Patrick Vallance: “Alltrials is not pushing for that level of data availability and neither are we”
“If I’m a shareholder, which I am, I don’t want a company to be hiding something that might come to light”…
Yesterday I posted an interview with GSK’s CEO Andrew Witty. In that interview Witty was very clearly (and visibly) uncomfortable when questioned by BBC’s Newsnight’s Evan Davis about GSK’s bribery scandal in China and their corruption of doctors.
Andrew Witty’s awkward body language said it all.
See here for more
In an interview (see Audio above) with BBC 4’s ‘Life Scientific‘ radio series today with Jim Al-Khalili, GSK’s (head of R and D and admitted GSK share-holder) Patrick Vallance, is asked about Seroxat harming kids, and his response is really very unsettling. He casually glosses over the harm to (potentially) millions of kids from GSK’s dangerous Paroxetine (Paxil/Seroxat/Aropax) over the past 15 years in a very matter of fact way, as if he was discussing a certain flavor of tooth-paste or the symptoms of a very mild head ache.
Vallance says (when asked about Seroxat killing kids) that:
“It’s inevitable that side effects things will occur from time to time”
“I’d rather know them than not know them”
(but isn’t this the whole point Pat- we weren’t warned of the side effects such as suicide, withdrawal and self harm so many millions of people didn’t know the side effects and were harmed by Seroxat- me included- purely on the basis that we didn’t know and were not told about them).
Wow, is that really your answer to the Seroxat scandal Pat? It’s inevitable that people get killed and maimed is it? It’s inevitable that GSK push drugs like Seroxat on under 18’s (when GSK knew from its own studies that Seroxat could harm them). That’s inevitable, all above board and expected is it? Is it all just inevitable really because that’s the nature of the drugs business? Or do scandals like Seroxat happen because of human greed, profit and sociopathic corporate behavior? I’d go with the latter…
It’s inevitable that it might rain tomorrow, it is not inevitable for a drug company to push its dangerous anti-depressant on young people when it knew it might make them kill themselves… How about making sure that your drugs are safe? Now there’s a novel idea Pat…
When asked about GSK’s endorsement of Alltrials GSK’s Pat Vallance admits that the Alltrials agenda is not about access to data at all ( data is the meat of the drugs industry, without access to it we just don’t know the dangers or efficacy of the drugs we take- see study329.org for more). Vallance also spins the well worn GSK yarn that they have been always publishing their trials on the clinical trials register but the truth (and what the GSK spin machine always omits) is that GSK were forced by two separate department of justice investigations into the company which have compelled them to publish trials- they did not do this willingly).
When asked by the interviewer, Jim Al-Khalili : “Is this about making clinical trial data available to all people”?
Pat Vallance responds that: “Alltrials is not pushing for that level of availability and neither are we”
Vallance’s answer is really very telling, and it reveals why GSK were so eager to jump on board the Alltrials/Ben Goldacre bandwagon. Access to data is what is needed here, not access to drug company’s published trials. Alltrials is a red herring, it gives GSK more control, and Ben Goldacre really has a lot to answer for in this regard. However since he seems to be enamored with Witty and Vallance, I won’t hold my breath for him to challenge them anytime soon. (I’ve written about these issues here, and Dr David Healy’s been banging the drum about Alltrials on his blog too- see here).
Furthermore, one of the only ways to get access to the data, is often only through litigation or department of justice investigations etc. People shouldn’t have to wait decades before they know the harms of a drug Mr Vallance. This is not acceptable nor inevitable. Seroxat has harmed immeasurably. The long term damage hasn’t even begun to be assessed.
Just like Andrew Witty, your attitude towards those damaged by your drugs like seroxat seems to be… “well that’s just tough”..
And your company still makes a profit on Seroxat, it’s still being sold, which means that you and Witty are still profiting directly (and knowingly) from death, human damage, addiction and child suicide…
How nice for you both..
For the red herrings see here
Sir Iain Chalmers, coordinator of the James Lind Initiative and co-founder of AllTrials:
“Among pharmaceutical companies, GSK under its current management has led the way in promoting clinical trial transparency and provides a practical mechanism to make trial re-analyses possible. The reanalysis of Study 329 illustrates the knowledge dividends from the company’s new policies and contrasts strikingly with the scientific misconduct that characterised the company’s behaviour under previous management. Today’s GSK has shown moral and scientific leadership that puts to shame many in the academic community.
Erm no Ian, today’s GSK (2014) were recently caught bribing hundreds of Chinese doctors and fined 500 Million dollars last year. You fail to mention this very recent moral indiscretion.
GlaxoSmithKline Found Guilty of Bribery in China
U.K. Drug Maker Handed Largest Ever Corporate Fine in China
This fine was hardly a sign of moral leadership Ian, so don’t be ridiculous..
In regards to GSK’s scientific leadership, while giving the access to data for study 329 is undoubtedly a good thing, the fact that GSK hid it for so long (and promoted Paxil/Seroxat off label to doctors/kids which resulted in kids killing themselves) is not. I am shocked that you would try to spin this as somehow good PR for GSK . Study 329 was abhorrent, Seroxat is a disgrace.
Seriously, what planet are you on Ian?
Where is GSK’s apology for all this carnage?
Publicity from Study 329 contributed to paroxetine being prescribed to “hundreds of thousands” of adolescents, Jureidini said.
Dr David Healy’s new post, ‘Data Wars‘, raises some very important points in regards to the ‘data transparency debate’.
I have long been suspicious of Alltrials, Ben Goldacre, Simon Wessely, Sense About Science and the various other ‘movers, shakers and consensus makers’ in this debate, and I’ve written several posts about them explaining why:
See these posts of mine for further details-
Call me suspicious by nature, and perhaps I am, however when you’ve been writing, and researching, about GSK’s various unethical shenanigans (for almost 9 years now) you tend to sense when something isn’t quite right. Couple that with a horrendous time on Seroxat, then finding out afterwards that it all could have been prevented if the whole psych/pharma system wasn’t so corrupt, and throw in my sheer determination -for over a decade now- to expose every corner of the Seroxat Scandal, and you end up down some very strange rabbit holes indeed.
