Guardian Health News

Action taken was effective and in proportion to threat but contract for GSK vaccine 'lacked flexibility'

The government's response to the swine flu pandemic was on the whole proportionate and effective, an independent review said today, but there are still lessons to be learned from the alert, which cost £1.2bn.

Dame Deirdre Hine, who spent three months interviewing the main players and scrutinising the strategy adopted by the devolved administrations, said that after more than 800,000 cases of swine flu across the UK and 457 deaths, including those of children and pregnant women, it would be wrong to suggest there had been an overreaction.

"The response that it was all [over] nothing I think is fallacious," she said at a press conference to launch the review.

But, she said, there was "a need for even more flexibility in the planning and response to such events. The unexpectedly mild nature of the pandemic emphasises that the only predictable thing about the flu virus is its unpredictability."

As a result, the government found itself tied into a contract with British drug giant GlaxoSmithKline to buy many more doses of vaccine than the country needed.

"There was significant flexibility in the amount the UK could purchase, ranging from 30m doses to 132m doses – enough to vaccinate the whole UK population with two doses. There was, however, less flexibility once contracts had been signed, with Baxter Healthcare agreeing a break clause but GSK not being willing to do so," said the review.

Hine recommended that the Department of Health should in future negotiate advance purchase agreements "that allow flexibility over the eventual quantities purchased".

GSK responded today that all flu vaccine contracts had to be fixed orders because demand from governments at the outbreak of the pandemic was greater than supply. The UK had opted for the maximum allocation of 20% of the first 300m doses made available in Europe.

"As the major supplier of H1N1 vaccines across Europe, it would not be possible to offer different allocations throughout the period of vaccine production without having a significant impact on availability for other countries," the company said in a statement. "A break clause that allows one country to exceed their allocation when supplies are limited and then pull out later would not be ethical."

The review put the cost of the pandemic at £1.2bn, taking into account both the preparedness and response phases. Most of that, around £1bn, went on pharmaceuticals, which included the antiviral drug Tamiflu, the vaccine, and antibiotics.

In an unpredictable situation such as the arrival of pandemic flu, there is a tendency, said Hine, "to assume the worst-case scenario and resource the response accordingly". But she suggested there is an alternative approach, "which is to take a view on the most likely outcome, while monitoring events closely and changing tack as necessary".

Flexibility in the response was also important because the pandemic did not spread evenly across the country, but was concentrated in some areas. It also attacked young children and pregnant women, and critical care beds for children came under severe pressure. "At one point every paediatric critical care bed was in use," said Hine.

Communications between health experts, government, media and the public worked well, the review found. There was confusion, however, over advice from the Scientific Advisory Group for Emergencies (Sage), which was given to ministers and made public, relating to "reasonable worst-case scenarios".

Under this scenario, there would be 65,000 deaths from pandemic flu. While the chief medical officer, Sir Liam Donaldson, attempted to explain that these numbers were for planning purposes, some of the media ran them as predictions. Hine recommended that the use of planning predictions should be the subject of further discussion.

On the whole, the flu strategy worked well, but Hine warned against complacency – because there will be another flu pandemic at some point.

"When you have a chip pan fire in the kitchen and, because you have a fire blanket and a smoke alarm, damage to the kitchen is minimal and to the rest of the house is non-existent, you don't thereafter throw out your insurance," she said.

The health secretary, Andrew Lansley, welcomed the report. "The UK response was the result of careful preparation, but it is vital that we learn lessons. The government will take these recommendations into consideration in planning for the future to ensure that we remain one of the best prepared countries in the world for any future pandemics," he said.

• Swine flu
• Health policy
• Health
• Flu pandemic
• GlaxoSmithKline

Independent review says government did not over-react to pandemic

The government's response to the swine flu pandemic was on the whole "proportionate and effective", an independent review said yesterday, but there are still lessons to be learned.

Dame Deidre Hine, who spent three months interviewing the main players and scrutinising the strategy adopted by the devolved administrations, said that after more than 800,000 cases of swine flu across the UK and 457 deaths, including those of children and pregnant women, it would be wrong to suggest there was an over-reaction.

"The response that it was all nothing I think is falliacious," she said at a press conference to launch the review this morning.

But among the lessons that could be learned, she said, was that the Department of Health should have negotiated a "break clause" in its contract with drug company GlaxoSmithKline for supplying a pandemic vaccine that, in the end, was needed only in relatively small quantities.

"There was significant flexibility in the amount the UK could purchase, ranging from 30 million doses to 132 million doses – enough to vaccinate the whole UK population with two doses. There was, however, less flexibility once contracts had been signed, with Baxter Healthcare agreeing a break clause but GSK not being willing to do so."

The review put the total cost of the pandemic at £1.2 billion, taking into account both the preparedness and response phases. The bulk of that – around £1 billion, went on pharmaceuticals, which included the antiviral drug Tamiflu, the vcacine and antibiotics.

