Seroxat/Paxil : Deception As A Marketing Tool
http://www.lasvegassun.com/news/2009/aug/24/deception-marketing-tool/
Drug industry writers behind some articles purportedly written by doctors
Monday, Aug. 24, 2009 | 2:05 a.m.
A student who hands in a term paper under his own name when in fact it had been written by someone else has committed a serious breach of ethics.
The same is true for doctors who allow their bylines to appear above articles published in medical journals when in fact the articles were largely produced by ghostwriters pushing a product.
According to stories published Wednesday by The New York Times and the Associated Press, many doctors have been persuaded by drug companies to cooperate on such articles.
A “sophisticated ghostwriting program” used by London-based drugmaker GlaxoSmithKline to promote an antidepressant pill called Paxil was an example given by AP. Although the company says it has discontinued the ghostwriting program, the news service obtained court documents showing that it had used this marketing tactic.
The danger here is that doctors are trusted. Readers who see a doctor’s name atop an article about a certain drug are apt to believe what is being stated. They would certainly be more skeptical if they knew the article was actually written by people working for the company that makes the drug.
Ghostwritten articles on Paxil, which highlighted doctors as their authors, appeared in five medical journals from 2000 to 2002. AP reported that today hundreds of people are pressing personal injury and wrongful death suits against GlaxoSmithKline, claiming the company downplayed the risks of Paxil.
The Times disclosed that there is “a growing body of evidence suggesting that doctors at some of the nation’s top medical schools have been attaching their names and lending their reputations to scientific papers that were drafted by ghostwriters working for drug companies — articles that were carefully calibrated to help the manufacturers sell more products.”
There are no laws prohibiting ghostwriting. But there is no question that the widespread practice is unethical and that universities and medical associations should crack down. We agree with a bioethics expert at Duke University who told the Times, “To blow this off is not acceptable.”
Seroxat : The Mainstream Media Investigates Again
The Seroxat scandal was originally brought to mass public consciousness by the BBC with their groundbreaking expose “The Secrets of Seroxat” in October 2002. Since that time a multitude of documentaries , blogs, news articles , forums , comment and opinion on Seroxat and the dangers of other SSRI medications has followed. For the past year, the mainstream media have been fairly quiet on the Seroxat situation, but in the last week, the excellent Sarah Boseley of the Guardian newspaper UK has once again began to investigate the dangers of Seroxat and SSRI drugs.
Here are the links to her new articles :
http://www.guardian.co.uk/society/2009/aug/07/antidepressants-drugs-health-risk
- , Friday 7 August 2009 22.10 BST
- Article history
Antidepressants once seen as miracle drugs: now risks are becoming evident
US courts to hear claims that insufficient attention was paid to dangers to foetus
Seroxat antidepressant pills. Photograph: Jack Sullivan/Alamy
Since the horror of the Thalidomide scandal in the 1960s, pharmaceutical companies and medicines regulators have been acutely aware of the dangers drugs may pose to the unborn child.
Establishing what the effect of a drug may be on a foetus, however, is no simple task. Companies must rely on animal studies in the early stages of research and hope that the drug will behave in humans in the same way. Trials on pregnant women are rarely carried out, for obvious reasons.
Depression and anxiety became big business for the pharmaceutical industry in the 1990s as doctors became better at diagnosing the problems, exposing a population of over-achieving, highly-stressed, worried-well.
Women, always more willing to see a doctor than men, were a large proportion of those diagnosed and put on SSRIs (selective serotonin reuptake inhibitors) such as Prozac and the British drug Seroxat, known as Paxil in the US. For a while, these seemed to be the new miracle drugs. They were safer than older antidepressants because the severely depressed could not overdose on them.
But in court cases about to begin in the US, it will be argued that insufficient attention was paid to the possible dangers for young women who were pregnant or might become pregnant and more particularly, for their babies.
Twenty years ago, when serotonin, a chemical which sends messages to the brain, was under investigation, it was recognised that it was likely to have an effect on the developing foetus, according to David Healy, professor of psychiatry in Bangor, Wales, and an expert witness in the legal action againstGlaxoSmithKline. It was not just a neurotransmitter, but played a role in organ development in the embryo.
Animal tests appear not to have been reassuring, he says. By 1991, a study by Shuey and Lauder had shown that all SSRIs were potentially teratogenic – could cause birth defects – in animals, albeit in small numbers. GSK denies this. “The animal and human studies did not show teratogenicity, and were made available to regulatory agencies as part of the approvals,” said a spokesman. But based on Lauder’s work, Pfizer which made a rival drug, Zoloft, recommended that women on their drug “should employ an adequate method of contraception”.
Datasheets
GSK launched Seroxat in 1992. It was recognised that insufficient work had been done to establish the safety of any of the SSRIs during pregnancy, and as a result, throughout the 1990s, the standard statement on the drug datasheets which go to doctors was that they “should not be used during pregnancy or by nursing mothers unless the potential benefit outweighs the potential risk”.
But pregnant women become depressed too. “I think depression is generally underestimated in pregnancy,” said Dr Tim Kendall, joint director of the National Collaborating Centre for Mental Health in the UK. “It is much more common than people think. It used to be thought you gave birth and you are suddenly depressed – the withdrawal of all those oestrogens. But in fact people who have postnatal depression are quite commonly depressed before the birth.”
GSK began to market Seroxat as the SSRI of choice for women who were depressed and pregnant, or might become pregnant, says Healy. GSK says marketing to women of childbearing age was valid, as women make up a high proportion of those diagnosed with depression and anxiety and most would be of childbearing age.
Seroxat was positioned as the best SSRI in cases where the benefits of treating depression outweighed any risk. It was found in only low concentrations in breast milk, the company said, which meant that breastfeeding would not be a problem. It pointed to studies which showed children born to mothers on Seroxat had no mental or behavioural problems.
GSK also argued that depression itself could harm the baby because an untreated mother is more likely to smoke, drink and take drugs and maybe even to harm herself. Healy says there is no evidence relating to women with depression during pregnancy – only to those who were diagnosed with postnatal depression.
From 2000, GSK in the US was running a targeted promotional campaign to increase sales of Paxil to pregnant women and women of reproductive age. The Mother Knows Best Campaign had three main objectives: to raise awareness of its greater claims for safety than other antidepressants, such as the low Paxil levels in breastmilk, to educate doctors and consumers generally on the benefits of the drug for women of childbearing age and to encourage women with depression to ask specifically for Paxil.
Influential psychiatrists, called in the business “key opinion leaders” were recruited to give talks and author articles on Paxil’s safety for mothers to be.
But in February 2005, the Lancet published an analysis of almost 100 cases from the World Health Organisation’s adverse drug effects monitoring centre in Sweden of babies who suffered from convulsions and other withdrawal symptoms after birth because their mother had been taking an SSRI for depression during her pregnancy.
The effects were most marked on Seroxat, it said, and recommended that all SSRIs “should be cautiously managed in the treatment of pregnant women with a psychiatric disorder”.
Malformations
In 2003, the Food and Drug Administration (FDA) which regulates medicines in the United States had asked GSK to look at the incidence of birth defects on Seroxat, or Paxil. In 2005, the company handed over a retrospective epidemiological study which found an increased risk of major congenital malformations in the babies of women who took it in the first three months of pregnancy.
GSK pointed out that data from other places did not show up a problem. Nonetheless, the FDA changed the pregnancy warning from category C, meaning not enough research has been done to be sure of safety, to category D, meaning there are signs it may not be safe.
“FDA is advising patients that this drug should usually not be taken during pregnancy, but for some women who have already been taking Paxil, the benefits of continuing may be greater than the potential risk to the foetus,” it said.
A later advisory notice from the FDA drew attention to a raised risk of a life-threatening lung condition called persistent pulmonary hypertension in babies whose mothers took Paxil later in pregnancy – up sixfold from the usual level of one or two per 1,000 babies born in the US. But at the same time it pointed to a study in the Journal of the American Medical Association showing women who stopped taking antidepressants while pregnant were five times more likely to relapse.
