Yet more on Paxil Study 329, Keller et al

This is from the always excellent CL Psych. As usual I have reproduced the whole of his article – it’s all here and a real eye opener.

If you need to catch up on Study 329, then read this. Otherwise just carry on:

A bombshell has just appeared [April 2008] in the International Journal of Risk & Safety in Medicine. The subject of the paper is Paxil study 329, which examined the effects of the antidepressant paroxetine in adolescents. The study findings were published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2001. These new findings show that I was wrong about Paxil Study 329. You know, the one that I said overstated the efficacy of Paxil and understated its risks. The one that I claimed was ghostwritten. Turns out that due to legal action, several documents were made available that shed more light on the study. The authors (Jureidini, McHenry, and Mansfield) of the new investigation have a few enlightening points. Let’s look at the claims and you can then see how wrong I was, for which I sincerely apologize.

The story is actually worse than I had imagined.

Here’s what I said then:

Article [quote from the study publication]: Paroxetine is generally well-tolerated and effective for major depression in adolescents (p. 762).

Data on effectiveness: On the primary outcome variables (Hamilton Rating Scale for Depression [HAM-D] mean change and HAM-D final score < 8 and/or improved by 50% or more), paroxetine was not statistically superior to placebo. On four of eight measures, paroxetine was superior to placebo. Note, however, that its superiority was always by a small to moderate (at best) margin. On the whole, the most accurate take is that paroxetine was either no better or slightly better than a placebo.

I went on to bemoan how the authors took differences either based on arbitrary cutoff scores or from measures that assessed something other than depression to make illegitimate claims that paroxetine was effective. Based upon newly available data from the study, here’s what happened.

  • The protocol for the study (i.e., the document laying out what was going to happen in the study) called for eight outcome measurements. To quote Jureidini et al: “There was no significant difference between the paroxetine and placebo groups on any of the eight pre-specified outcome measures.” So I was wrong. Paxil was not better on 4 of 8 measures — it was better on ZERO of eight measures. My sincerest apologies.
  • Another quote from Jureidini and friends: “Overall four of the eight negative outcome measures specified in the protocol were replaced with four positive ones, many other negative measures having been tested and rejected along the way.

Let’s break this thing down for a minute. The authors planned to look eight different ways for Paxil to beat placebo. They went zero for eight. So, rather than declaring defeat, the authors then went digging to find some way in which Paxil was better than a placebo. Devising various cutoff scores on various measures on which victory could be declared, as well as examining individual items from various measures rather than entire rating scales, the authors were able to grasp and pull out a couple of small victories. In the published version of the paper, there is no hint that such data dredging occurred. Change the endpoints until you find one that works out, then declare victory.

How About Safety?

I was incensed about the coverage of safety, particularly the magical writing that stated that a placebo can make you suicidal, but Paxil could not. I wrote:

It gets even more bizarre. Remember those 10 people who had serious adverse psychiatric events while taking paroxetine? Well, the researchers concluded that none of the adverse psychiatric events were caused by paroxetine. Interestingly, the one person who became “labile” [i.e., suicidal] on placebo – that event was attributed to placebo. In this magical study, a drug cannot make you suicidal but a placebo can. In a later document, Keller and colleagues said that “acute psychosocial stressors, medication noncompliance, and/or untreated comorbid disorders were judged by the investigators to account for the adverse effects in all 10 patients.” This sounds to me as if the investigators had concluded beforehand that paroxetine is incapable of making participants worse and they just had to drum up some other explanation as to why these serious events were occurring.

Turns out I missed a couple things. Based on looking at an internal document and doing some calculations, Jureidini et al. found that serious adverse events were significantly more likely to occur in patients taking paroxetine (12%) vs. placebo (2%). Likewise, adverse events requiring hospitalization were significantly disadvantageous to paroxetine (6.5% vs. 0%). Severe nervous system side effects — same story (18% vs. 4.6%). The authors of Study 329 did not conduct analyses to see whether the aforementioned side effects occurred more commonly on drug vs. placebo.