In a situation of unpredicabilty, as the arrival of this flu virus was, there is a tendency, said Dame Deidre, "to assume the worst case scenario and resource the response accordingly". But in her review she suggested there is an alternative approach, "which is to take a view on the most likely outcome, while monitoring events closely and changing tack as necessary.

"Ministers should be invited to make a conscious choice as to which approach to adopt."

Flexible planning was all important, she said. The pandemic did not spread evenly across the country, but concentrated in specific places. It also attacked young children and pregnant women – and critical care beds for children came under severe pressure at one time.

• Health
• Swine flu

You highlight a problem with scientific advice given by scientists with potential conflicts of interest (Report condemns swine flu experts' ties to big pharma, 4 June). Unfortunately, this is only the tip of an iceberg and reflects only one aspect of the problem with blind acceptance of scientific advice. Scientists are human beings and are driven by the same selfish desires as the rest of us. The altruistic scientist, driven only by "the search for truth", is a media fabrication. Fame and influence inflate egos. Hubris, arrogance and a woeful lack of self-awareness is common, in both scientific and medical communities.

In my experience many scientists cannot see beyond their limited horizons and only the most remarkable individuals are able to see the big picture. Wide-ranging controversies – such as the MMR scare, withholding of climate change data and the recent overreaction to the swine flu pandemic – show how powerful scientific evidence can be. This is neither intended to negate scientists nor scientific endeavour, but merely remind us that scientific advice must be tempered by a strong dose of common sense before public policy is altered.

Dr Tariq Ali

Oxford

• Marilynne Robinson (Mind over matter, Review, 5 June) offers a refreshing view that challenges the accepted dogma of neo-Darwinists and other scientific reductionists that the mysteries of nature have been sorted out through the application of unbiased science. They will have us believe that, given enough time, the chaotic laws of nature plus the simple mechanics of biological evolution explain everything.

An alternative possible scenario is that matter at its deepest level is characterised by: (a) a quality of "interconnectedness" or very primitive "mentality"; and (b) a natural law that drives matter towards complexity. Quantum theory provides evidence that supports premise (a). The evolution of matter, from the simple elements after the big bang to the complex elements of the periodic table, many of which are necessary as a basis for the biological evolution, which is also a manifestation of this general principle, provide evidence for premise (b). Both premises explain the gradual flowering of mentality from these simple elements that possess it in a most primitive and dilute form to that of the earliest micro-organisms capable of some overt communication and finally to us humans. There is no point of discontinuity at which suddenly the property of mentality emerged, just a sustained increase in material and mental complexity. Ergo, matter and mind are irrevocably entangled.

I am sorry to say that many scientists at present, contrary to the basic premise of science that all scientific explanations are temporary, proclaim views that they consider unshakable.

Professor Leon Freris

Radlett, Hertfordshire

• MMR
• Swine flu
• Marilynne Robinson
• Psychology
• Evolution
• Physics

Trio of scientists who urged stockpiling had previously been paid, says report

Scientists who drew up the key World Health Organisation guidelines advising governments to stockpile drugs in the event of a flu pandemic had previously been paid by drug companies which stood to profit, according to a report out today.

An investigation by the British Medical Journal and the Bureau of Investigative Journalism, the not-for-profit reporting unit, shows that WHO guidance issued in 2004 was authored by three scientists who had previously received payment for other work from Roche, which makes Tamiflu, and GlaxoSmithKline (GSK), manufacturer of Relenza.

City analysts say that pharmaceutical companies banked more than $7bn (£4.8bn) as governments stockpiled drugs. The issue of transparency has risen to the forefront of public health debate after dramatic predictions last year about a swine flu pandemic did not come true.

Some countries, notably Poland, declined to join the panic-buying of vaccines and antivirals triggered when the WHO declared the swine flu outbreak a pandemic a year ago this week. The UK, which warned that 65,000 could die as a result of the virus, spent an estimated £1bn stockpiling drugs and vaccines; officials are now attempting to unpick expensive drug contracts.

The cabinet office has launched an inquiry into the cost to the taxpayer of the panic-buying of drugs.

Today, the Council of Europe, produces a damning report into how a lack of openness around "decision making" has bedevilled planning for pandemics.

"The tentacles of drug company influence are in all levels in the decision-making process," said Paul Flynn, the Labour MP who sits on the council's health committee. "It must be right that the WHO is transparent because there has been distortion of priorities of public health services all over Europe, waste of huge sums of public money and provocation of unjustified fear."

Although the experts consulted made no secret of industry ties in other settings, declaring them in research papers and at universities, the WHO itself did not publicly disclose any of these in its seminal 2004 guidance. In its note, the WHO advised: "Countries that are considering the use of antivirals as part of their pandemic response will need to stockpile in advance."

Many nations would adopt this guidance, including Britain. In 2005, the government said it had begun bulk-buying the drug Tamiflu, initially ordering 14.6m doses after bird flu killed 40 in Asia.

