Seroxat Group action – latest news

Great news about the Seroxat Withdrawal Group Litigation in England… we are on our way to trial! AT LAST!!

I’m sure if you read Bob Fiddaman’s blog you know already – see here – but I thought I’d wait until we had passed the time limit for GSK to appeal Mr Justice Foskett’s judgement to proceed with the Seroxat Withdrawal Group Litigation. That time has passed and there was no appeal… we are on our way to trial! AT LAST!!


If you happen to be one of the group claimants and you HAVE NOT received forms from Fortitude Law in the past 2 weeks, then you should contact Fortitude Law via email at lcorr@fortitudelaw.uk or telephone on 0203 667 3775 without delay.


I think I’ll say it again, just because I can … ‘Judgment has been received from the Honourable Mr. Justice Foskett to proceed with the Seroxat Withdrawal Group Litigation’. 

I think there must be quite a few people on the other side who really thought this had gone away, but I can tell them now to look out – it hasn’t gone away and it’s all too real. I’ve said before that, for me, a trial is the only to resolve this issue

The publicity of a High Court hearing will mean the mainstream press  will be free to report on ALL the evidence presented. Now… I’m thinking that this will mean a lot of GSK documents that have until now remained secret will become very public knowledge. You see a case like this, while common in the USA, is unheard of in the UK and the publicity it will generate will be huge. And all those once-secret documents and the information they hold will be available the world over for future claimants to use. I think a whole new raft of claims will be kick-started in the USA alone. I wonder what GSK’s share price will look like after all this? And how institutional investors will view a company that breaks the law and lies & cheats its way to profit?

In the 21st century, ethos & culture – the way a company actually conducts its business – are as important to a PLC as having a blockbuster product to sell. Ethos & culture are intrinsic parts of a modern corporate brand, going way beyond the generic, meaningless mission statement that we see from GSK.

I’d like to finish on a personal note. Perhaps, after all these years, I’m getting nearer to closure. For me, that simply means people will believe what happened to me was real.

More importantly, I hope that Doctors will understand what happened to me was real – and perhaps then we can start to help others who are going through the horrors of withdrawing from Seroxat/Paxil today.

 

 

Why won’t GSK pay compensation in the UK?

I’ve asked this before, but the question is still very relevant – you see, the thing is, GSK has paid out millions in compensation to patients (and their children) in the USA who have been damaged by Seroxat/Paxil – but not a penny in the UK… I’m confused, is GSK admitting Paxil is a dangerous drug in America with the potential for terrible side effects, but saying Seroxat in the UK is completely safe and not dangerous at all?

And there’s me, thinking they were the same pills!

But of course, the answer to the question “Why not pay compensation in the UK as well?” has nothing to do with drug safety or patients’ suffering and everything to do with profits and business.

In the USA cases like this are heard before juries and lawyers will take cases on a ‘no win, no fee’ basis and settlements can be very high, so the drug companies are running scared. Because of this, most cases in the USA are settled out of court and Confidentiality Agreements ensure none of the truth ever comes to light (see below).

However, in the UK, cases are heard before a single High Court Judge, any settlements would be much lower than in America and funding is much harder to find – certainly Legal Aid is no longer an option in 2016.

So in the UK, GSK might use a legal firm, perhaps like Addleshaw Goddard, to obfuscate and ensure litigation drags out for years and years, to the point where many claimants just give up or are scared off or the momentum of the case simply grinds to halt – it’s a war of attrition and has nothing to do with justice or patient safety.

Behind the scenes it seems there are other pressures that can be brought to bear to ensure that big business has a better chance of winning. Business and government are far too close – but more of that on another day.

Certainly,this has been going on far too long in the UK – I wrote this in 2009 (and 2007):  Given the fact that Glaxo is currently on trial in Philadelphia (and will be in the High Court in London next year), [sic] I thought this repost (from March 2007) might of interest to you.

Drug companies usually favour the out of court settlement – they don’t like the public scrutiny that court cases bring – not to mention the previously secret information that all too often comes to light.

But along with the settlement comes the confidentiality ‘agreement’. The message the drug companies send out is “we pay up – you shut up” – while all the while never admitting any blame (for anything).

I’m not sure – are Glaxo admitting they’re settling Paxil (Seroxat) cases in the USA?