The recent expose (restoration of Seroxat Study 329) by the RIAT team, published in the BMJ, caused quite a stir online. Not only did it make headline news, but the responses on social media could warrant many studies in themselves. Paxil/Seroxat harmed many people. These are not ‘anecdotes’, these are people’s lives-
See these posts for details of the impact of Paroxetine world-wide:
The real world affects of Seroxat (Paroxetine/Aropax/Paxil) have been horrendous for those who were unfortunate enough to have been prescribed it. I’ve known that Seroxat is a dangerous drug since I was first prescribed it in 1998. It was only after I came off it, in late 2001 or thereabouts, that I discovered (courtesy of the BBC through their Panorama programme- “The Secrets of Seroxat‘ documentary) that the problems with Seroxat (of increases in suicide, self harm, akathisia, murder, aggression, withdrawal, dependence etc) were worldwide problems. There was some solace in finding this out from the BBC Seroxat series, however I won’t get those lost Seroxat years back. I won’t get my health back that I lost either, nonetheless an apology from GSK for almost killing me with their drug, lying in PIL’s, and corrupting doctors, would be nice though- but I won’t hold my breath. I was collateral damage, and harm to people like me is factored into GSK’s cost of doing business. To GSK, my life was disposable, so it’s insulting for me when I see people like Ben Goldacre and Sense About Science collude with sociopathic companies like GSK.
I find this extremely disturbing.
Alltrials is a redherring, so is Ben Goldacre’s transparency agenda. Simon Wessely is too, as are Sense About Science.
I don’t trust any of these people/organizations. I don’t believe patients should either.
Why do I say that?
Well, hundred thousands of kids were likely put at risk from GSK’s promotion of their dangerous Seroxat/Paxil drug off label. Many high profile psychiatrists put their names to the ghost written study 329 and subsequently- the lives of hundreds of thousands of kids were put at unnecessary risk. They were prescribed a drug (Seroxat/Paxil) which has been shown to be harmful. Many died and many were damaged, plus we haven’t even begun to assess the damage to the adults who were prescribed Seroxat.
I was one of those adults. I am one of those people who suffered. What is going to be done?
Where is the outcry about Seroxat killing kids from people like Prof Simon Wessely? (the head of the UK college of Psychiatry).
Where is the utter condemnation from people Dr Ben Goldacre? (A supposed patient advocate).
Where is the press release from Sense About Science castigating GSK for this disgraceful crime?
Where are their statements expressing their utter disgust at this flagrant abuse of vulnerable people? (Depressed people prescribed Seroxat).
They’re simply not there… none of these people/organizations have condemned this scandal.
Instead what we have are organizations like Alltrials basically congratulating GSK (for giving access to a study which was fraudulent in the first place) and helping GSK spin this abhorrent Seroxat study 329 scandal into something positive (quite how they can justify this is beyond me). Notice how Alltrials fail to condemn GSK for putting kids at risk, but how they try to spin this as GSK somehow being the good guys for providing the patient level data to David Healy and the RIAT team.
What Alltrials also fail to draw attention to is- the fact that the process itself was close to impossible (it also took years), and it was through sheer determination and tenacity on behalf of the RIAT team that they got to study the data never mind the pain staking process of attempting to analyze it. Furthermore, what Alltrials also don’t mention is- the RIAT process and Rxisk are looking for the Data – Access to all the data, not just the registering of trials. What use are the trial results and what use are the trials themselves without the data which makes them? We need access to all the data. Alltrials isn’t looking for this- that’s why I don’t trust them.
Alltrials is a red herring, so are Sense About Science- and along with the true extent of Seroxat harming kids (and adults) that’s what the RIAT team has also just exposed…
See David Healy’s Data Wars for more:
Sense about Science
Simon Wessely and Clare Gerrada are the power couple of British Medicine. He is the current President of the Royal College of Psychiatrists, and she is a recent President of the College of General Practitioners. When faced with questions about over-prescribing of antidepressants by GPs, she is quick to insist that GPs rarely treat distress and that almost all prescribing is for genuine illness and the drugs work well. He gives similar messages in respect of psychiatry.
Sense about Science began in Britain 15 years ago with donations from Corporations in the Risk Management Business – from Monsanto through Nuclear Power to Pharma. These donations have vanished from sight now, replaced by endorsements from all major UK universities and journals like The BMJ and support from Charitable Foundations.
SAS’s stated mission would have appealed to someone like SW who had come under attack from a lot of fringe groups in the 1990s for taking a balanced data-driven approach to Chronic Fatigue Syndrome (M.E.).
But SAS has now become a node to handle any messages in the media that might hurt the interests of a company or corporate sector – such as anything to do with vaccination or my recent editorial on So Long and Thanks for all the Serotonin. BMJ sent this article (as they send all articles) to SAS who got in touch with SW to rustle up statements from Jeff Lieberman types which can be disseminated widely to the media either for citing or as a means to close down stories:
You might not want to take Healy’s work seriously in the light of what these senior figures in the field are saying.
Sense about Science has since spread to Canada, Australia and now the United States and everywhere the mission is the same.
AllTrials & AllData
SAS was a founder of AllTrials. This sounds like AllData – the hashtag for Restoring Study 329 – but at the moment it is quite the opposite.
There has been close to radio silence from AllTrials in the face of the call for AllData, aside from one stunning press release that more or less credits GSK with the efforts to Restore Study 329.
17th September 2015
Many supporters of AllTrials will be interested in a study published in The BMJ today, a reanalysis of previously hidden clinical trial data. The new research used data from a 1990s clinical trial of the GlaxoSmithKline (GSK) antidepressant drug paroxetine. Today’s findings contradict a 14-year-old analysis of the data referred to as Study 329, which found paroxetine to be safe and effective for treating adolescents with major depression.
The new research is the first reanalysis of a drug study under the RIAT (Restoring Invisible and Abandoned Trials) initiative, which calls on companies and academic funders to publish detailed trial information for independent scrutiny. The RIAT team was able to access the original clinical trial data using GSK’s patient-level data access portal, where researchers can request access to this information.
Tracey Brown, Director, Sense About Science and co-founder of AllTrials:
“When all trials are registered and results reported, it becomes possible for researchers to work out what data are available. GSK has gone further and made its patient level data available to researchers. It is disappointing that there are still so many companies not reporting trials. Researchers, doctors, patients and, in July, their shareholders have said they want transparency about trial results. This will confirm their views.”