Funny how they had time to dredge through every conceivable efficacy outcome but couldn’t see whether the difference in severe adverse events was statistically significant.

One quote from the discussion section of the paper sums it all up:

There was no significant efficacy difference between paroxetine and placebo on the two primary outcomes or six secondary outcomes in the original protocol. At least 19 additional outcomes were tested. Study 329 was positive on 4 of 27 known outcomes (15%). There was a significantly higher rate of SAEs with paroxetine than with placebo. Consequently, study 329 was negative for efficacy and positive forharm.

But the authors concluded infamously that “Paroxetine is generally well-tolerated and effective for major depression in adolescents.”

Enter Ghostwriters. Documentary evidence as shown on indicated that the first draft of the study was ghostwritten. This leaves two roles for the so-called academic authors of this paper:

  • They were willing co-conspirators who committed scientific fraud.
  • They were dupes, who dishonestly represented that they had a major role in the analysis of data and writing of the study, when in fact GSK operatives were working behind the scenes to manufacture these dubious results.

Remember, this study was published in 2001, and there has still been no apology for the fictional portrayal of its results, wherein a drug that was ineffective and unsafe was portrayed as safe and effective. Physicians who saw the authorship line likely thought “Gee, this is a who’s who among academic child psychiatrists — I can trust that they provided some oversight to make sure GSK didn’t twist the results.” But they were wrong.

By the way, Martin Keller, the lead “independent academic” author of this tragedy of a study said, when asked about what it means to be a key opinion leader in psychiatry:

You’re respected for being an honorable person and therefore when you give an opinion about something, people tend to listen and say – These individuals gave their opinions; it’s worth considering.

So is completely misrepresenting the data from a study “honorable”? Is Keller’s opinion “worth considering?” As you know if you’ve read this blog for long, such behavior is, sadly, not a fluke occurrence. Many others who should be providing leadership are leading us on a race to the scientific and ethical bottom. What will Brown University, home of Keller, do? Universities don’t seem to care at all about scientific fraud, provided that the perpetrators of bad science are bringing home the bacon.

Not one of the “key opinion leaders” who signed on as an author to this study has said, “Yep, I screwed up. I didn’t see the data and I was a dupe.” Nobody. Sure, I don’t expect that every author of every publication can vouch for the data with 100% certainty. I understand that. But shouldn’t the lead author be taking some accountability?

This is a Fluke (?) Some may be saying: “But this is just a fluke occurrence.” Is it? I’ve seen much evidence that data are often selectively reported in a manner like this — looks like (sadly) it takes a lawsuit for anyone to get a whiff of the bastardization of $science that passes for research these days. If GSK had not been sued, nobody would have ever known that the published data from Study 329 were negative. A reasonably educated person could see that the writeup of the study was a real pimp job — lots of selling the product based on flimsy evidence, but nobody would have seen the extent of the fraud. Apparently lawyers need to police scientists because scientists are incapable of playing by some very basic rules of science.

See for Yourself. Documents upon which the latest Jureidini et al. paper are based can be found here. Happy digging.


Glaxo refuse to co-operate with the MHRA once again – read the letter

At the end of the recent 4 year long investigation into Glaxo by the MHRA (the probe began after disclosure that Glaxo withheld data from Seroxat clinical trials), Kent Woods (CEO of the UK’s medicines regulator the MHRA) wrote to JP Garnier at GlaxoS mithKline – a small section of the letter read:

“You will be aware that we have reviewed a large quantity of documents from GSK. Legal provisions prevent us from releasing publicly any information gained under our statutory powers in the course of a criminal investigation. However, there has been a significant level of quite legitimate public interest in this case, and I would there like to release that information into the public domain. This of course requires your consent. GSK has regularly asserted that it has nothing to hide in this matter and so I should be grateful if you could confirm in writing your consent to the release.”

