After Avandia: Does the FDA Have a Drug Problem?

Thursday, Aug. 12, 2010

HRR: How a drug company intentionally kills thousands for profit and no one goes to jail.

– the agency decided to keep the drug on the market — a move worth billions of dollars to GSK but that also may have put millions of patients at risk.

– The FDA relies on industry “user fees” for 65% of its budget for postmarket monitoring of the drugs it approves

GlaxoSmithKline: Where Billions in Fines Don't...
 (Photo credit: watchingfrogsboil)

FDA had inspected only 1% of clinical-trial sites from 2000 to 2005 and lacked financial disclosure data for clinical investigators in half of all industry drug reviews.

– The company didn’t want to do a long-term safety test at all

– the FDA and the drugmaker negotiate which tests the company will perform once large numbers of people are taking it on the open market. Continue reading “After Avandia: Does the FDA Have a Drug Problem?”

WHO and the pandemic flu “conspiracies” – The BMJ and the Bureau of Investigative Journalism report that was covered up

Conflicts of Interest

A joint investigation by the BMJ and the Bureau of Investigative Journalism has uncovered evidence that raises troubling questions about how WHO managed conflicts of interest among the scientists who advised its pandemic planning

The secrecy of the committee is also fuelling conspiracy theories, particularly around the activation of dormant pandemic vaccine contracts. A key question will be whether the pharmaceutical companies, which had invested around $4bn (£2.8bn, 3.3bn) in developing the swine flu vaccine, had supporters inside the emergency committee

The original advisory opinion was requested by...

– Was it appropriate for WHO to take advice from experts who had declarable financial and research ties with pharmaceutical companies producing antivirals and influenza vaccines?

– Why was key WHO guidance authored by an influenza expert who had received payment for other work from Roche, manufacturers of oseltamivir, and GlaxoSmithKline, manufacturers of zanamivir?

– Why does the composition of the emergency committee from which Chan sought guidance remain a secret known only to those within WHO?

–  Our investigation has identified key scientists involved in WHO pandemic planning who had declarable interests, some of whom are or have been funded by pharmaceutical firms that stood to gain from the guidance they were drafting

– FDA’s advisory committee voted by 13 to 4 not to approve zanamivir on the grounds that it was no more effective than placebo when the patients were on other drugs such as paracetamol. He said that it didn’t reduce symptoms even by a day.

– conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.”

– the advisory committee decided not to recommend zanamivir, the FDA’s management reassigned the oseltamivir review to someone else. Dr Elashoff believes that the approval of zanamivir paved the way for oseltamivir, which was approved by the FDA later that year.

– “WHO never publishes individual DOIs [declaration of interest], except after consultation with the Office of the Director-General.

Deborah Cohen, features editor, BMJ, Philip Carter, journalist, The Bureau of Investigative Journalism, London

dcohen@bmj.com

Key scientists advising the World Health Organization on planning for an influenza pandemic had done paid work for pharmaceutical firms that stood to gain from the guidance they were preparing. These conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.” Deborah Cohen and Philip Carter investigate

Next week marks the first anniversary of the official declaration of the influenza A/H1N1 pandemic. On 11 June 2009 Dr Margaret Chan, the director general of the World Health Organization, announced to the world’s media: “I have conferred with leading influenza experts, virologists, and public health officials. In line with procedures set out in the International Health Regulations, I have sought guidance and advice from an Emergency Committee established for this purpose. On the basis of available evidence, and these expert assessments of the evidence, the scientific criteria for an influenza pandemic have been met…The world is now at the start of the 2009 influenza pandemic.” Continue reading “WHO and the pandemic flu “conspiracies” – The BMJ and the Bureau of Investigative Journalism report that was covered up”

Are you Big Pharma’s new target market?

 

Taking a cue from Apple and Coca-Cola, pharmaceutical firms are humanizing their brands

Happy Smiley Face from Urine Samples

 

 

 

Version française

Montreal, February 4, 2014 — By 2018, it is estimated that the global pharmaceutical market will be worth more than $1.3 trillion USD. To corner their share of profits, established drug companies have to fight fierce competition from generic products, adhere to stringent government regulations and sway a consumer base that is better informed than ever before. Continue reading “Are you Big Pharma’s new target market?”

Video Health Research Report 27 JAN 2014

Topics:
Mouthwash is a Disaster for health Raises Blood Pressure and Stroke Risk
* Journal of Free Radical Biology and Medicine JAN 2014
Fever Reducing Medications increase virus activity/load and transmission
* Proceedings of Royal Society B Today JAN 2014
Medical Treatments now 3rd leading cause of death in developed nations
* New Scientist Jan 2014

The Psychiatric Drug Crisis / 20% of Americans now regularly take mind-altering drugs prescribed by their doctors

 

greenberg-magic-bullets-580.jpeg

 

It’s been just over twenty-five years since Prozac came to market, and more  than twenty per cent of Americans now regularly take mind-altering drugs  prescribed by their doctors. Almost as familiar as brands like Zoloft and  Lexapro is the worry about what it means that the daily routine in many  households, for parents and children alike, includes a dose of medications that  are poorly understood and whose long-term effects on the body are unknown.  Despite our ambivalence, sales of psychiatric drugs amounted to more than seventy  billion dollars in 2010. They have become yet another commodity that consumers  have learned to live with or even enjoy, like S.U.V.s or Cheetos.

Yet the psychiatric-drug industry is in trouble. “We are facing a crisis,”  the Cornell psychiatrist and New York Times contributor Richard Friedman  warned last week. In the past few years, one pharmaceutical  giant after another—GlaxoSmithKline, AstraZeneca, Novartis, Pfizer, Merck,  Sanofi—has shrunk or shuttered its neuroscience research facilities. Clinical  trials have been halted, lines of research abandoned, and the new drug pipeline  has been allowed to run dry.

Why would an industry beat a hasty retreat from a market that continues to  boom? (Recent surveys indicate that mental illness is the leading  cause of impairment and disability worldwide.) The answer lies in the history of  psychopharmacology, which is more deeply indebted to serendipity than most  branches of medicine—in particular, to a remarkable series of accidental  discoveries made in the fifteen or so years following the end of the Second  World War.

In 1949, John Cade published an article in the Medical Journal of Australia describing his discovery that lithium sedated people who experienced mania. Cade  had been testing his theory that manic people were suffering from an excess of  uric acid by injecting patients’ urine into guinea pigs, who subsequently died.  When Cade diluted the uric acid by adding lithium, the guinea pigs fared better;  when he injected them with lithium alone, they became sedated. He noticed the  same effect when he tested lithium on himself, and then on his patients. Nearly  twenty years after he first recommended lithium to treat manic depression, it  became the standard treatment for the disorder.

In the nineteen-forties and fifties, schizophrenic patients in some asylums  were treated with cold-induced “hibernation”—a state from which they often  emerged lucid and calm. In one French hospital, the protocol also called for  chlorpromazine, a new drug thought to increase the hibernation effect. One day,  some nurses ran out of ice and administered the drug on its own. When it calmed  the patients, chlorpromazine, later named Thorazine, was recognized in 1952 as the first drug treatment for  schizophrenia—a development that encouraged doctors to believe that they could  use drugs to manage patients outside the asylum, and thus shutter their  institutions.

In 1956, the Swiss firm Geigy wanted in on the antipsychotics market, and it  asked a researcher and asylum doctor, Roland Kuhn, to test out a drug that, like  Thorazine, was an antihistamine—and thus was expected to have a sedating effect.  The results were not what Kuhn desired: when the schizophrenic patients took the  drug, imipramine, they became more agitated, and one of them, according to a  member of the research team, “rode, in his nightshirt, to a nearby village,  singing lustily.” He added, “This was not really a very good PR exercise for the  hospital.” But it was the inspiration for Kuhn and his team to reason that “if  the flat mood of schizophrenia could be lifted by the drug, then could not a  depressed mood be elevated also?” Under the brand name Tofranil, imipramine went  on to become the first antidepressant—and one of the first blockbuster  psychiatric drugs.

American researchers were also interested in antihistamines. In 1957, Leo  Sternbach, a chemist for Hoffmann-La Roche who had spent his career researching  them, was about to throw away the last of a series of compounds he had been  testing that had proven to be pharmacologically inert. But in the interest of  completeness, he was convinced to test the last sample. “We thought the expected  negative pharmacological results would cap our work on this series of  compounds,” one of his colleagues later recounted. But the drug turned out to  have muscle-relaxing and sedative properties. Instead of becoming the last in a  list of failures, it became the first in a series of spectacular successes—the  benzodiazepenes, of which Sternbach’s Librium and Valium were the flagships.

By 1960, the major classes of psychiatric drugs—among them, mood stabilizers,  antipsychotics, antidepressants, and anti-anxiety drugs, known as  anxiolytics—had been discovered and were on their way to becoming a  seventy-billion-dollar market. Having been discovered by accident, however, they  lacked one important element: a theory that accounted for why they worked (or,  in many cases, did not).

That didn’t stop drug makers and doctors from claiming that they knew.  Drawing on another mostly serendipitous discovery of the fifties—that the brain  did not conduct its business by sending sparks from neuron to neuron, as  scientists previously thought, but rather by sending chemical messengers across  synapses—they fashioned an explanation: mental illness was the result of  imbalances among these neurotransmitters, which the drugs treated in the same  way that insulin treats diabetes.

The appeal of this account is obvious: it combines ancient notions of illness  (specifically, the idea that sickness resulted from imbalanced humors) with the  modern understanding of the molecular culprits that make us suffer—germs. It  held out the hope that mental illness could be treated in the same way as  pneumonia or hypertension: with a single pill. Drug companies wasted no time in  promulgating it. Merck, the manufacturer of Elavil, commissioned the  psychiatrist Frank Ayd to write a book called Recognizing the Depressed  Patient, in which he extolled the “chemical revolution in psychiatry” and  urged doctors to reassure patients they weren’t losing their minds, but rather  suffering a “common illness” with a “physical basis” and a pharmacological cure.  Merck sent Ayd’s book to fifty thousand doctors around the country. In 1965,  Joseph Schildkraut, a psychiatrist at the National Institute of Mental Health,  reverse-engineered antidepressants and offered an actual theory: at least when  it came to depression, the imbalances were to be found in the neurotransmitters  he thought were affected by the drugs, dopamine and norepinephrine. Seven years  after antidepressants were invented, and five years after Ayd asserted that  depression was a chemical problem, psychiatrists finally had a precise,  scientific explanation for why they worked. The paper quickly became one of the  most cited articles in the medical literature.

But Schildkraut was wrong. Within a few years, as technology expanded our  ability to peer into the brain, it became clear that antidepressants act mostly  by increasing the availability of the neurotransmitter serotonin—rather than  dopamine and norepinephrine, as previously thought. A new generation of  antidepressants—the selective serotonin reuptake inhibitors (S.S.R.I.s),  including Prozac, Zoloft, and Paxil—was developed to target it. The ability to  claim that the drugs targeted a specific chemical imbalance was a marketing boon  as well, assuring consumers that the drugs had a scientific basis. By the  mid-nineties, antidepressants were the best-selling class of prescription  medications in the country. Psychiatry appeared to have found magic bullets of  its own.

The serotonin-imbalance theory, however, has turned out to be just as  inaccurate as Schildkraut’s. While S.S.R.I.s surely alter serotonin metabolism,  those changes do not explain why the drugs work, nor do they explain why they  have proven to be no more effective than placebos in clinical trials. Within  a decade of Prozac’s approval by the F.D.A. in 1987, scientists had concluded  that serotonin was only a finger pointing at one’s mood—that the causes of  depression and the effects of the drugs were far more complex than the  chemical-imbalance theory implied. The ensuing research has mostly yielded more  evidence that the brain, which has more neurons than the Milky Way has stars and  is perhaps one of the most complex objects in the universe, is an elusive target  for drugs.

Despite their continued failure to understand how psychiatric drugs work,  doctors continue to tell patients that their troubles are the result of chemical  imbalances in their brains. As Frank Ayd pointed out, this explanation helps  reassure patients even as it encourages them to take their medicine, and it fits  in perfectly with our expectation that doctors will seek out and destroy the  chemical villains responsible for all of our suffering, both physical and  mental. The theory may not work as science, but it is a devastatingly effective  myth.

Whether or not truthiness, as one might call it, is good medicine remains to  be seen. No one knows how important placebo effects are to successful treatment,  or how exactly to implement them, a topic Michael Specter wrote about in the  magazine in 2011. But the dry pipeline of new drugs bemoaned by Friedman is an  indication that the drug industry has begun to lose faith in the myth it did so  much to create. As Steven Hyman, the former head of the National Institute of  Mental Health, wrote  last year, the notion that “disease mechanisms could … be inferred from drug  action” has succeeded mostly in “capturing the imagination of researchers” and  has become “something of a scientific curse.” Bedazzled by the prospect of  unraveling the mysteries of psychic suffering, researchers have spent recent  decades on a fool’s errand—chasing down chemical imbalances that don’t exist.  And the result, as Friedman put it, is that “it is hard to think of a single  truly novel psychotropic drug that has emerged in the last thirty years.”

Despite the BRAIN initiative recently announced by the  Obama Administration, and the N.I.M.H.’s renewed efforts to stimulate research  on the neurocircuitry of mental disorder, there is nothing on the horizon with  which to replace the old story. Without a new explanatory framework,  drug-company scientists don’t even know where to begin, so it makes no sense for  the industry to stay in the psychiatric-drug business. And if loyalists like  Hyman and Friedman continue to say out loud what they have been saying to each  other for many years—that, as Friedman told Times readers, “just because  an S.S.R.I. antidepressant increases serotonin in the brain and improves mood,  that does not mean that serotonin deficiency is the cause of the disease”—then  consumers might also lose faith in the myth of the chemical imbalance.

Gary  Greenberg is a practicing psychotherapist and the author of “The Book of Woe: The DSM and the Unmaking of Psychiatry.” 

Correction: Due to an editing error, the antidepressant Tofranil was  originally identified as Elavil.

Photograph by Paul Skelcher/Science  Faction/Corbis.

Read more: http://www.newyorker.com/online/blogs/elements/2013/09/psychiatry-prozac-ssri-mental-health-theory-discredited.html?printable=true&currentPage=all#ixzz2dzOplPbu

GSK China bribery co-ordinated at company level, says Xinhua

GSK investigation shows alleged bribery of doctors in China co-ordinated by British company, says Xinhua

Tuesday, 03 September, 2013, 4:45pm

Reuters in Shanghai

  • china_gsk.jpg
GSK has said some of its senior Chinese executives appear to have broken the law, and that it has zero tolerance for bribery. Photo: Reuters

A Chinese police investigation into drug maker GlaxoSmithKline has discovered that alleged bribery of doctors in China was co-ordinated by the British company and was not the work of individual employees, state media reported on Tuesday.

Police in July detained four senior Chinese executives at GSK over allegations the company funnelled up to 3 billion yuan (HK$3.8 billion) to travel agencies to facilitate bribes to doctors and officials to boost the sale of its medicines.

“It is becoming clear that it is organised by GSK China rather than … sales people’s individual behaviour,” the official Xinhua news agency reported.

GSK officials could not be reached for comment.

When the problems were exposed, the company pushed all responsibilities to individual employees
Guo Jianhua, GSK China

The company has said some of its senior Chinese executives appear to have broken the law, and that it has zero tolerance for bribery.

The GSK investigation is one of several into China’s pharmaceutical sector. Others have focused on how drug makers price their medicines in the world’s second-largest economy.

Xinhua quoted Huang Hong, general manager for GSK’s business operations in China and one of the detained executives, as saying the company had set goals for annual sales growth as high as 25 per cent. That rate was 7 to 8 percentage points above the average growth rate for the industry, Huang said.

GSK implemented salary policies based on sales volumes and such goals could not be achieved without “dubious corporate behaviour”, Huang said.