GSK insists that their drug has only ever been promoted for those who need it – in the case of pregnant women, those in whom the dangers of depression are greater than any possible risk from the drug. “GSK appropriately marketed paroxetine for use by the patients for whom it was indicated and who could benefit from it,” said the company in a statement.
http://www.guardian.co.uk/society/2009/aug/07/paxil-seroxat-antidepressants-glaxosmithkline
Family’s story: antidepressants to blame for child’s defects?
- , Friday 7 August 2009 22.10 BST
- Article history
Kaden Mendoza has just turned seven. His parents, Deborah and Kevin, gave him a big party. They do it every birthday. “It is another year that he has made it through,” says Deborah.
Kaden has undergone open heart surgery three times, the first when he was nine weeks old. “We didn’t find out about Kaden’s heart condition straight away and we almost lost him,” says his mother.
The fourth chamber of his heart was not visible on the ultrasound scan she had when she was pregnant. They didn’t know it was because it was not fully developed. He was two months old when she took the baby to the doctor because he was not breastfeeding.
“His lungs were full of blood,” she says. That was on 22 September 2002. On the 24th, he was airlifted to San Francisco from their home in Washington for his first heart operation.
Throughout her pregnancy, Deborah Mendoza had been taking the antidepressant Paxil, known in the UK as Seroxat. It had been prescribed by the doctor she had seen when she had a panic attack. It was a one-off, a bit of a funny turn, but her father had suffered from the same thing and had been on medication. So she took the advice and started on the tablets in June 2001.
Six months later, she was back at the doctor’s surgery for a different matter. “When I found out I was pregnant, I was concerned and asked if it was alright to take while pregnant, and they said yes,” she said.
Even so, she tried to stop, but found she could not. “It was awful. I was throwing up non-stop.” It was nothing to do with the pregnancy, she said. She was having withdrawal symptoms. “I called my sister and I was just laying there saying, ‘this is awful’.”
She went to see another doctor and was told it would be better to stay on the drugs through her pregnancy.
When Kaden’s heart defect was diagnosed, she had no idea that Paxil might have been responsible. It was not until 2005, when the Food and Drug Administration put out a warning that she realised what might have happened. The family is now suing GlaxoSmithKline, makers of Paxil.The future for Kaden does not look bright. His condition was made worse by complications after the insertion of an artificial tube into his heart. “He will need a heart transplant within two to ten years,” his mother says. “And there is a 50% chance he will need another one after that. He suffers a lot. He loves sports. He is so good at golf and baseball and basketball, but he can’t play them because he runs out of breath.
“It is hard not to be upset with GSK. No amount of money can ever make up for what’s happened and what will continue to happen to Kaden.”
http://www.guardian.co.uk/society/2009/aug/07/women-antidepressant-birth-defects
Women given antidepressant that can cause birth defects
Revealed: GPs still prescribing pill, despite evidence of risk in pregnancy
Sarah Boseley , Guardian UK , 7/08/2009
Thousands of women in the UK may be taking antidepressants prescribed by their GPs without knowing that the pills, which are hard to stop taking, could cause birth defects in unborn children.
The problems relate to a class of drug known as SSRIs (selective serotonin reuptake inhibitors), which includes Prozac and, in particular, the British-made Seroxat.
Several studies have shown a link to birth defects, particularly malformed hearts, in a small proportion of the babies born to women who were taking the drug in the early weeks ofpregnancy.
Most GPs in the UK believe that these drugs are safer than older antidepressants. Seroxat has been marketed to women as a drug to relieve anxiety and depression.
In the US, the Food and Drug Administration, which licences medicines, issued a warning in 2005 and changed the status of Seroxat, which is sold there under the brand name Paxil. The FDA warns doctors “not to prescribe Paxil in women who are in the first three months of pregnancy or are planning pregnancy, unless other treatment options are not appropriate”.
The UK regulator, the Medicines and Healthcare products Regulatory Authority (MHRA) wrote to doctors telling them to prescribe Seroxat for pregnant women only when the benefits outweigh the risks. The National Institute for Health and Clinical Excellence (Nice) also urged caution.
But experts including Dr Tim Kendall, joint director of the National Collaborating Centre for Mental Health which wrote the Nice guidelines on depression, say GPs are still giving SSRIs to pregnant women and other women of childbearing age without warning of the potential dangers.
Most psychiatrists he knew would no longer prescribe Seroxat, said Dr Kendall. “But in primary care it is still quite widely prescribed. GPs are quite flooded with advice. It is unlikely they will have picked up a specialist piece of advice from Nice about mental health.”
In the US, a series of legal actions is about to begin. Lawyers representing women suing the manufacturer of Seroxat, GlaxoSmithKline, say the British company knew or should have known about the birth defects more than 10 years ago. GSK denies it, saying it told the authorities as soon as it was aware of the issue.
All the SSRIs are implicated. According to David Healy, professor of psychiatry in Bangor, Wales, who has been asked to give evidence in the US cases, the rate of birth defects is doubled from 2% in the general population to 4% of those on the drugs. The rate of major defects rises from 1% to 2%. The general rate of miscarriages is 8%, but 16% of women on Seroxat miscarry.
Concern about depression in pregnancy has grown in recent years. Midwives at antenatal clinics are increasingly encouraged to ask pregnant women about their mood and feelings, to pick up any signs of depression which could cause them to harm themselves or fail to bond with the baby when it is born. Talking therapies should be an option but are often in short supply.
Kendall believes the issue of the SSRIs in pregnancy needs to be addressed. “They are addictive,” he said. “The question is should we warn young people before they take them that if they think they might be wanting to get pregnant, these drugs are quite hard to get off?”
“From the late 1980s there was work which very clearly showed that the SSRI group of drugs ought to be regarded as posing a high risk of birth defects to women in the early stages of pregnancy or when they didn’t even know they were pregnant,” said Healy.
One of the SSRI manufacturers, Pfizer which made Zoloft, indicated in the prescribers’ bible, the British National Formulary, that their drug was not recommended for women who might become pregnant. This warning, said Healy, “probably did very little to deter women from taking the drug or doctors from prescribing it, but GSK went further and actually promoted the drug to women of childbearing age”.
All SSRIs pose a risk, said Healy. The danger with recent warnings from the FDA and MHRA about Seroxat is that GPs will switch women to another drug of the same class.
Emily Jackson, professor of law at the London School of Economics, believes there may be a case for legal action in the UK. Cases could potentially be brought against either the GP or the manufacturer for a failure to warn of potential risks.
“The group of patients who often receive an inadequate warning are women who are not currently pregnant or trying to become so, but who are not warned that there is a danger that they will become addicted to paroxetine [Seroxat] while they are not pregnant, and will find themselves unable to stop taking it once they become pregnant, perhaps many years later,” she said.
She raises the possibility of an action under the Congenital Disabilities Act of 1976 on behalf of a child injured by antidepressants prescribed for the mother.
She compares the “no alcohol” message put out by the department of health to pregnant women to the “more equivocal advice” on Seroxat and pregnancy. In both cases, she says, “it seems that women are not to be trusted with making choices for themselves”.
GlaxoSmithKline argues there is still insufficient scientific evidence to prove that the drugs directly cause defects.
A spokesman said: “Tragically, birth defects can occur whether or not the mother was taking medication during pregnancy. We have monitored reports of foetal exposure to paroxetine since the first studies of the drug and there was no indication of increased risk from studies, adverse event reports or any other source until the summer of 2005.
“As soon as we became aware of a potential increased risk, we promptly notified regulatory authorities and physicians. We strongly believe that doctors should be advised of the potential risk of medicines before prescribing them, and the potential risk of paroxetine use during pregnancy is detailed in the information provided with the medicine.”
SSRI’s : Paxil/Seroxat : Russian Roulette
I came across this interesting article in the LA Times :
http://www.latimes.com/features/health/la-he-depression-stopping-drugs3-2009aug03,0,3113680.story
SPECIAL ISSUE: DEPRESSION
Stopping antidepressants can cause side effects
Recognizing withdrawal symptoms and working with your doctor are key.