The specific guidance on antivirals was written by Professor Fred Hayden. He has confirmed in an email that he was being paid by Roche for lectures and consultancy work at the time the guidance was produced and published. He received payments from GSK for consultancy and lecturing until 2002. He said "[declaration of interest] forms were filled out for the 2002 consultation".

The previous year Hayden was also one of the main authors of a Roche-sponsored study that asserted what was to become a main Tamiflu selling point – its claim of a 60% reduction in flu hospitalisations.

Dr Arnold Monto was the author of the WHO annex dealing with vaccine usage in pandemics. Between 2000 and 2004, and at the time of writing the annex, Monto had openly declared consultancy fees and research support from Roche and GSK. No conflict of interest statement was included in the annex published by the WHO.

When asked if he had signed a declaration of interest form for WHO, Dr Monto said "conflict of interest forms are requested before participation in any WHO meeting".

The third scientist, Professor Karl Nicholson, is credited with the WHO's influential work Pandemic Influenza. According to declarations he made in the BMJ and Lancet in 2003, he had received sponsorship from GSK and Roche.

Even though the previous year these declarations had been openly made, no conflict of interest statement was included in the annex. Nicholson said he last had "financial relations" with Roche in 2001.

When asked if he had signed a declaration of interest form for WHO, he replied: "The WHO does require attendees of meetings, such as those held in 2002 and 2004, to complete declarations of interest."

A WHO official told the BMJ it had to balance an individual's privacy with the robustness of guidelines, which were subject to a wide external review process.

• Swine flu
• Pharmaceuticals industry
• Drugs
• Health policy
• World Health Organisation
• Controversies in science

Two types of vaccine generate good immune responses with only minor side-effects, say researchers

Swine flu vaccines given to children during last year's pandemic have mostly minor side-effects and should provide "good protection" against infection, researchers revealed today.

The vast majority showed a "good response" in producing antibodies vital to fighting the infection, in a trial of more than 900 children conducted during the 2009/10 pandemic.

Some 98% of children under three responded well to two doses of an "adjuvanted" vaccine, which contains an emulsion to boost immunity. This vaccine – also known as a "split-virus" vaccine – was the most common type given to children last year.

Two doses of a second "whole-virus" version of the vaccine, without the booster, produced a weaker result, with 80% of under-threes responding.

In children over three, the difference between the two types of vaccines was less pronounced, with 99% responding to the adjuvanted vaccine and 95% to the vaccine without a booster.

While the adjuvanted vaccine was the most likely to produce side-effects such as fever, most children experienced only minor reactions.

The study, a collaboration between the Health Protection Agency and the Universities of Bristol, Oxford, Southampton, Exeter, and St George's in London, assessed both vaccines for safety, tendency to cause reactions and ability to induce an antibody response.

During last year's pandemic, children were infected at four times the rate of adults and more commonly admitted to hospital with swine flu, making them a priority group for vaccination.

Dr Matthew Snape, of the Oxford Vaccine Group at the University of Oxford, said: "Children were a high priority for immunisation in the swine flu pandemic, and therefore last autumn we set out to study how well children responded to the two H1N1 influenza vaccines available in the UK.

"We showed that two doses of both vaccines generated good immune responses, with significantly higher antibody levels seen after immunisation with the most commonly used vaccine.

"This vaccine contained a new adjuvant (an emulsion) specifically designed to enhance the immune response, and did cause slightly higher rates of local reactions and fever. However, most children receiving either vaccine had no more than minor reactions, and this study provides reassuring evidence that both vaccines were well tolerated and likely to provide good protection against swine flu."

The experts were able to recruit 900 children into this study in just over a month, after funding was provided by the National Institute for Health Research.

The success of the vaccine among under-threes could now help improve the immune response of young children to the annual "seasonal" flu vaccine. Dr Snape explained: "What was especially interesting is the good immune response rates of the under-threes to the adjuvanted vaccine.

"Traditionally, the under-threes don't tend to respond well to flu vaccines. This could show us the way to improve seasonal flu vaccines and help make a vaccine that generates a better response in young children."

The department of health purchased two H1N1 vaccines for the national immunisation programme - an adjuvanted split virion vaccine derived from egg culture, and a non-adjuvanted whole virion vaccine derived from cell culture.

The study rapidly delivered information to government planners during the actual pandemic. The adjuvanted vaccine was subsequently recommended for use in a single-dose schedule, in contrast to the two-dose schedule assessed in this study.

The study, published in the British Medical Journal today, is the first to be carried out comparing the immune response rates to the two vaccines in children aged between six months and 12 years.

Children were grouped by age and randomly assigned for immunisation with either the adjuvanted (split-virus) vaccine or the non-adjuvanted (whole-virus) vaccine in two doses, 21 days apart.

Data on reactions such as fever, tenderness, swelling and redness of the skin were collected for one week after each vaccination.

Blood samples were also taken before vaccination and after the second dose to measure rises in antibody levels.

• Swine flu
• Flu pandemic
• Health
• Children