Official media routinely get access to detainees in China. Other detained GSK executives have been interviewed on state TV.

China accounts for just 3.5 per cent of GSK’s global drug sales but demand is growing fast – up 17 per cent last year – and the company is investing heavily, with more than 7,000 staff in China, as well as five factories and a research centre.

Guo Jianhua, head of recruitment at GSK China, was quoted by the official People’s Daily newspaper as saying the company had turned a blind eye to illegal behaviour.

“When the problems were exposed, the company pushed all responsibilities to individual employees,” Guo said.

It was unclear which problems Guo was referring to or if he was one of the detained executives.

Corruption in China’s pharmaceutical industry is widespread, fuelled in part by low base salaries for doctors at the country’s 13,500 public hospitals.

Industry executives say ties to doctors at hospitals are key to sales, with pharmaceutical companies as well as medical device makers often sponsoring research conferences to win their favour.

The People’s Daily quoted Huang as saying GSK had set up a special team dedicated to maintaining relationships with key hospital officials, with an annual budget of nearly 10 million yuan.

Since the GSK scandal broke whistleblowers from other foreign drug makers have come forward to make accusations of bribery against their companies in China.

http://www.scmp.com/news/china/article/1302583/gsk-china-bribery-co-ordinated-company-level-says-xinhua

 

Eli Lilly ‘concerned’ by China bribery allegations

23   Aug   2013
SHANGHAI (AFP)

US drugmaker Eli Lilly said it was “deeply concerned” about allegations it bribed Chinese doctors to prescribe its products, the latest accusations of malpractice by foreign firms in the country.

A former Eli Lilly sales manager claimed the firm paid at least 30 million yuan ($4.9 million) in kickbacks to doctors for promoting two insulin drugs in Shanghai and neighbouring Anhui province, the 21st Century Business Herald reported Thursday.

The whistleblower, using a pseudonym, said bribery was a “very common” practice at the company, which also offered doctors payments through speeches and conferences, the paper said.

“We are deeply concerned about the allegations made against Lilly China,” the drugmaker said in an emailed statement late Thursday.

It admitted being aware of similar allegations last year and had conducted an “exhaustive” investigation through employee interviews, email monitoring and expense report audits.

“Although we have not been able to verify these allegations, we take them seriously, and we are continuing our investigation,” the statement said.

Eli Lilly is the third foreign drug firm embroiled in corruption scandals in China, after similar accusations against Britain’s GlaxoSmithKline (GSK) and France’s Sanofi emerged over the past two months.

Authorities have detained four Chinese GSK executives and formally arrested a foreign husband-and-wife team of fraud investigators whose firm did work for GSK, after allegations that GSK employees used nearly $500 million in bribes to boost sales.

Chinese regulators have opened an investigation into Sanofi, state media reported earlier this month.

It is common practice in China for pharmaceutical firms to offer doctors and hospitals bribes to have their products used, industry insiders say.

 

http://www.afp.com/en/news/topstories/eli-lilly-concerned-china-bribery-allegations

Chinese police allege Glaxo sales reps trained to offer sexual bribes

Chinese police have released new details of GlaxoSmithKline’s alleged crimes in China, claiming that sales representatives were given “clear directives” to offer bribes to doctors and were trained to cater “to their pleasures.”

Chinese police allege GSK sales agents offered sexual bribes

Xinhua reported that a woman, named as Ms Wang, said she would even go so far as fulfilling some doctors’ “sexual desires” in order to “meet their needs” and persuade them to prescribe more drugs. Photo: Reuters

By Tom Philips, in Shanghai

1:01PM BST 26 Jul 2013

GSK sales reps “established good personal relations with doctors by catering to their pleasures or offering them money, in order to make them prescribe more drugs,” China’s official news wire Xinhua reported on Friday.

Citing police investigations, Xinhua quoted a 35-year-old female “medical representative” who reportedly worked for a GSK regional sales manager named only as Mr Li.

The woman, named as Ms Wang, said “some executives gave clear directives to the sales department to offer bribes to doctors with money or opportunities to attend academic conferences.”

Ms Wang said she would even go so far as fulfilling some doctors’ “sexual desires” in order to “meet their needs” and persuade them to prescribe more drugs.

A doctor from a “reputable hospital” whose real name was not given, claimed that one GSK representative had “blatantly offered kickbacks to doctors”.

“For example, 20 yuan [£2.11] for each pack of Seretide, an asthma-treating inhaler; and 10 yuan [£1.05] for each dose of Flixotide, an asthma-treating spray.”

If a doctor appeared reluctant to accept cash, GSK “salespeople” would offer them “gifts, free travel after meetings and lecture fees.”

“In fact, many doctors received lecture fees even when the lectures did not exist,” Xinhua reported.

The state-run news agency claimed that a cut of between seven and ten percent of prescribed drugs went directly into “doctors’ personal accounts”.

A spokeman for GSK said: “As we have previously said, we are deeply concerned by allegations of fraudulent behaviour and ethical misconduct by individuals in our China business

“We have zero tolerance for any kind of corrupt behaviour amongst our employees, suppliers and business partners and will take action wherever and whenever we find it

“This behaviour is a clear breach of GSK’s systems, governance, values and standards

“We will continue to cooperate fully with the Chinese authorities in their investigation and take any and every action that is required.”

On Wednesday, the company’s chief executive, Sir Andrew Witty, conceded that “senior figures” in GSK’s China business might have been engaged in “inappropriate and illegal” behavior. Sir Andrew described the allegations as “shameful”.

The scandal erupted in early July when police officials said that during a six-month investigation they had turned up evidence that GlaxoSmithKline had behaved like a criminal “godfather”.

The company had used hundreds of middlemen to channel money to doctors and health workers in order to convince them to prescribe their drugs, it was claimed.

Chinese police alleged that GSK had used travel agents to distribute as much as £323m in kickbacks, bribing “without restraint government officials, drug associations, medical foundations, hospitals and doctors.”

The British director of GSK’s operations in China, Mark Reilly, left China on July 5 and has now been replaced by Herve Gisserot, who previously headed its pharmaceutical operations in Europe. Four Chinese GSK executives have been detained.

http://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/10204304/Chinese-police-allege-Glaxo-sales-reps-trained-to-offer-sexual-bribes.html

 

GlaxoSmithKline finance head banned from leaving China

The BBC’s Martin Patience in Beijing: “Business leaders say foreign companies operating in China have never faced a tougher time”

Chinese authorities looking into alleged bribery by GlaxoSmithKline have banned the UK drugmaker’s British head of finance from leaving China.

The travel ban was imposed on Steve Nechelput at the end of June, said a company spokesperson.

On Monday, police in China said GSK had transferred 3bn yuan ($489m; £321m) to travel agencies and consultancies to facilitate bribes to doctors.

GSK has said it is deeply “concerned and disappointed” by the allegations.

The company said Mr Nechelput had not been questioned, arrested or detained by police.

The BBC understands that the British embassy in Beijing is providing consular assistance.

‘Abide by law’

Chinese authorities have taken into custody four Chinese executives at GSK in connection with the allegations.

They accuse GSK of using travel agencies to bribe government officials, doctors and hospitals in order to boost sales and prices of their drugs. The investigation began at the end of June, police said.

One of the four executives, vice-president and operations manager Liang Hong, appeared on state television on 16 July and said he had funnelled money through travel agencies for arranged conferences, some of which were never held.

Martin Patience, BBC’s correspondent in Beijing, said the reputation of the drugs giant has taken a huge hit in China where it has been widely condemned in the state media

An article on the China Daily website said: “This case should serve as a warning to other Chinese companies and their transnational counterparts that they must abide by the law when promoting their products”.

GSK’s general manager for China, Mark Reilly, is said to have left the country for Britain last month.

On Monday, Gao Feng, head of the economic crimes investigation unit, said similar transfers had been made by other pharmaceutical multinationals. He did not name any other foreign companies.

GSK has said it is taking immediate action, including terminating links with the travel agencies that the Chinese authorities have identified, and conducting a review of its transactions related to the travel agencies.

http://www.bbc.co.uk/news/business-23352844

 

Glaxo used travel agencies for China bribes – police / Over $489 million

Source: Reuters – Mon, 15 Jul 2013 12:39 PM

Author: Reuters

A Chinese national flag is seen in front of a GlaxoSmithKline office building in Shanghai, July 12, 2013 REUTERS/Aly Song

 

* GSK used travel agencies to funnel bribes – Chinese police

* Four senior Chinese executives from GSK detained – police

* Police say examining $490 million in transfers

* Similar practices found at other foreign drug firms

* GSK says very concerned, stops use of travel agencies

By Michael Martina

BEIJING, July 15 (Reuters) – Chinese police on Monday accused British drugmaker GlaxoSmithKline of channelling bribes to Chinese officials and doctors through travel agencies to boost sales illegally and raise the price of its medicines in the country.

The charges make the GSK case the highest profile corporate investigation in China since four executives from mining giant Rio Tinto Plc were jailed in March 2010 for taking bribes and stealing commercial secrets.

Gao Feng, head of the economic crimes investigation unit at China’s Ministry of Public Security, said since 2007, GSK had transferred as much as 3 billion yuan ($489 million) to more than 700 travel agencies and consultancies over six years.

Four senior Chinese executives from GlaxoSmithKline had been detained, Gao said at a news conference. The Ministry of Public Security had said last week that GSK executives in China had confessed to bribery and tax violations.

GSK said it was deeply concerned by the developments and had stopped using the travel agencies identified by the investigation. It said it was reviewing all third party agencies and all historic transactions related to the travel agencies.

“GSK shares the desire of the Chinese authorities to root out corruption,” it said in a brief statement. “These allegations are shameful and we regret this has occurred.”

GSK supplies key products such as vaccines in China, as well as drugs for lung disease and cancer.

The probe into Britain’s biggest drugmaker is one of a string of investigations into foreign firms and their pricing practices in the world’s second-biggest economy.

The official People’s Daily newspaper said GSK collaborated with travel agencies to funnel bribes to doctors and officials by creating fake “conference services” as expenditure for GSK to misappropriate funds, some of which would be spent on bribes.

“We have sufficient reason to suspect that these transfers were conducted illegally,” Gao said at the ministry’s headquarters in Beijing.

“You could say the travel agencies and GSK were criminal partners. Among the partners, GSK was mainly responsible. In a criminal organisation there is always a leader.”

Gao gave no examples of how the bribery involving the GSK executives worked. He said there were also instances of “sexual bribery”, although he did not elaborate.

He said police had uncovered information that pointed to similar money transfers made by other multinational pharmaceutical companies in China.

“Whether they were engaged in illegal behaviour, you can go interview them … You just need to ask them one question: Are you sleeping well at night?” Gao said.

He did not name any other foreign companies.

 

KEY MARKET

China has targeted foreign firms on multiple fronts in the past few months, including alleged price-fixing, quality controls and consumer rights, forcing companies to defend their reputations in a country where international brands often have a valuable edge over local competitors in terms of public trust.

European food groups Nestle and Danone recently said they would cut the price of infant milk formula in China after Beijing launched an investigation into the industry.

China is increasingly important for international drugmakers, which rely on growth in emerging markets to offset slower sales in Western markets where many former top-selling medicines have lost patent protection.

IMS Health, which tracks pharmaceutical industry trends, expects China to overtake Japan as the world’s second-biggest drugs market behind the United States by 2016.

China accounts for around 3.5 percent of GSK’s overall pharmaceuticals sales. Its shares in London were up 0.3 percent in morning trade, after rising nearly 5 percent since July 1, when Xinhua first reported the police investigation.

The detained GSK executives include Liang Hong, vice president and operations manager of GSK (China) Investment Co Ltd and Zhang Guowei, the company’s vice president and human resources director, the official Xinhua news agency reported.

It was not immediately clear if the executives had legal representation.

Xinhua said it was given access to one detained travel agent who said he did business with Liang. The agent said he sometimes arranged money for bribes and delivered it to the recipient. The agent also paid kickbacks to Liang, Xinhua reported.

Xinhua, given access to Liang by the authorities, quoted the detained executive as saying medicine which cost 30 yuan to make could be sold to patients for 300 yuan. It did not specifically say Liang was referring to GSK drugs.

The police last Thursday said the case against GSK involved many staff, with bribes offered to Chinese government officials, medical associations, hospitals and doctors.

Under China’s legal system, formal charges would only be announced after preliminary investigations are completed.

“The police would not usually reveal the details of cases they are handling,” said Yang Zhaodong, partner at Chinese law firm King & Capital, who declined to comment on the GSK case. “If they are already revealing such information, it means that they feel they have a fairly complete set of evidence.”

Police said they had taken no action against any British nationals in the GSK case. No information had been received from GSK’s UK headquarters, they said

China says GlaxoSmithKline execs confess to bribery and tax crimes

Source: Reuters – Thu, 11 Jul 2013 04:32 PM

Author: Reuters

* Biggest graft case involving foreign firm for years

* GSK says it is cooperating fully with authorities

* Lawyer says too early to say what punishment might be

By Michael Martina and Adam Jourdan

BEIJING/LONDON, July 11 (Reuters) – GlaxoSmithKline executives in China have confessed to bribery and tax violations, the country’s security ministry said on Thursday, during one of a string of investigations into foreign firms in the world’s second-biggest economy.

The ministry said the case against Britain’s biggest drugmaker involved a large number of staff and a huge sum of money over an extended period of time, with bribes offered to Chinese government officials, medical associations, hospitals and doctors to boost sales and prices.

GlaxoSmithKline Plc (GSK) executives also used fake receipts in unspecified tax law violations, it added.

China has targeted foreign firms on multiple fronts in recent months, including alleged price-fixing, quality controls and consumer rights, forcing companies to defend their reputations in a country where international brands often have a valuable edge over local competitors in terms of public trust.

Last week, European food groups Nestle and Danone said they would cut the price of infant formula milk in China after Beijing launched an investigation into the industry.

China is an increasingly important country for international drugmakers such as GSK, which are relying on growth in emerging markets to offset slower sales in Western markets where many former top-selling medicines have lost patent protection.

IMS Health, which tracks pharmaceutical industry trends, expects China to overtake Japan as the world’s second biggest drugs market behind the United States by 2016.

“We take all allegations of bribery and corruption seriously,” GSK said in a statement.

“We continuously monitor our businesses to ensure they meet our strict compliance procedures – we have done this in China and found no evidence of bribery or corruption of doctors or government officials,” it added, saying it would cooperate with the authorities.

The charges of bribery make the GSK case the highest profile probe in China since four executives of mining giant Rio Tinto Plc  were jailed in March 2010 for taking bribes and stealing commercial secrets.

The four – one a China-born Australian citizen and three Chinese nationals – received jail terms of between seven and 14 years after being found guilty of getting information from confidential strategy meetings of the body representing China’s steel industry in negotiations with iron ore suppliers.

Under China’s legal system, the GSK executives will be formally charged after the completion of the preliminary investigations.

The security ministry did not give details on the number of executives questioned, their identities, nor when the questioning took place.

GOVERNMENT BRIBES

It is still too early in the process to know the extent of potential punishments, said Jerry Ling, a Shanghai-based partner for law firm Jones Day who specialises in U.S. and Chinese anti-bribery law.

However, according to guidance set by China’s top court last December, there are a number of factors about the case that could increase any fine or punishment, including the involvement of bribes to government officials and the sensitivity of medicine prices.

“The fact that the Ministry of Public Security is running this investigation means that the exposure is more serious,” added Ling.

In smaller bribery cases, China’s State Administration for Industry and Commerce tends to take the lead. While these cases could lead to fines, they rarely results in criminal sentences.

A full confession – which China says the executives have given – could mean GSK benefits from leniency measures linked to voluntary disclosure.

A Britain-based analyst, who covers GSK and who declined to be named, said the company had worked hard to eradicate malpractice. It pleaded guilty to misdemeanour charges in the United States and paid a $3 billion fine a year ago.

