WHO swine flu experts 'linked' with drug companies

WHO swine flu experts 'linked' with drug companies
Page last updated at 11:14 GMT, Friday, 4 June 2010 12:14 UK
Governments around the world stockpiled antiviral drugs Key scientists behind World Health Organization advice on stockpiling of pandemic flu drugs had financial ties with companies which stood to profit, an investigation has found.

The British Medical Journal says the scientists had openly declared these interests in other publications yet WHO made no mention of the links.

It comes as a report from the Council of Europe criticised the lack of transparency around the handling of the swine flu pandemic.

A spokesman for WHO said the drug industry did not influence its decisions on swine flu.

Guidelines recommending governments stockpile antiviral drugs were issued by WHO in 2004.

The advice prompted many countries around the world into buying up large stocks of Tamiflu, made by Roche, and Relenza manufactured by GlaxoSmithKline.

A year after the swine flu pandemic was declared, stocks are left unused in warehouses and governments are attempting to unpick contracts.

Conflict of interest

The BMJ, in a joint investigation with The Bureau of Investigative Journalism, found that three scientists involved in putting together the 2004 guidance had previously been paid by Roche or GSK for lecturing and consultancy work as well as being involved in research for the companies.

Analysis
Continue reading the main story
Fergus Walsh
Medical correspondent, BBC News
Be open. Be transparent. That seems to be the key learning point for the WHO from this joint investigation.

It is common practice for academic experts to work closely with the pharmaceutical industry, such as getting funding for drug trials, or to be paid for attending meetings.

On all clinical papers authors must publicly declare any competing interests.

So it is surely advisable that the WHO follows the same policy with its advisors.

And there is surely no logic in refusing to name the members of the emergency committee which advised the WHO about the pandemic.

To fail to do so presents an own goal to critics and conspiracy theorists.
Although the scientists involved had freely declared the links in other places and said WHO asked for conflicts of interest forms prior to expert meetings, the ties were not publically declared by WHO.

It is not clear whether these conflicts were notified privately by WHO to governments around the world, the BMJ said, and a request to see conflict of interest declarations was turned down.

In addition, membership of the "emergency committee" which advised WHO's director general Margaret Chan on declaring an influenza pandemic has been kept secret.

It means the names of the 16 committee members are known only to people within WHO, and as such their possible conflicts of interest with drug companies are unknown.

On its website, WHO says: "Potential conflicts of interest are inherent in any relationship between a normative and health development agency, like WHO, and a profit-driven industry.

"Similar considerations apply when experts advising the Organization have professional links with pharmaceutical companies.

"Numerous safeguards are in place to manage possible conflicts of interest or their perception."

AstraZeneca 'suppressed' drug test data

Seroquel brings in almost 10% of AstraZeneca's revenues

The marketing team sued over a drug's alleged side effects tried to suppress key data, an ex-employee has claimed.

Seroquel's former UK medical adviser told the BBC he was pressured to approve promotional material which said weight gain was not an issue.

Maker AstraZeneca, which faces fresh legal action next month, said it took concerns about its conduct seriously.

In the same programme, the British Medical Journal editor urged that the medicine licensing system be reviewed.

Dr Fiona Godlee said industry should no longer provide the evaluations of its own drugs which the licensing body considered.

'Job threat'

Thousands of patients are suing AstraZeneca in US courts, claiming the anti-psychotic drug Seroquel caused weight gain and diabetes.

The patients allege Seroquel, its second biggest selling drug worth $4.5bn (£2.7bn) a year, was marketed without adequate warning about possible side effects such as massive weight gain and the development of diabetes. However, this is denied by the company.

AstraZeneca, which is facing renewed legal action next month, said the company took concerns about its conduct seriously.

FROM FILE ON 4 More from File on 4

Seroquel was launched in 1997 for treating schizophrenia and later for bipolar disorder. Dr John Blenkinsopp, the company's former UK medical manager, claimed he was pressurised by the company's marketing arm to approve claims about the drug which he felt did not reflect the medical evidence.