This was the MHRA beating its breast in a very public manner.

Unfortunately it seems that Glaxo’s reply has not been treated in the same way. The MHRA actually had a reply dated 18 March and a pdf file is hidden away on the MHRA website. Perhaps the MHRA’s embarrassed silence over Glaxo’s reply can be explained by the very final paragraph of the two page letter:

“Finally, it is our strong wish to be as transparent as possible in disclosing information around this investigation. However, from GSK’s standpoint there are legitimate concerns which would need to be addressed prior to any disclosure. These include, for example, the identification of individual employees, independent clinicians and patients, as well as the need to preserve commercial confidentiality of certain information. On this basis, we would be happy to consider requests for information, under the Freedom of Information Act, on a case by case basis in relation to specific documents or categories of documents.”

There you have it. GSK will consider FOI requests (which will have to sent to the MHRA as the FOI Act does not cover GSK) to release “specific documents or categories of documents”.

The only problem is that I can’t ask for“specific documents or categories of documents” as the MHRA can’t release any information into the public domain without GSK’s consent. Oh and another thing – approximately 1,000,000 pages of documentation were reviewed by the MHRA in its investigation.

So – I’m looking for a needle in a haystack, but I’m not allowed to know which haystack it’s in or even if it’s in a haystack – or even if it’s a needle I’m looking for.

GSK is in no way being “as transparent as possible” in this matter – their reply to the MHRA is a de facto refusal to release any of the information the MHRA has reviewed.

For more on this subject please look here and here.

To read the full MHRA report on the investigation read here.

Seroxat withdrawal warnings ignored by Glaxo…

…and do you know the worst thing about this… the clinical trial talked about here is from the end of the 1980s

This exchange is from Taken on Trust – a Panorama programme from 2004 (thanks to Truthman30).

JOFRE: One psychiatrist above all others has insured that we’ve heard information about Seroxat that its
manufacturer would rather we hadn’t. On Panorama’s previous programme Doctor David Healy explained
what he’d found in the secret archives of GlaxoSmithKline during an American legal action, evidence he
says proves the company has known all along that Seroxat can make all age groups suicidal.
In your view does Seroxat make some adults self harm and become suicidal?

Head of Psychological Medicine
Imperial College
Yes, I’ve had a patient that I treated myself who found this effect. He found it only on a certain dose and
when the dose was changed it disappeared, but the fact is, it was clearly related and she actually
experimented with the dosage and found that she could almost predict the suicidal effects.

Head of Psychological Medicine
Imperial College
For a time, even only in a matter of a few years, almost critical scepticism, the objectivity were suspended
in favour of the all out rush to develop these new drugs and develop new markets.

JOFRE: Because there was such an excitement created about them.

TYRER: Yes, as the head of GlaxoSmithKline once said: “There’s a lot of runway space out there for
Seroxat you know, let’s get the planes down.”

JOFRE: Getting the planes down, would the company hoped, lead to their second billion. It applied to
extend Seroxat’s licence for the treatment of five more illnesses, some familiar like obsessive compulsive
disorder, some not so familiar like social phobia. Each of Glaxo’s planes landed safely with the regulator’s
full approval. As more and more people are being prescribed Seroxat for a bewildering array of illnesses,
another massive problem has emerged, a problem not as devastating as suicide, but one that affects a much
larger number of patients, many people on the drug say they’ve become hooked. Again, the regulator has
failed to issue proper warnings, even though the evidence has been staring them in the face for years. When
Seroxat was first licensed it was marketed with the regulator’s approval as a safe non addictive drug, back
then even Dr Healy believed the hype.

JOFRE: In the late 1980s, before Seroxat was licensed, GlaxoSmithKline funded a clinical trial into the
drugs affects on depressed patients. The man they asked to conduct it was Professor Peter Tyrer a world
expert on drug dependence. He came across a problem that would go on to affect millions of patients
around the world. After six weeks on Seroxat some of his patients were feeling better, but some of them
were also hooked.