Regina Nuzzo, Los Angeles Times Staff Writer
Ryan Yorke, now 21, started taking Paxil after an out-of-the-blue panic attack his freshman year of high school. At first it worked great. But he gained weight and had other problems — he started acting up in school and failing classes, for example. So after a year, he — along with his mother and his psychologist — decided it was time to stop.
Every time he reduced his dose, things got out of control, says his mother, Laurie Yorke, a registered nurse and now an administrator of paxilprogress.org, an antidepressant-withdrawal support site.
After the first big dose drop, Ryan slashed his wrists in front of his mother in the living room. “It was a six-hour psychotic episode. He was quoting Shakespeare and saying he wanted to die,” she recalls.
A few weeks later, after more gradual dose changes, Ryan was still so sensitive to light and sound that he taped shut the window shades in his bedroom. His memory and concentration were poor. He dropped out of school and got his GED later, after the withdrawal process was over.
Mental health professionals aren’t sure how many people have problems when stopping antidepressant medication. It’s not even clear how to define the cluster of withdrawal symptoms people report, or even what causes the effects. “It’s a difficult corner of the field,” says Dr. Kenneth Duckworth, medical director of the National Alliance on Mental Illness and psychiatry professor at Harvard Medical School. “It’s hard to know whether the person’s depression is worsening or if they’re having a variation on a discontinuation syndrome.”
Knowing what to look out for when you and your doctor start the stopping process (which the medical community ƒè terms “antidepressant discontinuation syndrome”) can help minimize issues.
All approved antidepressant medications either come with documented discontinuation problems or a manufacturer’s warning of the possibility. Typical symptoms can depend on the class of antidepressant.
Drugs that affect serotonin levels — selective serotonin reuptake inhibitors, or SSRIs, such as Prozac, and serotonin-norepinephrine reuptake inhibitors, or SNRIs, such as Effexor — can cause dizziness, upset stomach, headache and flu-like symptoms when stopped. Some people also report electric-shock sensations that zap through the body.
Other serotonin-stopping symptoms can mimic those of depression: lethargy, sleep problems, sadness, anxiety and thoughts of suicide.
Tricyclic antidepressants, which were introduced in the 1950s and include Sinequan and Tofranil, can trigger withdrawal symptoms similar to those of SSRIs and SNRIs. But since these drugs work on dopamine as well as serotonin and norepinephrine, stopping them can cause balance problems or Parkinson’s-like tremors.
Even more dramatic are problems from quitting the oldest kind of antidepressants: monoamine oxidase inhibitors, or MAO inhibitors. These work on several brain chemicals; withdrawal symptoms include agitation, nightmares, aggression and psychosis.
Many people have no symptoms when they quit taking antidepressants. And any problems are usually mild and short-lived, Duckworth says. But sometimes the effects can be so bad as to require time off work or, rarely, to send people to the emergency room.
Estimates vary as to how often problems will happen. And some of the symptoms that patients report may not in fact be linked to withdrawal from the drug. One clinical trial from 1995 found that 35% of patients taking Paxil had mild to moderate discontinuation symptoms — but so did 14% of patients who had been taking a placebo.
Symptoms usually appear within three days after a change in dose and disappear after two weeks, says Dr. Christopher Kratovchil, an American Psychiatric Assn. spokesman and psychiatry professor at the University of Nebraska Medical Center. A 1993 study of the SSRI Luvox found that the average number of symptoms shot up within the first few days after a missed dose, peaked during the fifth day and then gradually dwindled over the next week or so.
Doctors can’t really predict who will have problems. One study in 2002 found that women were likely to have more severe symptoms, but other studies have found no gender difference. Genetics likely plays a role.
Some drugs get more complaints than others. In a 2006 study of antidepressant-withdrawal calls to a help line in England, about 40% were from people who had problems stopping Paxil, and about 14% were from those quitting Effexor. No other drug accounted for more than 10% of calls.
Drugs with more users would be more likely to garner more complaints, of course. So when researchers took into account the relative usage of each of the drugs, Paxil and Effexor fell to fifth and ninth place on the complaints list. The top three spots all went to MAO inhibitors.
The biology behind symptoms is unclear. Antidepressants boost levels of brain chemicals such as serotonin and dopamine, but they also dampen the system that transports these chemicals, researchers believe. When there’s suddenly less drug in the brain, it takes time for the system to pick itself up again. And since these brain chemicals control more than just mood (they also influence digestion, sleep and motor control, for example) withdrawal reactions can be broad.
Faster-metabolized drugs are generally more likely to cause discontinuation symptoms, Kratovchil says. The shorter a drug’s half-life, the faster it’s cleared from your body, and so the more abrupt the change in your brain’s chemical system when you don’t replenish the medication.
A typical dose of Paxil (which among SSRIs has some of the highest reported rates of discontinuation symptoms) has a half-life of less than a day, for example. The half-life of a typical dose of Prozac is three to six days. For that reason, Prozac has some of the fewest reported problems.
This means that stopping antidepressants cold turkey can be a bad idea, especially for short half-life drugs. A gradual taper gives the brain more time to right itself. “If a plane wants to land in Los Angeles, it’s nice to start going down very, very slowly over Denver,” Duckworth says. “I make changes gently.”
There’s no one right way to taper. A schedule for Paxil, for example, may involve stepping down the daily dose from the full amount by 10 milligrams or less a week.
Another option is to switch to a drug in the same class with a longer half-life — say, from Zoloft to Prozac. That should allow a quicker step-down.
Some patients try exotic regimens to wean themselves even more gradually. They count individual granules from a capsule, use a nail file and a jeweler’s scale to measure tablet shavings, or try the “orange juice” strategy. This last trick might involve dissolving a capsule into a measured glass of orange juice every day and drinking 90% of it for the first week, 80% of it during the second week, and so on.
But a small 2008 study suggests that long step-down schedules might not help that much.
In a group of 28 patients taking SSRI and SNRI antidepressants, about half had significant withdrawal symptoms — no matter whether they had been randomly assigned to three-day or 14-day tapering.
“Every person is unique,” Duckworth says. “This needs to be a collaborative effort between patients and doctors.”
Read more about antidepressant discontinuation at www.aafp.org/afp/20060801/499.html.
health@latimes.com
SSRI’s : Dying For A Cure
Rebekah Beddoe is a 30 something Australian woman who has written a fascinating account of her horrific experiences with SSRI drugs, Psychiatric medication and her awful experiences with psychiatry. Her book is called “Dying for a Cure” and is recommended reading for anyone who wishes to know the raw human story of how people get lured into a spiral of psychiatric drug addiction and misdiagnosis. The incompetence and ignorance of the medical community when it comes to the problems that SSRI drugs and the psychiatric profession can cause is truly astounding, but also it’s all too often way too common an occurrence.
I myself can relate to Rebekah’s story, check out this link to an interview with Rebekah on ABC News Australia.
http://www.abc.net.au/reslib/200704/r135904_459621.mp3
This is Rebekahs Website with information about her story and book :
I notice there is also a detailed piece in the Independent UK from Rebekah’s book :
It’s well worth a read :
The Seroxat/Paxil Online Petition Tips Over The 10,000 Mark
I would like to bring attention to an online petition regarding Seroxat/Paxil .
This petition now has over 10,000 signatures from people residing all over the world.
These are the voices and comments of 10,000 people suffering from Paxil/Seroxat side effects and withdrawal.
These people are signing this petition because they believe that Seroxat/Paxil/Aropax is a highly dangerous drug and I have to say I wholeheartedly agree.
These people and their suffering demands to be addressed and needs to be highlighted.
If 10,000 people have actively bothered signing an online petition about the dangers of Seroxat, then how many people are there out there suffering from the dangerous and debilitating side effects that this drug induces?