"The clinical studies at the time of the launch of Seroquel showed patients developed significant weight gain, significant both statistically and clinically," he told the BBC's File on 4.

"They [the marketing team] came at me with a number of potential claims all of which were trying to intimate that Seroquel was not associated with weight gain - the data pointed in the opposite direction," added Dr Blenkinsopp who was speaking publicly for the first time since he left the company in 2000.

He said: "I understood where they were coming from. I had some robust discussions and exposed them to the data but that didn't seem to stop them because they were desperate for a differential advantage over one of the competitor products and they didn't have one.

"In the end I was put under quite a significant amount of pressure by the marketeers to sign off claims with regards to the lack of weight gain and I was unwilling to sign that off. The marketeers made it clear it could be career limiting for me," Dr Blenkinsopp added.

In the US the drug was marketed with claims that it would not cause weight gain. That was not done in the UK except for one advertisement, published in the British Journal of Psychiatry in April 2004.

Licensing reform

Astra Zeneca said it would not comment specifically in reference to its former employees, but said it took seriously any concerns regarding the firm's conduct and compliance procedures and it was currently reviewing issues raised by File on 4's investigation.

It said Seroquel was an important medicine and its safety and efficacy has been evaluated in clinical trials with thousands of patients

Dr Godlee, Editor of the British Medical Journal, told File on 4 that the system of developing and licensing drugs needed a major overhaul to give an independent evaluation of the effects of medications.

She said the pharmaceutical industry had grown enormously and delivered many good and effective drugs. But she warned that its power and influence needed to be controlled.

She has called for independent trials for all new drugs. At present, the regulator - the Medicines and Healthcare products Regulatory Authority - has to rely on research provided by the drug companies when it licences a medicine.

Dr Godlee said the regulator could sometimes be swamped by the amount of information it was given.

The MHRA says it has seen no evidence of this and maintains it carries out thorough and detailed reviews of any application.

File on 4 is on BBC Radio 4 on Tuesday, 26 January , at 2000 GMT, repeated Sunday, 31 January, at 1700 GMT. You can also listen via the BBC iPlayer after broadcast or download the

Pregnant women were prescribed the drug

Apology to thalidomide survivors

Mike O'Brien: "Government wishes to express sincere regret"

The government has expressed its "sincere regret" and "deep sympathy" to the victims of the thalidomide scandal.

Health minister Mike O'Brien made the apology in a statement to MPs - it comes after he unveiled a compensation package for survivors in December.

Pregnant women were prescribed the drug in the 1950s and 1960s as a treatment for morning sickness or insomnia.

It was withdrawn from sale in 1961 after babies were born with limb deformities and other damage.

Mr O'Brien said: "The government wishes to express its sincere regret and deep sympathy for the injury and suffering endured by all those affected.

THALIDOMIDE Developed in Germany in the 1950s Prescribed as a 'wonder drug' for insomnia, coughs, colds, morning sickness and headaches Link with birth defects shown in 1961 leading to the drug being taken off the market Affected babies commonly suffered missing or deformed limbs and severe shortening of arms or legs The drug also caused malformations of the eyes and ears, heart, genitals, kidneys and digestive tract Scientists believe the drug harmed the growth of new blood vessels in the developing embryo

"We acknowledge both the physical hardship and the emotional difficulties that have faced both the children affected and their families as a result of this drug, and the challenges that many continue to endure often on a daily basis."

His public statement follows the decision by the government to make more money available to the 466 thalidomide survivors in the UK.

The drug's UK manufacturer, Distillers Biochemicals, paid around £28m compensation in the 1970s following a legal battle by the families of those affected.

This has been subsequently topped up over the years by successor companies, although the average payout to the 466 survivors in the UK remains below £20,000 a year.

The government's £20m funding package is on top of this and will be shared out over the next three years.

It reflects the fact that survivors are living longer than expected and as a result will have increasing health needs.