Well they are – this download – Glaxo settlement agreement – tells its own story, I guess. Pay particular attention to section 3 – Confidentiality of Settlement…

What I find ironic is that Glaxo, being an English company, is prepared to open its cheque book in America, but not in the UK.

So then, Glaxo:

Why won’t you settle in the UK?

Why won’t you help the thousands of people in the UK who have suffered because of Seroxat?

Haven’t you made enough money from the drug?

Why are we having to slug it out with you in the High Court?

Links to the Philadelphia trial details are herehere and here.

This from Seroxat Sufferers details some of the settlements GSK has made in the USA:

…since 2002 GSK have paid out compensation to victims of Seroxat, including over 3,000 people who became addicted to Seroxat, over 800 women whose children were born with serious heart defects because of Seroxat, and also being found guilty of Seroxat causing, in part, the death of Donald Schell and his family members.

And just to underline how GSK does business here are a few links from a Google search for ‘GSK fines’:

Seroxat/Paxil Study 329 – the truth at last.

I’m feeling re-energised today for a number of reasons, one of them being the fact that I’ve discovered the final chapter in the story of Study 329 has arrived.

I suggest you visit Restoring Study 329 for the latest news.

Also have a look here at Bob Fiddaman’s excellent take on today’s news.

If you don’t already know, Study 329 is arguably the most controversial drug study ever, published in July 2001.

In a nutshell Study 329:

– concluded that Seroxat was a safe and effective medication for treating major depression in adolescents;
– is still widely cited in the medical literature, providing physicians with assurance about the usefulness of paroxetine;
– was criticised by a few alert and concerned journalists, academics and bloggers. (However, their voices were buried by a tsunami of positive marketing and promotion by vested interests);
– resulted in a successful New York state fraud lawsuit against GSK;
– resulted in 2012 in the biggest fine in corporate history – $3 Billion,
and
– remains unretracted.

I have written about the scandal of Study 329 for many years and this link collects my posts about the Study 329.

From one blunt Yorkshireman to another – I hope you’re paying attention Andrew Witty, this hasn’t gone away… oh, and I don’t just mean Study 329.

What I believe

I believe Seroxat is defective and dangerous.

I believe that Glaxo has hidden clinical trial data that shows exactly how dangerous a drug it is.

I believe that Seroxat is addictive.

I believe that Seroxat can cause anger, aggression and violence.

I believe that something must be done to help people who suffer terrible problems with withdrawal, as they desperately try to stop taking Seroxat.

I believe that doctors have taken large sums of money from Glaxo to lie about the efficacy and safety of the drug.

I believe that GlaxoSmithKline puts profits before patients – their wealth before our health.

I took Seroxat for 9 years and it took me 22 months to withdraw from the drug little by little.

Believe me – I know what I’m talking about.

The drugs don’t work: a modern medical scandal – by Dr Ben Goldacre

Here’s an extract from Ben Goldacre’s soon to be published (next week) latest book. To order a copy go to guardian.co.uk/bookshop or Amazon, of course. I’m very pleased that Ben has got to the same page as I’m on… he’s got a few more readers than me.

Ben’s website is here if you’d like to get to know him better.

Now read on…

The doctors prescribing the drugs don’t know they don’t do what they’re meant to. Nor do their patients. The manufacturers know full well, but they’re not telling. Drugs are tested by their manufacturers, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that exaggerate the benefits.

Reboxetine is a drug I have prescribed. Other drugs had done nothing for my patient, so we wanted to try something new. I’d read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It’s approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.

But we had both been misled. In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.

It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients’ worth of data was left unpublished, and this unpublished data showed that patients on reboxetine did worse than those on other drugs. If all this wasn’t bad enough, there was also the side-effects data. The drug looked fine in the trials that appeared in the academic literature; but when we saw the unpublished studies, it turned out that patients were more likely to have side-effects, more likely to drop out of taking the drug and more likely to withdraw from the trial because of side-effects, if they were taking reboxetine rather than one of its competitors.

I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.

Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us. These problems have been protected from public scrutiny because they’re too complex to capture in a soundbite. This is why they’ve gone unfixed by politicians, at least to some extent; but it’s also why it takes detail to explain. The people you should have been able to trust to fix these problems have failed you, and because you have to understand a problem properly in order to fix it, there are some things you need to know.

Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects. Regulators see most of the trial data, but only from early on in a drug’s life, and even then they don’t give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.