Could we multiply that number by 10? Could we multiply that number by 100? Could we multiply that number by 1000? If we were to take the lowest reasonable average and multiply that number by 10, we have a potential of 100,000 people suffering side effects such as Seroxat induced suicidal thoughts, aggression, akathisia and self harm . 100,000 people in danger from a defective drug… quite shocking don’t you think?
Well, even more shocking is the fact that this horrible drug is still being prescribed.
How many lives have to be destroyed, blighted and ruined from a defective and deadly drug before that substance is pulled from the market?
When will something be done ?
Video Diary of Seroxat (Paxil) Withdrawal
Amongst the many youtube videos documenting Paxil/Seroxat withdrawal I discovered this one recently . How doctors and psychiatrists can still prescribe this poisonous, deadly and addictive crap is beyond my comprehension. Seroxat should be banned . Period.
Watch and learn.
Paxil And The Corrupt Psychiatrists Who Pimped It (June 2009)
Over the past year, many prominent psychiatrists have been exposed by the Wall Street Journal for having unscrupulous dealings with the pharmaceutical industry. The following articles are in relation to Paxil-Seroxat and how this dangerous , harmful and defective medication was promoted by the top brass of Psychiatry. The words “bias” , “conflict of interest” and “corruption” don’t even come close to describing the magnitude of the crime against humanity involved here. Check out some of these articles from the Wall Street Journal for more on this :
- UNE 10, 2009, 1:11 PM ET
Another Emory Psychiatrist Draws Fire for Payments From Glaxo
By David Armstrong
More details are coming out about the relationship between Emory University psychiatrist Zachary Stowe and GlaxoSmithKline, which made payments to Stowe at the same time he was conducting federal research about the use of antipressants, such as Glaxo’s Paxil, in pregnant women.
Emory has reprimanded Stowe, who was instructed to immediately eliminate conflicts related to current federal grants. In a statement, the school said Stowe had informed it of “previously unreported activities and has disclosed his failure to abide by Emory policies.” Stowe, through the university, declined an interview request. Here’s more on the story.
In a letter this month to Emory, Sen. Charles Grassley said records he obtained from Glaxo indicated Stowe was paid $154,400 by the drug company in 2007 and $99,300 during the first 10 months of 2008. Stowe is listed as the primary investigator on at least three National Institutes of Health grants, beginning in 2003 and continuing through last year, that involve antidepressant use in pregnant women and the effects on children delivered by those women.
Meanwhile, Stowe outlined some dealings with Glaxo in a deposition last year taken as part of a lawsuit claiming that Paxil isn’t safe for pregnant women. Stowe was questioned in detail about a 2000 email from an outside public-relations firm to a marketing executive at Glaxo about a planned press release for a new study. The study, conducted by Stowe, found Paxil is safe for breast-feeding mothers. The PR firm’s email to Glaxo reads:
Please review the attached press release and forward me any comments/edits. As you may know, Dr. Stowe is on board for publicity efforts and Sherri and I are coordinating time to meet with him next week to arm him with key messages for this announcement, which is slated for early February. We are sending the release for his review at the same time in efforts to secure distribution on Emory letterhead (as you know, would provide further credibility to data for the media).
In the deposition, Stowe said the quotes in the press release were his own. “They wrote it, we said it,” Stowe said of the involvement of the public-relations agency. As for the assertion by the PR official that Stowe was being provided with “key messages,” the psychiatrist called that “just typical public relations crap” and he said in the deposition he never received help from the PR officials.
Stowe is the second Emory psychiatrist to run into problems related to his work with the drug industry. Charles Nemeroff stepped down as chairman of the psychiatry department last year after an Emory investigation concluded that he failed to report more than $800,000 he received from Glaxo from 2000 to 2006. In December, he said in a statement that he acted “in good faith to comply with the rules as I understood them to be in effect at the time.”
http://online.wsj.com/article/SB122304669813202429.html
- CTOBER 4, 2008
Doctor Didn’t Disclose Glaxo Payments, Senator Says
![[Paxil]](http://s.wsj.net/public/resources/images/OB-CL473_1003_p_D_20081003122811.jpg)
Getty Images
The senator alleges Dr. Nemeroff did not report that he was giving promotional talks for Glaxo on the anti-depressant Paxil.
http://blogs.wsj.com/health/2009/02/26/what-did-emory-tell-nih-about-nemeroffs-pharma-pay/
By Sarah Rubenstein
Emory University continues to feel the heat over Sen. Charles Grassley’s investigation into conflicts of interest among doctors: The federal government is investigating whether Emory misled the National Institutes of Health over payments that prominent psychiatrist Charles Nemeroff received from GlaxoSmithKline, the WSJ reports.
Nemeroff stepped down from the chairmanship of Emory’s psychiatry department, but remains a professor there, amid allegations that he failed to disclose hundreds of thousands of dollars in payments from Glaxo, maker of antidepressant Paxil.
A probe by the inspector general for the Department of Health and Human Services is looking into whether Emory failed to tell the NIH about Nemeroff’s potential conflicts, or misrepresented the kind of work he did for Glaxo, as he served as lead investigator on NIH-funded research on five Glaxo drugs for use as antidepressants, WSJ says. The NIH last year suspended a $9.3 million grant to Emory amid Grassley’s probe.
Grassley has been encouraging the HHS inspector general to look into the matter to make sure “Emory did not, either directly or indirectly, mislead the NIH about the nature of Dr. Nemeroff’s promotional talks for GSK and advocacy on behalf of Paxil,” as he wrote (click the letter at right).
A spokeswoman for the inspector general wouldn’t comment on whether the office was investigating. Emory said it will continue to cooperate with NIH; NIH declined to comment. Nemeroff didn’t return the WSJ’s call but has said before he believes he complied with relevant disclosure requirements.
Parallels : Myodil & Seroxat
The Scandalous story of Glaxo’s “Myodil” is eerily similar to the “Seroxat” Scandal…
Thousands of people harmed and maimed by a toxic GSK chemical..
Decades of denial ..
Then finally the truth emerges…
Notice a pattern of behavior here ?..
http://www.myodil.plus.com/
MYODIL
Myodil Adhesive Arachnoiditis is a chronic condition of the spinal cord. Myodil injected into the spinal cord was used to show if there were any problems in the tissue surrounding the spinal cord or the discs between the vertebrae. Myodil was a toxic dye and caused Adhesive Arachnoiditis. A condition that affects many hundreds of thousands through out the World today.
Myodil, also known as Pantopaque in America, had been in use since approximately 1945. Myodil became the medium of choice for use as a diagnostic procedure known as a myleogram. In 1985 Myodil was subject to a court case against GlaxSmithKline, unfortunately this case was settled out of court and no other legal action could then be taken against the makers of Myodil. This left the remaining people who had been injected with Myodil with no means to take further legal action. It is possible that if the Myodil Court Action, conducted by Alexander Harris Solicitors, hadn’t been settled out of Court the sufferers of Myodil Adhesive Arachnoiditis would be still be able to claim damages for the harm caused by Myodil.
Myodil is still in use in other Countries around the World and therefore Myodil will still be the cause of more suffering. The makers of Myodil have now taken Myodil off the market in the UK, however, Myodil is still the cause of chronic pain and the makers of Myodil should, at the very least, make public the testing that Myodil had to undergo to gain a Product Licence. TheGlaxo Myodil Legacy will not just simply disappear as much as the makers of Myodil would wish it.
SEROXAT – PAXIL
Seroxat News : April 09
Bob Fiddaman of the brilliant “Seroxat Sufferers” Blog has some hard-hitting new posts on the Antics of GSK and the Seroxat Scandal. As usual, GSK seems to be up to its dirty tricks again. Bob updates his blog almost everyday, without fail and I have to say I have never seen such tireless work for a mental health campaigner. Bob is truly an unsung hero to those who have been damaged from psychiatric drugs and the deeds of dodgy pharmaceutical companies. Check out these recent Posts by Bob on Seroxat Sufferers.
