Sense about Science: Follow the Lawsuit

Editorial Note:  This is a third in a series of posts about Sense about Science and Access to Clinical Trial Data that began with Follow the Rhetoric and followed up with First Admit no Harm.

There are some facts in the last few posts. There are also some extrapolations that may not be right.

Tracey Brown has gone on the Parliamentary Record to make clear what AllTrials are asking for – its not the data and not even full Clinical Study Reports.  If This is the AllTrials position, it is easy see why GSK felt they could sign up.  Even ghostwriting companies have signed up. But perhaps AllTrials have moved on.

It may be that the GSK periscope is an invention of subversives within GSK who saw a way to persuade AW1 that this would block access to the data for ever – all the time intending to gradually make it more and more user friendly and accessible.  Perhaps AW1 is the mastermind trying to leverage things forward.

Partnering Pharma

I’ve been a consultant to pharma and an expert for both plaintiffs and pharmaceutical companies in lawsuits.  These contacts definitely bias me – as much by virtue of the people you meet as the money you might be paid.  Under oath when asked if I’m biased I have always said yes – absolutely.

But I’ve never thought when it comes to science that it matters whether I or anyone linked to RxISK are moral or even nice people.  Science might be better served if I’ve got some strange biases or am being paid to try and find the flaws in an argument.  The key thing is access to the data, and given access to the data the more biases the better. Sometimes it takes a true weirdo to see how the data hangs together.

Being motivated whether because you have suffered an adverse event or because you’re being paid makes a difference to the effort you put in to solving problems.  But at the end of the day, if you aren’t free to access the data it’s not science.  If you’re a doctor and accept not being given access to the data – such as all doctors and statins –  that’s quackery not medicine.

Science moves ahead, when people with different biases have their views challenged by the data.  This is the very definition of science as opposed to philosophy or the humanities or business.

Medicine moves ahead when things happen to patients and when doctors and patients work to understand what has happened.

Business would likely do better in the long run if it built on this framework of doctors and patients working together to generate new knowledge. But instead at the moment business is not open for business on this issue. Why?

Study 329 & The Lawsuit that Didn’t Bark

Linked to Peter Doshi’s RIAT initiative, a group of us are working on re-authoring Study 329 – close to the most famous RCT of all time.  In this study GSK’s paroxetine (Paxil) was compared to imipramine and placebo in a group of children.

Those of us taking on this re-authoring job were among the first to be introduced to the GSMA-ESK scope – a periscope for looking at the data on which the GSK seagull regularly sits blocking the view.

The periscope gives the outside world the illusion GSK are offering transparency but it’s not meaningful transparency.

But periscopes are not the crux of the matter.

Damaging Children

Children became suicidal on paroxetine in Study 329.

Before they had the results of Study 329, GSK had seen patients in clinical practice and clinical trials become suicidal and homicidal on paroxetine where the company had coded the event as caused by their drug.  They knew the profile of what happens when an SSRI causes a problem.  In their adult trials from the late 1980s, there was a doubling of the rate of suicidal acts on paroxetine compared to placebo.

They have run clinical trials that use the fact that paroxetine caused people to become suicidal to hide the fact that paroxetine caused people to become suicidal.

In breach of FDA regulations they had moved wash-out suicidal acts into the placebo column in clinical trials to hide the problem.

But in public, they have consistently denied there is a problem.

In Study 329, paroxetine didn’t work and wasn’t safe.  Sally Laden ghostwrote the 329 paper and made paroxetine safe and effective.  There were 22 authors on the authorship line, possibly none of which barring company personnel had seen the full dataset.

Informed Consent? 

The consent form says that in this trial you will be treated in just the same way as you would in normal clinical practice.  Even from the protocol it was clear this was a lie.

The children taking imipramine were to be force titrated to 300mg where possible – this is just not normal clinical practice.  This is double the standard dose for adults.  It’s dangerous and seems designed to make imipramine look worse than paroxetine.

Even so imipramine wasn’t worse than paroxetine.  There was a statistically significant elevation in the number of children on paroxetine who had a suicidal event in this trial alone compared to placebo.

In normal clinical practice if someone becomes suicidal on an SSRI it would be usual to make the link for them and tell them that in future they should try an antidepressant from another group.  They are much more likely than the average person to become suicidal if exposed to another SSRI.

If the drug has caused the problem, it’s very important to their self-image that they know this.  They are being done a further injury, in this case an unnecessary one, if this information is withheld from them.