Head of Psychological Medicine
Imperial College
After the trial ended they said: “Can we continue on these tablets because we feel we’ve got to have them
because they seem to be so effective”, but more concerning.. was more concerning to us was the fact that
they were saying: “I cannot tolerate the symptoms when I stop it”.

JOFRE: As far as you were concerned then were these people dependant on Seroxat?

TYRER: They were showing yes signs of dependence…

JOFRE: And this was after..

TYRER: ..after only six weeks.

JOFRE: …just six weeks on the drug.


JOFRE: Some of the withdrawal effects were very disturbing.

TYRER: They also felt more anxious, they felt this feeling of dysphoria, the feeling of being depressed and
in some cases entertaining suicidal thoughts.

JOFRE: That sounds pretty serious then if people were thinking of suicide when they stopped.

TYRER: Yes it is serious and in particular we were led to believe that these drugs were particularly
effective against suicidal thoughts and therefore, having them at any stage during the course of treatment..
and on withdrawal was a matter of great concern.

JOFRE: Professor Tyrer didn’t investigate these problems any further at the time, but he did tell
GlaxoSmithKline what he found, he says they weren’t very interested.

TYRER: It was very important to concentrate on the positive, so we didn’t expect that they would rush in
and investigate this problem as a matter of priority.

JOFRE: And as far as you’re aware they didn’t investigate the problem.


JOFRE: We asked GlaxoSmithKline if further studies were commissioned as a result of Professor Tyrer’s
findings on withdrawal. They didn’t say. What they did tell us was ‘The company reviewed reports of such
symptoms in all its clinical trials as a matter of course’. If the drug company didn’t investigate it, what
about the regulator? Since the early 90s its Yellow Card scheme has been throwing out signals that many
patients are hooked on Seroxat, the drug has attracted more Yellow Card complaints about withdrawal
problems than any other prescription medicine. The MHRA says: “Patients should have been well aware of
the risks before they started taking it.”
JOFRE: Really, up until last year the patient leaflet said that withdrawal symptoms were “not common”
and “you cannot become addicted to Seroxat”. The leaflets wording was approved by the regulator.

So was it helpful to tell patients that they couldn’t become addicted to Seroxat?

TYRER: No it wasn’t.

JOFRE: What do you think patients would have understood by that?

TYRER: Well they would have understood that it wasn’t habit forming and that really when the time came
for them to stop their drugs they would have no problem in stopping them, and clearly, the evidence didn’t
support that.

JOFRE: Do you think the regulator should have insisted on something clearer in the patient information


Steptoe & Johnson – Seroxat FOI request to the MHRA

It seems that you can’t keep away from Bob Fiddman’s blog Seroxat sufferers for too long, otherwise you’ll miss something.

Following on from my last post it seems a law firm made an interesting Freedom of information request to the MHRA about Seroxat:

From: [redacted]
Sent: 15 December 2005
To: Pharmacovigilance, [MHRA]
Cc: Subject: Request for Information

Dear Sirs
Attention: Pharmacovigilance Team

I wish to make a request for information pursuant to the Freedom of Information Act 2000 for the following information:

1. please identify the statute(s) and regulations which obligate the pharmaceutical industry to report suspected serious adverse drug reactions to the MHRA, and which include a definition of “serious” adverse drug reactions; and

2. a Drug Analysis Print for paroxetine [Seroxat/Paxil]which lists all of the adverse drug reactions which have been reported to the MHRA (and the former MCA) by all sources (including those reported by the marketing application holder) up to 1 May 2001.

I would prefer to receive the information electronically via email, but you may otherwise post the requested information to my attention at: Steptoe & Johnson, Clements House, 14-18 Gresham Street, London EC2V 7JE.

So who does Steptoe & Johnson work for I wonder…

Read the whole story here

MHRA staff co-operate with Glaxo to monitor critical comment on the internet..