Revelations : Seroxat : February 2009
An incredible new document has been discovered and released on to the web. The document examines and reveals the background behind the failure of the MHRA and GSK to protect the public from the lethal effects of Seroxat. It is essentially a critique and it comes from the BMJ (British Medical Journal).It is quite revealing in nature; in that it asks some very tough questions in regards to the MHRA’s criminal investigation of GSK. Followers of the Seroxat Scandal will be aware that GSK were essentially let off the hook after a four and half year criminal investigation of the company. The original charge was in relation to GSK suppressing data about suicide in under-18’s prescribed Seroxat. The UK authorities claimed that there were “insufficiently robust laws” in place at the time so therefore GSK were not held accountable. Myself and others have long been dubious about the criminal investigation and its unjust outcome and with the release of the following document that belief and cynicism proves to have been completely justified. In this post I am going to paste the PDF in its entirety. Please read the following document and while doing so, ask yourself the question, what is the price of human life?
(for further reading and more issues raised , check out Bob Fiddaman’s blog)
http://fiddaman.blogspot.com/2009/02/mhra-did-they-fail-to-prosecute-gsk.html
doi:10.1136/jme.2008.025361 2009;35;107-112 J. Med. Ethics
L McGoey and E Jackson
regulatory failure and the uses of legal ambiguity
Seroxat and the suppression of clinical trial data:
http://jme.bmj.com/cgi/content/full/35/2/107Updated information and services can be found at:
Seroxat and the suppression of clinical trial data:
regulatory failure and the uses of legal ambiguity
L McGoey,1 E Jackson2
1
James Martin Institute, Saı ̈d
Business School, Oxford
University, Oxford, UK; 2 London
School of Economics and
Political Science, London, UK
Correspondence to:
Professor E Jackson, Law
Department, London School of
Economics and Political Science,
Houghton Street, London WC2A
2AE, UK; e.jackson@lse.ac.uk
Received 28 March 2008
Revised 28 July 2008
Accepted 14 August 2008
ABSTRACT
This article critically evaluates the Medicines and
Healthcare products Regulatory Agency’s announcement,
in March 2008, that GlaxoSmithKline would not face
prosecution for deliberately withholding trial data, which
revealed not only that Seroxat was ineffective at treating
childhood depression but also that it increased the risk of
suicidal behaviour in this patient group. The decision not
to prosecute followed a four and a half year investigation
and was taken on the grounds that the law at the relevant
time was insufficiently clear. This article assesses the
existence of significant gaps in the duty of candour which
had been assumed to exist between drugs companies
and the regulator, and reflects upon what this episode
tells us about the robustness, or otherwise, of the UK’s
regulation of medicines.
In October 2008, the Medicines and Healthcare
products Regulatory Agency (MHRA), the body
responsible for licensing medicines in the UK,
announced an amendment to the 1994 Medicines
for Human Use (Marketing Authorisations Etc)
Regulations which is intended to address one of the
gravest failures in pharmacovigilance since the
Medicines Act 1968 came into force nearly 40
years ago.
1
This amendment became necessary following
the MHRA’s revelation, on 6 March 2008, that
there would be no prosecution of GlaxoSmithKline
(GSK) for withholding clinical trial data, which
suggested not only that Seroxat was ineffective at
treating childhood depression, but also that it
increased the risk of suicidal behaviour in this
patient group.
The MHRA’s March announcement came at the
end of a four and half year investigation into
whether GSK had acted illegally by withholding
this data from the regulator. In a press release
published on 6 March, Professor Kent Woods,
MHRA Chief Executive, said:
I remain concerned that GSK could and should
have reported this information earlier than they
did. All companies have a responsibility to
patients, and should report any adverse data
signals to us as soon as they discover them. This
investigation has revealed important weaknesses
in the drug safety legislation in force at the time.
2
In the article, we examine the background to the
failure to prosecute GSK, and reflect upon what
this episode tells us about the robustness, or
otherwise, of the UK’s regulation of medicines. In
the first section, we provide a brief history of the
MHRA’s investigation into GSK’s failure to report
data which revealed safety concerns as well as a
lack of efficacy. Secondly, we examine the defects
in the legal framework which have enabled GSK to
avoid prosecution. Finally, we suggest that these
gaps in the law are not the only factor affecting the
MHRA’s ability to regulate effectively. We draw
attention to the role of the agency’s funding
structure, and in particular its need to compete
with other European regulators for licensing fees,
as well as its desire to avoid ‘‘reputational risk’’.
3
We conclude that the case of Seroxat and the
missing trial data casts doubt upon that MHRA’s
capacity to fulfil its own ‘‘mission statement’’:
We enhance and safeguard the health of the public
by ensuring that medicines and medical devices
work and are acceptably safe. … Underpinning all
our work lie robust and fact-based judgements to
ensure that the benefits to patients and the public
justify the risks.
4
Methodologically, the article draws on an
analysis of the relevant legislation and regulations,
and documents released by the MHRA, and Linsey
McGoey’s (LM) interviews with key individuals
such as Kent Woods.
5
THE MHRA’S INVESTIGATION INTO
GLAXOSMITHKLINE
The MHRA’s investigation into GSK was launched
in October 2003, following GSK’s submission, in
May 2003, of data from Studies 329 and 377,
clinical trials which tested the efficacy of parox-
etine (Seroxat/Paxil) in children and adolescents in
the mid-1990s in 11 countries. As soon as they
were received, the relevant data were analysed by
the Committee on the Safety of Medicines (CSM),
which found that they provided clear evidence (a)
that ‘‘there is no good evidence of efficacy in major
depressive disorder in the population studied’’,
6
and
(b) that there was ‘‘a clear increase in suicidal
behaviour versus placebo’’.
6
Following this CSM
review, the MHRA published advice to all doctors
that Seroxat should not be prescribed to under-18s,
and launched a criminal investigation into GSK’s
failure to submit this data in a timely manner.
In early 2004, suspicions of illegality were
bolstered by the leaking of a confidential, internal
GSK document that indicated that there had been
a deliberate decision to withhold Studies 329 and
377 from regulators. The GSK document, dated
October 1998 and entitled Seroxat/Paxil adolescent
depression—position piece on the phase III clinical
studies was first described in an article in the
Canadian Medical Association Journal,
7
and is now
widely available on the internet.
8
It stipulates that
company representatives should be cautious in
disseminating the results of Study 329 and 377,
stressing that ‘‘it would be commercially unacceptable to
include a statement that efficacy had not been demonstrated,
as this would undermine the profile of paroxetine’’, and that it was
necessary ‘‘to effectively manage the dissemination of these
data in order to minimise any potential negative commercial impact’’
(emphasis added).
8
It seems unarguable, then, that for five years, GSK
deliberately failed to disclose clinical trial data which provided
evidence that Seroxat should not be prescribed to under-18s.
Given that, in 1999 alone, 32 000 prescriptions for Seroxat had
been issued to children in the UK, it is clear that in the time-lag
between the completion of the relevant clinical trials (1998) and
the CSM’s warning notices (2003), tens of thousands of under-
18s were prescribed a drug that was unlikely to work, and
which carried an unacceptable risk of a serious, indeed fatal,
adverse reaction. We do not know how many, if any, under-18s
actually committed suicide between 1998 and 2003 as a result of
taking Seroxat, but given the large number of children involved,
it is certainly possible that deaths occurred which could have
been avoided by prompt disclosure of this information.
It was the understanding of MHRA staff that the Medicines
Act 1968 and Regulations which transpose a series of EU
Directives impose a legal duty on pharmaceutical companies to
give the regulator all clinical trial data which has a bearing on a
medicine’s safety and efficacy. This point was stressed by Kent
Woods (KW) during testimony before the House of Commons
Health Select Committee on 9 September 2004, as part of the
Select Committee’s 2004–2005 inquiry into the influence of the
pharmaceutical industry on UK health policy:
Q39: Siobhain McDonagh MP: How many clinical trials does the
MHRA examine before approving a drug application? Is the
MHRA confident that it completely reviews all the findings
necessary, both within and outside the public domain, before
licensing a drug?