Have any of the children who became suicidal on paroxetine been told that paroxetine may have caused their problem?

No.

Whose Baby is it?

GSK say it’s the doctors – the non-authors of the paper – who know these children, whose responsibility it is to say whatever needs to be said to any of these children.

These are doctors who refuse to retract a paper that has been deemed fraudulent by New York State Attorney General Elliott Spitzer’s office.  (Elliott Spitzer of Good Wife fame).

To come full circle, this is the paper that led to the data access story we have today.  In response to a fraud charge in 2004, GSK agreed to post the CSRs on the company website in downloadable (non-periscope form).

Without Study 329 and the subsequent fraud charge and later $3 billion fine, GSK would likely never have felt the need to sign on to AllTrials.

Tomorrow and Tomorrow and Tomorrow

This is not a piece of history.  This is our future.

Right now today GSK are refusing to tell the children who have been injured by their drug in Study 329 that they were injured by their drug.  Tomorrow GSK will do the same and tomorrow and tomorrow.

Their drugs never injure people.

The reason GSK, Pfizer, Lilly and AbbVie don’t want anyone to get access to the data is so that no-one can access the damage.  No-one can find out about the Dan Markingsons who die or are injured in company trials.

They are not doing this out of a concern for Dan Markingson’s confidentiality.  They are doing it in order to avoid being sued.

This, Ben and Iain, is why I think GSK are playing the confidentiality card.

What do you think?  And what should we do about it?

The Cowardice of a Pampered Society

Tracey Brown and Dick Taverne of Sense about Science (SAS) have a publication:

Over-precautionary Tales: The precautionary principle represents the cowardice of a pampered society.

Is this Sense about Science?

What would the real SAS – the Short Arm Squad – say?

See SAS to Lisbeth


RxISK: Research and report prescription drug side effects on RxISK.org.

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You and your meds. Give the real story. Get the real story.

Pharmageddon

Pharmaceutical companies have hijacked healthcare in America, and the results are life-threatening.

 

Dr. David Healy documents a riveting and terrifying story that affects us all.

 

University of California Press (2012)

 

Available on Amazon.com

 

Comments

  1. It is likely that the flavour of the book by Brown and Taverne is reflected in an article by Sense About Science trustee Michael Fitpatrick, ‘The Price of Precaution’. In it Fitzpatrick argued or the exclusion of the victims of failed technology and science from public inquiries. A sample extract:

    “One train derailment led to the prolonged paralysis of the whole rail network. An outbreak of foot-and-mouth disease has resulted in the paralysis of much of the country, and has now led to the postponement of the general election. If the economic cost of the precautionary measures far exceeds that of the problems that they are responding to, the cost in terms of the demoralisation of society is even higher.

    “A more insidious result of the precautionary principle is the way it elevates public opinion over professional expertise and subordinates science to prejudice. One of the distinctive features of the BSE inquiry was the prominent role it gave to the relatives of victims of variant CJD…”

    http://www.spiked-online.com/newsite/article/11745#.U56glCjb4YU

    What they have also successfully done with their sister organisation Science Media Centre is campaigned for the exclusion of dissenting groups and persons from the media. Is it significant that we are not reading about both sides of this present great public matter in the mainstream media? The most important decisions these days mostly occur without them coming to wider public notice. Most people – even most most people who are supporting the new measures – will not know what is at stake. But at least “the morale of society” will have been preserved.

  2. Readers should be aware that David Healy is repeatedly making claims on this blog that are simply untrue.

    http://davidhealy.org/sense-about-science-follow-the-rhetoric/#comment-106400
    http://davidhealy.org/fucked/#comment-105894
    etc

    I fully support researchers having access to unredacted CSRs and full individual patient data.

    David knows full well that this is the case, he has been told so repeatedly, and it’s a matter of extensive public record, as I’ve written it repeatedly in my extensive campaigning for transparency over many years. David Healy continues to misrepresent the positions of others in order to further his own peculiar commercial goals. Anyone reading his work should be aware that David Healy is simply writing a bizarre series of untruths.

    The one thing I do have some caution over is whether detailed descriptions of individual patients’ adverse events should always be posted openly and publicly on the internet for all to see without their prior consent. Sometimes those reports can contain rather a lot of intrusive and personal information that some individuals would find embarrassing if posted publicly. Caution on posting this publicly seems to me to be a reasonable courtesy to the people who participated in trials.