Sir Iain Chalmers, coordinator of the James Lind Initiative and co-founder of AllTrials:
“Among pharmaceutical companies, GSK under its current management has led the way in promoting clinical trial transparency and provides a practical mechanism to make trial re-analyses possible. The reanalysis of Study 329 illustrates the knowledge dividends from the company’s new policies and contrasts strikingly with the scientific misconduct that characterised the company’s behaviour under previous management. Today’s GSK has shown moral and scientific leadership that puts to shame many in the academic community.”
Faced in 2012 with questions about the $3 Billion fine imposed on GSK, triggered by a sequence of events starting with Study 329 – is it just the cost of doing business? – Andrew Witty snapped back:
“Although corporate malfeasance cases end up looking very big, they often have their origin in just… one or two people who didn’t quite do the right thing. It’s not about the big piece. The 100,000 people who work for GSK are just like you, right? I’m sure everybody who reads the BMJ has friends who work for drug companies. They’re normal people… Many of them are doctors”.
Everything about Study 329 suggests that Andrew is comprehensively wrong. Corporate malfeasance happens when the system is set up so that the efforts of 100,000 well-meaning people get transformed into the worst of outcomes and it then takes the efforts of a few brave people within GSK to alert the outside world to how things are going wrong.
That got your attention didn’t it…
Of course, the title of this post is merely a parody and satire on the current Alltrials debate which is currently raging across the social media- blog and -twitter universe (so no need to be running to the lawyers Ben and Andrew – it’s merely black humor).
Ben is not an arrogant,.. Of course he is not…
He’s not a Pharma shill either (as some people claim)… he is NOT those things OK!..
I repeat.. Ben Goldacre is NOT those things…
He’s merely a misguided geek with patient interests at heart… isn’t he?… yes..
The following quotes from David Healy’s latest post are an illustration of why I trust that he has patient’s interests at heart and the photo after it, of Ben Goldacre , is … well… that kind of speaks for itself.. (as does Ben’s recent belittling and sarcastic comments to me, Bob Fiddaman, David Healy and others in this debate).
I don’t see Ben Goldacre or Sense About Science engaging with people like me, or Bob Fiddaman- both damaged by GSK’s Seroxat. I don’t see them highlighting the plight and the horror stories of the hundreds of thousands of people who are damaged by pharmaceutical drugs either.
In fact, the attitude from doctors like Ben seems to me to be- ‘avoid pharmaceutical drug casualties like the plague- call us conspiracy theorists if we ask questions -and deem our criticisms as mere smears- our drug horror stories as anecdotal…’…
…the game seems to be to ‘silence us with ridicule and disparagement’ or ‘ignore us and we’ll go away’…
I can guarantee Ben, that if he was prescribed a damaging drug like Seroxat, and treated the way those injured and harmed by pharmaceutical drugs are treated and if he had to endure the lies of drug companies- he would be a little angry about it too.. and quite rightly so…
When doctors, the regulators, the medical system, and even the government abandons you, often all you have left is the ability to shout..
We stand up for ourselves, because the people we entrusted with our health and our lives refuse to…
From David Healy’s latest:
“The simple act of defining doctors or patients concerned about adverse events as “critics” is a rhetorical stroke that marginalizes concerns – makes you a one percenter rather than one of the ninety-nine”
“Despite doctors being trained to be ever more civil, patients who have a Drug Traffic Accident become nearly invisible to their doctors. They are just healthcare kill.”
“When something does go wrong, the patient becomes a loser and is ostracised. The herd moves on leaving the wounded animal to the hyenas”
“In essence, doctors have a choice. They are either the steamroller that rolls over their patient or the steamroller rolls over them. The moment needs its John Le Carre to write The Doctor who came in from the Cold. Just as I write this, news is coming in that some senior doctors have had the temerity to go public with claims – that despite Ben Goldacre’s paper on statins – these drugs cause significant problems. Will they be shot as they attempt to get over the Wall?”
The press coverage of AbbVie’s withdrawn legal action suggests that most major companies have now embraced an option for transparency pioneered by GSK.
All Trials are among those taking credit for pressuring AbbVie into submission. They have aggressively welcomed the offer by GSK to make clinical trial data available with no questioning of the terms on which the data is being produced.
But GSK’s offer is a manoeuvre worthy of Ulysses himself. You’d never guess from company self-congratulation that it was forced on GSK by a New York Court as part of the resolution of a Fraud action. The Fraud Action happened because GSK had written up a positive portrayal of a trial when in fact the company itself thought the trial had shown their antidepressant, Paxil, did not work.
The trial – Study 329 – was test of Paxil in children. As mandated by the Courts in the wake of Study 329, GSK put up company study reports for all of their trials, Paxil and other drugs including the diabetes drug Avandia. These could be downloaded. Steve Nissen of the Cleveland Clinic did just this for the Avandia reports and was able to show that Avandia killed. A company blockbuster was stopped in its tracks.
Poacher turned Game-Keeper?
Putting study results up on the web must have seemed like a very bad idea to GSK. So why are they now championing data access?
GSK and other companies are reaping kudos for apparent transparency. And they can say with a straight face to any TV anchorman or Congressional committee that they are making data available.
But in fact here is what is happening. Having seen what happened with the Avandia study reports GSK now know what to do when writing a Study Report to avoid a repeat. Suitably Doctored Study Reports for other drugs will go up on their website.
The Study Reports however do not contain the data. A first approximation to the data in the case of Study 329 comes in a series of 7 appendices to the 329 Study Report – something GSK did not put up on the company website until the omission was spotted nearly 10 years later by Peter Doshi and New York State required them to do so.
In the case of Study 329, the ghostwritten article that led to GSK being sued for fraud, is 11 pages. The Study Report is over 700 pages. There are then 7 appendices that between them come close to 5500 pages. Even this however is not the raw data.The raw data lies in Clinical Report Forms.
You can Look but you cannot See
As things stood before GSK’s offer of transparency, the 5,500 page of appendices and 700+ pages of the Study Report could be downloaded and printed off. Finding what went on in a clinical trial from paperwork like this is a bit like playing Memory – where there a bunch of cards with faces or plants or whatever turned face down and if you turn one up you have to remember where the matching face you turned up before is. It can be done with 5,500 pages printed off.