My last post bemoaned the fact after during the recent 4 year long investigation into Glaxo by the MHRA (the probe began after disclosure that Glaxo withheld data from Seroxat clinical trials), it was announced by the MHRA that Glaxo and individual Glaxo employees declined “invitations to attend interviews…”

Glaxo employees simply decided not to co-operate with the criminal investigation into their actions and said they would not answer questions.

However, in an ironic twist we now have evidence that Glaxo, the MHRA and Glaxo’s lawyers, are happy to work together to monitor the internet, in particular Bob Fiddaman, who has noticed some interesting recent visitors to his blog (Seroxat Sufferers).

Now, I’ve always said the MHRA and Glaxo were too close by half, but it seems that some MHRA employees are even closer than I thought..

Makes you think, doesn’t it?

Glaxo staff decide not to co-operate with the MHRA’s criminal investigation

A very interesting answer to a Freedom of information request from Bob Fiddaman.

In the recent 4 year long investigation into Glaxo by the MHRA (the probe began after disclosure that Glaxo withheld data from Seroxat clinical trials), it was announced by the MHRA that Glaxo and individual Glaxo employees declined “invitations to attend interviews… but did provide three written witness statements – two on behalf of the drugmaker and one on behalf of an unnamed employee.

One of the questions Bob asked was this:

“Why were MHRA enforcement investigators unable to question GSK staff?”

The MHRA replied to him:

Under UK criminal law suspects in criminal investigations can not be compelled to answer questions, they have a right to remain silent. Lengthy negotiations were conducted with solicitors acting for individual members of GSK staff and for GSK itself with a view to persuading them to attend interviews under caution. The conclusion of the correspondence was that all the potential interviewees indicated that they would not attend an interview under caution.

The individual suspects (as opposed to the corporate entity GSK) could have been arrested and required to attend an interview under caution. However they could still not be compelled to answer questions and, given that their solicitors had clearly indicated that they would not answer questions, the investigation team concluded that there was nothing to gain by carrying out arrests.

So there you have it, in black and white. Glaxo employees simply decided not to co-operate with a criminal investigation into their actions and said they would not answer questions.

Good to know that Glaxo employees are serious about the safety profile of their drugs and are seen to be acting in best interests of us patients at all times.

I wonder why they decided not to co-operate?

I wonder who they are?

Glaxo hides yet more trial data

I wonder, can you see a pattern forming here?

This time it’s not Seroxat but Avandia – read on from the Chicago Tribune:

GlaxoSmithKline PLC, Europe’s largest drugmaker, failed to properly disclose studies of Avandia, the diabetes pill linked to potentially deadly side effects, U.S. regulators said.

The violations “are serious and may be symptomatic of underlying post-marketing safety reporting failures,” the Food and Drug Administration said in a letter posted on its Web site. The agency said it was never told about nine studies, and an additional 11 weren’t included in required annual reports from 2001 to 2007.

Avandia sales plunged last year after a May 21 report in the New England Journal of Medicine linked the drug to a 43 percent increased risk of heart attacks, prompting U.S. and European regulators to strengthen warnings on its prescribing information. The FDA found unreported research while inspecting paperwork at London-based Glaxo’s offices in Research Triangle Park, N.C., from August to November, according to the letter.

Meanwhile, Glaxo said 247 lawsuits have been filed in the U.S. over Avandia.

And just one other thing – I thought’d read somewhere that Glaxo proudly boasts it places all clinical trial data on the internet… well, almost all it seems.

Direct to consumer advertising for Europe…

I wrote about ‘Pharma TV’ back in May 2007 – here, here, here, here and here.

I also wrote about DTC drug advertising here and here.

But it’s not advertising – it’s simply providing information for patients – yeah, right!

Charles Medawar at Social Audit has been asked to write to the European Commission on this matter:


Dear Sirs,

I feel unable to respond to your consultation on ‘patient information’ on the point-by-point basis proposed. But I do wish to register the strongest objections to your plans, not least for the reasons explained in the statement you have received from the consortium of eleven European organisations, led by ISDB, MiEF, HAI and AIM, also in papers from the Picker Institute and others.