Needed

The UK was the second biggest user of the drug after Germany. About 2,000 babies were born with problems linked to the drug with half of them dying within months of birth.

Another 5,000 were born elsewhere in the world.

Guy Tweedy, of the Thalidomide Trust, which distributes aid to survivors, described the apology as "absolutely wonderful".

www.richimag.co.uk/

Thalidomide campaigners' reaction to the decision

"I'm highly delighted and so glad that it actually came, 50 years too late but never mind.

"It's an apology not just to thalidomide victims but to the parents who lost their children in the early days."

Mr Tweedy added the apology "means as much in some ways as the money".

Nick Dobrik, a thalidomide victim and campaigner, added the apology was "very significant".

He said in particular it meant a lot to the parents of children who had died as it was a way of saying it was the "government's fault, not theirs".

Stephen O'Brien, the Conservative health spokesman, said: "I welcome the minister's remarks. Many thalidomiders have indeed waited a long time for this."

nhs profit themselves

Drug export warning to NHS trusts

Drugs are more expensive outside the UK

NHS hospital trusts in England have been warned against any attempt to cash in by exporting medicines intended for NHS patients.

The Health Service Journal reports some trusts have considered taking advantage of the weak pound to make a profit.

But the government's chief pharmaceutical offer Dr Keith Ridge has written to all NHS trusts, calling the practice irresponsible.

Dr Ridge warned it could threaten the quality of patient care.

It is shocking and disgraceful that some NHS managers are said to be considering plans to export medicine Norman Lamb Liberal Democrat health spokesman

He said it was particularly irresponsible to export pharmaceuticals at a time when the supply chain was threatened by the swine flu pandemic.

The low value of the pound means drugs could be bought in sterling, then sold on in countries where prices are higher.

This, combined with the Department of Health's pharmaceutical price regulation scheme, which keeps UK medicine prices low, has presented trusts in theory with a chance to make substantial financial gains.

Commenting on the report, a Department of Health spokesperson said: "Exporting medicines for short term financial gain is an unacceptable practice.

"We are confident that the vast majority of hospital pharmacists are behaving responsibly.

"However, Dr Ridge has written to all hospital pharmacists to underline that such practices are contrary to acceptable professional behaviour."

Naming and shaming

Norman Lamb, Liberal Democrat health spokesman, said pharmacists had been warning for some time that medicine shortages were having a negative impact on patient care.

He said: "It is shocking and disgraceful that some NHS managers are said to be considering plans to export medicine, rather than addressing this serious problem.

"With concerns about swine flu already putting the NHS under pressure, we must ensure that we do not run short of vital drugs in the UK.

"There is a strong case for naming and shaming those trusts involved and taking appropriate disciplinary action."

drug cancer link

Tamoxifen

Tamoxifen is given to most women with breast cancer

Long-term use of a common breast cancer drug may hike the risk of developing a deadly second tumour, a study suggests.

Tamoxifen, given to thousands of British women, prevents tumours being fuelled by the sex hormone oestrogen, and stops them returning after surgery.

But a US study links use of the drug to a four-fold raised risk of developing a more aggressive, difficult-to-treat tumour, not dependent on oestrogen.

However, women are strongly advised not to stop taking tamoxifen.

Women should be reassured that the benefits of taking hormone-blocking drugs, such as tamoxifen, after their first diagnosis of breast cancer far outweigh any potential risks Dr Alison Ross Cancer Research UK

Experts stress any risks of taking the drug are far outweighed by the benefits.

They said the odds of developing a second, non-hormone sensitive tumour remained very low.

Each year around 45,500 women in the UK are diagnosed with breast cancer and 12,000 die from the disease.

Around two thirds of breast cancers are sensitive to the hormone oestrogen.

Tamoxifen become the "gold standard" treatment for these hormone-sensitive tumours, although in recent years newer drugs have started to be preferred.