But playing Memory is much harder to do now with the new improved access GSK is offering.
If you apply to access a GSK trial now you are forced to submit an analytic plan which essentially stops an applicant from accessing any adverse events on the drug. Adverse events are the material the company tries hardest to hide.
Should you get access to the full set of appendices that contain company listings of adverse events, there is almost no way to play the Memory Game because access is through a remote desktop. It may be that a younger generation used to playing Digital Memory will be able to work the system, but it’s not easy. It takes multiple passwords to access the desktop. You are logged out regularly. And while on the desktop, GSK can monitor your every keystroke.
Nightmare in Harlow
But here’s the rub. To really nail down what’s going on, you need access to the approximately 70,000 pages of patient level data. Through a remote desktop this becomes a nightmare.
This scheme to deliver frustration cloaked in the appearances of transparency was devised several years ago.
The history of the idea was outlined two years ago in May Fool’s Day. Last year the details of GSK’s scheme were outlined in April Fool in Harlow.
– See more at: http://davidhealy.org/welcome-to-troy/#comments
For more on The Ben Goldacre/GSK/Data Debacle See My Previous Posts Here: https://truthman30.wordpress.com/tag/ben-goldacre/
Ben Goldacre has become somewhat of a ‘key opinion leader’ in the arena of science and pharmaceutical practices. His approachable persona, backed by his best selling books and much-read Guardian column, has made him into something of a celebrity in the UK. He has done TED talks and even appeared in Stephen Fry’s QI TV show. He has over 250,000 twitter followers and many more fans who comment on his bad science blog. He is asked his opinion on a range of different issues, from health care to public policy. When Goldacre expresses his opinion- people listen…he’s quite popular.
Perhaps this is why GSK are so keen to be associated with him?
Ben has been running a campaign for access to all clinical trial data, through his Alltrials organization, and he’s even managed to get GSK to sign up to it. Although it sounds fairly promising (if you believe the PR sound-bites) ,GSK haven’t actually delivered on anything yet, but they have made some half-baked promises about access to their clinical trial data in the coming years (how, when, or in what form- this transparency will be- is still very vague and unclear). Of course transparency itself is all well and good (and indeed I applaud Ben for such a noble aspiration) however, what use is the clinical trial data (or evidence based medicine) when it is manufactured, analysed and selectively interpreted by the drug makers themselves? (and of course there is also the possibility of destroying the unfavorable data altogether and never letting it see the light of day- if it no longer exists – you can’t be expected to show it). It’s issues like those mentioned, as well as many others, which highlights the impotence of Ben Goldacre’s quest for transparency from the industry. Nonetheless, the good PR generated for pharma for appearing to usher in an era of transparency earns companies like GSK many ethical brownie points (which are undoubtedly invaluable in a highly competitive market with so much public mistrust and cynicism towards it from the general public).
Ben’s argument rests upon the premise that randomized clinical trial data (RTC’s) presented by the pharmaceutical industry is the gold standard of assessing risks and benefits of medications. He calls for access to all clinical trials because he claims that the industry suppresses the negative trials and promotes the positive ones. He is correct here- this is what industry does and this is of course unethical and wrong, and it’s been going on for decades. Of course all data should be published, and it’s amazing how the industry have gotten away with this sham for so long.
Nevertheless, this focus on suppression of negative trial data is really a bit of a red herring, because not only do companies like GSK hide negative data about their drugs, but they also have the power to manipulate the trials both in their design and interpretation- in order to generate an appearance of efficacy and safety. They control the whole process, they create the data, they design the methods and they interpret the results, therefore it is the process itself which is corruptible. This is far from a gold standard, and many dangerous medications still make it to market- despite regulatory approval based on clinical trials! (Vioxx, Avandia, Seroxat, Zyprexa … to name but a few of the recent past).
“There are a few ways that RCTs can hide effects. First, the process doesn’t encourage anyone to look closely at particular things that happen on a drug—the focus is instead on the group and on average effects. That’s true of all trials. In company trials there are more specific problems like miscoding, where suicidality becomes “nausea” or “emotional lability” or even “treatment non-responsiveness.”
There is also the problem of mislocation—patients on placebo end up being given problems they never had—and of nonexistent patients, who don’t of course have adverse events.
Beyond that, there are more sophisticated tricks that companies can and do play—such as claiming that increased rates of a problem on a drug are not really evidence of an increase in rates if the data are not statistically significant. In this way, companies have hidden many more heart attacks on Vioxx and Avandia or suicidal acts on SSRIs than have been hidden by miscoding or mislocation.
Isn’t what you’re describing tantamount to
fraud? I’m all in favor of clinical trials—if done right, wouldn’t they give us the correct answer?
Actually no, when it comes to adverse events, trials almost never get the right answer.
Let’s assume in a trial that we have 3,000 depressed patients on Paxil who had 10 suicidal acts and 1,750 on placebo who had 0 suicidal acts. Paxil clearly causes suicidal acts here. Now let’s take 200 depressivepersonality disorder patients on Paxil who have 30 suicidal acts and 200 depressive personality disorder patients on placebo who have 25 suicidal acts—again, that’s an increased rate of suicidal acts on Paxil. But add these two increases together and you end up with a reduced rate of suicidal acts on the SSRI compared to placebo—40 suicidal acts in 3,200 patients is less than 25 in 1,950.
Hey presto—problem gone. Exactly the same thing can happen in every clinical trial where we don’t fully understand the condition we’re treating—which is, frankly, most conditions from back pain to diabetes to psychosis. We mix patients who superficially appear the same but who in fact have different conditions.
That is just one trick that no-one ever mentions—I’ve laid out several more on davidhealy.org.
Is there any way to overcome such tricks and masking problems?
Yes, actually, there is. One way is to do trials in healthy volunteers—these are the true drug trials. Companies do these but rarely publish them. There’s no register of these trials and no data are made available, though there’s no issue of clinical confidentiality involved. Given that these trials tell us so much—10 years before Zoloft came on the market, for instance, they indicated that the drug made healthy volunteers suicidal—it’s a huge scandal that these data in particular are buried.”