From a health perspective, the proposal to expose people to more and more disease awareness messages from pharmaceutical companies seems destitute. It is especially unacceptable that DG Enterprise & Industry should be trying to legalise direct-to-consumer promotion of prescription drugs, yet again by dressing it up as a proposal to liberate consumers with better drug information.

The Commission’s proposals stand for principles that, after 30 years of professional engagement in this field, I have learned to abhor. An abbreviated Curriculum Vitae is attached at Appendix Two.

As a prescription for health, this consultation exercise seems essentially cynical. The main objective of DG Enterprise and Industry (DGEI) is to promote European trade and economic development. That is a legitimate interest in its own right, but it presents grotesque conflicts of interest when it comes to shaping health policy – and these proposals exemplify them. DGEI greatly over-estimates the support they deserve, no doubt partly in the expectation of strong backing from the industry-funded patient groups that it has traditionally promoted and preferred.

The consultation document lacks any coherent health impact assessment. Its proposals further blur the distinction between high and low quality information, and take no account of the health impact of the far greater quantities of partial information to which people will now be exposed. That is a crucial omission.

Professional judgment underpins my fear that the longer-term impact of these proposals will be to damage health and beckon Pharmageddon. See Appendix One. It is of great concern that the European Commission should so vigorously and uncritically promote the cause of an industry whose behaviour is routinely seductive, deceptive, manipulative and grasping, and whose output of useful new drugs is low and in decline.

The activities of the leading pharmaceutical companies – all deeply engaged with DGEI – mainly distract from the health problems we face. Medicinal drugs are of course sometimes extremely valuable – but can only ever be a small part of the effective solutions we need. Real health grows from the roots up, not from cabals down.

Europeans need to take personal responsibility for their own health, and to understand how much it depends on the health of local and global community. DG Enterprise & Industry completely fails to appreciate that you paralyse the healthy human response, once people come to believe that their genes, body chemistry, and social and cosmetic camouflage are key to developing health and well-being. These proposals take absurdly for granted the benefits of technological and medical intervention

People can never take responsibility for health if bombarded with disease awareness propositions – relentless reminders of their vulnerability, with the promise of drug solutions always to hand. This drive to medicalisation not only makes people feel resourceless and ill; it also threatens the very existence of national health services, by creating unsustainable demand.

What do these proposals have to offer in terms of promoting clear and general understanding of the real benefits, risks and harms that come from pharmaceutical interventions? Possibly one step forward; probably three or more steps back.

Health is basically to do with eating sensibility and sufficiently, taking enough exercise, avoiding toxic exposures, and social security and justice. Disease awareness propaganda diminishes these imperatives and makes the situation worse. Medicines have their place, but it is folly to promote them as if they were the bedrock of health development and the key to maintaining good enough levels of personal confidence, social equilibrium and mental and physical health.

These dismal and potentially dangerous proposals from DG Enterprise seem to me a portent of the health chaos that the European leadership on medicines might first precipitate and then hopelessly fail to contain.
I would be happy to further explain and justify these observations, if required.

Yours faithfully

Charles Medawar
Executive Director
Social Audit Ltd
P O Box 111
London NW1 8XG

Why would pharmaceutical companies hid bad data for years?

It’s a fair question – why would bad data be hidden for years? What’s in for pharma companies to do that?

Well, I think we may have found a reason (or 5 billion reasons!)… Alex Berenson in the New York Times is writing about Merck and Schering-Plough and their delayed trial results for Vytorin and Zetia.

The results were delayed for two years and last year these two drugs had sales in the USA of $5 billion….

Read on:

The lead outside investigator on a crucial trial of two widely used heart drugs said in an e-mail message last July that Merck and Schering-Plough, the companies that make the drugs, were deliberately delaying the release of the trial results “to hide something.”