    For David Healy to repeatedly misrepresent a sensible discussion on how this kind of material can be shared shows that he is incapable of making a serious contribution. This is very sad, and very destructive, because the battle for trials transparency – where academics are every bit as guilty as industry – needs as many positive allies as it can get.

    • As someone who devotes a great deal of time every day to publishing mostly anonymized patient reports of adverse events here http://tinyurl.com/3o4k3j5, I must respectfully disagree with Dr. Goldacre’s position on this information from clinical trials.

      The public health menace from corrupted RCT information is so great, physicians and the public have been indoctrinated with them for so long, and opposition to the truth is so well-funded that public (though anonymized) airing of the underlying patient data is necessary for corroborating corrective criticisms.

      The patient level of detail is absolutely necessary for making the case that the RCT has been misinterpreted.

      Keeping such data sequestered in pharma’s archives gives the corporate interests opportunities to quibble over such things as how adverse events were classified. Having individual (anonymized) patient adverse event reports available will close off that avenue of misdirection.

  3. I should say that as well as misrepresenting my own views, David Healy is repeatedly misrepresenting the positions and actions of the AllTrials campaign. But nobody else can be bothered to write down how any more. Unsurprisingly. What a destructive mess.

    • Dr. Goldacre, I don’t think your own personal reputation is really the main issue. It’s more the direction of a movement. As a non-insider all I can do is read the official statements published on the Alltrials website – and much as I’d like to tell David Healy he’s getting all worked up over nothing, I can’t.

      I’m glad we could all join together to oppose the idiotic dodge of this screen-only access system – and I’m glad you remain concerned about the redaction policies and the draconian legal “agreements” researchers are to sign. I’m still not sure I understand what kinds of redactions you would consider OK rather than “excessive.”

      As for the issue of access to patient-level data – well, I’d just recommend you take a look at the two current articles in the BMJ on duloxetine by Emma Maund, Peter Gotzsche et al. They found big differences between the “results” reported on official registries and those in full, uncensored Clinical Study Reports. They also found important gaps between the CSR’s and the stories told on individual patient narratives, on the crucial issue of suicidality.

      These papers are the fruits of the short-lived open data policy that existed from 2011-2013, and unless we fight for that whole package we have to face the fact that we will get no more chances to do work like this, or to benefit from it as patients. As one who’s had nasty personal experiences with Cymbalta the Wonder Drug, and who regularly meets doctors with no clue as to its potential downsides, I think this is incredibly important. And as one who has both participated in research studies, and used the Internet to research health concerns, I worry far, far more about Google and Facebook than whether anyone would figure out that Patient 38 in Study Center 25 was me. That is at the bottom of my long list of real data privacy concerns.

      I’m also concerned by the statement in AllTrials’ June 2 letter to the EMA that “some companies and most academic institutes are throwing off the culture of secrecy and moving forward.” Which companies, please? If you mean GSK, well, they seem to have been full participants in the “screen-only” debacle. Most if not all of their current reform initiatives have come as part of a criminal plea agreement with the U.S. Department of Justice. The data-access system they’ve set up with five other Pharmas at http://www.clinicaltrialdatarequest.com puts an “independent” board in charge of deciding whose requests for data are granted – and those four characters don’t look very independent to me. That’s to say nothing of their continued stonewalling on paroxetine.

      We’ve arrived at the stage most movements will after gathering some steam. The powers that be stop ignoring you, and start offering you stage-managed “reform” plans that look good at a press conference, but are actually designed to head off your movement at the pass. Anyway, that’s what worries me, and that’s what I think we’re debating. Let’s have at it! I’d love for someone to convince me I’m wrong, I really would.

  4. Excuse me, Mr. Goldacre, are you, or are you not, aware that GlaxoSmithKline market Paroxetine as a safe drug?

    Are you aware that children and adults become suicidal on Paroxetine?

    Are you aware how many deaths have occurred from Paroxetine?

    Are you aware of four Panorama programmes on Paroxetine?

    This is why we do not understand why GlaxoSmithKline are in your promotional video for Alltrials.

    As a severe casualty myself, I have not the faintest idea what you think you are doing.

    There is not one word about GlaxoSmithKline in your comments.

    Try it out…..well, GlaxoSmithKline are a bit shady, a bit dubious, a bit of bad luck in the US with billions in fines re Paroxetine, criminal damage payouts and thousands on forums trying to get themselves off the damn stuff…

    Try it out…

    Then you might find you might earn yourself a bit more credibility.