Another problem is- although clinical trial data can be useful, most clinical trials of psychiatric drugs are merely 6 to 12 weeks in duration– they are way too short to assess risks. Short trials give little (or virtually no) indication of long term affects for a lot of drugs. In the case of psychiatric drugs, it can take some weeks (and even months) for the drug to fully metabolize in the body. It can take even longer for the body to develop tolerance and dependence. Each individual is different therefore they will have a different reaction and the side effects will vary. It is often – only after a few years on the drug -that people realize that they are having serious side effects. In the case of Seroxat – it seems the longer the individual remains on Seroxat the greater the risks increase, and the harder it is to come off it. Problems like withdrawal, addiction, and issues of toxicity, are often only discovered long after the drug is approved thus only after many millions of people have been taking it for a few years.
GSK have altered the Seroxat PIL so many times over the years that if you compare the first PIL from 1991 to the ones from the last few years they are barely recognizable as so many side effects (and rates of occurrence of side effects) have been added.
Corruption of clinical trials and falsification of data does happen, therefore in trusting in clinical trials, we have to also trust that the people involved in the trials are ethical. Seroxat Secret has highlighted this problem on his blog : see here
GlaxoSmithKline is the subject of more bad publicity after a researcher was allegedly found to have falsified data in trials about Paxil. Meanwhile, the drug maker faces lawsuits alleging newborns suffered Paxil Birth defects when they were exposed to Paxil prior to birth.
The psychiatrist who reportedly falsified clinical data, Dr. Maria Carmen Palazzo, was a clinical investigator on studies conducted by SmithKline Beecham (doing business as GlaxoSmithKline). According to CNBC on 8/20/10, Palazzo has now pleaded guilty to 15 counts of failing to prepare and maintain records with the intent to defraud and mislead.
Palazzo reportedly included children in a study that involved diagnoses the children did not have. Prosecutors claimed that Palazzo also reported symptoms that her study subjects did not exhibit. She was sentenced to 13 months in prison, which she is serving at the same time as an 87-month term for healthcare fraud.
According to BNET (08/19/10), Palazzo was charged after the Federal Drug Administration (FDA) accused her of enrolling children in studies of obsessive-compulsive disorder and major depressive disorder even though the children she studied did not have the proper diagnosis for inclusion in the study.
Paxil now carries a black box warning about the risk of suicide in children. It also carries a warning about the risk of birth defects in babies exposed to the antidepressant prior to birth.
Remember, Glaxo has a track record of hiding negative clinical trial data that would knock sales of its drugs – the story of Seroxat and Study 329 is truly shocking.
Read more about Seroxat here:
More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”
And what happens in the UK when the MHRA undertakes a criminal investigation into Glaxo and the withholding of clinical trial data?… and finds Glaxo guilty…?
Even when some companies get a negative result from a clinical trial, they can hire ghost writers to fluff up the results and make it appear that the trial was a positive one. This happened with Seroxat study 329 and tragically many children and young people were prescribed an extremely harmful drug because of it. See here :
The court documents released as a result of one of the lawsuits in October 2008 indicated that GSK “and/or researchers may have suppressed or obscured suicide risk data during clinical trials” of Seroxat. One of the investigators, “Charles Nemeroff, former chairman of the Department of Psychiatry at Emory University, was the first big name ′outed′. In early October 2008, Nemeroff stepped down as department chair amid revelations that he had received over $960,000 from GSK in 2006, yet reported less than $35,000 to the school. Subsequent investigations revealed payments totaling more than $2.5 million from drug companies between 2000 and 2006, yet only a fraction was disclosed”.
Disclosure of all clinical trial data is a step in the right direction, and it is a major issue which needs to be addressed, and I sincerely applaud Ben Goldacre for highlighting what he believes to be an important issue, but the problems of drug regulation, broken ethics, undue influence of industry on academia, and corruption in the industry itself, also need to be addressed if we are to avoid patient deaths from defective and dangerous drugs which should not have been approved.
Companies like GSK operate above the law in the UK, they are virtually untouchable. Perhaps if Ben Goldacre was to concentrate his efforts on attaining justice for those harmed by medications such as Seroxat and Avandia, GSK might begin to manifest a sense of real atonement and change, or at the very least they might say sorry. It is only through the courts that GSK would be forced to reveal and disclose hidden information and data. But again, unfortunately, in the UK, pharma-litigation cases are usually squashed before they get to trial. The establishment have a vested interest in protecting GSK, they are a major UK cash-cow… and despite an utterly dire track record of harm to consumers, corruption, lies and fraud for decades, they even have the UK prime minister defending them. What hope is there, for damaged patients from GSK drugs, in a situation like that? What hope is there for justice?
“I don’t think GSK will be the only company to sign up. I think we’re going to enter a very interesting era where potentially the market is differentiated by ethical companies who’ve made a commitment to sharing all their trial results, and unethical companies who are still aggressively defending their ability to withhold information from doctors and patients.”
I agree with Ben here, that era is now upon us, and GSK have gained more positive publicity than any other company for basically promising to be more ethical.
Essentially they have positioned themselves quite strongly within this frame because it is in their economic interest to appear to want to be an ethical company.
They haven’t actually delivered on any of this yet and I sincerely hope that they do, but I have a feeling that they will find a way around it while still seeming to be the good guys.(they are a clever bunch). But for the time being, they are certainly generating a lot of column inches full of positive praise because of all this (such great PR for them).
Furthermore, ironically, GSK have said they will only give access to data for drugs released after the company merger (after 2000) therefore the hidden trials of the most dangerous and infamous of their drugs- Seroxat (1991) and Avandia (1999)- will likely never see the light of day…
How convenient for them
How tragic for the families of the dead and the damaged..
As David Healy said:
“Now it is unfair to say if Ben Goldacre didn’t exist perhaps Andrew Witty would have to invent him?”