KW: The legal responsibility is on the applicant to ensure that in
applying for a trial’s authorisation they do give us all the data,
whether or not it is in the public domain. That is clearly spelt out
in the medicines legislation, and, of course, it is fundamental to
our assessment of a product that we do have access to all the
available data. … If we have evidence that there has been a breach
of the regulations, then we have an inspection and enforcement
division which will take the necessary action to pursue
investigations; the legal framework is clear, that we must have for the
assessment process all the data which the applicant possesses
(emphasis added).
9
In practice, however, as John Abraham has pointed out, the
penalties for failing to submit clinical trial data, which include
fines and imprisonment, remain untested, as to date in the UK
no company has ever been prosecuted for withholding
information that has a bearing on a drug’s safety profile.
10
Woods confirmed this point during his interview with LM in
January 2007:
LM: While you were a witness before the Health Select
Committee, you noted there have been a number of instances
when the MHRA’s enforcement group has been called in to
assess whether there has been appropriate disclosure of data by
industry. [Observers suggest] there has never been a prosecution
of a company for suppression of data. Is that the case?
KW: I believe that’s the case. I’ve been in the agency for three
years. In fact, I’m pretty certain that that’s the case. I would
qualify that by saying firstly that our first stop is to achieve
compliance and prosecution is very much a long stop. And
secondly, industry has a very strong vested interest in not
actually stepping over the line. … The suppression of data would
particularly willing and able to take enforcement action. It is not
something which is in a company’s best interest to do.
Given Woods’ assertion that the MHRA is committed to
prosecuting breaches of the regulations, the Agency’s decision to
refer GSK’s suppression of trial data to the MHRA’s
Enforcement Group in October 2003 is not surprising. What is
perhaps surprising is the length of time it took the MHRA to
realise that prosecution would not be possible. Surely the five
year time-lag between GSK’s completion of trials which
revealed inefficacy and lack of safety, and their eventual
disclosure—not to mention the fact that the disclosure in
2003 came in the form of a briefing paper about a possible future
application to extend the indication for use of Seroxat in
children, as opposed to an urgent risk/benefit alert—spoke for
itself. It is hard to imagine any explanation of the non-
disclosure of this data that did not amount to a breach of
pharmacovigilance regulations. Yet, after a very long and
complex investigation, during which the MHRA ‘‘obtained
and examined over a million pages of documentation’’,i the final
decision was that the case could not proceed to prosecution.
Importantly, however, this decision was not taken because
the MHRA’s intensive investigation revealed that GSK had
acted properly in relation to the data in question. On the
contrary, as the leaked memo makes clear, GSK had deliberately
suppressed data which revealed that Seroxat should not be
prescribed to under-18s. Rather, once the evidence had been
gathered, Counsel’s advice was sought in order to determine
whether a prosecution should proceed, and the advice was ‘‘the
legislation was sufficiently unclear as to make a criminal
prosecution impossible’’.
11
BARRIERS AND LOOPHOLES WITHIN THE LEGISLATIVE
FRAMEWORK
This conclusion prompts a number of questions, the first and
most obvious of which is that if it is indeed true that the law
was insufficiently clear in March 2008, then it must also have
been insufficiently clear in October 2003, when the decision was
taken to launch a criminal investigation. Of course, if there was
a degree of ambiguity in the law, then it might be especially
important to spend time trying to assemble a clear-cut case of
illegal activity on the part of GSK. But the important point
about the MHRA’s March 2008 announcement was not that
there was some slight ambiguity which could have been ‘‘cured’’
by decisive evidence of wrongdoing. On the contrary, as we see
below, the defects in the law which were identified in 2008 are
potentially so broad that, regardless of the robustness of the
MHRA’s evidence of illegality, prosecution would be pointless.
The existence of gaps in the law which make prosecution futile
does not depend on the weight of evidence against GSK, rather
it is an independent fact which, if detected by a competent
lawyer in 2008, should have been detectable in 2003. If the law
as it existed between 1998–2003 made a successful prosecution
impossible ab initio, a four and a half year investigation into the
possibility of prosecution may have been a colossal waste of
time and money.
Secondly, was it, in fact, the case that the law at the relevant
time was insufficiently clear? It is certainly true that the
provisions which GSK were suspected of breaching consist, at
least in part, of a shifting set of Regulations—the Medicines
for Human Use (Marketing Authorisations Etc) Regulations
i
Linsey McGoey interview with Kent Woods, January 2007.
108 J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361
1994—which have, over the period in question, implemented a
number of new EU Directives. Without rehearsing every shift in
the content of the 1994 Regulations between 1998 and 2003,
two provisions are of particular importance.
From February 2002, para 8 of Schedule 3 of the Regulations
provided that: ‘‘Any person responsible for placing a relevant
medicinal produce on the market who fails to report to the
licensing authority any suspected adverse reaction, or to submit
to the licensing authority any records of suspected adverse
reactions… shall be guilty of an offence’’ (emphasis added).
More important still is para 10, which went further and
required the qualified person to provide ‘‘any other information
relevant to the evaluation of the benefits and risks afforded by a
medicinal product’’ (emphasis added). The regulations do not
apply retrospectively, so both these particular provisions applied
to GSK in the time period between February 2002 and May 2003
(when the data were eventually disclosed).
The MHRA’s view, which we share, was that ‘‘the informa-
tion eventually provided to the MHRA about adverse reactions
experienced in the trials of Seroxat in children was clearly …
relevant to the risks and benefits of the product’’.
11
On the face
of it, then, the provision that there is a duty to provide ‘‘any
information relevant to the evaluation of benefits and risks’’
does not look particularly vague or ambiguous, and would
appear to capture precisely the non-provision of data by GSK.
How then could the decision be taken that, contrary to
appearances, this provision is ‘‘insufficiently clear’’ to justify
prosecution?
In brief, the lawyers whose advice had been sought detected a
number of possible loopholes, described below, which would
have enabled GSK to avoid conviction, and this meant that a
prosecution would have represented a further waste of public
resources.
The first loophole relates to the duty to notify the MHRA of
adverse reactions. This, apparently, could be read to apply only
to adverse reactions ‘‘in the normal conditions of use of the
product’’. Though first licensed for adult use in the UK in 1990,
Seroxat had not been specifically licensed for use in under-18s
because enrolling children in clinical trials was not encouraged.
As a result, its prescription as a treatment for childhood
depression was effectively ‘‘off-label’’, albeit that GSK knew
that thousands of children were taking it, and had certainly not
advised doctors against prescribing it to children. It should be
noted that reluctance to enrol children in clinical trials means
that off-label prescription to children is the norm rather than
the exception, with obvious implications for patient safety.
Until the CSM issued their warning notices in 2003, being
under-18 was not listed as a contraindication to prescription of
Seroxat, and so it could be freely and lawfully prescribed as a
treatment for childhood depression.
Unusually then, GSK had conducted clinical trials of Seroxat
in under-18s. This fact, somewhat ironically, led to the second
legal loophole. Because the data which revealed an elevated risk
of suicide did not emerge ‘‘during normal conditions of use’’,
but instead from clinical trials, again they were not captured by
the regulations.
These two defects in the law might have been ‘‘cured’’ if
instead the MHRA could have invoked the duty to report
adverse reactions which occur during clinical trials, which is
contained in Section 31 of the Medicines Act 1968, and
governed by orders made under the Act. Yet, conveniently for
GSK, there are two further loopholes here in that this duty
applies only to trials conducted in the UK, and, at the relevant
time, failure to comply would not have been a criminal offence.
An EU Directive which came into force too late—in May 2004—
introduced a criminal offence for the failure to report adverse
reactions which occur during clinical trials, but again this
remains limited to trials which take place within the European
Economic Area (EEA).
It is worth noting that pharmaceutical companies have
always been entitled to rely on non-UK or now non-EEA trials
when submitting applications for marketing authorisations.