  5. Annie

    It is perhaps instructive to study the rules of Goldacre’s Bad Science website to find out where he is coming from. It is evidently alway been policy dismiss reports of adverse reactions to industrial products. This from the rules:

    “I really don’t think it’s a good idea for you to post anecdotes about your own health problems and treatments here. It’s extremely unlikely that they will inform a discussion about evidence, and experience here suggests that you may become offended and angry when other commenters disagree with your interpretation (as they are very entitled to do). Invite people elsewhere to discuss your anecdote, and if they want to, they will follow your link.”

    http://www.badscience.net/how-to-use-this-website/

    This replaced the comment:

    “.. personal anecdotes about your MMR tragedy will be deleted for your own safety”

    http://www.bmj.com/rapid-response/2011/11/01/and-maudsley-should-be-transparent-too

    Goldacre has a history of being openly hostile to people discussing adverse events, preferring to depend on big studies which may hide them (in the case of MMR none too successfully at that). It has also been the long term policy of Sense About Science to drive such discussion from the media.

    It should be obvious that some gentlemanly agreement beween a self-appointed lobby organisation with industrial connections and the pharmaceutical manufacturers is not what is needed to protect the public interest.

  6. Please, Dr. Healy and Dr. Goldacre, let the mutual ad hominems cease.

    As for Sense about Science and partnership with industry, it may be more instructive to view these positions in the context of neo-liberalism, which dismisses product flaws and opposes regulation in favor of expanding sales and economic growth.

    From the London School of Economics http://youtu.be/ehrjP2_ffPc

    Neo-liberalism thinks corporations have rights equivalent to individual people. In the face of its widespread corporate dishonesty, whether pharma has such rights is a subject of legitimate debate (and, I hope, the defeat of neo-liberal thinking on this subject).

  7. Actually, it might be relatively gratifying if the result is “a destructive mess” (in Ben Goldacre’s words above) rather than a gentleman’s agreements with industry and sham transparency. Some of us also remember how hard he worked to damp down concern about GSK’s HPV vaccine, Cervarix.

    http://www.theguardian.com/science/2009/oct/10/ben-goldacre-cervical-cancer-jab

    I have often wondered why he was more concerned about the reputation of the product and its manufacturer GSK rather than the adverse reports, lack of evidence about long term efficacy etc.?

  8. I agree with Annie and I really have no clue what Ben Godacre wants to say here.
    I am an almost fatal casualty of Seroxat/Paroxetine and would never have swallowed the jagged little pill if I had known what was already emerging from the reports and TV documentaries around 2002. But because GlaxoSmithKLine withheld all data and refised to explain about the withdrawal syndrome in the leaflets my life would not have been devastated for about 7 years.

    GSK is one of the most powerful organisations in the world and responsible for the death of thousands of innocent people, among them children.
    They should held accountable for that and I really hope that the day comes that they do not get away anymore with their bribery, lies and plain murder.

    All claims of Andrew Witty about transparency are completely fake until he addresses the Seroxat Scandal and offers total compensation to all victims of this so-called “non -addicitve wonder drug”.
    But something inside me tells me that he is not even capable of feeling remorse, just like most officials at this “company”.

  9. Annie wrote:
    “Are you aware that children and adults become suicidal on Paroxetine?”
    “Are you aware how many deaths have occurred from Paroxetine?”
    “Are you aware of four Panorama programmes on Paroxetine?”
    “This is why we do not understand why GlaxoSmithKline are in your promotional video for Alltrials.”
    “As a severe casualty myself,”

    But that’s all just anecdotal so doesn’t count. At least that’s the understanding in the world of Mr Goldacre, who follows the fallacy that “the plural of anecdote is not evidence”.
    In the real world, even the SINGULAR of anecdote is evidence, albeit of greater or lesser significance. For instance one autistic child recovering is solid evidence that autistics can recover. By contrast a nine hundred autistic children having been vaccinated shortly before their autism might not be solid evidence of anything if the two things tend to occur at that same age anyway.

  10. It is simply astounding how Ben Goldacre consistently refuses to engage with the major concerns many of us have about the current data transparency debacle. His responses here, on Healy’s blog posts, and on others have been nothing more than an ad-hominem mantra. There is no proper engagement or discourse, coming from his direction, and that to me speaks volumes.