“Given the past experience they’ve had with depression drugs in the U.S., they would be ultra cautious on anything to do with corrupt practices,” the analyst said.

However, the analyst noted that China was an under-developed market where it would be difficult to monitor all sales practices and, in addition, authorities were likely to take a hard line with foreign firms.

GSK shares closed down 0.6 percent on Thursday, compared with a 0.6 percent rise in the wider FTSE 100 index.

GSK has had problems in China before.

It said on Monday it was investigating separate allegations that its staff had used improper tactics to market the cosmetic treatment Botox in China, but had so far found no evidence of bribery or corruption.

GSK, Merck & Co Inc and other foreign and domestic drugmakers are also being investigated by China’s top economic planning agency on cost and pricing issues.

http://www.trust.org/item/20130711163257-ctya2/?source

‘Medical stocks are down by 90 percent’: Greece accuses pharma giants of slashing imports

Published time: February 28, 2013 01:36                                                                            
AFP Photo / Louisa Gouliamaki

AFP Photo / Louisa Gouliamaki

The Greek government has reportedly accused 50 leading pharmaceutical companies of cutting off supplies of key medications to the country, sparking a run on pharmacies. Drug companies say the cheap medicines they supply merely get re-exported at a profit.

Pfizer, Roche, GSK and AstraZeneca are among the producers the government says have either stopped providing certain medicines to the debt-stricken country, or plan to do so, according to the UK’s Guardian newspaper. Pfizer and Roche admit that they have done so, but GSK and AstraZeneca deny that they have reduced supplies so far.

 

“It’s a disgrace. The government is panic-stricken and the multinationals only think about themselves,” said Dimitris Karageorgiou, secretary of the Panhellenic Pharmaceutical Association.

 

As the news has spread, patients with prescriptions for antibiotics, statins and other medicines totalling over 200 brand names, began queuing outside pharmacies.

 

“I would say supplies are down by 90%,” said Karageorgiou.

 

“The companies are ensuring that they come in dribs and drabs to avoid prosecution. Everyone is really frightened. Customers tell me they are afraid of losing access to medication altogether.”

 

But the multinationals say the government’s own lack of regulation has created this crisis, which has been more than two years in the making.

 

Under the current system, individuals in Greece buy medicines from pharmacies, and are later reimbursed by the state, with the state setting the prices the drug stores can charge. In the wake of the country’s financial crisis, the government ordered its pharmacies to sell drugs at much lower prices, to cut down its own budget expenditure.

 

But as Greek prices are now 20 percent below the next-cheapest country in Europe, this has created an incentive for pharmacists to simply re-sell drugs to other countries in the EU, creating a “parallel trade”. The health ministry estimates that over 25 percent of all drugs entering Greece are then re-exported.

 

Pharmaceutical companies have already lowered their prices for the Greek market, but are now saying that the re-export is starting to eat into their profits in other European countries.

 

They also point out that as well as paying less, Greek insurance funds and hospitals owe €1.9 billion to drug manufacturers.

 

“We are insisting that the public hospitals fulfil their contracts and this is something we do in any country … We are withholding medicines until they meet their obligations,” said Daniel Grotsky, a Roche spokesman.

 

The Swiss company is owed €200 million. Grotsky said Roche is still supplying individual pharmacies, and only drugs where alternatives are available have been held back.

 

Frouzis Konstantinos, of Novartis, another drug giant, says the government needs to pay up its existing debt, and stop squeezing the profit margins of pharmacies.

 

“The government needs to correct these wrong prices to avoid a surge of exportation,” he told the Guardian.

 

But this is unlikely.

 

Under the austerity budget the state’s allocation for medicines has fallen from €3.7 billion in 2011 to €2.44 last year, and the number for 2013 is likely to be even lower.

 

Instead, the government has banned exports of more than 60 drugs altogether, and says it will levy fines of between €2,000 and €20,000 on those pharmacies that re-export illegally.

http://rt.com/news/greece-list-pharma-parallel-export-debt-574/

 

Increased risk of sleep disorder in children who received swine flu vaccine : Up to 16-fold increased risk

Contact: Emma Dickinson edickinson@bmjgroup.com 44-020-738-36529 BMJ-British Medical Journal

Results consistent with findings from Finland and Sweden, but may still be overestimated

The results are consistent with previous studies from Finland and Sweden and indicate that the association is not confined to Scandinavian populations. However, the authors stress that the risk may still be overestimated, and they call for longer term monitoring of the cohort of children and adolescents exposed to Pandemrix to evaluate the exact level of risk.

In 2009, pandemic influenza A (H1N1) virus spread rapidly, resulting in millions of cases and over 18,000 deaths in over 200 countries. In England the vaccine Pandemrix was introduced in October 2009. By March 2010, around one in four (24%) of healthy children aged under 5 and just over a third (37%) aged 2-15 in a risk group had been vaccinated.

In August 2010 concerns were raised in Finland and Sweden about a possible association between narcolepsy and Pandemrix. And in 2012 a study from Finland reported a 13-fold increased risk in children and young people aged 4-19.

But a lack of reported cases in other countries led to speculation that any possible association might be restricted to these Scandinavian populations.

Narcolepsy is a chronic disorder of excessive daytime sleepiness, often accompanied by sudden muscle weakness triggered by strong emotion (known as cataplexy). To evaluate the risk after vaccination in England, a team of researchers reviewed case notes for 245 children and young people aged 4-18 from sleep centres and child neurology centres across England.

Of these, 75 had narcolepsy (56 with cataplexy) with onset after 1 January 2008. Eleven had been vaccinated before onset of symptoms; seven within six months.

After adjusting for clinical conditions, vaccination at any time was associated with a 14-fold increased risk of narcolepsy, whereas vaccination within six months before onset was associated with a 16-fold increased risk.

In absolute numbers, this means that one in 52,000 to 57,500 doses are associated with narcolepsy, say the authors.

They write: “The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.”

While further use of this vaccine for prevention of seasonal flu seems unlikely, they say their findings “have implications for the future licensure and use of AS03 adjuvanted pandemic vaccines containing different subtypes such H5 or H9.”

And they conclude: “Further studies to assess the risk, if any, associated with the other A/H1N1 2009 vaccines used in the pandemic, including those with and without adjuvants, are also needed to inform the use of such vaccines in the event of a future pandemic.”

Study finds that ‘Big Pharma’ fails at self-policing ED drug advertising: Sex, lies and television?

“The mechanism set up by PhRMA for consumers to make complaints does not function: the FAX machine is typically not connected and complaints go unanswered.”

 

Contact: Buffie Stephens buffiestephens@uncc.edu 704-687-5830 University of North Carolina at Charlotte

CHARLOTTE, N.C. –Feb. 14, 2013– The pharmaceutical industry’s efforts to self-regulate its direct-to-consumer (DTC) advertising are “an industry-sponsored ruse,” intended to deflect criticism and collectively block new Federal regulation, a study released today in the Journal of Health Politics, Policy and Law found.

The paper, “The Politics and Strategy of Industry Self-Regulation: The Pharmaceutical Industry’s Principles for Ethical Direct-to-Consumer Advertising as a Deceptive Blocking Strategy,” was written by Denis Arnold, Associate Professor of Management and Surtman Distinguished Scholar in Business Ethics in the Belk College of Business at UNC Charlotte, with Jim Oakley, Associate Professor of Marketing at Montana State University.

Arnold and Oakley studied the marketing campaigns for erectile dysfunction (ED) drugs over a four-year period, 2006 to 2010. These products include sildenafil citrate, manufactured and marketed as Viagra in the U.S. by Pfizer; tadalafil, manufactured and marketed as Cialis in the U.S. by Eli Lilly; and vardenafil HCI, manufactured by Bayer Healthcare and jointly marketed as Levitra in the U.S. by Bayer Healthcare, GlaxoSmithKline and Merck.

All of these companies have certified compliance with the “PhRMA Guiding Principles,” developed by the Pharmaceutical Research and Manufacturers of America trade organization and first introduced in 2005. Under these guidelines, a company must commit to internal processes to ensure compliance with the principles, complete an annual certification of compliance, and submit a document to PhRMA signed by the CEO and chief compliance officer attesting to compliance.

“The Guiding Principles were introduced, as least in part, to preclude the need for additional federal regulation of broadcast drug advertising,” Arnold said. “In this regard they have been largely successful.”

Arnold and Oakley’s analysis found that rather than a serious effort to facilitate the education of consumers, the Guiding Principles were often ignored, putting consumers at possible risk and exposing children to inappropriate content.

“Cumulatively, our data shows that ED marketing campaigns fail to responsibly educate consumers about health conditions and appropriate treatments,” Arnold said. “Instead of facilitating a balancing of interests between company profits and public health, the illusion of industry self-regulation is primarily serving the interest of pharmaceutical companies at the expense of the public’s interest in genuine health education and welfare.”

Among the findings in the study:

  • Advertising for ED drugs grew from $200 million in 2006 to $313 million in 2009, a 56 percent increase. Television advertising accounts for about 80% of the DTC ad spending. 

     

  • There was a clear pattern of non-compliance to the “Guiding Principles” for the three drugs under study, and Arnold and Oakley note that PhRMA does not make public violations of its guiding principles, nor does it sanction member violations.
    • Eli Lily’s Cialis campaign consistently violated six principles, partially complied with two principles, and fully complied with one principle.
    • Pfizer’s Viagra campaign consistently violated five principles, partially complied with one principle, and fully complied with two principles.
    • Bayer Healthcare, GlaxoSmithKline, and Merck’s Levitra campaign consistently violated five principles, partially complied with three principles, and fully complied with one principle.

     

     

     

  • In the four-year time span studied, there were nearly 100,000 television advertising occurrences for ED drugs.
    • American consumers have been exposed to approximately 500 billion ED television advertising impressions since 2006, of which over 100 billion were seen by consumers under the age of 18, in violation of the Guiding Principles.
    • In response to the introduction of H.R. 2175, the Families for ED Advertising Decency Act,, in 2009 (introduced by Rep. James Moran (D-VA8), each of the companies has stated that they are in compliance with the Guiding Principles requirement that 90% of the audience for adult-themed broadcast advertisements be 18 or older, but Arnold and Oakley’s analysis of AC Nielsen Monitor-Plus data documents that this claim has not been true for any quarter during the four-year period of the study.

     

     

     

  • Patient information and print ads were consistently found to exceed recommendations for consumer legibility violating the Guiding Principles. 

     

  • Each of the drugs is presented in ads as the most appropriate first stage treatment for impotence, despite known risks such as priapism and sudden loss of hearing or vision. – None of the ED drugs effectively informed consumers of alternative options for treatment, in violation of the Guiding Principles. 

     

  • The mechanism set up by PhRMA for consumers to make complaints does not function: the FAX machine is typically not connected and complaints go unanswered.

 

“We were surprised by the findings,” Arnold said. “We did not expect this level of non-compliance. It is troubling to discover that executives at these companies are engaged in this level of duplicity.”

Arnold and Oakley make a number of recommendations to rectify the ineffectiveness of the industry-developed self-regulation, including maintaining bans on DTC advertising where they currently exist.  In countries without a ban, most notably the U.S. and New Zealand, the study recommends a more robust regulatory climate. Options might include:

  • Implementing restrictions on advertising that might reach children, such as those as outlined in the Families for ED Advertising Decency Act; 
  • Requiring that non-pharmacological treatment options and comparative treatment costs be addressed; 
  • Requiring FDA approval of advertisements take place before advertisements are broadcast for the first time, as opposed to the current practice of allowing the ad to run as long as it has been submitted for review; 
  • Assessing a fee for each DTC advertising broadcast, to enable the National Library of Medicine to produce and widely distribute plain-English information about the benefits, harms, and cost of the drugs advertised, as well as information about the condition and non-pharmacological treatment options.

 

“In the case of New Zealand, some of these changes could be introduced via amendments to the existing Code for Therapeutic Advertising by the Advertising Standards Authority, while others could be introduced by the Ministry of Health,” Arnold explained. “In the U.S., the ability for Congress and FDA to implement such regulatory changes will be subject to the evolving role of the Supreme Court in assessing what constraints may be placed on commercial speech. However, Congress could empower existing agencies or departments to penalize firms for making false claims about their advertising.”

Arnold and Oakley also recommend that additional resources be provided, within existing regulatory frameworks, so regulatory agencies can more rigorously enforce of statutory requirements.

“The ultimate goal of these recommendations is to better balance the interests of pharmaceutical companies and the public,” Arnold said.

###

The full study appears online February 11, 2013 and will appear in print in the June 2013 issue of the Journal of Health Politics, Policy and Law, published by Duke University Press. Visit jhppl.dukejournals.org for additional information.

Sources: Denis Arnold: 704.687.7703,  denisarnold@uncc.edu

Insight: Evidence grows for narcolepsy link to GSK swine flu shot : Doctors are fearful of having their reputations ruined by reporting possible links

By Kate Kelland, Health and Science Correspondent | Reuters – 8 mins ago

STOCKHOLM (Reuters) – Emelie is plagued by hallucinations and nightmares. When she wakes up, she’s often paralyzed, unable to breathe properly or call for help. During the day she can barely stay awake, and often misses school or having fun with friends. She is only 14, but at times she has wondered if her life is worth living.

Emelie is one of around 800 children in Sweden and elsewhere in Europe who developed narcolepsy, an incurable sleep disorder, after being immunized with the Pandemrix H1N1 swine flu vaccine made by British drugmaker GlaxoSmithKline in 2009.

Finland, Norway, Ireland and France have seen spikes in narcolepsy cases, too, and people familiar with the results of a soon-to-be-published study in Britain have told Reuters it will show a similar pattern in children there.

Their fate, coping with an illness that all but destroys normal life, is developing into what the health official who coordinated Sweden’s vaccination campaign calls a “medical tragedy” that will demand rising scientific and medical attention.

Europe’s drugs regulator has ruled Pandemrix should no longer be used in people aged under 20. The chief medical officer at GSK’s vaccines division, Norman Begg, says his firm views the issue extremely seriously and is “absolutely committed to getting to the bottom of this”, but adds there is not yet enough data or evidence to suggest a causal link.

Others – including Emmanuel Mignot, one of the world’s leading experts on narcolepsy, who is being funded by GSK to investigate further – agree more research is needed but say the evidence is already clearly pointing in one direction.

“There’s no doubt in my mind whatsoever that Pandemrix increased the occurrence of narcolepsy onset in children in some countries – and probably in most countries,” says Mignot, a specialist in the sleep disorder at Stanford University in the United States.

30 MILLION RECEIVED PANDEMRIX

In total, the GSK shot was given to more than 30 million people in 47 countries during the 2009-2010 H1N1 swine flu pandemic. Because it contains an adjuvant, or booster, it was not used in the United States because drug regulators there are wary of adjuvanted vaccines.

GSK says 795 people across Europe have reported developing narcolepsy since the vaccine’s use began in 2009.

Questions about how the narcolepsy cases are linked to Pandemrix, what the triggers and biological mechanisms might have been, and whether there might be a genetic susceptibility are currently the subject of deep scientific investigation.

But experts on all sides are wary. Rare adverse reactions can swiftly develop into “vaccine scares” that spiral out of proportion and cast what one of Europe’s top flu experts calls a “long shadow” over public confidence in vaccines that control potential killers like measles and polio.

“No-one wants to be the next Wakefield,” said Mignot, referring to the now discredited British doctor Andrew Wakefield who sparked a decades-long backlash against the measles, mumps and rubella (MMR) shot with false claims of links to autism.

With the narcolepsy studies, there is no suggestion that the findings are the work of one rogue doctor.

Independent teams of scientists have published peer-reviewed studies from Sweden, Finland and Ireland showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between seven and 13 times higher for children who had Pandemrix than for their unvaccinated peers.

“We really do want to get to the bottom of this. It’s not in anyone’s interests if there is a safety issue that needs to be addressed,” said GSK’s Begg.