They have, in short, been able to benefit from the positive
results of trials conducted abroad, while at the same time, it
appears that they have not been under a corresponding duty to
reveal the negative results of non-UK, or non-EEA trials.ii
The existence of so many qualifications to what initially
looks like a clear and comprehensive duty to submit ‘‘any other
information relevant to the evaluation of the benefits and risks
afforded by a medicinal product’’ is perhaps surprising.
Certainly, two ordinary rules of statutory interpretation would
militate against this conclusion. First, the words used in
legislation are normally assumed to have their ‘‘ordinary
language meaning’’, unless otherwise specified. Use of the word
‘‘any’’, according to the Oxford English dictionary, captures the
idea of ‘‘indifference as to the particular one or ones that may be
selected’’, which would suggest that ‘‘any relevant information’’
should not, without a clear indication to the contrary, be
qualified to mean ‘‘only information gathered in a particular
setting’’.
The second rule of statutory interpretation which is at odds
with the existence of these legal loopholes is that, in the event
of statutory ambiguity, it is legitimate to ask what the
legislator’s intention was in drafting the provision in question.
Here the intention was evidently to create a duty to report all
relevant data, and in particular, to disclose suspected adverse
reactions and other information relevant to the regulator’s
evaluation of risks and benefits.
The interpretation of the law which has led to the decision
not to prosecute would seem to subvert the intention of the
creators of the regulatory regime, which was indubitably not to
provide a series of ‘‘get-out’’ clauses for drugs companies who
withhold, deliberately, evidence of lack of efficacy and serious
side effects for a group of patients who are routinely being
prescribed the drug in question.
Against this, it is of course true that there is a further rule of
statutory interpretation according to which, where there is any
ambiguity in the definition of a criminal offence, that ambiguity
has to be interpreted in the defendant’s favour, and so, if the
loopholes outlined above exist, the MHRA are clearly right that
the prosecution of GSK would be likely to fail, and so embarking
on it would be a further waste of time and money.
GAPS IN THE REGULATORY FRAMEWORK: NICE, MHRA AND
ACCESS TO DATA
It now seems likely, therefore, that the legal framework which
governs the licensing of medicines in the UK, set up by the 1968
Act in the light of the Thalidomide tragedy, has always been
seriously defective. The duty of candour owed to the regulator,
and referred to by Woods in his evidence to the Select
Committee, to provide ‘‘all the data which the applicant
possesses’’, backed up by the possibility of criminal sanctions
in the event of breach, has been revealed to be heavily qualified.
It does not exist where adverse reactions become apparent in
off-label use, even where that off-label use is both common and
well known, or where they occur in clinical trials that took place
ii
We are grateful to Catherine Will for this point.
J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361 109
outside the UK (or, since 2004, the EEA). These are significant
gaps in the regulatory scheme, which, as is apparent from the
Seroxat episode, subvert the purposes of regulation, and
undermine the powers of the regulator.
In short, there can be no sanctions despite clear evidence that
GSK withheld data which ensured that tens of thousands of
adolescents have been prescribed drugs which do not work, and
which may cause an elevated risk of suicide. In addition to the
implications for patient safety, this also represents a huge waste of
NHS resources: between 1998 and 2003, the NHS paid for hundreds
of thousands of prescriptions of Seroxat for under-18s, despite the
existence of (withheld) evidence proving (a) that it would not work,
and (b) that it might cause a serious adverse reaction.
This latter question raises important issues for the National
Institute for Health and Clinical Excellence (NICE). It might be
argued that not only should the MHRA have had access to this
evidence much earlier, on safety grounds, but that it would also
be relevant to any guidance NICE might issue on the treatment
of depression in children. Significantly, however, NICE does not
have the same rights as the MHRA has always been assumed to
have to require pharmaceutical manufacturers to supply clinical
trial data. According to Kent Woods, the two bodies are
exercising different functions. The MHRA decides whether a
drug is safe—using the powers it thought it had to require the
provision of ‘‘any relevant information’’, and NICE can then
rely upon that assessment in order to decide whether this safe
and efficacious drug is also sufficiently cost-effective to justify
prescription in the NHS. Woods elaborated on this point in his
interview with LM:
LM: Would you like to see it move to a system where NICE
policymakers had access to the same data as the MHRA?
KW: No.
LM: Why not?
KW: It’s important to understand firstly what NICE is there for.
NICE is an NHS organisation. And its job is to give advice and
guidance to the NHS. I mean, the NHS is just a very large health
maintenance organisation. We have a statutory responsibility to
the nation as a whole, and therefore our remits are somewhat
different… I think we need to keep separate in our minds the job
that this agency does, which is about weighing up risk and
benefit and quality, and what NICE does, which is about
effectiveness and cost-effectiveness.
Yet it is not clear that the roles of the MHRA and NICE can
be neatly separated in this way. If a drug does not work, then
that information is critical to a decision about cost-effectiveness,
since regardless of its cost, its lack of efficacy will make its
prescription in the NHS a waste of money. It is also critically
important that this two stage process for drug provision in the
UK means that any failure by the MHRA to gain access to
information about adverse reactions or lack of efficacy will be
magnified by NICE’s reliance on the robustness of the MHRA’s
conclusions on safety and efficacy. If the MHRA cannot detect
that a drug is unsafe and inefficacious, because a drug company
can withhold data without penalty, NICE’s dependence on
MHRA data analyses means that unsafe and inefficacious drugs
may subsequently be widely prescribed in the NHS.
A positive result of the Seroxat episode may be that the
inequality of access to data described by Woods may be
revisited. Indeed, we understand the MHRA is currently
negotiating with NICE about revising shared data arrange-
ments. But restructuring access to data alone may not solve
some of the problems that compounded the MHRA’s inability
to prosecute GSK. In the next section, we examine some further
structural factors that may be hindering effective drugs
regulation in the UK.
MHRA, INDUSTRY RELATIONSHIPS AND REPUTATIONAL RISK
Fallout from the MHRA’s decision not to prosecute GSK is not
the first time that the Agency has attracted criticism. John
Abraham
12 13
has consistently highlighted the existence of a
number of barriers that make it difficult for the UK regulator to
effectively monitor the safety of medicines.
14
The first is the
MHRA’s funding structure. The Medicines Control Agency
(MCA), which preceded the MHRA, was established in 1989
when the UK government decided to make the drugs regulator
semi-autonomous from the Department of Health. Unlike its
predecessor, the new MCA, like the MHRA today, became
entirely funded by fees paid by pharmaceutical companies in
exchange for drug licensing services. Within the EU, this model
of industry funding is becoming increasingly common.
15 16
In
comparison, the Food and Drug Administration (FDA), the US
equivalent of the MHRA, originally received no private funding
at all, and while its reliance on industry fees has grown, to
about 50%, it retains a degree of financial independence from
the pharmaceutical industry.
17 18
There is, as Breckenridge and Woods have pointed out, a
logical reason for the MHRA’s funding arrangements.
19
Why
should the UK taxpayer carry the burden of paying for the
licensing process, when private companies profit from drug
sales? And it is true that in many other sectors, the cost of
regulation is borne by the regulated, rather than by the
taxpayer. The particular problem industry-funded regulation
poses for the MHRA is that, unlike most other regulators, the
MHRA is effectively in competition for industry fees with other
EU regulators.
The reason for this is that drugs can be licensed throughout
the EU through what is known as the ‘‘mutual recognition
procedure’’.
20
Drugs companies choose to apply to a national
regulator, whose decision to grant a product licence will then be
recognised throughout Europe. Because the majority of licensing
fees go to the regulator to which the pharmaceutical company
first applied, an internal EU market has emerged, in which
national regulatory agencies compete for ‘‘regulatory business’’
by lightening the regulatory burden and speeding up approval
times. In the first nine years of this system’s existence, the
average assessment time for new drugs in the UK fell from 154
working days to 44.