    There is a case to answer for the numerous individuals and organizations, who not only signed up to the Alltrials and pledged support, but also to those who donated money on the premise that they were donating to a cause of FULL DATA TRANSPARENCY – not this shambles which seems to amount to nothing more than a big GSK joke…

    It’s difficult for most of us to admit we were misled… it bruises our fragile human ego’s
    Believe me … I know what it’s like.. my doctor told me for 4 years that Seroxat was safe and effective… but then again GSK told him that…

    But Ben thinks GSK are trustworthy doesn’t he? And their CEO is a nice guy too apparently….

    Surreal…

  11. Ben needs to answer says:

    From 2005 House of Commons Health Committee Report ‘The Influence of the Pharmaceutical Industry':

    “The use of PR to counter negative publicity

    “221. Public relations is particularly important during times of bad publicity, especially when the safety of brands is called into question. Considerable resources are invested into building long-term, sustainable relationships with stakeholders and ‘key opinion leaders’ and journalists. These relationships are used to promote the use of certain brands and counter concerns relating to safety. Efforts to undermine critical voices in particular were identified, under terms of “issues management”. ”

    http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/42/42.pdf

  12. ROBIN told the best truth about the one versus the many, it is all depending on on wich side of the divider you are!

    If “the one” can be interpreted as benefitial for you, it’s an evidence.
    If “the many” sufferers of Paroxetin is simply a possible expense, then they are also merly sufferers of coincidental tragedy!

    If I lived in a Clinical trial, I would ofcourse accept the Clinical trial to show all possible side effects, but I have tried to live in the real World.
    So if what happens in the real World, in peoples lives, that can be be repeatadly
    acredited back to a common medication, is not any evidence.

    Then I will simply give up!

    • I think Ove may have misconstrued my comments about the usefulness of anecdotal evidence. It’s not a question of whether the change is beneficial or harmful. Rather it’s a question of whether it admits of alternative explanation.

      Referring to the examples I gave above:
      “For instance one autistic child recovering is solid evidence that autistics can recover.”
      ….because there’s no way of interpreting that evidence that’s compatible with autistics not being able to recover.
      “By contrast a nine hundred autistic children having been vaccinated shortly before their autism might not be solid evidence of anything if the two things tend to occur at that same age anyway.”
      ….because that data is not incompatible with an interpretation that the vaccinations and autism were not causally connected, just happened to coincide anyway.

      • David_Healy says:

        Unfortunately, in the case of drug effects that come on after a drug and stop when the drug is stopped and restart when the drug is restarted – that really permit of no other explanation – such effects will still be dismissed as anecdotal, while on the other hand RCT data that is rarely if ever unambiguous and permits multiple interpretation is never termed anecdotal.

        DH

  13. Anne-Marie says:

    I do not fully understand all the different types of trials e.t.c I like probably the majority of the general public only see what’s in front of us. For example if you or someone you know has one or two symptoms i.e. depression and anxiety then take’s a pill and end’s up with five or more problems such as detachment, obsessional thinking/behaviours, alcoholism and insomnia it is obvious it was the pill that caused it. The person then comes off the pill and those five problems disappear. How can this anecdotal evidence be dismissed especially in cases where someone life was damaged as a result and how and what are the authority’s doing about it to help these people ?.

    Psychiatry, drug companies and regulator have to have some responsibility in correcting the damage that was done to that individual. How can anyone put trust into a system that then turns its back on them when things go wrong. Its not much different to the captain and the crew of a sinking ship to jump off and leave their passengers fighting for their own survival.

    My advice to anyone considering taking a psychiatric drug is to seriously bear in mind that if it all goes wrong you “WONT” be helped, you’re on your own.

  14. I was rather surprised to see your comment “even ghostwriting companies have signed up [to AllTrials]“.

    I didn’t realise that there were any ghostwriting companies these days. Could you possibly share the name of these ghostwriting companies and what evidence you have that they are engaged in ghostwriting?

  15. I wonder whether Adam Jacobs recalls an exchange we had in BMJ Rapid Responses in 2005 during the House Commons Health Committee’s investigation of the influence of the pharmaceutical industry? His response was titled “Let’s abandon the term ‘ghostwriting’ ” to which I rejoindered with “A ghost by any other name would smell as sweet”. I am not sure what has changed since then except that his company website now carries an abbreviated list of clients.

    http://www.bmj.com/content/330/7484/163.1/rapid-responses

    http://dianthus.co.uk/about-us

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