LIFE CHANGED

Emelie’s parents, Charles and Marie Olsson, say she was a top student who loved playing the piano, taking tennis lessons, creating art and having fun with friends. But her life started to change in early 2010, a few months after she had Pandemrix. In the spring of 2010, they noticed she was often tired, needing to sleep when she came home from school.

But it wasn’t until May, when she began collapsing at school, that it became clear something serious was happening.

As well as the life-limiting bouts of daytime sleepiness, narcolepsy brings nightmares, hallucinations, sleep paralysis and episodes of cataplexy – when strong emotions trigger a sudden and dramatic loss of muscle strength.

In Emelie’s case, having fun is the emotional trigger. “I can’t laugh or joke about with my friends anymore, because when I do I get cataplexies and collapse,” she said in an interview at her home in the Swedish capital.

Narcolepsy is estimated to affect between 200 and 500 people per million and is a lifelong condition. It has no known cure and scientists don’t really know what causes it. But they do know patients have a deficit of a brain neurotransmitter called orexin, also known as hypocretin, which regulates wakefulness.

Research has found that some people are born with a variant in a gene known as HLA that means they have low hypocretin, making them more susceptible to narcolepsy. Around 25 percent of Europeans are thought to have this genetic vulnerability.

When results of Emelie’s hypocretin test came back in November last year, it showed she had 15 percent of the normal amount, typical of heavy narcolepsy with cataplexy.

The seriousness of her strange new illness has forced her to contemplate life far more than many other young teens: “In the beginning I didn’t really want to live any more, but now I have learned to handle things better,” she said.

TRIGGERS?

Scientists investigating these cases are looking in detail at Pandemrix’s adjuvant, called AS03, for clues.

Some suggest AS03, or maybe its boosting effect, or even the H1N1 flu itself, may have triggered the onset of narcolepsy in those who have the susceptible HLA gene variant.

Angus Nicoll, a flu expert at the European Centre for Disease Prevention and Control (ECDC), says genes may well play a part, but don’t tell the whole story.

“Yes, there’s a genetic predisposition to this condition, but that alone cannot explain these cases,” he said. “There was also something to do with receiving this specific vaccination. Whether it was the vaccine plus the genetic disposition alone or a third factor as well – like another infection – we simply do not know yet.”

GSK is funding a study in Canada, where its adjuvanted vaccine Arepanrix, similar to Pandemrix, was used during the 2009-2010 pandemic. The study won’t be completed until 2014, and some experts fear it may not shed much light since the vaccines were similar but not precisely the same.

It all leaves this investigation with far more questions than answers, and a lot more research ahead.

WAS IT WORTH IT?

In his glass-topped office building overlooking the Maria Magdalena church in Stockholm, Goran Stiernstedt, a doctor turned public health official, has spent many difficult hours going over what happened in his country during the swine flu pandemic, wondering if things should have been different.

“The big question is was it worth it? And retrospectively I have to say it was not,” he told Reuters in an interview.

Being a wealthy country, Sweden was at the front of the queue for pandemic vaccines. It got Pandemrix from GSK almost as soon as it was available, and a nationwide campaign got uptake of the vaccine to 59 percent, meaning around 5 million people got the shot.

Stiernstedt, director for health and social care at the Swedish Association of Local Authorities and Regions, helped coordinate the vaccination campaign across Sweden’s 21 regions.

The World Health Organization (WHO) says the 2009-2010 pandemic killed 18,500 people, although a study last year said that total might be up to 15 times higher.

While estimates vary, Stiernstedt says Sweden’s mass vaccination saved between 30 and 60 people from swine flu death. Yet since the pandemic ended, more than 200 cases of narcolepsy have been reported in Sweden.

With hindsight, this risk-benefit balance is unacceptable. “This is a medical tragedy,” he said. “Hundreds of young people have had their lives almost destroyed.”

PANDEMICS ARE EMERGENCIES

Yet the problem with risk-benefit analyses is that they often look radically different when the world is facing a pandemic with the potential to wipe out millions than they do when it has emerged relatively unscathed from one, like H1N1, which turned out to be much milder than first feared.

David Salisbury, the British government’s director of immunization, says “therein lies the risk, and the difficulty, of working in public health” when a viral emergency hits.

“In the event of a severe pandemic, the risk of death is far higher than the risk of narcolepsy,” he told Reuters. “If we spent longer developing and testing the vaccine on very large numbers of people and waited to see whether any of them developed narcolepsy, much of the population might be dead.”

Pandemrix was authorized by European drug regulators using a so-called “mock-up procedure” that allows a vaccine to be authorized ahead of a possible pandemic using another flu strain. In Pandemrix’s case, the substitute was H5N1 bird flu.

When the WHO declared a pandemic, GSK replaced the mock-up’s strain with the pandemic-causing H1N1 strain to form Pandemrix.

GSK says the final H1N1 version was tested in trials involving around 3,600 patients, including children, adolescents, adults and the elderly, before it was rolled out.

The ECDC’s Nicoll says early warning systems that give a more accurate analysis of a flu strain’s threat are the best way to minimize risks of this kind of tragedy happening in future.

Salisbury agrees, and says progress towards a universal flu vaccine – one that wouldn’t need last-minute changes made when a new strain emerged – would cuts risks further.

“Ideally, we would have a better vaccine that would work against all strains of influenza and we wouldn’t need to worry about this ever again,” he said. “But that’s a long way off.”

With scientists facing years of investigation and research, Emelie just wants to make the best of her life.

She reluctantly accepts that to do so, she needs a cocktail of drugs to try to control the narcolepsy symptoms. The stimulant Ritalin and the sleeping pill Sobril are prescribed for Emelie’s daytime sleepiness and night terrors. Then there’s Prozac to try to stabilize her and limit her cataplexies.

“That’s one of the things that makes me feel most uncomfortable,” she explains. “Before I got this condition I didn’t take any pills, and now I have to take lots – maybe for the rest of my life. It’s not good to take so many medicines, especially when you know they have side effects.”

(Reporting by Kate Kelland; Editing by Will Waterman)

http://news.yahoo.com/insight-evidence-grows-narcolepsy-gsk-swine-flu-shot-070212916–finance.html

 

WHO and the pandemic flu “conspiracies” – FULL report from the BMJ and The Bureau of Investigative Journalism 2010

2010 report posted for filing

Conflicts of Interest

WHO and the pandemic flu “conspiracies”

Deborah Cohen, features editor, BMJ, Philip Carter, journalist, The Bureau of Investigative Journalism, London

dcohen@bmj.com

Key scientists advising the World Health Organization on planning for an influenza pandemic had done paid work for pharmaceutical firms that stood to gain from the guidance they were preparing. These conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.” Deborah Cohen and Philip Carter investigate

Next week marks the first anniversary of the official declaration of the influenza A/H1N1 pandemic. On 11 June 2009 Dr Margaret Chan, the director general of the World Health Organization, announced to the world’s media: “I have conferred with leading influenza experts, virologists, and public health officials. In line with procedures set out in the International Health Regulations, I have sought guidance and advice from an Emergency Committee established for this purpose. On the basis of available evidence, and these expert assessments of the evidence, the scientific criteria for an influenza pandemic have been met…The world is now at the start of the 2009 influenza pandemic.”

It was the culmination of 10 years of pandemic preparedness planning for WHO—years of committee meetings with experts flown in from around the world and reams of draft documents offering guidance to governments. But one year on, governments that took advice from WHO are unwinding their vaccine contracts, and billions of dollars’ worth of stockpiled oseltamivir (Tamiflu) and zanamivir (Relenza)—bought from health budgets already under tight constraints—lie unused in warehouses around the world.

 

A joint investigation by the BMJ and the Bureau of Investigative Journalism has uncovered evidence that raises troubling questions about how WHO managed conflicts of interest among the scientists who advised its pandemic planning, and about the transparency of the science underlying its advice to governments. Was it appropriate for WHO to take advice from experts who had declarable financial and research ties with pharmaceutical companies producing antivirals and influenza vaccines? Why was key WHO guidance authored by an influenza expert who had received payment for other work from Roche, manufacturers of oseltamivir, and GlaxoSmithKline, manufacturers of zanamivir? And why does the composition of the emergency committee from which Chan sought guidance remain a secret known only to those within WHO? We are left wondering whether major public health organisations are able to effectively manage the conflicts of interest that are inherent in medical science.

Already WHO’s handling of the pandemic has led to an unprecedented number of reviews and inquiries by organisations including the Council of Europe, European Parliament, and WHO itself, following allegations of industry influence. Dr Chan has dismissed these as “conspiracies,” and earlier this year, during a speech at the Centers for Disease Control and Prevention in Atlanta, she said: “WHO anticipated close scrutiny of its decisions, but we did not anticipate that we would be accused, by some European politicians, of having declared a fake pandemic on the advice of experts with ties to the pharmaceutical industry and something personal to gain from increased industry profits.”

The inquiry by British MP Paul Flynn for the Council of Europe Parliamentary Assembly—due to be published today—will be critical. It will say that decision making around the A/H1N1 crisis has been lacking in transparency. “Some of the outcomes of the pandemic, as illustrated in this report, have been dramatic: distortion of priorities of public health services all over Europe, waste of huge sums of public money, provocation of unjustified fear amongst Europeans, creation of health risks through vaccines and medications which might not have been sufficiently tested before being authorised in fast-track procedures, are all examples of these outcomes. These results need to be critically examined by public health authorities at all levels with a view to rebuilding public confidence in their decisions.”

The investigation by the BMJ/The Bureau reveals a system struggling to manage the inherent conflict between the pharmaceutical industry, WHO, and the global public health system, which all draw on the same pool of scientific experts. Our investigation has identified key scientists involved in WHO pandemic planning who had declarable interests, some of whom are or have been funded by pharmaceutical firms that stood to gain from the guidance they were drafting. Yet these interests have never been publicly disclosed by WHO and, despite repeated requests from the BMJ/The Bureau, WHO has failed to provide any details about whether such conflicts were declared by the relevant experts and what, if anything, was done about them.

It is this lack of transparency over conflicts of interests—coupled with a documented changing of the definition of a pandemic and unanswered questions over the evidence base for therapeutic interventions1—that has led to the emergence of these conspiracies.

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.”

Another factor that has fuelled the conspiracy theories is the manner in which risk has been communicated. No one disputes the difficulty of communicating an uncertain situation or the concept of risk in a pandemic situation. But one world expert in risk communication, Gerd Gigerenzer, director of the Centre for Adaptive Behaviour and Cognition at the Max Planck Institute in Germany, told the BMJ/The Bureau: “The problem is not so much that communicating uncertainty is difficult, but that uncertainty was not communicated. There was no scientific basis for the WHO’s estimate of 2 billion for likely H1N1 cases, and we knew little about the benefits and harms of the vaccination. The WHO maintained this 2 billion estimate even after the winter season in Australia and New Zealand showed that only about one to two out of 1000 people were infected. Last but not least, it changed the very definition of a pandemic.”

WHO for years had defined pandemics as outbreaks causing “enormous numbers of deaths and illness” but in early May 2009 it removed this phrase—describing a measure of severity—from the definition.2

 

The beginnings

The routes to the Council of Europe’s criticisms can be traced back to 1999, a pivotal year in the influenza world. In April that year WHO—spurred on by the 1997 chicken flu outbreak in Hong Kong—began to organise itself for a feared pandemic. It drew up a key document, Influenza Pandemic Plan: The Role of WHO and Guidelines for National and Regional Planning.

WHO’s first influenza pandemic preparedness plan was stark in the scale of the risk the world faced in 1999: “It is impossible to anticipate when a pandemic might occur. Should a true influenza pandemic virus again appear that behaved as in 1918, even taking into account the advances in medicine since then, unparalleled tolls of illness and death would be expected.”

In the small print of that document it states: “R Snacken, J Wood, L R Haaheim, A P Kendal, G J Ligthart, and D Lavanchy prepared this document for the World Health Organization (WHO), in collaboration with the European Scientific Working Group on Influenza (ESWI).” What this document does not disclose is that ESWI is funded entirely by Roche and other influenza drug manufacturers. Nor does it disclose that René Snacken and Daniel Lavanchy were participating in Roche sponsored events the previous year, according to marketing material seen by the BMJ/The Bureau.

Dr Snacken was working for the Belgian ministry of public health when he wrote about studies involving neuraminidase inhibitors for a Roche promotional booklet. And Dr Lavanchy, meanwhile, was a WHO employee when he appeared at a Roche sponsored symposium in 1998. His role at that time was in the WHO Division of Viral Diseases. Dr Lavanchy has declined to comment.

In 1999 other members of the European Scientific Working Group on Influenza included Professor Karl Nicholson of Leicester University, UK, and Professor Abe Osterhaus of Erasmus University in the Netherlands. These two scientists are also identified in Roche marketing material seen by this investigation which was produced between 1998 and 2000. Professor Osterhaus told the BMJ that he had always been transparent about any work he has done with industry. Professor Nicholson similarly has consistently declared his connections with pharmaceutical companies, for example, in papers published in journals such as the BMJ and Lancet.

Both experts were also at that time engaged in a randomised controlled trial on oseltamivir supported by Roche. The trial was subsequently published in the Lancet in 2000.3 It remains one of the main studies supporting oseltamivir’s effectiveness—and one that was subsequently shown to have employed undeclared industry funded ghostwriters.1

The influence of the European Scientific Working Group on Influenza would continue as the decade wore on and the calls for pandemic planning became more strident. Founded in 1992, this “multidisciplinary group of key opinion leaders in influenza aims to combat the impact of epidemic and pandemic influenza” and claims links to WHO, the Robert Koch Institute, and the European Centre for Disease Prevention and Control, among others.4 Despite the group’s claims of scientific independence its 100% industry funding does present a potential conflict of interest. One if its roles is to lobby politicians, as highlighted in a 2009 policy document.5

At a pre-pandemic preparation workshop of the European Scientific Working Group on Influenza in January last year, Professor Osterhaus said: “I can tell you that ESWI is working on that idea [that is, convincing politicians] quite intensively. We have contact with MEPs [members of the European Parliament] and with national politicians. But it is they who have to decide at the end of the day, and they will only act at the request of their constituencies. If the latter are not prompted, nothing will happen.”

The group’s policy plan for 2006-10 specifically stated that government representatives needed to “take measures to encourage the pharmaceutical industry to plan its vaccine/antivirals production capacity in advance” and also to “encourage and support research and development of pandemic vaccine” and to “develop a policy for antiviral stockpiling.” It also added that government representatives needed to know that “influenza vaccination and use of antivirals is beneficial and safe.” It said that the group provided “evidence based, palatable information”; and also “networking/exchange with other stakeholders (eg, with industry in order to establish pandemic vaccine and antivirals contracts).” In the meantime, in Roche’s own marketing plan, one goal was to “align Roche with credible third party advocates”. They “leveraged these relationships by enlisting our third-party partners to serve as spokespeople and increase awareness of Tamiflu and its benefits.”6

Barbara Mintzes, assistant professor in the Department of Pharmacology and Therapeutics at the University of British Columbia, is currently part of a group working with Health Action International and WHO developing model curricula for medical and pharmaceutical students on drug promotion and interactions with the industry, including conflicts of interest. She thinks that caution is advised when working with medical bodies of this sort.

“It is legitimate for WHO to work with industry at times. But I would have concerns about involvement with a group that looks like it is for independent academics that is actually mainly industry funded,” she told the BMJ/The Bureau, adding: “The Institute of Medicine has raised concerns about the need to have a firewall with medical groups. To me this does not sound like an independent group, as it is mainly funded by manufacturers.”

She also thinks that there is a difference between the conflict of interest in having a clinical trial funded by a company and the conflict of interest in being involved in marketing a drug—for example, on a paid speaker’s bureau or in marketing material. “Some academic medical departments, for example Stanford University, have banned staff from being involved in marketing or being on a paid speakers bureau,” she said.