In their 40 years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it’s not in anyone’s financial interest to conduct any trials at all.

Now, on to the details.

In 2010, researchers from Harvard and Toronto found all the trials looking at five major classes of drug – antidepressants, ulcer drugs and so on – then measured two key features: were they positive, and were they funded by industry? They found more than 500 trials in total: 85% of the industry-funded studies were positive, but only 50% of the government-funded trials were. In 2007, researchers looked at every published trial that set out to explore the benefits of a statin. These cholesterol-lowering drugs reduce your risk of having a heart attack and are prescribed in very large quantities. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. They found that industry-funded trials were 20 times more likely to give results favouring the test drug.

These are frightening results, but they come from individual studies. So let’s consider systematic reviews into this area. In 2003, two were published. They took all the studies ever published that looked at whether industry funding is associated with pro-industry results, and both found that industry-funded trials were, overall, about four times more likely to report positive results. A further review in 2007 looked at the new studies in the intervening four years: it found 20 more pieces of work, and all but two showed that industry-sponsored trials were more likely to report flattering results.

It turns out that this pattern persists even when you move away from published academic papers and look instead at trial reports from academic conferences. James Fries and Eswar Krishnan, at the Stanford University School of Medicine in California, studied all the research abstracts presented at the 2001 American College of Rheumatology meetings which reported any kind of trial and acknowledged industry sponsorship, in order to find out what proportion had results that favoured the sponsor’s drug.

In general, the results section of an academic paper is extensive: the raw numbers are given for each outcome, and for each possible causal factor, but not just as raw figures. The “ranges” are given, subgroups are explored, statistical tests conducted, and each detail is described in table form, and in shorter narrative form in the text. This lengthy process is usually spread over several pages. In Fries and Krishnan (2004), this level of detail was unnecessary. The results section is a single, simple and – I like to imagine – fairly passive-aggressive sentence:

“The results from every randomised controlled trial (45 out of 45) favoured the drug of the sponsor.”

How does this happen? How do industry-sponsored trials almost always manage to get a positive result? Sometimes trials are flawed by design. You can compare your new drug with something you know to be rubbish – an existing drug at an inadequate dose, perhaps, or a placebo sugar pill that does almost nothing. You can choose your patients very carefully, so they are more likely to get better on your treatment. You can peek at the results halfway through, and stop your trial early if they look good. But after all these methodological quirks comes one very simple insult to the integrity of the data. Sometimes, drug companies conduct lots of trials, and when they see that the results are unflattering, they simply fail to publish them.

Because researchers are free to bury any result they please, patients are exposed to harm on a staggering scale throughout the whole of medicine. Doctors can have no idea about the true effects of the treatments they give. Does this drug really work best, or have I simply been deprived of half the data? No one can tell. Is this expensive drug worth the money, or has the data simply been massaged? No one can tell. Will this drug kill patients? Is there any evidence that it’s dangerous? No one can tell. This is a bizarre situation to arise in medicine, a discipline in which everything is supposed to be based on evidence.

And this data is withheld from everyone in medicine, from top to bottom. Nice, for example, is the National Institute for Health and Clinical Excellence, created by the British government to conduct careful, unbiased summaries of all the evidence on new treatments. It is unable either to identify or to access data on a drug’s effectiveness that’s been withheld by researchers or companies: Nice has no more legal right to that data than you or I do, even though it is making decisions about effectiveness, and cost-effectiveness, on behalf of the NHS, for millions of people.

In any sensible world, when researchers are conducting trials on a new tablet for a drug company, for example, we’d expect universal contracts, making it clear that all researchers are obliged to publish their results, and that industry sponsors – which have a huge interest in positive results – must have no control over the data. But, despite everything we know about industry-funded research being systematically biased, this does not happen. In fact, the opposite is true: it is entirely normal for researchers and academics conducting industry-funded trials to sign contracts subjecting them to gagging clauses that forbid them to publish, discuss or analyse data from their trials without the permission of the funder.

