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.”

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

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

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.

http://www.paxilprogress.org/

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

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 :

http://www.dyingforacure.com/

I notice there is also a detailed piece in the Independent UK from Rebekah’s book :

It’s well worth a read :

http://www.independent.co.uk/life-style/health-and-families/features/ssris-when-antidepressants-go-wrong-1763108.html

I would like to bring attention to an online petition regarding Seroxat/Paxil .

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. 

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 : 

http://blogs.wsj.com/health/2009/06/10/another-emory-psychiatrist-draws-fire-for-payments-from-glaxo/

• 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

 

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.

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/

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

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.

http://fiddaman.blogspot.com/2009/04/classic-glaxosmithkline-uk-seroxat.html
http://fiddaman.blogspot.com/2009/04/martin-keller-to-step-down-in-june.html

Another Excellent blog about Seroxat is the brilliantly informative and excellently researched “Seroxat Secrets” Blog. A recent post about Seroxat and alcohol makes another damning case against the effectiveness of this hellish drug.  

http://seroxatsecrets.wordpress.com/2009/04/01/seroxat-and-alcohol-paxil-and-alcohol/

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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J Med Ethics 2009;35:107–112. doi:10.1136/jme.2008.025361 107 

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