated. Consequently, it recommends that health ministries ensure high rates of uptake of vaccine by individuals who might be at risk of developing complications, in particular pregnant women and healthcare workers. It is advising national authorities to start or enhance awareness-raising activities among individuals at risk for complications from influenza, emphasizing the need to seek medical advice or care early on. In addition, WHO says, governments need to alert family doctors, hospitals, and intensive care units to the expected increase in influenza patients, so that they can start triage and early treatment of pneumonia patients, especially in resource-poor environments. It urges clinicians to "start treatment for influenza when they suspect the illness, without relying on rapid diagnostic tests or waiting for laboratory confirmation."

Access to drug information

On the subject of better access to drug information, not only has the EMA moved toward greater transparency, but its shift of position has even won applause from one of its most vigorous official critics, the European Ombudsman.

During 2009, the ombudsman, Nikiforos Diamandouros, who acts as a watchdog of the public interest in the European Union, sharply and repeatedly criticized the EMA's reluctance to provide more access to its documents and called for major improvements.

Late last year, the EMA confirmed that it was widening public access to drug data through a new policy of "proactive disclosure of documents." The EMA said it was responding to increasing public demand, and would work on a presumption that documents would be released once regulatory decisions had been made. It said its aim was to permit "stakeholders to understand the basis for the agency's scientific decision-making and provide for the basis on which patients and healthcare professionals can have confidence in our opinions and information relating to medicines."

The new policy gives access to all business-related documents unless there is a need to respect arrangements with non-EU regulators or international organizations, or to protect the privacy and integrity of a natural or legal person. Documents submitted to the agency as part of a marketing authorization application, such as clinical trial reports, can now also be released, provided the decision-making process for the application in question is finalized, the EMA said. There will be freer access to information from clinical trials, allowing patient groups and members of the public more opportunities to scrutinize the results of trials. Noel Wathion, one of the most senior officials at the EMA, described the move as a culture change.

Now Diamandouros has issued a statement welcoming the EMA announcement. "I am greatly encouraged and applaud EMA's constructive approach to improving its transparency policy," he said. He has repeatedly argued that the EMA's work has a direct impact on the health of European citizens and it is therefore crucial that it should "give the widest possible access to documents and pursue a pro-active information policy for the benefit of citizens."

The new EMA arrangements do not provide total access—yet. Safeguards are built in for sensitive personal and commercial data. The question that concerns many in the clinical trials community is that as criticisms of EU health regulation mounts—as the H1N1 debate exemplifies—pressure may build for the safeguards to be progressively dismantled too.

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.

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