The presence of leading influenza scientists at promotional events for oseltamivir reflected not just the concern of an impending pandemic, but the excitement over the potential of a new class of drugs—neuraminidase inhibitors—to offer treatment and protection against seasonal influenza.

In 1999 two new drugs first came to market: oseltamivir, from Roche; and zanamivir, manufactured by what is now GlaxoSmithKline. The two drugs would battle it out over the coming years, with oseltamivir—aided by its oral administration—trumping its rival in global sales as the decade wore on.

The potential was quickly grasped. Indeed, that year Professor Osterhaus published an article proposing the use of neuraminidase inhibitors in pandemics: “Finally, during a possible future influenza pandemic, in view of their broad reactivity against influenza virus neuraminidase subtypes and the expected lack of sufficient quantities of vaccine, the new antivirals will undoubtedly have an essential role to play in reducing the number of victims.”7

However, he also warned that antivirals should not be seen as a replacement for vaccinations. “Close collaboration and consultation between, on the one hand, companies marketing influenza vaccines and, on the other, those marketing antivirals will therefore be absolutely essential. It is important that a clear and uniform message indicating the complementary roles of vaccines and antivirals is delivered.”

That article appeared in the European Scientific Working Group on Influenza’s bulletin of April 1999; Professor Osterhaus signs off with the affiliation of WHO National Influenza Centre Rotterdam, The Netherlands.

Other experts soon followed suit—recommending the role neuraminidase inhibitors could play in any future pandemic—in both the academic literature and in the general media.

Food and Drug Administration

While the excitement over these drugs fuelled scientific symposiums, the US Food and Drug Administration (FDA) was less than convinced. The BMJ/The Bureau has since spoken to people from within the American and European drug regulators, the FDA and the European Medicines Agency (EMEA), who said that both regulators struggled with the paucity of the data presented to them for zanamivir and oseltamivir, respectively, during the licensing process. At the end of last year, the BMJ called for access to raw data for key public health drugs after the Cochrane Collaboration found the effectiveness of the drugs impossible to evaluate.8 The group are continuing to negotiate access to what they say they need to fully assess the effectiveness of antivirals.

In the US, the FDA first approved zanamivir in 1999.9 Michael Elashoff, a former employee of the FDA, was the statistician working on the zanamivir account. He told the BMJ how the FDA advisory committee initially rejected zanamivir because the drug lacked efficacy.

After Dr Elashoff’s review (he had access to individual patient data and summary study reports) the FDA’s advisory committee voted by 13 to 4 not to approve zanamivir on the grounds that it was no more effective than placebo when the patients were on other drugs such as paracetamol. He said that it didn’t reduce symptoms even by a day.

 

“When I was reviewing the data, I tried to replicate the analyses in their summary study reports. The issue was not of data quality, but sensitivity analyses showed even less efficacy,” he said. “The safety analysis showed there were safety concerns, but the focus was on if Glaxo had demonstrated efficacy.” Dr Elashoff’s view was that zanamivir was no better than placebo—and it had side effects. And when the FDA medical reviewer made a presentation, her conclusion was that it could either be approved or not approved. It was a fairly borderline drug.

There were influenza experts on the FDA’s advisory committee and much of the discussion hinged on why a drug that looked so promising in earlier studies wasn’t working in the largest trials in the US. One hypothesis was that people in the US were taking other drugs for symptomatic relief that masked any effect of zanamivir. So zanamivir might have no impact on symptoms over and above the baseline medications that people take when they have influenza.

Two other trials—one in Europe and one in Australia— showed a bit more promise. But there was a very low rate of people taking other medications. “So in the context of not being allowed to take anything for symptomatic relief, there might be some effect of Relenza. But in the context of a typical flu, where you have to take other things to manage your symptoms, you wouldn’t notice any effect of Relenza over and above those other things,” Dr Elashoff said. The advisory committee recommended that the drug should not be approved.

Nevertheless, FDA management decided to overturn the committee’s recommendation.

 

“They would feel better if there was something on the market in case of a pandemic. It wasn’t a scientific decision,” Dr Elashoff said.

While Dr Elashoff was working on the zanamivir review, he was assigned the oseltamivir application. But when the review and the advisory committee decided not to recommend zanamivir, the FDA’s management reassigned the oseltamivir review to someone else. Dr Elashoff believes that the approval of zanamivir paved the way for oseltamivir, which was approved by the FDA later that year.

 

European Medicines Agency

In Europe the EMEA was similarly troubled by the evidence for oseltamivir. By early 2002 Roche had sought a European Union-wide licence from the EMEA. It was a lengthy process, taking three meetings of the Committee for Medicinal Products for Human Use as well as expert panels, according to one of the two rapporteurs, Pekka Kurki of the Finnish Medicines Agency. Echoing the Cochrane Collaborations’s 2009 findings6 Kurki told us: “We discussed the same issues that are still discussed today: does it show clinically significant benefits in treatment and prophylaxis of flu and what was the magnitude of the benefits presented in the RCTs? Our assessment and Cochrane’s in 2009 are very similar with regard to the effect size in RCTs. The data show that the effects of Tamiflu were clear but not very impressive.

“What was unclear and is still unclear is what is the impact of Tamiflu on serious complications. Circulating influenza was very mild when Tamiflu was developed and therefore it is very difficult to say anything about serious complications. The data did not clearly show an effect on serious complications—it was not demonstrated by the RCTs.”

In documents obtained under the freedom of information legislation, two of the experts who provided opinions during the EMEA licensing process have also featured in Roche marketing material: Annike Linde and Rene Snacken. In Dr Snacken’s EMEA presentation dated 18 February 2002, he discussed the need for chemoprophylaxis and called for the use of oseltamivir during a pandemic. He made his presentation as a representative of the Belgian Ministry of Public Health. At the time Dr Snacken was also “liaison officer” for the European Scientific Working Group on Influenza. He also played a key role in the Belgian government during its pandemic planning, and he later became a senior expert at the Preparedness and Response Unit, European Centre for Disease Prevention and Control. We do not know what, if anything, he declared to the EMEA about his relationship with Roche.

Annike Linde has confirmed in an email that she has had connections with Roche over a number of years. She made a presentation to the EMEA on “influenza surveillance” in her capacity as a representative of the Swedish Institute for Infectious Disease. Again, it is not clear what, if anything, she declared to the EMEA concerning her previous relationship with Roche.

Dr Linde, now the Swedish state epidemiologist, has told the BMJ/The Bureau that she received payments from Roche International in respect of various pieces of work she did for the company until 2002. She has subsequently given occasional lectures for Roche Sweden. All money she has received from Roche was given, Dr Linde says, to the Swedish Institute for Infectious Disease Control.

We asked the scientists whether they declared their relationship with Roche at the time to the EMEA. Neither has answered that question entirely satisfactorily. Dr Snacken has not replied to repeated emails posing this question. Dr Linde responded by telling the BMJ/The Bureau: “We contribute with our expertise to the regulatory agencies when asked. When we do so, a declaration of interest, where e.g. participation at advisory meetings at Roche, is given and evaluated by the regulatory agency.” The BMJ/The Bureau requested Linde and Snacken’s declaration of interest statements for the 2002 meeting from the EMEA under the freedom of information act. The EMEA was unable to provide statements for those particular people at that time.

Developing the guidelines

In October 2002 WHO convened a meeting of influenza experts at its Geneva headquarters. Their purpose was to develop WHO’s guidelines for the use of vaccines and antivirals during an influenza pandemic.

Included at this meeting were representatives from Roche and Aventis Pasteur and three experts who had lent their name to oseltamivir’s marketing material (Professors Karl Nicholson, Ab Osterhaus, and Fred Hayden).

Two years later the WHO published a key report from that meeting, WHO Guidelines on the Use of Vaccines and Antivirals during Influenza Pandemics 2004. The specific guidance on antivirals, Considerations for the Use of Antivirals During an Influenza Pandemic, was written by Fred Hayden. Professor Hayden has confirmed to the BMJ/The Bureau in an email that he was being paid by Roche for lectures and consultancy work for the company at the time the guidance was produced and published. He also told us in an email that he had received payments from GlaxoSmithKline for consultancy and lecturing until 2002. According to Prof Hayden: “DOI [declaration of interest] forms were filled out for the 2002 consultation.”

The WHO guidance concluded that: “Based on their pandemic response goals and resources, countries should consider developing plans for ensuring the availability of antivirals. Countries that are considering the use of antivirals as part of their pandemic response will need to stockpile in advance, given that current supplies are very limited.” Many countries around the world would adopt this guidance.

The previous year Professor Hayden was also one of the main authors of a Roche sponsored study that claimed what was to become one of oseltamivir’s main selling points—a claimed 60% reduction in hospitalisations from flu, which the Cochrane Collaboration was later unable to verify.8

Our investigation has also identified relevant and declarable interests relating to the two other named authors of annexes to WHO’s 2004 guidelines. Arnold Monto was the author of the annexe dealing with vaccine usage in pandemics. Between 2000 and 2004—and at the time of writing the annexe—Dr Monto has consistently and openly declared honorariums, consultancy fees, and research support from Roche, 10 11 12 consultancy fees and research support from GlaxoSmithKline 10 12 13 14; and also research funding from ViroPharma.15

No conflict of interest statement was included in the annex he wrote for WHO. When asked if he had signed a declaration of interest form for WHO, Dr Monto told the BMJ/The Bureau: “Conflict of Interest forms are requested before participation in any WHO meeting”.

Professor Karl Nicholson is the author of the third annex, Pandemic Influenza. According to declarations made by Professor Nicholson in the BMJ16and Lancet in 2003,17 he had received travel sponsorship and honorariums from GlaxoSmithKline and Roche for consultancy work and speaking at international respiratory and infectious diseases symposiums. Before writing the annexe, he had also been paid and declared ad hoc consultancy fees by Wyeth, Chiron, and Berna Biotech.

Even though the previous year these declarations had been openly made in the Lancet and the BMJ, no conflict of interest statement was included in the annex he wrote for WHO. Professor Nicholson told the BMJ/The Bureau that he last had “financial relations” with Roche in 2001. When asked if he had signed a declaration of interest form for WHO, Prof Nicholson replied: “The WHO does require attendees of meetings, such as those held in 2002 and 2004, to complete declarations of interest.”

Leaving aside the question of what declarations experts made to WHO, one simple fact remains: WHO itself did not publicly disclose any of these conflicts of interest when it published the 2004 guidance. It is not known whether information about these conflicts of interest was relayed privately to governments around the world when they were considering the advice contained in the guidelines.

The year before WHO issued the 2004 guidance, it published a set of rules on how WHO guidelines should be developed and how any conflicts of interest should be handled. This guidance included recommendations that people who had a conflict of interest should not take part in the discussion or the piece of work affected by that interest or, in certain circumstances, that the person with the conflict should not participate in the relevant discussion or work at all. The WHO rules make provision for the director general’s office to allow declarations of interest to be seen if the objectivity of a meeting has been called into question.18

The BMJ/The Bureau has asked WHO for the conflict of interest declarations for the Geneva 2002 meeting and those related to the guidance document itself. WHO told us that the query went directly up to Margaret Chan’s office. “WHO never publishes individual DOIs [declaration of interest], except after consultation with the Office of the Director-General. In this case, we put in a request on your behalf but it was not granted. In more recent years, many WHO committees have published summaries of relevant interests with their meeting reports.”

In a BMJ interview (see film on bmj.com), WHO spokesperson Gregory Hartl reiterated the fact that Dr Margaret Chan, “is very committed personally to transparency.” Yet her office has turned down repeated requests for declaration of interest statements and declines to comment on the allegations that authors of the guidelines had declarable interests.

Nevertheless, Prof Hayden told the BMJ/The Bureau: “I strongly support transparency in declarations of interest, in part because this allows those reading documents, particularly ones authored by specific individuals (eg, Annex 5) [the part he wrote], to make their own judgments about the possible relevance of any potential conflicts.”

While experts need to work with industry to develop the best possible drugs for illnesses, questions remain about what level of involvement experts with industry ties should have in the formulation of public health policy decisions and guidelines. Professor Nicholson told the BMJ/The Bureau: “The WHO and decision makers must be informed of ongoing developments and research findings to ensure that they are as up to date as possible. Some of the most relevant expertise and information are held by companies or individuals with conflicts of interest. I understand the view that experts with conflicts of interest should not advise governments or organisations such as the WHO. But to exclude such people from discussions could deprive WHO and decision makers of important new information.”

But not everyone agrees. Barbara Mintzes is unequivocal about what role they should play. “No one should be on a committee developing guidelines if they have links to companies that either produce a product—vaccine or drug—or a medical device or test for a disease. It would be preferable that there are no financial ties when it comes to making big decisions on public health—for example, stockpiling a drug—and that includes if they have a currently funded clinical trial,” she said.

“Ideally, what you want are independent experts who are in the public sector to provide expertise on drugs and vaccines. But they can be hard to find. One solution is consult with the experts who are involved in industry, but not put them on any decision making committee. You need a firewall,” she added.

Indeed, Professor Harvey Fineberg, president of the Institute of Medicine and chairman of the panel reviewing WHO’s management of the pandemic, takes a similarly hard line. His own institution went through a detailed review of how they interact with industry and experts with conflicts of interests last year.19 “Sometimes publication of conflict of interests is enough—for example with a journal. But if you are giving expert judgment to influence policy, revealing is not enough,” he told the BMJ, referring to the Institute of Medicine’s policy.

WHO also says that it takes conflicts of interests seriously and has the mechanisms in place to deal with them. But what action does it take when a scientist declares a conflict of interest, and when does it judge a scientist to be too conflicted to play a leading role in the formulation of global health policy? Since WHO has not provided us with an answer to this question, we are left to guess.

As it stands, this situation is the worst possible outcome for WHO, according to Professor Chris Del Mar, a Cochrane Review author and expert on WHO’s Strategic Advisory Group of Experts on Immunization group. “If it proves to be the case that authors of WHO guidance which promoted the use of certain drugs were being paid at the same time by the makers of those drugs for other work they were doing for these companies that is reprehensible and should be condemned in the strongest possible terms.”

WHO’s endorsement of oseltamivir was not lost on Roche. In an advert placed by the company for the drug in the main conference programme of the European Scientific Working Group on Influenza’s 2005 conference in Malta, it says: “Antivirals will initially be the principal medical intervention in a pandemic situation and Roche is working as a responsible partner with governments to assist in their pandemic planning.” The source reference for this is the WHO Global Influenza Preparedness Plan.

Throughout the following years, WHO would appear to have been inconsistent in how it treated conflicts of interest. Updated pandemic plans would continue to be prepared by experts who openly had work funded and acted as consultants to manufacturers of vaccines and antivirals. WHO produced its global influenza preparedness plan in 2005, and in 2006 it constituted an interim Influenza Pandemic Task Force. No public declarations of interest have been made and to date no details have been provided by WHO in response to our requests.

WHO’s stance that it does not publish declarations of interest from its experts is far from consistent. It is undermined, for example, by the position WHO adopts in relation to the Strategic Advisory Group of Experts on Immunization, its standing vaccine advisory body. Here, contrary to its approach to pandemic planning advisers, WHO does publish summaries of declarations of interest.

Emergency Committee

These seeming inconsistencies in WHO’s approach to transparency and its handling of conflicts of interest extend into the workings of the Emergency Committee formed last year to advise the director general on the pandemic. The identities of its 16 members are unknown outside WHO. This secret committee has guided WHO pandemic policy since then—including deciding when to judge that the pandemic is over.

WHO says it has to keep the identities secret to protect the scientists from being influenced or targeted by industry. In a phone call to the BMJ/The Bureau in March, WHO spokesperson Gregory Hartl explained: “Our general principle is we want to protect the committee from outside influences.”