This is such a secretive and shameful situation that even trying to document it in public can be a fraught business. In 2006, a paper was published in the Journal of the American Medical Association (Jama), one of the biggest medical journals in the world, describing how common it was for researchers doing industry-funded trials to have these kinds of constraints placed on their right to publish the results. The study was conducted by the Nordic Cochrane Centre and it looked at all the trials given approval to go ahead in Copenhagen and Frederiksberg. (If you’re wondering why these two cities were chosen, it was simply a matter of practicality: the researchers applied elsewhere without success, and were specifically refused access to data in the UK.) These trials were overwhelmingly sponsored by the pharmaceutical industry (98%) and the rules governing the management of the results tell a story that walks the now familiar line between frightening and absurd.

For 16 of the 44 trials, the sponsoring company got to see the data as it accumulated, and in a further 16 it had the right to stop the trial at any time, for any reason. This means that a company can see if a trial is going against it, and can interfere as it progresses, distorting the results. Even if the study was allowed to finish, the data could still be suppressed: there were constraints on publication rights in 40 of the 44 trials, and in half of them the contracts specifically stated that the sponsor either owned the data outright (what about the patients, you might say?), or needed to approve the final publication, or both. None of these restrictions was mentioned in any of the published papers.

When the paper describing this situation was published in Jama, Lif, the Danish pharmaceutical industry association, responded by announcing, in the Journal of the Danish Medical Association, that it was “both shaken and enraged about the criticism, that could not be recognised”. It demanded an investigation of the scientists, though it failed to say by whom or of what. Lif then wrote to the Danish Committee on Scientific Dishonesty, accusing the Cochrane researchers of scientific misconduct. We can’t see the letter, but the researchers say the allegations were extremely serious – they were accused of deliberately distorting the data – but vague, and without documents or evidence to back them up.

Nonetheless, the investigation went on for a year. Peter Gøtzsche, director of the Cochrane Centre, told the British Medical Journal that only Lif’s third letter, 10 months into this process, made specific allegations that could be investigated by the committee. Two months after that, the charges were dismissed. The Cochrane researchers had done nothing wrong. But before they were cleared, Lif copied the letters alleging scientific dishonesty to the hospital where four of them worked, and to the management organisation running that hospital, and sent similar letters to the Danish medical association, the ministry of health, the ministry of science and so on. Gøtzsche and his colleagues felt “intimidated and harassed” by Lif’s behaviour. Lif continued to insist that the researchers were guilty of misconduct even after the investigation was completed.

Paroxetine is a commonly used antidepressant, from the class of drugs known as selective serotonin reuptake inhibitors or SSRIs. It’s also a good example of how companies have exploited our long-standing permissiveness about missing trials, and found loopholes in our inadequate regulations on trial disclosure.

To understand why, we first need to go through a quirk of the licensing process. Drugs do not simply come on to the market for use in all medical conditions: for any specific use of any drug, in any specific disease, you need a separate marketing authorisation. So a drug might be licensed to treat ovarian cancer, for example, but not breast cancer. That doesn’t mean the drug doesn’t work in breast cancer. There might well be some evidence that it’s great for treating that disease, too, but maybe the company hasn’t gone to the trouble and expense of getting a formal marketing authorisation for that specific use. Doctors can still go ahead and prescribe it for breast cancer, if they want, because the drug is available for prescription, it probably works, and there are boxes of it sitting in pharmacies waiting to go out. In this situation, the doctor will be prescribing the drug legally, but “off-label”.

Now, it turns out that the use of a drug in children is treated as a separate marketing authorisation from its use in adults. This makes sense in many cases, because children can respond to drugs in very different ways and so research needs to be done in children separately. But getting a licence for a specific use is an arduous business, requiring lots of paperwork and some specific studies. Often, this will be so expensive that companies will not bother to get a licence specifically to market a drug for use in children, because that market is usually much smaller.

So it is not unusual for a drug to be licensed for use in adults but then prescribed for children. Regulators have recognised that this is a problem, so recently they have started to offer incentives for companies to conduct more research and formally seek these licences.

When GlaxoSmithKline applied for a marketing authorisation in children for paroxetine, an extraordinary situation came to light, triggering the longest investigation in the history of UK drugs regulation. Between 1994 and 2002, GSK conducted nine trials of paroxetine in children. The first two failed to show any benefit, but the company made no attempt to inform anyone of this by changing the “drug label” that is sent to all doctors and patients. In fact, after these trials were completed, an internal company management document stated: “It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.” In the year after this secret internal memo, 32,000 prescriptions were issued to children for paroxetine in the UK alone: so, while the company knew the drug didn’t work in children, it was in no hurry to tell doctors that, despite knowing that large numbers of children were taking it. More trials were conducted over the coming years – nine in total – and none showed that the drug was effective at treating depression in children.