The companies did not release the preliminary results of the trial, called Enhance, until January, almost two years after the trial was finished. When they were finally released, the trial’s results showed that the drugs, Vytorin and Zetia, did not work to reduce plaque in arteries. The results led a panel of cardiologists to recommend on Sunday that the drugs be used only as a last resort.

The new information was contained in e-mail messages to executives at Schering-Plough that were released Monday by Senator Charles E. Grassley of Iowa, the ranking Republican on the Senate Finance Committee. The committee has been investigating the delay in the release of the Enhance trial results.

It is likely to inflame the controversy over the way that Merck and Schering-Plough handled the Enhance trial, as well as their heavy promotion of Vytorin and Zetia. The drugs are used to lower cholesterol and are among the most widely prescribed medicines in the United States, with sales of $5 billion last year. Shares of Merck and Schering plunged on Monday.

The full article is here.

GSK Lawyers target Seroxat campaigner Bob Fiddaman – what next?

What next indeed – I think we should all carry on discussing this matter and it seems like more and more people are…

I think that particular attention should be paid to this link – where Bob Fiddaman himself posts a copy of the letter from Glaxo’s solicitors, Addleshaw & Goddard, and asks a few questions that Benbow or Addleshaw & Goddard should answer.

Benbow in particular does have some serious answering to do. He has to explain in detail why public comments he made were truthful (or otherwise). If not truthful, he has to explain whether he lied, was duped by his employer, or whether he failed to examine the facts before making public statements. He has to respond in detail both as a scientist and as a medical doctor. And he has to respond in public. It is inappropriate for a public scientific figure to claim harassment when asked to justify crucial (and potentially lethal) public scientific statements that he made.

In all this let’s not forget what Benbow is defending at the moment – that being the way Glaxo has wriggled out of a criminal prosecution in the UK on a technicality.

Here’s a handy timeline of events:

1998 — GSK completed two trials involving the use of Seroxat in children, which failed to demonstrate that it was effective at treating major depression in children.

September 2002 — In a further seven trials, the last of which ended in September 2002, Seroxat’s efficacy for treating children with major depression was not demonstrated.

November 2002 — The MHRA asked GSK about the status of clinical trials in children and the company indicated that it intended to submit an application for paediatric indications. It did not raise any concerns about a lack of efficacy or adverse reactions during clinical trials.

February 2003 — Unprompted, GSK sent an update to the MHRA on clinical trial data it held in relation to suicidal behaviour. However, adult and paediatric data were not differentiated and any safety signal from the paediatric studies was lost when the two populations were mixed since the adult population was much larger.

May 2003 — At the end of a meeting with the MHRA to discuss the safety of Seroxat, GSK handed out a briefing document relating to an application to extend indications for Seroxat to include children. In it a safety concern related to suicidal behaviour among depressed children taking Seroxat was highlighted. The MHRA subsequently requested full clinical trial data from GSK, which showed that the safety concern became apparent after a meta-analysis of the trials was conducted.

June 2003 — The lack of efficacy together with evidence of a causal association between Seroxat and suicidal behaviour in children led the MHRA to advise that it should not be used in the treatment of depressive illness in the under 18s.

March 2008 – the MHRA’s CEO Kent Woods concluded “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”. The prospect of obtaining a criminal conviction wasn’t “realistic,” because the legislation in force in 2003 – when the investigation began – wasn’t clear enough, especially concerning the disclosure of data and off-label use, the MHRA said in a statement. Glaxo and individual Glaxo employees declined “invitations to attend interviews,” the MHRA says, but did provide three written witness statements – two on behalf of the drugmaker and one on behalf of an unnamed employee.

For the full story on the investigation see:

Glaxo fails in its responsibility to patients and it hid Seroxat data – it’s official

This is how Glaxo hid data and fooled us all

Glaxo’s spin on hidden Seroxat data scandal and Alastair Benbow’s memory loss between October 1998 and May 2003

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