The committee advised the WHO director general on phase changes as well as temporary recommendations. According to WHO, When the Emergency Committee met to discuss a possible move to a declaration of a pandemic, the meeting additionally included members who represented Australia, Canada, Chile, Japan, Mexico, Spain, the UK, and the US, eight countries that experienced widespread outbreaks at the time. These national representatives were present to ensure full consideration of the views and possible reservations of the countries expected to bear the initial brunt of economic and social repercussions.

WHO says all members of the Emergency Committee sign a confidentiality agreement, provide a declaration of interests, and agree to give their consultative time freely, without compensation. However, only one member of the committee has been publicly named: Professor John MacKenzie, who chairs it.

This is a troubling stance: it suggests that WHO considers other advisory groups whose members are not anonymous —such as the Strategic Advisory Group of Experts on Immunization—to be potentially subject to outside influences, and it allows no scrutiny of the scientists selected to advise WHO and global governments on a major public health emergency.

Under the International Health Regulations framework, the membership of the Emergency Committee is drawn from a roster of about 160 experts covering a range of public health areas. This framework provides guidelines about how WHO deals with acute public health risks. The BMJ/The Bureau has identified approximately 15 scientists from the International Health Regulations roster with influenza expertise and has emailed them to ask if they were on the Emergency Committee. Under the framework at least some of these scientists are members of the Emergency Committee. Yet because of the confidentiality agreements they have signed, these scientists cannot acknowledge their membership of the committee, putting them in an invidious position.

David Salisbury, chair of WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) committee at the time of the pandemic and a member of the International Health Regulations, says the secrecy has caused problems for his group. “It certainly caused problems for SAGE. Since all of the details of SAGE are in the public domain, there was a perception that it had been SAGE that had given advice about the changing of definitions or the pandemic levels—when we had not done so. SAGE members came in for unfair personal abuse by journalists,” he told the BMJ/The Bureau.

“Given the importance of the advice, the transparency of the source of the advice was important. I believe it is necessary to keep confidential the source of advice if revealing details might put individuals at risk, for example when bioterrorism is being discussed. This does not seem to be the case for pandemic flu,” he added.

The secrecy of the committee is also fuelling conspiracy theories, particularly around the activation of dormant pandemic vaccine contracts. A key question will be whether the pharmaceutical companies, which had invested around $4bn (£2.8bn, 3.3bn) in developing the swine flu vaccine, had supporters inside the emergency committee, who then put pressure on WHO to declare a pandemic. It was the declaring of the pandemic that triggered the contracts.

The BMJ/The Bureau can confirm that Dr Monto, Dr John Wood, and Dr Masato Tashiro are members of the Emergency Committee.

Although Dr Monto did not answer the question directly, his Infectious Disease Society of America biography states that he is a member.20

Last year, according to figures made public in the US by GlaxoSmithKline, Professor Monto received $3000 speakers fees from the company in the period between the second quarter and the last quarter of 2009. As a national official of the Japanese government, Dr Tashiro says that he must “have nothing concerning conflict of interest with private companies”. Dr John Wood works for the UK National Institute for Biological Standards and Control (NIBSC). Dr Wood, like Dr Tashiro, has no personal conflict of interests but he told the BMJ/The Bureau that as part of its statutory role in developing standards for measurement of biological medicines to ensure accurate dosing and carrying out independent control testing to assure their safety and efficacy, the institute must work closely with the pharmaceutical industry. This is made clear on their website.

“The International Federation of Pharmaceutical Manufacturers and Associations has also made publicly available the nature of their close interaction with NIBSC and similar organisations in order to develop influenza vaccines,” he said.21

Those who said that they were not on the committee include David Salisbury, Alan Hampson, Albert Osterhaus, Donato Greco, and Howard Njoo. Maria Zambon, from the UK’s Health Protection Agency told the BMJ: “I undertake various advisory roles to WHO. Declaration of interest statements are prepared before undertaking such roles.

“The HPA Centre for Infection, as part of its role in national infectious disease surveillance, provision of specialist and reference microbiology and vaccine efficacy monitoring, works closely with vaccine manufacturers and biotechnology companies.”

International Health Regulations review

WHO’s own review into the operation of the International Health Regulations and WHO’s handling of the pandemic is now being conducted by Harvey Feinberg, president of the US Institute of Medicine, and will report its findings next year. Dr Chan and Professor Feinberg have both made clear the need for a thorough investigation. But questions are already arising about how independent the review will turn out to be. According to the International Health Regulations list in our possession, some 13 of the 29 members of the review panel are members of the International Health Regulations itself and one is the chair of the Emergency Committee. To critics that might suggest a somewhat incestuous approach.

Professor Mintzes does not agree with WHO’s explanation that secrecy was needed to protect against the influence of outside interest on decision making. “I can’t understand why the WHO kept this secret. It should be public in terms of accountability like the expert advisory committees. If the rationale of secret membership is not to be unduly influenced, there are other ways of dealing with this through strong conflict of interest provisions,” she said.

She also believes that the very nature of allowing a trigger point for vaccine contracts opens the system up unnecessarily to exploitation. “It seems a problem that this declaration might trigger contracts to be realised. There should be safeguards in place to make sure those with an interest in vaccine manufacturers can’t exploit the situation. The WHO will have to look long and hard at this in future,” she said.

The number of victims of H1N1 fell far short of even the more conservative predictions by the WHO. It could, of course, have been far worse.. Planning for the worst while hoping for the best remains a sensible approach. But our investigation has revealed damaging issues. If these are not addressed, H1N1 may yet claim its biggest victim—the credibility of the WHO and the trust in the global public health system.

Cite this as: BMJ 2010;340:c2912

——————————————————————————–

Competing interests: PC declares no competing interests. DC has been paid expenses by WHO for giving talks at two conferences.

Parkinson’s sufferer wins six figure payout from GlaxoSmithKline over drug that turned him into a ‘gay sex and gambling addict’

Father-of-two says he developed an uncontrollable passion for gay sex and gambling – at one point even selling his children’s toys to fund his addiction

Rob Williams

Thursday, 29 November 2012

A French appeals court has upheld a ruling ordering GlaxoSmithKline to pay €197,000 (£159,000) to a man who claimed a drug given to him to treat Parkinson’s turned him into a ‘gay sex addict’.

Didier Jambart, 52, was prescribed the drug Requip in 2003 to treat his illness.

Within two years of beginning to take the drug the married father-of-two says he developed an uncontrollable passion for gay sex and gambling – at one point even selling his children’s toys to fund his addiction.

He was awarded £160,000 in damages after a court in Rennes, France, upheld his claims.

The ruling, which is considered ground-breaking, was made yesterday by the appeal court, which awarded damages to Mr Jambart.

Following the decision Mr Jambart appeared outside the court with his wife Christine beside him.

Jambart broke down in tears as judges upheld his claim that his life had become ‘hell’ after he started taking Requip, a drug made by GSK.

Mr Jambart began taking the drug for Parkinson’s in 2003, he had formerly worked as a well-respected bank manager and local councillor, and is a father of two.

After beginning to take the drug he claimed he attempted to commit suicide eight times.

In total Mr Jambert said he gambled away 82,000 euros, mostly through internet betting on horse races. He also said he engaged in frantic searches for gay sex.

He started exhibiting himself on websites and arranging encounters, one of which he claimed resulted in him being raped.

He said his family had not understood what was going on at first.

Mr Jambert said he realised the drug was responsible when he stumbled across a website that made a connection between the drug and addictions in 2005. When he stopped the drug he claims his behaviour returned to normal.

“It’s a great day,” he said. “It’s been a seven-year battle with our limited means for recognition of the fact that GSK lied to us and shattered our lives.”

He added: ‘I am happy that justice has been done. I am happy for my wife and my children. I am at last going to be able to sleep at night and profit from life. ‘

He added that the money awarded would, ‘never replace the years of pain.’

The court heard that Requip’s side-effects had been made public in 2006, but had reportedly been known for years.

Mr Jambert said that GSK patients should have been informed earlier.

 

http://www.independent.co.uk/news/world/europe/parkinsons-sufferer-wins-six-figure-payout-from-glaxosmithkline-over-drug-that-turned-him-into-a-gay-sex-and-gambling-addict-8368600.html#

Seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu by 68%

2010 study posted for filing

Contact: Andrew Hyde press@plos.org 44-122-346-3330 Public Library of Science

Did seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu?

Press release from PLoS Medicine

Did seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu?

In September 2009, news stories reported that researchers in Canada had found an increased risk of pandemic H1N1 (pH1N1) influenza in people who had previously been vaccinated against seasonal influenza. Their research, consisting of four different studies, has now undergone further scientific peer review and is published in the open access journal PLoS Medicine.

Did previous vaccination against seasonal flu increase the risk of getting pH1N1 flu? Based on these studies – conducted by a large network of investigators across Canada led by Principal Investigator Danuta Skowronski of the British Columbia Centre for Disease Control in Vancouver, in collaboration with provincial leads Gaston De Serres in Quebec, Natasha Crowcroft in Ontario and Jim Dickinson in Alberta – the answer remains: “possibly.”

In a school outbreak of pH1N1 in spring 2009, people with cough and fever were found to have received prior seasonal flu vaccination more often than those without. Several public health agencies in Canada therefore undertook four additional studies during the summer of 2009 to investigate further. Taken together, the four studies included approximately 2,700 people with and without pH1N1.

The first of the studies used an ongoing sentinel monitoring system to assess the frequency of prior vaccination with the 2008󈝵 seasonal vaccine in people with pH1N1 influenza (cases) compared to people without evidence of infection with an influenza virus (controls). This study confirmed that the seasonal vaccine provided protection against seasonal influenza, but found it to be associated with an increased risk of approximately 68% for pH1N1 disease.

The further 3 studies (which included additional case-control investigations in Ontario and Quebec, as well as a transmission study in 47 Quebec households where pH1N1 influenza had occurred) similarly found between 1.4𔃀.5 times increased likelihood of pH1N1 illness in people who had received the seasonal vaccine compared to those who had not. Prior seasonal vaccination was not associated with an increase in hospitalization among those who developed pH1N1 illness.

These studies do not show whether there was a true cause-and-effect relationship between seasonal flu vaccination and subsequent pH1N1 illness (as might occur if, for example, the seasonal vaccine modified the immune response to pH1N1), or whether the observed association was not a result of vaccination, but was instead due to differences in some unidentified factor(s) among the groups being studied.

If the findings from these studies are real they raise important questions about the biological interactions between pre-existing and novel pandemic influenza strains. The researchers note, however, that the World Health Organization has recommended that pH1N1 be included in subsequent seasonal vaccine formulations. This will provide direct protection against pH1N1 and thereby obviate any risk that might have been due to the seasonal vaccine in 2009, which did not include pH1N1.

In an accompanying commentary in PLoS Medicine, Lone Simonsen and Cécile Viboud, who were not involved in the studies, write: “Given the uncertainty associated with observational studies, we believe it would be premature to conclude that increased the risk of 2009 pandemic illness, especially in light of six other contemporaneous observational studies in civilian populations that have produced highly conflicting results.” They conclude that “this perplexing experience should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts for unexpected risk factors.”

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Citation: Skowronski DM, De Serres G, Crowcroft NS, Janjua NZ, Boulianne N, et al. (2010) Association between the 2008󈝵 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada. PLoS Med 7(4): e1000258. doi:10.1371/journal.pmed.1000258

Funding: This project was funded by the Canadian Institutes of Health Research, the British Columbia Ministry of Health and the British Columbia Centre for Disease Control, Alberta Health and Wellness, the Ontario Agency for Health Protection and Promotion, the Ontario Ministry of Health and Long Term Care, the Ministère de la santé et des services sociaux du Québec, the Institut national de santé publique du Québec and the Fonds de la recherche en santé du Québec (FRSQ). Although agencies of the investigators provided infrastructure in support of the reported studies, the funders did not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: DMS has previously received research grant funding from GlaxoSmithKline and Sanofi-Pasteur for separate studies. GDS and NB have received research grant funding from GlaxoSmithKline and Sanofi-Pasteur for separate studies. GB has received funding from GlaxoSmithKline for unrelated projects. SAVOIR contributor Allison McGeer has received investigator initiated research grant funding from GlaxoSmithKline, and speaking honoraria from GlaxoSmithKline and Sanofi-Pasteur.

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000258

PRESS-ONLY PREVIEW OF THE ARTICLE: www.plos.org/press/plme-07-04-skowronski.pdf

CONTACTS:

Danuta Skowronski BC Centre for Disease Control Epidemiology Services
655 West 12th Avenue Vancouver, British Columbia V5Z 4R4 Canada
+1 604-707-2511 +1 604-707-2516 (fax) Danuta.Skowronski@bccdc.ca

Ritinder Harry Communications Leader, BC Centre for Disease Control (BCCDC) 655 West 12th Avenue Vancouver, BC V5Z 4R4 Canada +1 604 707-2412 ritinder.harry@bccdc.ca

Perspective article by Cecile Viboud:

Citation: Viboud C, Simonsen L (2010) Does Seasonal Influenza Vaccination Increase the Risk of Illness with the2009 A/H1N1 Pandemic Virus? PLoS Med 7(4): e1000259. doi:10.1371/journal.pmed.1000259

Competing Interests:CV declares no competing interests. LS is a paid consultant for SDI health (a health data business), and has received research support since 2008 from Wyeth (now Pfizer) for pneumococcal vaccine modelling.

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000259

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-07-04-viboud.pdf

CONTACT:

Cécile Viboud National Institutes of Health Fogarty International Center 16 Center Drive Bethesda, MD 20892 United States of America
1-301-496-2146 1-301-496-8496 (fax) viboudc@mail.nih.gov

Pig Virus DNA Found in Rotavirus Vaccine : Millions of children worldwide, including 1 million in the U.S. exposed

2010 report posted for filing

FDA: No Problems Seen in 1 Million U.S. Kids Who Got Rotarix Vaccine

WASHINGTON — U.S. health officials urged pediatricians Monday to temporarily stop using one of two vaccines against a leading cause of diarrhea in babies, after discovering that doses of GlaxoSmithKline’s Rotarix were contaminated with bits of an apparently benign pig virus.

Glaxo’s vaccine has been used in millions of children worldwide, including 1 million in the U.S., with no signs of safety problems – and the pig virus isn’t known to cause any kind of illness in people or animals, said Dr. Margaret Hamburg, commissioner of the Food and Drug Administration.

But vaccines are supposed to be sterile, and because there is a competing vaccine against diarrhea-causing rotavirus that has tested clean – Merck’s RotaTeq – the FDA decided to err on the side of caution.

“We don’t want to scare parents,” Hamburg told reporters. “This was a difficult decision for us to make because there is no evidence at this time that there is a risk to patients who have received this vaccine, and we know there are real benefits for children to be vaccinated against rotavirus.”

Rotavirus causes severe diarrhea and is a leading child killer in developing countries. In the U.S., with better health care, about 55,000 children a year were hospitalized for rotavirus infections and several dozen died each year before vaccination began – with Merck’s vaccine in 2006 and Glaxo’s in 2008.

Glaxo said Monday that regulators abroad have decided not to change how Rotarix is used while scientists probe the relevance of the discovery.

A group of scientists testing a new way to detect viruses in a variety of products stumbled onto fragments of genetic material – broken pieces of DNA – from what’s called porcine circovirus-1 in Rotarix and alerted Glaxo, which confirmed the findings and in turn alerted FDA, Hamburg said.

Story continues below

Rotarix, an oral vaccine, is made from a weakened strain of human rotavirus that has to be grown inside living cells before being purified into a vaccine dose. Glaxo uses a line of monkey kidney cells, or vero cells. Hamburg said the pig virus DNA fragments have been found in Glaxo’s cell bank, meaning they were present from the vaccine’s earliest development. How the original contamination occurred is under investigation.

Merck’s competing rotavirus vaccine RotaTeq is made by a very different process, and FDA’s testing showed no sign of the pig virus in it.

It’s not the first time unwanted viruses have been discovered in vaccines. Best known is a monkey virus that contaminated some polio vaccine in the 1950s; years later, scientists investigated if the SV40 virus might have increased vaccine recipients’ risk of later-in-life cancer but concluded it didn’t.