It gets much worse than that. These children weren’t simply receiving a drug that the company knew to be ineffective for them; they were also being exposed to side-effects. This should be self-evident, since any effective treatment will have some side-effects, and doctors factor this in, alongside the benefits (which in this case were nonexistent). But nobody knew how bad these side-effects were, because the company didn’t tell doctors, or patients, or even the regulator about the worrying safety data from its trials. This was because of a loophole: you have to tell the regulator only about side-effects reported in studies looking at the specific uses for which the drug has a marketing authorisation. Because the use of paroxetine in children was “off-label”, GSK had no legal obligation to tell anyone about what it had found.

People had worried for a long time that paroxetine might increase the risk of suicide, though that is quite a difficult side-effect to detect in an antidepressant. In February 2003, GSK spontaneously sent the MHRA a package of information on the risk of suicide on paroxetine, containing some analyses done in 2002 from adverse-event data in trials the company had held, going back a decade. This analysis showed that there was no increased risk of suicide. But it was misleading: although it was unclear at the time, data from trials in children had been mixed in with data from trials in adults, which had vastly greater numbers of participants. As a result, any sign of increased suicide risk among children on paroxetine had been completely diluted away.

Later in 2003, GSK had a meeting with the MHRA to discuss another issue involving paroxetine. At the end of this meeting, the GSK representatives gave out a briefing document, explaining that the company was planning to apply later that year for a specific marketing authorisation to use paroxetine in children. They mentioned, while handing out the document, that the MHRA might wish to bear in mind a safety concern the company had noted: an increased risk of suicide among children with depression who received paroxetine, compared with those on dummy placebo pills.

This was vitally important side-effect data, being presented, after an astonishing delay, casually, through an entirely inappropriate and unofficial channel. Although the data was given to completely the wrong team, the MHRA staff present at this meeting had the wit to spot that this was an important new problem. A flurry of activity followed: analyses were done, and within one month a letter was sent to all doctors advising them not to prescribe paroxetine to patients under the age of 18.

How is it possible that our systems for getting data from companies are so poor, they can simply withhold vitally important information showing that a drug is not only ineffective, but actively dangerous? Because the regulations contain ridiculous loopholes, and it’s dismal to see how GSK cheerfully exploited them: when the investigation was published in 2008, it concluded that what the company had done – withholding important data about safety and effectiveness that doctors and patients clearly needed to see – was plainly unethical, and put children around the world at risk; but our laws are so weak that GSK could not be charged with any crime.

After this episode, the MHRA and EU changed some of their regulations, though not adequately. They created an obligation for companies to hand over safety data for uses of a drug outside its marketing authorisation; but ridiculously, for example, trials conducted outside the EU were still exempt. Some of the trials GSK conducted were published in part, but that is obviously not enough: we already know that if we see only a biased sample of the data, we are misled. But we also need all the data for the more simple reason that we need lots of data: safety signals are often weak, subtle and difficult to detect. In the case of paroxetine, the dangers became apparent only when the adverse events from all of the trials were pooled and analysed together.

That leads us to the second obvious flaw in the current system: the results of these trials are given in secret to the regulator, which then sits and quietly makes a decision. This is the opposite of science, which is reliable only because everyone shows their working, explains how they know that something is effective or safe, shares their methods and results, and allows others to decide if they agree with the way in which the data was processed and analysed. Yet for the safety and efficacy of drugs, we allow it to happen behind closed doors, because drug companies have decided that they want to share their trial results discretely with the regulators. So the most important job in evidence-based medicine is carried out alone and in secret. And regulators are not infallible, as we shall see.

Rosiglitazone was first marketed in 1999. In that first year, Dr John Buse from the University of North Carolina discussed an increased risk of heart problems at a pair of academic meetings. The drug’s manufacturer, GSK, made direct contact in an attempt to silence him, then moved on to his head of department. Buse felt pressured to sign various legal documents. To cut a long story short, after wading through documents for several months, in 2007 the US Senate committee on finance released a report describing the treatment of Buse as “intimidation”.