“He’d like to see all of the clinical study reports ever completed brought out of “dry storage archive…and everywhere else that people stack their old, crinkly, yellow paperwork” and made publicly available — ideally on his new website, AllTrials.net, which recently signed on GlaxoSmithKline (GSK) to release every study the company has ever done. (Mistake — anything after the merger (2000)… NOT every study the company has ever done
Beverly Richards-Smith, PhD”02/24/13
“How will Dr. Goldacre or AllTrials.net ensure that GSK, or any pharmaceutical company that registers in the future, actually provides all its “old, crinkly, yellow paperwork?” It will remain up to the corporations to determine what trial results are “located” and made public. I suspect that results from older trials for drugs that have been superseded by newer products will be provided in their entirety when possible, but those for drugs that are sources of significant current corporate income will be cherry-picked to exclude negative data of a sort that might reduce the drug’s prescription rate. The threat of lawsuits resulting from lethal or severe side effects is less likely to keep a study off the Web site, as Big Pharma regards lawsuit settlements, even on what appears to outsiders to be a large scale, simply as part of the cost of doing business. If the side effects can be “justified” by the supposed benefits of the drug – e.g., 1-2% risk of diabetes vs. the claims of protection from heart attacks for statin drugs – then prescription numbers won’t be affected..”
Our “evidence-based” medicine is only as good as the “evidence”. So if the “evidence” is bad—meaning poorly constructed studies, badly interpreted or just plain fraudulent data—then so is the recommendations, policies and practices developed using that “evidence”..
“What a waste of time, as Dr. Goldacre, like many before him, think the data should be on his site where evidently he can judge its importance. What a crock. As far as I know, GSK has already reneged on their promise. They never will release all their data and others will not also. The same is true for almost all funded research. Not all data is released and even if it were released, it would likely not be possible to analyze it because many internal information items would be missing. It’s a pipedream and please tell me how “evidence-based medicine” would improve. It sounds to me that Dr. Goldacre is after fame that is not his due..”
Bay Area MD
“The application of evidence-based medicine is often misguided and indiscriminately applied to a larger population than what the studies often show with few if any postmarketing studies showing the true insignificant benefits and/or greater harm created. The withholding of negative data is unethical and prevents real peer review. Evidence based medicine is quite a disappointment..”
Three days ago I wrote a blog post titled: “Would The Real Ben Goldacre Please Stand Up?”. The gist of the blog post was a general illustration of how people (particularly doctors, psychiatrists and academics) can be seduced and manipulated by the pharmaceutical industry. I used Ben Goldacre as an example because quite frankly- his stance on the pharmaceutical industry confused me. On the one hand- he writes about drug company corruption and advocates for better access to clinical trail data- but on the other- he accepts awards from GSK (one that I am aware of anyhow) and gushes undue praise on the management of the company (GSK ) that he criticizes in his books.
I find this attitude baffling. I really do.
I understand that there are obvious overlaps within the pharmaceutical world between the industry, regulation, academia, universities, marketing and science etc. It is common for scientists and academics to receive bursaries and funding for research (particularly early on in their careers) and this doesn’t always mean that a conflict of interest, a bias, or corruption comes along with that -but what really frustrates me is how the industry (and those attached to it) doesn’t seem to see anything wrong with this generally. It’s as if there is an attitude of- “it’s so rampant and ingrained” that they wonder why anyone would question it? The attitude seems to be- “everyone has either done it- is doing it- or will do it” so what’s the problem?
And herein lies exactly the problem…
Because it is so widespread: this forms the crux of the problem! Industry has too much power and influence. That’s the problem!
Companies like GSK have their monetary tentacles in literally every facet of UK society. Globally they are powerful too- but it is on their home-turf where they are virtually untouchable. They basically operate above the law.
Why is this?
It’s simply because they are the UK’s biggest drug company (and second biggest globally)- they are massively important for the UK economy- not just in terms of jobs in research, development, factories etc- but also in terms of what they donate to, support, and sponsor in regards to universities, science, scholarship etc. They are massively influential. Too influential.
Often it is difficult to entangle who is indirectly being funded by pharmaceutical companies because they can sometimes donate to organizations (patient groups, astro-turfing) who then funnel funding through to different people and on to individuals. And then we have the problem of who owns stocks and shares in companies like GSK? How does that influence policy? How much influence and power do GSK have over politicians, the government, regulation, academia, etc etc etc.
From what I have researched- GSK have immense power in the UK. Too much power.
This wouldn’t be a problem if GSK were an ethical and moral drug company who cared about patients before profits. But, alas they are not. They are just simply not ethical and they have never given any reason for us to believe that they ever will be.
I could rattle off dozens of instances of GSK’s unethical behavior but I won’t as I have almost 500 blog posts documenting that.. and I think anyone who knows the industry would have to be aware that GSK are amongst the worst offenders of corporate crime of recent times…but anyhow all that has been documented on this blog and all over the web so I won’t talk about that now…
But what I would like to talk about is Ben Goldacre’s comments on my blog-post.
I did not expect Ben Goldacre to comment on the blog-post and I was surprised when I noticed views coming from the Guardian. I did not expect the comments after the post to turn into something of a debate either. Furthermore, I honestly have had little interest in Ben Goldacre until recently. I was aware that he was involved in Alltrials and wrote Bad Pharma, but it wasn’t until I began to think to myself that he was possibly being manipulated by GSK that I started to research stuff online.
I don’t think that Ben Goldacre is corrupt at all. Not in the slightest bit. I think his heart is sincerely in the right place. I honestly think he is one of the good guys and I think he genuinely wants to do the right thing, but I do think he could be being misled by GSK and I think it could be precisely because of his trusting nature that GSK have endorsed him and his Alltrials organization. I also think GSK are cynically using his celebrity and popularity for PR purposes – and I hope Ben begins to see that too, or at least becomes a little aware of it…
That’s just what I think and that’s my opinion- and that was the purpose of the blog post. I hope I am proved wrong and that GSK will give access to all their trials- particularly the raw data- nobody would like that more than me- it’s what I have been calling for – for several years on this blog! I was prescribed Seroxat and I would love to know what GSK have hidden about that!
However, I have been scrutinizing GSK for a long time now- and I just do not trust them- nor will I ever -and I think it’s foolish to approach them with anything but mistrust and caution. They have broken every promise in relation to trial data so far so it is likely that they will not change their policy now, or they will find a way around all this… they always do. If they do give data it will be on their terms- they will not do anything that goes against their interest- they never do.
I could go on and on about how corrupt, fraudulent and criminal GSK are but everyone knows that- or at least they should!