21
While regulatory efficiency is, of course, to
be welcomed, making regulators compete with each other in
this way undoubtedly creates perverse incentives towards the
minimisation of regulatory oversight, or a ‘‘race to the bottom’’
in medicines regulation.
13 15
Another factor at stake may be what Michael Power has
described as the imperative to minimise ‘‘reputational risk’’.
3
The failure to gain access to Studies 377 and 329 is not the first
time the MHRA has found that its decisions have been based
upon inadequate or partial data analysis. During a 2003–4
investigation into the safety of all selective serotonin reuptake
inhibitor (SSRI) antidepressants (including Seroxat), the
MHRA’s expert working group discovered that daily doses of
SSRIs of more than 20 mg were no more effective at treating
depression, regardless of its severity, than doses of 20 mg or less.
At the time 17 000 individuals in Britain were receiving daily
doses of SSRIs at 30, 40 or 60 mg, thus increasing their risk of
suffering adverse effects,
22 23
and increasing the costs to the
NHS, without any improvement in efficacy. For our purposes,
the important point about the new advice about safe dosing
levels which resulted from this investigation was that it was not
110 J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361
prompted by newly submitted information, but following a
reanalysis of data which had been in the MHRA’s possession for
over 10 years.
14
Abraham has drawn attention to other examples of the
MHRA’s failure to act swiftly on evidence of the adverse effects
of licensed drugs, such as its handling of Halcion, a triazolo-
benzodiazepine (tranquiliser) manufactured by Upjohn.
24
First
licensed in 1978, the UK’s Committee on Safety of Medicines
began investigating reports of adverse effects as soon as the drug
was licensed for use in the UK. Despite the existence of data
dating back to the 1978 which proved that Halcion was not
safe, the drug was only removed from the market in 1991. Far
from being an aberration then, the MHRA’s inability to gain
access to all relevant trial data in relation to Seroxat indicates
that there was a failure to learn lessons following the Halcion
episode.
24 iii
This point resonates with recent work by David
Demortain, who has suggested that one of the reasons why
drug crises so often fail to produce any regulatory change is
because accountability is ‘‘determined by the action of a group
which, ironically, is likely to minimise the novelty of lessons
publicly drawn from the crisis in an attempt to defend its
ownership and minimise its responsibility’’.
25
It is worth noting that regulators in the US have a rather
different record. There are obvious similarities between GSK’s
withholding of the Seroxat trials and a case in the US, 20 years
ago, in which Eli Lilly had failed to report a number of fatal and
serious adverse reactions, in UK patients, to the drug
benoxaprofen (an anti-inflammatory drug marketed as Opren
in the UK and Oraflex in the US). According to the US
regulations, companies are required to report to the FDA any
‘‘unexpected side effect, injury or toxicity within 15 days’’ of
receiving notice of such an event. In the case of benoxaprofen,
because the adverse reactions had occurred in the UK rather
than the US, Eli Lilly’s lawyers argued that there was a lack of
clarity over whether the regulations required the company to
report them. Despite the existence of a degree of ambiguity, the
FDA successfully prosecuted Lilly for failing to report four
fatalities and six illnesses which were relevant to the safety of
benoxaprofen. As Abraham as pointed out, in the US, the
argument that non-US adverse reactions did not fall within the
word ‘‘any’’ was given short shrift, and the spirit behind the
regulations was decisive.
26
This episode is in sharp contrast to the MHRA’s compara-
tively lax treatment of GSK. In the absence of any serious threat
of sanctions for withholding data from the MHRA, have
companies in the UK, in fact, always been free to hide negative
trial results with impunity? Unlike the FDA, the MHRA has
never prosecuted a company for failing to submit relevant data.
As Tim Kendall, joint director of the UK’s National
Collaborating Centre for Mental Health, suggests in an inter-
view with LM:
The 1998 GlaxoSmithKline memo, which suggested suppressing
trial data on paroxetine use in children, is unlikely to be a lone
aberration. I think it is absolutely necessary for physicians,
psychiatrists and indeed the public, to publicly and forcefully say
that this is completely unacceptable. This threatens the
evidentiary basis of contemporary medicine. It’s nothing short of
a battle for the truth.
27
The failure to detect unsafe dosing levels; the failure to learn
the lessons from Halcion, and the failure to prosecute GSK
might all be said to cast doubt over the MHRA’s ability to
regulate effectively, raising the prospect of risks to its
reputation. For the regulator to reveal that it did not know of
the existence of evidence which casts serious doubt upon the
safety or efficacy of a widely prescribed drug immediately raises
an inference that the regulator, which is under a duty to
demand and analyse all such data, has not done its job properly.
In relation to their inability to gain access to GSK’s missing trial
data, perhaps fortuitously, the MHRA has been able to manage
this potential reputational risk by blaming the law itself.
CONCLUSIONS
We agree with the MHRA’s conclusion that the legislation and
regulations which cover drug safety in the UK have been
revealed to be insufficiently robust to ensure that companies
submit all data relevant to determining a drug’s risks and
benefits, and we would support measures, such as compulsory
pre-trial registration, to ensure that trials with inconvenient or
‘‘commercially unacceptable’’
7
results, such as Studies 329 and
377, cannot simply disappear. We are also pleased to see that the
Agency announced in October 2008 new amendments that aim
to close the gaps in the law described above. When the
Medicines for Human Use (Marketing Authorisations Etc)
Amendment Regulations 2008 come into force, there will be a
duty to provide ‘‘information arising from use of the product (a)
in a country or territory outside the European Economic Area;
and (b) outside the terms of the marketing authorisation,
including use in clinical trials’’. It is to be hoped that the law
will now be sufficiently clear to ensure that the duty of candour
which had always been assumed to attach to information about
a product’s risk/benefit profile has teeth.
Where our analysis diverges from the MHRA’s is with their
assumption that the only problem this incident has revealed is
the existence of loopholes in the legal framework. In our view,
there are other factors at stake, which create incentives towards
increasingly, and perhaps dangerously light-touch regulation of
medicines in the UK. Many of these were highlighted by the
House of Commons Health Select Committee in 2005, which
found that:
The regulator, the Medicines and Healthcare products
Regulatory Agency (MHRA), has failed to adequately scrutinise
licensing data and its post-marketing surveillance is inadequate.
The MHRA Chairman stated that trust was integral to effective
regulation, but trust, while convenient, may mean that the
regulatory process is not strict enough. The organisation has been
too close to the industry, a closeness underpinned by common
policy objectives, agreed processes, frequent contact, consultation
and interchange of staff.
9
Seen in this light, it could even be argued that defects in the
regulatory scheme were convenient for the regulator. Instead of
blaming its own structures and mechanisms, or, perhaps worse,
having to face a high-profile criminal trial in which GSK’s
lawyers would skilfully pick over documents, memos and
emails, in minute detail, in order to find fault with the regulator
and its processes, the MHRA has been able to avoid these
threats to its reputational status by blaming shoddy statutory
drafting.
Kent Woods’ letter to the CEO of GSK, Jean Pierre Garnier,
informing him of the decision not to proceed to prosecution,
suggests that a strengthening of the law ‘‘should be unnecessary
in an industry which relies so heavily on public trust and aspires
to high ethical standards’’.
28
The ‘‘moral responsibility’’ to
provide data, Woods goes on to say, ‘‘now needs to be insisted
upon by the unambiguous force of law’’ (emphasis added).iii See also McGoey 2007, p226 for further discussion of these points.
14
J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361 111
Deftly, therefore, Woods criticises GSK for failing to meet their
moral responsibilities, and the law for being too ambiguous. GSK
has avoided prosecution, and the MHRA has avoided the intense
negative scrutiny which would have been the inevitable con-
sequence of a criminal prosecution. For both, then, could this
almost be a win-win situation, four and half years in the making?
AUTHORS’ NOTE
Following its acceptance in August, this paper was amended to
include a reference to the announcement, in October 2008, that
the Medicines for Human Use (Marketing Authorisations Etc)
Regulations 1994 were to be amended.
Competing interests: None.
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