But we are more concerned with the safety and efficacy data. In 2003 the Uppsala drug monitoring group of the World Health Organisation contacted GSK about an unusually large number of spontaneous reports associating rosiglitazone with heart problems. GSK conducted two internal meta-analyses of its own data on this, in 2005 and 2006. These showed that the risk was real, but although both GSK and the FDA had these results, neither made any public statement about them, and they were not published until 2008.

During this delay, vast numbers of patients were exposed to the drug, but doctors and patients learned about this serious problem only in 2007, when cardiologist Professor Steve Nissen and colleagues published a landmark meta-analysis. This showed a 43% increase in the risk of heart problems in patients on rosiglitazone. Since people with diabetes are already at increased risk of heart problems, and the whole point of treating diabetes is to reduce this risk, that finding was big potatoes. Nissen’s findings were confirmed in later work, and in 2010 the drug was either taken off the market or restricted, all around the world.

Now, my argument is not that this drug should have been banned sooner because, as perverse as it sounds, doctors do often need inferior drugs for use as a last resort. For example, a patient may develop idiosyncratic side-effects on the most effective pills and be unable to take them any longer. Once this has happened, it may be worth trying a less effective drug if it is at least better than nothing.

The concern is that these discussions happened with the data locked behind closed doors, visible only to regulators. In fact, Nissen’s analysis could only be done at all because of a very unusual court judgment. In 2004, when GSK was caught out withholding data showing evidence of serious side-effects from paroxetine in children, their bad behaviour resulted in a US court case over allegations of fraud, the settlement of which, alongside a significant payout, required GSK to commit to posting clinical trial results on a public website.

Nissen used the rosiglitazone data, when it became available, and found worrying signs of harm, which they then published to doctors – something the regulators had never done, despite having the information years earlier. If this information had all been freely available from the start, regulators might have felt a little more anxious about their decisions but, crucially, doctors and patients could have disagreed with them and made informed choices. This is why we need wider access to all trial reports, for all medicines.

Missing data poisons the well for everybody. If proper trials are never done, if trials with negative results are withheld, then we simply cannot know the true effects of the treatments we use. Evidence in medicine is not an abstract academic preoccupation. When we are fed bad data, we make the wrong decisions, inflicting unnecessary pain and suffering, and death, on people just like us.

Bad Pharma: How drug companies mislead doctors and harm patients

Here’s an unashamed plug for new book by Dr Ben Goldacre that’s out in a week or so.

‘Bad Science’ hilariously exposed the tricks that quacks and journalists use to distort science, becoming a 400,000 copy bestseller. Now Ben Goldacre puts the $600bn global pharmaceutical industry under the microscope. What he reveals is a fascinating, terrifying mess.

Doctors and patients need good scientific evidence to make informed decisions. But instead, companies run bad trials on their own drugs, which distort and exaggerate the benefits by design. When these trials produce unflattering results, the data is simply buried. All of this is perfectly legal. In fact, even government regulators withhold vitally important data from the people who need it most. Doctors and patient groups have stood by too, and failed to protect us. Instead, they take money and favours, in a world so fractured that medics and nurses are now educated by the drugs industry.

Patients are harmed in huge numbers.

‘Bad Pharma’ is a clear and witty attack, showing exactly how the science has been distorted, how our systems have been broken, and how easy it would be to fix them.

The Amazon link for pre order is here.

If you live in London and want to see Ben talk about this in person, then head to the Royal Institution on 2 October

The link for tickets is here.

Inside Paxil Study 329, Courtesy the Justice Department

This is from Dr Howard Brody’s blog – Hooked: Ethics, Medicine, and Pharma

It sums up the story of Study 329 (with links to the original DoJ documents) and dovetails with the current scandal over Glaxo’s record $3 billion fine for witholding negative drug trial data for Avandia, the illegal marketing of drugs and bribing doctors to prescribe Glaxo products.

Remember, Study 329 was not covered by the latest $3 billion fine – Study 329 was yet another example of Glaxo’s lying and cheating to sell its drugs.

Now read on:

I’ve previously discussed the now-infamous Study 329, which took discouraging data on the efficacy and safety of paroxetine (Paxil) in kids and spun it into an article claiming excellent results:
http://brodyhooked.blogspot.com/2011/11/will-brown-university-investigate.html

Thanks to the U.S. Justice Dept. complaint in the suit recently settled by GlaxoSmithKline for a record $3B: http://www.justice.gov/opa/documents/gsk/us-complaint.pdf
–we can follow the history of this study in more detail, based on the internal GSK documents discovered during the proceedings, and see just how the data were manipulated for marketing purposes.