But I would like to sincerely say to Ben..
and if you would like to contact Bob Fiddaman – he has information that he would like to pass on to you- it might help..
E-mail him here:
Good luck 🙂
And are they perhaps being too trusting?
It seems some people aren’t afraid to ask these awkward questions…
Reposted from 1boringoldman’s blog (who is far from boring by the way- and possibly one of the best writers around on these issues ).
“I notice GSK is a member of both organizations. Is this GSK’s policy on data sharing as well? If so, I think it poses a real question for the AllTrials group and particularly those who have expressed enthusiasm for GSK’s data sharing initiative. (I like a number of things Ben Goldacre has done but I am really puzzled as to why he wants to “do cartwheels” over GSK’s offerings in this field so far. And I fear he and AllTrials could get manipulated into total irrelevancy, or worse, if they get too trusting.)”
Posted on Sunday 28 July 2013I’ll have to admit that my iPhone® skills are mostly limited to receiving. Typing with thumbs is a recently evolved skill that passed me by, so I’m reduced to using an inaccurate index finger. That post from on the road a week ago was from a motel lobby computer on a very rainy day [an irreducible conflict…]. But these days, WiFi is everywhere, even on coastal Maine, so I could keep up with things of interest. Pharmagossip is a favorite site of mine, and Jack Friday has kept me riveted to the GSK China·Gate story [great reading with a harbor restaurant lobster roll]. In writing about it, I mentioned this Guardian piece from last week:Leaked memo from industry bodies reveals strategy to combat calls by regulators to force companies to publish resultsThe Guardianby Ian Sample21 July 2013
The pharmaceutical industry has “mobilised” an army of patient groups to lobby against plans to force companies to publish secret documents on drugs trials. Drugs companies publish only a fraction of their results and keep much of the information to themselves, but regulators want to ban the practice. If companies published all of their clinical trials data, independent scientists could reanalyse their results and check companies’ claims about the safety and efficacy of drugs. Under proposals being thrashed out in Europe, drugs companies would be compelled to release all of their data, including results that show drugs do not work or cause dangerous side-effects.
While some companies have agreed to share data more freely, the industry has broadly resisted the moves. The latest strategy shows how patient groups – many of which receive some or all of their funding from drugs companies – have been brought into the battle. The strategy was drawn up by two large trade groups, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the European Federation of Pharmaceutical Industries and Associations (EFPIA), and outlined in a memo to senior industry figures this month, according to an email seen by the Guardian.The memo, from Richard Bergström, director general of EFPIA, went to directors and legal counsel at Roche, Merck, Pfizer, GSK, AstraZeneca, Eli Lilly, Novartis and many smaller companies. It was leaked by a drugs company employee. The email describes a four-pronged campaign that starts with “mobilising patient groups to express concern about the risk to public health by non-scientific re-use of data”. Translated, that means patient groups go into bat for the industry by raising fears that if full results from drug trials are published, the information might be misinterpreted and cause a health scare. The lobbying is targeted at Europe where the European Medicines Agency (EMA) wants to publish all of the clinical study reports that companies have filed, and where negotiations around the clinical trials directive could force drug companies to publish all clinical trial results in a public database…I wasn’t surprised. We can hardly expect the Pharmaceutical Industry to embrace Data Transparency given their past behavior and the Billions they’ve made from their over-rated “blockbusters.” Then I got home yesterday and read this [also linked by Pharmagossip]:Exclusive: The Devil is in the Detailseye·for·pharma
Market Accessby Craig SharpJul 26, 2013
The ongoing battle for clinical trial transparency took an unexpected turn this past Sunday, 21st July, when the Guardian ran a story featuring details of a leaked memo, apparently containing a plan to conceal “secret documents on drugs trials” from the public and concerned medical practitioners.On Wednesday, 24thJuly, EFPIA and PhRMA responded to the ongoing argument with a joint set of new principles aimed at addressing these transparency concerns. Speaking exclusively to eyeforpharma, Richard Bergström, EFPIA Director General, explains the intentions of the joint position document and the real story behind that leaked memo…The “real story” comes from an interview with the memo’s author, Richard Bergström, director general of EFPIA,:Following the Sunday scandal and the resulting press coverage, eyeforpharma reached out to Richard Bergström to get the full story behind the memo and find out what the intention really was, and as it turns out the Guardian story wasn’t only incomplete, it was grossly biased in its assumptions…I’ll not paraphrase it. It’s there for the reading and not that long. In essence, the memo’s author explains that the intent of the memo was not to mount a fight, but simply to find the best way to cooperate while protecting the clinical trial subject’s privacy and PHARMA’s legitimate interests. There’s a bit of confusing parsing of word meanings. It even has a response from the Guardian’s article author, Ian Sample. Their two accounts of the interaction between the author and Richard Bergström prior to the article’s publication were widely divergent. And who iseye·for·pharma anyway [the link takes you to their about·us page]?eye·for·pharma is a hub for senior-level pharma executives, patient advocacy groups and other health experts to exchange ideas and stay up to date with shifting trends and practices within the pharmaceutical industry.It’s The Guardian [home to Ben Goldacre’s long-runningBad Science column] versus eye·for·pharma [“a hub for senior-level pharma executives, patient advocacy groups…”] each accusing the other of misbehavior. If this were an episode on Masterpiece Mystery, it would be titled “Who’s Black? The Pot or The Kettle?” [speaking of conflict of interests].
In case you haven’t noticed, both The Guardian and eye·for·pharma talk about the Memo they’ve seen without showing it to us! Which is the whole point of this post and Data Transparency in the first place.
Without the Memo, we’re left to our own biases and the biases of these two articles’ authors and their media venues. Apparently, I’m not the only person who noticed that the Memo itself was missing in action. Mercifully, in an Update,eye·for·pharma later appended it to the end of their article with this comment:UPDATE: I’ve had a few requests now for the memo to be printed [we didn’t run it originally as it’s around 600 words long], for privacy reasons all names and contact details have been redacted. That aside, you can [read] the memo in it’s entirety below:
Dear members and colleagues,
please find below a message from Richard Bergstroem, EFPIA DG with respect to the various elements of the Clinical Data sharing debate, the assignment of responsibilities (including work with US PhRMA colleagues) and next stepsA. Forthcoming industry commitment, incl advocacy:The EFPIA Board has approved the draft position paper developed jointly by PhRMA and EFPIA. The final version is attached, and is now subject to confirmation by the PhRMA Board two weeks from now. PhRMA and EFPIA plan concomitant press releases in the week of July 22. The advocacy plan, previously approved by the two Boards is underway, and follows four strands:
- Mobilising patient groups to express concern about the risk to public health by non-scientific re-use of data.