The latest study, by the Fred Hutchinson Cancer Research Center in Seattle, looked at long-term use of the drug among more than 1,000 women.

The researchers, writing in the journal Cancer Research, found that tamoxifen reduced the chances of oestrogen-positive breast cancer returning by 60%.

But they also found that five or more years of treatment was associated with a 440% increase in the chance of an aggressive, non-hormone sensitive tumour appearing in the opposite breast.

These tumours can be particularly difficult to treat.

Many women in the UK cease tamoxifen treatment after five years to avoid side effects, but several thousand woman have been on the drug for a longer time.

Risks and benefits

Lead researcher Dr Christopher Li said: "It is clear that oestrogen-blocking drugs like tamoxifen have important clinical benefits and have led to major improvements in breast cancer survival rates.

"However, these therapies have risks, and an increased risk of ER negative (oestrogen receptor negative) second cancer may be one of them.

"Still, the benefits of this therapy are well established and doctors should continue to recommend hormonal therapy for breast cancer patients who can benefit from it."

Professor Jack Cuzick, head of Cancer Research UK's Centre for Epidemiology, Mathematics and Statistics at Queen Mary, University of London, stressed that tamoxifen had a proven track record.

He said: "There is overwhelming evidence that tamoxifen, and newer more effective hormone blocking treatments, prevent far more recurrences, new breast cancers and cancer-related deaths than they might stimulate."

Professor Cuzick said some of the non-hormone sensitive tumours recorded in the study may have started out as hormone-sensitive, but had been kept at bay by tamoxifen treatment.

Dr Alison Ross, senior science information officer at Cancer Research UK, said: "Women should be reassured that, based on extensive scientific evidence, the benefits of taking hormone-blocking drugs, such as tamoxifen, after their first diagnosis of breast cancer far outweigh any potential risks.

"More research will be needed to confirm the possible link between its long-term use and the relatively rare occurrence of an aggressive form of the disease in the other breast."

Go natural

Older people on 'drugs cocktail'

People were taking a combination of presrciption, OTC and herbal drugs

Nearly half of over 65s are taking five or more drugs, and without regular reviews this may be both dangerous and costly to the NHS, pharmacists say.

The Royal Pharmaceutical Society (RPSGB) says not only are lots of older people taking a "cocktail" of drugs, many are not taking them as prescribed.

Over 60% of 500 polled believed they may be suffering side-effects from the drugs, but many did not tell a doctor.

Older people account for about half of the NHS's £4bn drug bill.

Many of these drugs are on repeat prescriptions, the society notes, and could have been prescribed for conditions the patient no longer has.

GPs are excellent at prescribing, but they are not always so good at knowing when to stop, and they may not always have the time to conduct a through review. Jonathan Silcock University of Leeds

The RPSGB polled 457 people aged 65 and above on their medications - which included prescriptions, drugs bought over the counter and herbal medications.

The society is urging all older people to request a medication review from their pharmacist. Regular monitoring of drugs regimens was a recommendation of the 2001 national service framework for older people, with the aim of maximising the benefits and minimising harm.

According to the RPSGB research one in five are not taking medications as prescribed, and one in seven do not take their pills at the recommended time.

Mixed reactions

The medication of older people has long been an area of concern: the combination of ageing bodies less able to cope with drugs, treatment by multiple doctors for multiple conditions, and known problems in adhering to the instructions, all raise the risk of adverse reactions.

Statistics show that the over-65s are three times more likely to be admitted to hospital because of such reactions, which can lead to falls, delirium and gastrointestinal bleeds among others.

This is something that all primary care health professionals need to engage with Dr Finbarr Martin Consultant in geriatric medicine

As many as 17% of hospital admission are due to these adverse reactions, and it is estimated that over three-quarters of these "are predictable and preventable", the RPSGB says.

Jonathan Silcock, lecturer in pharmacy at the University of Leeds, said research painted a mixed picture as to the effectiveness of regular reviews by pharmacists in reducing hospital admissions, but a well-trained professional could potentially pick up problems.