Study 329, directed by Dr. Martin Keller of Brown University, was one of 3 clinical studies in children and adolescents that were all interpreted by GSK scientists between August and October, 1998 to be discouraging. Study 329’s protocol specified two primary endpoints, and on neither measure did Paxil do better than placebo. The study also logged in 11 serious adverse reactions to Paxil, much more than in the placebo group, including 5 with agitated or suicidal behavior, the major risk for which eventually the FDA issued a black-box warning for the SSRI class of antidepressants.

Undaunted, GSK contracted in April 1998 with Scientific Therapeutics Information, Inc. to prepare an article for journal publication based on 329. As we know from other sources, STI writers basically wrote the paper and later did revisions, with minimal input from the supposed scientific authors, meaning that the paper was largely if not completely ghostwritten. As part of the laundering process, STI decided to downplay the primary endpoints and instead inserted 8 “efficacy measures,” none of which had been specified in the original study protocol. By what’s called data-dredging, STI was able to show that Paxil was statistically better than placebo on 4 of the 8 newly invented measures.

Initially the purported authors sent the paper to JAMA, claiming in the abstract that Paxil was “a safe and effective treatment for major depression in adolescents.” In December, 1999 JAMA rejected the paper, and reviewers’ comments indicated that the scientific reviewers had seen through the fog and realized that there were no solid data to show the superiority of Paxil. One internal memo then indicated that GSK and Dr. Keller agreed to send the manuscript to “a less demanding journal.”

Even the less-demanding Journal of the American Academy of Child and Adolescent Psychiatry originally couldn’t swallow the revised manuscript that Keller and company sent them in June 2000. Their reviewers detected some of the same problems as the earlier JAMA review.  GSK had STI go back to work responding to the reviewers’ comments and eventually JAACAP accepted the manuscript in February 2001.

According again to the Federal complaint, even with the recommended changes, GSK and STI (with the willing acquiescence of Dr. Keller and his co-authors, we presume) managed to slip in a number of incorrect and misleading statements. The abstract stated that the drug “is generally well tolerated and effective for major depression in adolescents.” The article mentioned the primary endpoints but failed to make clear that by neither was Paxil statistically superior to placebo. The article falsely implied that Paxil was superior on one of the primary endpoints by deliberately conflating one of the later “efficacy measures” with that endpoint. The article consistently downplayed all the measures where Paxil failed to show superiority to placebo and focused on the few, invented-later measures where a statistically significant result had been found.

More important, the 11 patients with serious adverse reactions due to Paxil, and the 5 of them with specifically suicidal or agitated symptoms, magically disappeared. In the revised manuscript the investigators suddenly decided that only one of the reactions (headache) was actually caused by Paxil, and the other bad outcomes were unrelated to the drug. When the FDA got its hands on the raw data from 329, it eventually determined that 10 of 93 patients taking Paxil had experienced a potentially suicidal reaction–a far different and scarier picture than that portrayed in any of the drafts or in the final manuscript.

To be sure that child psychiatrists heard the correct marketing message, GSK sponsored 8 “Forum” meetings at lavish resorts such as Rio Mar Beach Resort in Hawaii and Renaissance Esmerelda Resort in Palm Springs, CA. The psychiatrists who attended had their airfare and hotel paid plus a $750 honorarium, and in many cases their spouses were also paid for (a practice supposedly prohibited in the 2002 PhRMA code of conduct). The hired speakers who told them how wonderful Paxil was for treating kids received $2500 honoraria in addition.

Talking of speakers’ bureaus, another media summary of the complaint:
http://finance.yahoo.com/news/glaxosmithklines-gsk-3-billion-whistleblower-154800879.html
–reported that GSK had enrolled 49,000 health professionals to be on its speakers’ bureau for Paxil and other drugs. Two conclusions are possible: 1) there are 49,000 really excellent and scientifically informed speakers out there whose talents are needed to inform their fellow practitioners; or 2) a “speaker’s bureau” is really nothing but a disguised bribe to get all those docs to prescribe a lot of the drugs they are paid to speak about.

Hat tip to Dr. Roy Poses of Health Care Renewal blog for sending me the link to the full complaint (all 76 pages, for anyone who wants some fun reading).

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