“We live in a world that’s teeming with microbes,” Hamburg said, but until now this particular pig virus is not one that FDA thought vaccine makers needed to check their products against.

Parents should switch to the Merck vaccine for now – it requires three doses instead of Glaxo’s two – because rotavirus is too serious a disease to ignore, said Dr. William Schaffner, a vaccine specialist at Vanderbilt University who was briefed on FDA’s decision.

He’s bracing for calls from worried parents and will tell them that “this has been an extraordinarily safe vaccine,” and that the discovery is “a consequence of our improved science and ability to detect things that we never could before.”

Study suggests too much risk associated with SSRI usage and pregnancy: Elevated risk of miscarriage, preterm birth, neonatal health complications and possible longer term neurobehavioral abnormalities, including autism

Contact: Kelly Lawman klawman@bidmc.harvard.edu 617-667-7305 Beth Israel Deaconess Medical Center

Antidepressants should only be prescribed with great caution

BOSTON – Elevated risk of miscarriage, preterm birth, neonatal health complications and possible longer term neurobehavioral abnormalities, including autism, suggest that a class of antidepressants known as selective serotonin reuptake inhibitors (SSRI) should only be prescribed with great caution and with full counseling for women experiencing depression and attempting to get pregnant, say researchers at Beth Israel Deaconess Medical Center, Tufts Medical Center and MetroWest Medical Center.

“Depression and infertility are two complicated conditions that more often than not go hand in hand. And there are no definitive guidelines for treatment,” says lead author Alice Domar, Ph.D, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Executive Director of the Domar Center for Mind/Body Health at Boston IVF. “We hope to provide a useful analysis of available data to better inform decisions made by women and the providers who care for them.”

Domar and colleagues conducted a review of published studies evaluating women with depressive symptoms who took antidepressants while pregnant. The results appear online October 31 in the journal Human Reproduction.

“There are three main points that stand out from our review of the scientific studies on this topic,” says senior author Adam Urato, MD, Chairman of Obstetrics and Gynecology at MetroWest Medical Center and a Maternal-Fetal Medicine specialist at Tufts Medical Center. “First, there is clear and concerning evidence of risk with the use of the SSRI antidepressants by pregnant women, evidence that these drugs lead to worsened pregnancy outcomes. Second, there is no evidence of benefit, no evidence that these drugs lead to better outcomes for moms and babies. And third, we feel strongly that patients, obstetrical providers, and the public need to be fully aware of this information.”

Over the last 20 years antidepressant usage has increased 400 percent. Antidepressants are now the most commonly prescribed medication in the United States for people between 18 and 44 years of age, the childbearing years for most women. And as women enter their late 30s and early 40s they are more likely to experience infertility.

“According to the Centers for Disease Control, more than 1 percent of the babies born in the USA each year are the result of an IVF cycle,” write the authors. “And most women will report symptoms of depression during infertility treatment, especially following unsuccessful treatment cycles.”

As many as 11 percent of women undergoing fertility treatment report taking an SSRI to combat depressive symptoms, but Domar and colleagues found no evidence of improved pregnancy outcomes with antidepressant usage, and in fact, found the opposite. They also found plenty of controversy around SSRI efficacy. Many studies found SSRIs to be no more effective or only slightly more effective than placebos in treating depression. “More broadly, there is little evidence of benefit from the antidepressants prescribed for the majority of women of childbearing age–and there is ample evidence of risk,” the authors write.

For starters, there is mounting evidence that SSRIs may decrease pregnancy rates for women undergoing fertility treatment. Additionally, studies consistently show that women using antidepressants experience increased rates of miscarriage. There is also a strong signal of congenital abnormalities, the most noted of which is the association between the use of the antidepressant, Paxil, and cardiac defects. In 2005, this association prompted the FDA to ask Paxil’s manufacturer, GlaxoSmithKline to change Paxil’s risk factor from a C to a D, where a D rating indicates a demonstrated risk to the fetus.

“Preterm birth is, perhaps, the most pressing obstetrical complication,” write the authors. In more than 30 studies, the evidence overwhelmingly points to increased risk for early delivery in women who are taking antidepressants. “This is a significant finding because we know that babies born before 37 weeks are at risk for many short and long-term health problems,” says Urato. “Caring for premature babies adds up to billions of dollars in healthcare expenditures.”

Available data also suggests that antidepressant usage, especially if it extends beyond the first trimester, leads to an increased risk of pregnancy-induced hypertension and preeclampsia. “Given the importance of the hypertensive disorders of pregnancy in terms of maternal and newborn morbidity and mortality, and the widespread use of antidepressants during pregnancy, further investigation into this area will be essential,” write the authors.

Similarly, long-term exposure to SSRIs appears to correspond to an increased incidence of birth weight falling below the 10th percentile, coupled with increased rates of respiratory distress.

The health complications associated with antidepressant usage can be carried into infancy and beyond. A 2006 study showed that infants exposed to antidepressants in utero had a 30 percent risk of Newborn Behavioral Syndrome, most commonly associated with persistent crying, jitteriness and difficulty feeding. In more rare instances the syndrome can produce seizures and breathing difficulties leading to the need for intubation. Studies have also shown delayed motor development in babies and toddlers. And a Kaiser Permanente study showed a “two-fold increased risk of autism spectrum disorders associated with maternal treatment with SSRI antidepressants during the pregnancy, with the strongest effect associated with treatment during the first trimester.”

“There is enough evidence to strongly recommend that great caution be exercised before prescribing SSRI antidepressants to women who are pregnant or who are attempting to get pregnant, whether or not they are undergoing infertility treatment,” says Domar. “We want to stress that depressive symptoms should be taken seriously and should not go untreated prior to or during pregnancy, but there are other options out there that may be as effective, or more effective than SSRIs without all the attendant risks.”

Domar and team looked at studies assessing different treatment modalities for depression in the general population, including psychotherapy, exercise, relaxation training, yoga, acupuncture and nutritional supplements. While many of these options were shown to provide some benefit, psychotherapy, specifically cognitive behavioral therapy (CBT) showed the most promise. “There is overwhelming evidence that CBT is equivalent to antidepressant medication in the treatment of mild to moderate depression and more recent research indicates that it is effective in the treatment of severe depression as well,” write the authors.

A 2008 study showed impressive results for CBT in depressed women undergoing infertility treatments. The results showed that 79 percent of women who received CBT reported a significant decrease in symptoms, compared with 50 percent of women in the medication group.

“These alternative treatment options may not be appropriate for everyone, still we think it’s important for women on an antidepressant who are considering becoming pregnant to have a conversation with their physician about the risks and benefits of continuing to take their medication,” says Domar. “Because at this point in time, with no data to indicate an advantage to taking an SSRI during pregnancy, the research all points to increased risk.”

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In addition to Domar and Urato, other co-authors include: Vasiliki A. Moragianni, MD, MS and David A. Ryley, MD of Beth Israel Deaconess Medical Center and Boston IVF.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

MetroWest Medical Center is a full-service community teaching hospital system dedicated to meeting the health care needs of the MetroWest region of Massachusetts by providing advanced care with a community touch. The 269-bed health care system — the largest between Worcester and Boston — includes Framingham Union Hospital, Leonard Morse Hospital in Natick, MetroWest HomeCare and Hospice, and The MetroWest Wellness Center, an outpatient diagnostic imaging and rehabilitation center.

Tufts Medical Center is an exceptional, not-for-profit, 415-bed academic medical center that is home to both a full-service hospital for adults and Floating Hospital for Children. Conveniently located in downtown Boston, the Medical Center is the principal teaching hospital for Tufts University School of Medicine. Floating Hospital for Children is the full-service children’s hospital of Tufts Medical Center and the principal pediatric teaching hospital of Tufts University School of Medicine. Tufts Medical Center is affiliated with seven community hospitals and with New England Quality Care Alliance, its community physicians’ network. For more information, please visit www.tuftsmedicalcenter.org.

Health Canada suspends dispersal of Novartis flu shots after discovery of virus particle clumps

By Helen Branswell, The Canadian  PressOctober 27, 2012

TORONTO – Canada is following the lead of several European countries and  suspending distribution of flu vaccine made by the pharmaceutical firm  Novartis.

The decision relates to the discovery by the company of tiny clumps of virus  particles in some batches of flu vaccines made at the Novartis production  facility in Italy.

Health Canada, which announced the move, said Novartis has agreed to suspend  distribution of its vaccines — sold in Canada as Fluad and Agriflu — while the  department investigates the situation. All the Novartis vaccine Canada purchases  is made at the Italian plant.

The department is also telling doctors and others who administer flu shots to  hold off using Novartis product for the time being.

“We think it’s prudent, given the response of certain European countries to .  . . request of Novartis — and they will be complying — to stop distributing and  then to recommend to practitioners to refrain from using the (Novartis) vaccine  just until this review is completed,” Dr. Paul Gully, senior medical advisory  for Health Canada, said Friday.

Italy, Germany and Switzerland have suspended distribution of some Novartis  flu vaccine, and in the case of Germany recalled some lots of vaccine, after the  clumping issue came to light.

In a statement issued Friday night, the company said more than one million  doses of its flu vaccines have been administered in Europe so far this season  and no unexpected adverse events have been reported.

As well, it said that it has already delivered about 70 per cent of its  Canadian order (roughly 1.5 million doses), again without hearing of problems in  people who have received Novartis flu shots. The company said people who have  received Novartis flu shots are not at risk.

Novartis said finding minute clumps of virus protein in vaccines is not  unusual. They said their vaccines passed quality inspections and they are  confident the products are safe.

“The aggregate proteins are predominantly influenza virus-derived (mainly  hemagglutinin), all normal and necessary components of influenza vaccines,” the  company said. “Aggregation of these proteins is not unusual in vaccines  manufacturing.”

Hemagglutinin is the protein on the outside of flu viruses that locks onto  cells in the human respiratory tract to start the process of infection. Flu  vaccines are designed to provoke the immune system to produce antibodies to  hemagglutinin to protect against infection.

In fact, this isn’t the first time protein clumping has disrupted Canada’s  flu vaccine supply.

During the 2009 pandemic, there was a delay in delivery of unadjuvanted  vaccine for pregnant women when GlaxoSmithKline, Canada’s pandemic vaccine  supplier, found visible protein aggregation in some of the vaccine.

Adjuvants are compounds that boost the response a vaccine generates. Canada  used adjuvanted vaccine during the pandemic, but bought some unboosted product  for pregnant women as a precaution.

Novartis makes only about 20 per cent of Canada’s annual flu vaccine  purchase. GlaxoSmithKline makes the bulk of Canada’s seasonal flu vaccine,  though a variety of other suppliers have a share of the Canadian market.

Still, because of the way vaccine orders are placed, the hold on Novartis  vaccine could put some provinces and territories in a position where they face a  temporary vaccine shortfall, just at the time when flu shot programs are getting  underway, Gully admitted.

He said Health Canada hopes there is a rapid resolution of the situation. But  if provinces or territories have a problem with supply, efforts will be made to  share across jurisdictions, he said.

Both Fluad and Agriflu are sold in single-dose formulations, pre-loaded into  a syringe.

Fluad contains an adjuvant and is licensed for use in people 65 and older.  Older adults do not mount a good response to flu vaccine and the inclusion of an  adjuvant is an effort to improve the protection they get from flu  shots.

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Most heart attack patients’ cholesterol levels did not indicate cardiac risk: half of the patients with a history of heart disease had LDL cholesterol levels lower than 100 mg/dL

Contact: Rachel Champeau
rchampeau@mednet.ucla.edu
310-794-2270
University of California – Los Angeles

A new national study has shown that nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event, according to current national cholesterol guidelines.

Specifically, these patients had low-density lipoprotein (LDL) cholesterol levels that met current guidelines, and close to half had LDL levels classified in guidelines as optimal (less than 100 mg/dL).

“Almost 75 percent of heart attack patients fell within recommended targets for LDL cholesterol, demonstrating that the current guidelines may not be low enough to cut heart attack risk in most who could benefit,” said Dr. Gregg C. Fonarow, Eliot Corday Professor of Cardiovascular Medicine and Science at the David Geffen School of Medicine at UCLA and the study’s principal investigator.

While the risk of cardiovascular events increases substantially with LDL levels above 40󈞨 mg/dL, current national cholesterol guidelines consider LDL levels less than 100� mg/dL acceptable for many individuals. The guidelines are thus not effectively identifying the majority of individuals who will develop fatal and non-fatal cardiovascular events, according to the study’s authors.

Researchers also found that more than half of patients hospitalized for a heart attack had poor high-density lipoprotein (HDL) cholesterol levels, according to national guidelines.

Published in the January issue of the American Heart Journal, the study suggests that lowering guideline targets for LDL cholesterol for those at risk for cardiovascular disease, as well as developing better treatments to raise HDL cholesterol, may help reduce the number of patients hospitalized for heart attack in the future.

“The study gives us new insight and intervention ideas to help reduce the number of heart attacks,” said Fonarow, who is also director of the Ahmanson–UCLA Cardiomyopathy Center.

“This is one of the first studies to address lipid levels in patients hospitalized for a heart attack at hospitals across the entire country.”

The research team used a national database sponsored by the American Heart Association’s Get with the Guidelines program. The database includes information on patients hospitalized for cardiovascular disease at 541 hospitals across the country.

Researchers analyzed data from 136,905 patients hospitalized for a heart attack nationwide between 2000 and 2006 whose lipid levels upon hospital admission were documented. This accounted for 59 percent of total hospital admissions for heart attack at participating hospitals during the study period.

Among individuals without any prior cardiovascular disease or diabetes, 72.1 percent had admission LDL levels less than 130 mg/dL, which is the current LDL cholesterol target for this population. Thus, the vast majority of individuals having their first heart attack would not have been targeted for effective preventative treatments based on the criteria used in the current guidelines.

The team also found that half of the patients with a history of heart disease had LDL cholesterol levels lower than 100 mg/dL, and 17.6 percent of patients had LDL levels below 70 mg/dL, which are guideline targets for LDL cholesterol in those at fair risk and at high risk for cardiovascular disease, respectively.

The study also showed that HDL cholesterol, or “good cholesterol,” levels have dropped in patients hospitalized for heart attack over the past few years, possibly due to increasing rates of obesity, insulin resistance and diabetes.

Researchers found that 54.6 percent of patients had HDL levels below 40 mg/dL. Developing more effective treatments to boost HDL levels may help reduce the number of patients hospitalized for heart attacks, according to the authors.

“We found that less than 2 percent of heart attack patients had both ideal LDL and HDL cholesterol levels, so there is room for improvement,” said Fonarow.

Fonarow said that only 59 percent of patients in the database had their lipid levels checked upon admission, which should be increased, since these early measurements can often help guide treatment decisions.

He also noted that only 21 percent of patients in the study were taking lipid-lowering medications before admission, despite almost half having a prior history of cardiovascular events, which would prompt treatment.

 

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The national cholesterol guidelines are set by the National Cholesterol Education Program, part of the National Heart, Lung and Blood Institute of the National Institutes of Health.

The study was sponsored by the Get with the Guidelines program, which is supported by the American Heart Association in part through an unrestricted education grant from the Merck Schering Plough Partnership.

Fonarow has conducted research for GlaxoSmithKline and Pfizer and serves a consultant and has received honorarium from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Pfizer and Schering Plough companies. He is also chair of the Get with the Guidelines steering committee.

Other authors include: Dr. Amit Sachdeva, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA; Dr. Christopher P. Cannon, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA; Dr. Prakash C. Deedwania, Department of Cardiology, VA Medical Center/UCSF School of Medicine, San Francisco, CA; Dr. Kenneth A. LaBresh, Masspro, Waltham, MA; Dr. Sidney C. Smith, Jr., University of North Carolina School of Medicine, Chapel Hill, NC; David Dai, MS and Dr. Adrian Hernandez, Duke Clinical Research Institute, Durham, NC.