"Inevitably people do get put on more drugs when they get older because they suffer from more chronic conditions - this is often the right thing to do, but the problem is we don't necessarily know how these drugs are going to work in combination.

"GPs are excellent at prescribing, but they are not always so good at knowing when to stop, and they may not always have the time to conduct a through review. That's where the well-trained pharmacist could have a key role."

Dr Finbarr Martin, consultant in general and geriatric medicine at Guy's & St Thomas' NHS Foundation Trust, said while pharmacists had an important role, "this is something that all primary care health professionals need to engage with.

"Some older people will be fine on a variety of medications - some will not - and there's not been enough research. We have to really look into constructing a model that makes sure the needs of the frail at the primary care level are met and regularly reviewed - involving GPs, pharmacists and community matrons."

Michelle Mitchell, charity director for Age Concern and Help the Aged said: "When people are buying over-the-counter medicines it is vital they inform the pharmacist of any other prescription drugs and medicines they are taking.

"Getting the correct advice and reassurance could very well be the best medicine of all."

co-proxamol

Painkiller ban 'has cut suicides'

Co-proxamol is linked to fatal overdoses

The controversial withdrawal of a common painkiller has dramatically cut suicides, say researchers.

A gradual phase-out of co-proxamol led to 350 fewer suicides and accidental deaths in England and Wales, a study in the British Medical Journal reports.
Regulators removed the drug's licence in 2007 after fears about the risk of overdose but the move proved unpopular with some patients and doctors.
Arthritis Care says some patients now struggle to control their pain.
The Medicines and Healthcare Products Regulatory Agency announced the withdrawal in 2005.

There is no robust evidence that co-proxamol offers any advantage over paracetamol or ibuprofen at normal doses MHRA spokesman

GPs were encouraged to move patients to other painkillers before the drug's licence was revoked in 2007.
After that time doctors could prescribe the drug on a "named patient basis" for those who could not manage their pain with alternatives but as it is unlicensed they did so at their own risk.
Study leader Professor Keith Hawton, director of the Centre for Suicide Research at Oxford University, said before the restrictions co-proxamol was responsible for a fifth of all drug-related suicides.
By the 2007 deadline, prescribing of the drug had fallen by 59%, his analysis showed.
Over the two-year period, deaths from co-proxamol fell by 62%.
Specifically there were 295 fewer suicides and 349 fewer deaths from the drug including accidental overdoses.
The research also showed that had been no increase in deaths from other painkillers, despite large increases in their use.
Initiative 'effective'
Professor Hawton said authorities in the US were now considering withdrawing co-proxamol, which is a mixture of paracetamol and an opioid drug.
"This marked reduction in suicides and accidental poisonings involving co-proxamol during this period, with no evidence of an increase in deaths involving other analgesics, suggests the initiative has been effective," he added.
In 2008, there were 380,831 prescription items for co-proxamol, showing some GPs are still prescribing the drug.
A spokesman for the Medicines and Healthcare Products Regulatory Agency (MHRA) said prior to its withdrawal co-proxamol was involved in 300-400 self-poisoning deaths each year, of which around a fifth were accidental.
"Co-proxamol is extremely dangerous in overdose - only a small overdose can be fatal, and death can occur very rapidly - before medical attention can be sought."
He added: "There is no robust evidence that co-proxamol offers any advantage over paracetamol or ibuprofen at normal doses."
But Federico Moscogiuri, head of policy and campaigns at Arthritis Care, said many people who used to be prescribed co-proxamol were now struggling to control their pain.
A survey done last year by the charity found most people could no longer get prescriptions of the drug from their GPs and many said they had not found an effective alternative.
"For them, co-proxamol makes the difference between being able to perform simple everyday activities and living in chronic, debilitating pain.
"This is an intolerable situation for a society committed to high quality care for all.
"If the named patient system is to work, GPs should feel supported in prescribing co-proxamol for patients who really need it."