FDA ties pneumonia deaths to infant vaccine

Repost from 2008

 

WASHINGTON – GlaxoSmithKline Plc’s rotavirus vaccine is associated with increased pneumonia-related deaths and other adverse reactions, U.S. regulatory staff said in documents posted on Friday.

The review comes ahead of a Food and Drug Administration advisory meeting next Wednesday to consider approval of the oral vaccine to prevent the most common cause of severe diarrhea and dehydration among infants and young children in the world.

FDA staff said its analysis of 11 studies revealed that in the largest trial, there was a statistically significant increase in deaths related to pneumonia compared with placebo, documents posted on the FDA’s Web site said.

That study, which enrolled about 63,000 children, also found an increase in convulsions in children given the drug, named Rotarix. Another study found an increased rate of bronchitis, compared with placebo.

 

In a conclusion section, the FDA documents noted the pneumonia-related deaths and convulsions, but did not appear to make a recommendation to the advisory panel.

That expert panel will weigh the staff review, but makes its own recommendation, which is typically followed by the FDA

Glaxo chief: Our drugs do not work on most patients

Request Reprint From 2003:

By Steve Connor, Science Editor The Independent
Monday 08 December 2003

A senior executive with Britain’s biggest drugs company has admitted that most prescription medicines do not work on most people who take them.

Allen Roses, worldwide vice-president of genetics at GlaxoSmithKline (GSK), said fewer than half of the patients prescribed some of the most expensive drugs actually derived any benefit from them.

It is an open secret within the drugs industry that most of its products are ineffective in most patients but this is the first time that such a senior drugs boss has gone public. His comments come days after it emerged that the NHS drugs bill has soared by nearly 50 per cent in three years, rising by £2.3bn a year to an annual cost to the taxpayer of £7.2bn. GSK announced last week that it had 20 or more new drugs under development that could each earn the company up to $1bn (£600m) a year.

Dr Roses, an academic geneticist from Duke University in North Carolina, spoke at a recent scientific meeting in London where he cited figures on how well different classes of drugs work in real patients.

Drugs for Alzheimer’s disease work in fewer than one in three patients, whereas those for cancer are only effective in a quarter of patients. Drugs for migraines, for osteoporosis, and arthritis work in about half the patients, Dr Roses said. Most drugs work in fewer than one in two patients mainly because the recipients carry genes that interfere in some way with the medicine, he said.

“The vast majority of drugs – more than 90 per cent – only work in 30 or 50 per cent of the people,” Dr Roses said. “I wouldn’t say that most drugs don’t work. I would say that most drugs work in 30 to 50 per cent of people. Drugs out there on the market work, but they don’t work in everybody.”

Some industry analysts said Dr Roses’s comments were reminiscent of the 1991 gaffe by Gerald Ratner, the jewellery boss, who famously said that his high street shops are successful because they sold “total crap”. But others believe Dr Roses deserves credit for being honest about a little-publicised fact known to the drugs industry for many years.

“Roses is a smart guy and what he is saying will surprise the public but not his colleagues,” said one industry scientist. “He is a pioneer of a new culture within the drugs business based on using genes to test for who can benefit from a particular drug.”

Dr Roses has a formidable reputation in the field of “pharmacogenomics” – the application of human genetics to drug development – and his comments can be seen as an attempt to make the industry realise that its future rests on being able to target drugs to a smaller number of patients with specific genes.

The idea is to identify “responders” – people who benefit from the drug – with a simple and cheap genetic test that can be used to eliminate those non-responders who might benefit from another drug.

This goes against a marketing culture within the industry that has relied on selling as many drugs as possible to the widest number of patients – a culture that has made GSK one of the most profitable pharmaceuticals companies, but which has also meant that most of its drugs are at best useless, and even possibly dangerous, for many patients.

Dr Roses said doctors treating patients routinely applied the trial-and-error approach which says that if one drug does not work there is always another one. “I think everybody has it in their experience that multiple drugs have been used for their headache or multiple drugs have been used for their backache or whatever.

“It’s in their experience, but they don’t quite understand why. The reason why is because they have different susceptibilities to the effect of that drug and that’s genetic,” he said.

“Neither those who pay for medical care nor patients want drugs to be prescribed that do not benefit the recipient. Pharmacogenetics has the promise of removing much of the uncertainty

In the Age of Anxiety, are we all mentally ill?

NEW YORK (Reuters) – When Cynthia Craig was diagnosed with postpartum depression eight years ago, she told her family doctor she felt anxious about motherhood. She wondered whether she had made a catastrophic mistake by quitting her job, whether she could cope with the long, lonely hours stay-at-home mothers face – and even whether she should have had children.

              “Anxiety is something I have always had, especially during times of change,” said Craig, 40, who lives in Scotland, Ontario. “But I was never worried about the level of anxiety, and it never prevented me from leaving the house, driving, socializing or even speaking in front of people.”

              Her doctor referred her to an anxiety clinic, where a nurse asked Craig dozens of yes-or-no questions – are you afraid of snakes? do you hear voices? do you vomit from anxiety? – and made a diagnosis. “She said, ‘Let’s call it Generalized Anxiety Disorder with a touch of social phobia,'” Craig said.

              That didn’t feel right to her, but the clinic’s psychiatrist agreed with the nurse and said Craig’s concerns about motherhood constituted an anxiety disorder, a form of mental illness, and prescribed Pfizer’s Effexor and then GlaxoSmithKline’s Paxil. Craig says the drugs exacerbated the very anxiety that she doubted required medication.

              Craig’s case is one of millions that constitute an extraordinary trend in mental illness: an increase in the prevalence of reported anxiety disorders of more than 1,200 percent since 1980.

              In that year, 2 percent to 4 percent of Americans suffered from an anxiety disorder, according to the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM) of Mental Disorders, used by psychiatrists and others worldwide to diagnose mental illness.

              In 1994, a study asking a random sample of thousands of Americans about their mental health reported that 15 percent had ever suffered from anxiety disorders. A 2009 study of people interviewed about their anxiety repeatedly for years raised that estimate to 49.5 percent – which would be 117 million U.S. adults.

              Some psychiatrists say the increase in the prevalence of anxiety from about 4 percent to 50 percent is the result of psychiatrists and others “getting better at diagnosing anxiety,” as Dr. Carolyn Robinowitz, a past president of the APA who is in private practice in Washington, D.C., put it. “People who criticize that are showing their bias,” she said. “When we get better at diagnosing hypertension, we don’t say that’s terrible.”

Critics, including other leading psychiatrists, disagree. They say the apparent explosion in anxiety shows there is something seriously and dangerously wrong with the DSM. Its next edition, due in May, would lower the threshold for identifying anxiety.

The criticism rests on three arguments. First, the DSM fails to recognize that anxiety is normal and even beneficial in many situations, so it conflates a properly functioning brain system with a pathology. Second, the DSM’s description of anxiety is more about enforcing social norms than medicine.

Finally, they say, anxiety is adaptive. Its brain circuitry was honed by evolution for a purpose. Only when that mechanism misfires should a person be diagnosed as mentally ill.

“No human emotion is more basic than anxiety,” said sociologist Allan Horwitz of Rutgers University. “Many forms of it simply should not be categorized as disorders, because they’re the result of the way people evolved thousands of years ago, rather than something going wrong.”

IDENTIFYING THE TRULY ILL

Horwitz and other critics recognize that when the brain’s anxiety system misfires it can prevent people from functioning, as when someone is unable to leave home, interact with friends and family or walk past even a leashed dog. But the anxiety system is working properly when it makes someone afraid of heights or wild dogs or threatening strangers.

“Anxiety or panic symptoms that have been severe, persistent and cause clinically significant distress or impairment need to be diagnosed promptly,” said Dr. Allen Frances, a psychiatrist who led the previous DSM revision and questions some of the new criteria. “Very effective treatments are available.”

“We don’t oppose people getting treatment,” said Horwitz, co-author of the new book “All We Have to Fear: Psychiatry’s Transformation of Natural Anxieties into Mental Disorders.” “But people are much too willing to think they have a disorder that requires treatment.”

Many psychiatrists don’t see it that way. Under changes for the DSM-5 proposed by experts convened by the APA, symptoms such as excessive worry, restlessness, feeling on edge, avoiding activities that cause anxiety, and being overly concerned about health or finances or family would have to be present for only three months rather than six to justify a diagnosis of Generalized Anxiety Disorder (GAD). And people would have to display one physical symptom, not the current three.

“Because its threshold for GAD is set so ridiculously low, DSM-5 will mislabel as mentally ill many people who are experiencing no more than the normal and expected worries of everyday life,” said Frances.

Dr. Donna Rockwell, a clinical psychologist who has organized opposition to aspects of the DSM-5 process, warned that “unless come to their senses, GAD will be identical to the existential worries all of us face as part of being human.” That will bring “a bonanza to the drug companies,” she added, opening the floodgates to “more inappropriate, expensive and potentially harmful drug use.”

Drugmakers reported $661 million in U.S. sales of anti-anxiety drugs last year, according to IMS Health. Most psychiatrists see that as evidence people suffering from mental illness are getting help. On Thursday the Pharmaceutical Research and Manufacturers of America issued a report touting the many drugs being developed for mental illnesses, including 26 for anxiety.

“When anxiety symptoms impair a person’s functioning, what’s so bad about helping them get back to a normal state and using medication if appropriate?” asked Robinowitz.

The message that what used to be considered part of the human condition is pathological is getting through, at least to some people.

              James Heaney, 44, told his family physician in 2000 that he often felt shy or mildly depressed in social situations – “like I saw on the TV commercial” telling viewers to “ask your doctor” about social anxiety. “There was no in-depth evaluation of my symptoms,” said Heaney, then a network administrator for a school district near Rochester, New York. After a 10-minute interview, he had a diagnosis of “mild social anxiety” and a prescription for Paxil. “For such a powerful drug,” he said, “it was remarkably easy to get.”

              EVOLUTIONARY RESPONSE

Research over the past decade shows that feeling anxious is how the brain’s emotion centers send signals to its thinking centers that something is amiss.

For instance, it is normal to be anxious over a sick child, a loved one’s illness, unemployment or other setbacks in life, said New York University sociologist Jerome Wakefield, co-author of “All We Have to Fear.”

“The feeling of anxiety tells you something poses a threat, which can motivate you to stay vigilant” – about, say, a change in a sick child’s symptoms, he said.

              In the Paleolithic era, when our prehistoric ancestors lived in small clans, how people were viewed by strangers and kin could determine survival. So when people fret over going to a party, giving a speech or otherwise subject themselves to judgment, it reflects an adaptive response to the millennia-old need to be attuned to other people’s disapproval, researchers say. Anxiety about public speaking accounts for about half the diagnoses of social anxiety disorder.

              “There is great evolutionary and survival value in anxiety, which makes it difficult to identify as an illness or pathology,” said psychologist Frank Farley of Temple University.

Anxiety was working properly among survivors of Hurricane Katrina, Wakefield and Horwitz contend. Years after the devastating 2005 storm, schools, housing, policing and other aspects of life in New Orleans had still not returned to normal. Using DSM criteria, a 2007 study concluded that half the surviving residents were “mentally ill” because they experienced anxiety about those lingering effects.

              “If you survived Katrina, anxiety is not a sign of mental illness; it’s the brain working as it should,” said Wakefield. Such emotions can spur survivors to agitate for rebuilding neighborhoods, he said.

              Another concern is that by labeling normal human variation – being more anxious, fearful or worried than the average person – a mental illness, psychiatry is venturing into social control.

“To suggest that anyone who’s afraid to speak in front of hundreds of strangers has a mental illness creates social pressure to change,” said Wakefield. “And that pushes psychiatry away from medicine and into enforcing social values.”

BAD REACTIONS

In retrospect, Marla Royce (who asked that her real name not be used) thinks her brain’s anxiety system was working as evolution intended. A successful Texas novelist, she was upset about the death of her father in 2004. Her anxiety was compounded when her publisher did not promote her new book, leading Royce to worry that her writing career was over.

“It was just garden-variety situational anxiety,” she says now about the agitation and disorientation she felt.

Royce said she went along “trustingly and blithely” when a family physician diagnosed her with GAD. “He said the pharma sales rep had just left some samples, so he gave me Lexapro,” to which a psychiatrist added Paxil, Xanax and Klonopin.

              She became dependent on the drugs, taking ever-higher doses. Her psychiatrist told her that “was proof my anxiety disorder was out of control and that I would have to be medicated for life.” She suffered “steadily declining mental and physical health” until she stopped the meds five years ago and shared her story with the online support group PaxilProgress.

              James Heaney’s shyness turned to numbness on Paxil. “It made me insular and nonresponsive to my friends and family,” he said. “My mood became very variable,” and co-workers told him they felt uncomfortable asking him for computer help as they once did “because they weren’t sure which James they would get.”

              He weaned himself off psychiatric drugs in 2011. The social anxiety he still occasionally feels “is a relatively easy problem to deal with,” he said.

              For Cynthia Craig, the drugs she was prescribed triggered “excruciating anxiety symptoms like I had never experienced in my entire life.”

              “I told my doctor I don’t want to be on anything,” she said. “My anxiety is predictable and something I can handle.”

              (Reporting by Sharon Begley; Editing by Michele Gershberg and Douglas Royalty)

Ads for SSRI antidepressants are misleading, say researchers

Consumer ads for a class of antidepressants called SSRIs often claim that depression is due to a chemical imbalance in the brain, and that SSRIs correct this imbalance, but these claims are not supported by scientific evidence, say researchers in PLoS Medicine.

Although scientists in the 1960s suggested that depression may be linked to low brain levels of the chemical serotonin (the so-called “serotonin hypothesis”), contemporary research has failed to confirm the hypothesis, they say.

The researchers–Jeffrey Lacasse, a doctoral candidate at Florida State University and Dr. Jonathan Leo, a neuroanatomy professor at Lake Erie College of Osteopathic Medicine–studied US consumer advertisements for SSRIs from print, television, and the Internet.  They found widespread claims that SSRIs restore the serotonin balance of the brain. “Yet there is no such thing as a scientifically established correct ‘balance’ of serotonin,” the authors say.

According to Lacasse and Leo, in the scientific literature it is openly admitted that the serotonin hypothesis remains unconfirmed and that there is “a growing body of medical literature casting doubt on the serotonin hypothesis,” which is not reflected in the consumer ads.

For instance, the widely televised animated Zoloft (setraline) commercials have dramatized a serotonin imbalance and stated, “Prescription Zoloft works to correct this imbalance.” Advertisements for other SSRIs, such as Prozac (fluoxetine), Paxil (paroxetine), and Lexapro (escitalopram), have made similar claims.

In the US, the FDA is responsible for regulating consumer advertisements, and requires that they be based on scientific evidence. Yet, according to Lacasse and Leo, the mismatch between the scientific literature and the SSRI advertisements is “remarkable, and possibly unparalleled.”

And while the Irish equivalent of the FDA, the Irish Medicines Board, recently banned GlaxoSmithKline from claiming in their patient information leaflets that paroxetine (Paxil) corrects a chemical imbalance, the FDA has never taken any similar action on this issue.

Commenting on Lacasse and Leo’s work, Professor David Healy of the North Wales Department of Psychological Medicine, said: “The serotonin theory of depression is comparable to the masturbatory theory of insanity.  Both have been depletion theories, both have survived in spite of the evidence, both contain an implicit message as to what people ought to do.  In the case of these myths, the key question is whose interests are being served by a widespread promulgation of such views rather than how do we test this theory.”

Dr Joanna Moncrieff, Senior Lecturer in Psychiatry at University College London, said: “It is high time that it was stated clearly that the serotonin imbalance theory of depression is not supported by the scientific evidence or by expert opinion.  Through misleading publicity the pharmaceutical industry has helped to ensure that most of the general public is unaware of this.”