- Engaging with scientific associations to shape the industry commitment for data sharing, and to discuss concerns about re-use of data.
- Work with other business sectors that are also concerned about release of trade secrets and commercially confidential data.
- For the long-term, build a network of academics across Europe that has the capacity to counteract mis-use of data (that is deemed to be happen in any case).There will be a series of meetings in Brussels, organised jointly by PhRMA and EFPIA, in the week of August 26 to advance these strands. This work (commitment and advocacy) is coordinated by [Redacted], in close cooperation with PhRMA ([Redacted] and [Redacted]), with oversight by Richard Bergstroem and [Redacted], PhRMA.B. EMA consultation on draft :On June 24th , the EMA published its revised policy on the publication and access to clinical trial data for consultation. Comments are invited and should be provided to the EMA by 30 September 2013. Whereas the press release was quite balanced, the detailed proposal raises concerns:
- No process outlined to discuss CCI in CSRs prior to release.
- Raw data: unenforceable controls to ensure robust and scientifically credible secondary analyses.
- Requirement for anonymised raw data to be supplied at submission negates EMA’s responsibility for release of PP information.
- Publication of CSRs from withdrawn or unsuccessful submissions could undermine future commercial viability of product.
- Identification of study personnel.The EMA document takes into consideration the outcome of the process run by the 5 CT advisory groups earlier in the year to which EFPIA contributed through the input prepared by the 5 Temporary Working groups (TWG) set up under the SRM PC auspices.A detailed response will be prepared by a joint EFPIA-PhRMA team. The work will be led by [Redacted], Lilly, [Redacted]. From the EFPIA side the EFPIA TWG chairs (Rules of engagement, Patient confidentiality, good analysis practice, CT data format, legal aspects) will be part of the drafting group: [Names of four individuals within the drafting group redacted] PhRMA will assign a small group of people from the bigger EMA data disclosure WG. The drafting group will tentatively have a TC July 9. The final draft will be shared for consultation with the broader membership later this month.C: EFPIA-PhRMA intervention in the AbbVie case:[Name], Pfizer, leads this work, in close cooperation with PhRMA and external legal counsel.D: Clinical Trial Regulation:Advocacy directed at Council (and EC and EP) will focus on:
- avoiding definitions of CCI in the CTR itself,
- seek to delete preamble text that CSRs do not “in general” include CCI (even if current text is acceptable as fall-back position).The EFPIA PACT(Public Affairs on Clinical Trials) is responsible and will work closely with national associations and Brussels staff.Regards,[Redacted]
I have rarely been afforded the luxury of writing such a satisfying post. Whether you agree with The Guardian or eye·for·pharma, or even land in some completely different place, the point remains the same. With the Memo there in front of you, you’re able to reach your own conclusions – deal with your own biases and conflicts of interest unimpeded. Your opinion is worth a whole lot more than it was before you read it. Very satisfying.I rest my case for Data Transparency…
For those who believe in the fairy-tale that Glaxo will ever manifest any real sense of transparency -or give uncensored/uncontrolled access to their private trove of clinical trial data..
Glaxo ‘Falls Short Of Open Data Disclosure:’ Jureidini Explains
Over the past few months, a group of researchers has been haggling with GlaxoSmithKline over access to detailed data for an infamous 2001 study of its Paxil antidepressant called 329 that tested the pill for treating depression in adolescents. The researchers, who are led by Jon Jureidini, a clinical professor of psychiatry at the University of Adelaide in Australia, want a 1998 clinical study report that they hope to reanalyze and republish. The original results reported that Paxil was effective, but the trial actually missed its endpoints and figured in a ghostwriting controversy (here is the study). As a result, Glaxo signed a consent order with the New York State Attorney General to publicly disclose trial data and has since vowed to do so. But the drugmaker says that Jureidini, who also led an unsuccessful quest to have the study retracted (see this), must follow its new system for submitting proposals (back story and more here). We spoke with Jureidini about his efforts. This is an excerpt of our conversation…
Pharmalot: Why did you make this request?
Jureidni: I’ve been occupied with trying to get some truth about that study for a long time. And just because it had such an impact in child psychiatry in Australia at the time it came out. It was used to try to shift the approach to (treating) childhood depression and (Paxil) became first line (therapy). I looked at it the first time I read it and thought perhaps medication is the answer. But then, I reread it and spotted some problems. I then had others look at it, and it seemed flaw and then deliberately so. This was in 2002 and 2003.
Pharmalot: Why does this matter now, though?
Jureidini: We have an editorial failure by a major medical journal. We have a failure of the peer review process. We have misconduct by a major pharmaceutical company. Most worrying for me is that we have a careless, at least, and probably more than careless, work by senior academics. And we have the whole issue of ghostwriting. Most of all, we have harm potentially done to children. Those sound like pretty significant issues to me.
Pharmalot: So what exactly are you seeking?
Jureidini: The primary goal is to get the data… We want to use the data to check what they published… Our guess is that the representation of the efficacy data in the clinical study report is accurate, but we have real concerns about the accuracy with which the adverse event data that has been transferred from individual patient records to the clinical study report, which is why we wanted individual patient records. The fact that it serves as a test of GSK resolve (to disclose trial data) is welcome to us, but not our primary interest.
Pharmalot: Glaxo has said publicly, though, that it has procedures for releasing data now and will review researcher requests.
Jureidini: The procedure doesn’t meet our requirements. That’s the problem. One of the positive things about us testing their process is that we’ve already illustrated we’re carrying out a project with GSK data, but the system doesn’t meet the needs of the research group.
Pharmalot: Which is….?
Jureidini: They won’t provide individual patient records. They’ve defined what they will make available and make it sound that’s all anybody what would want in order to behave ethically. We’re concerned that this (approach) gives them a level of control over the data, which might facilitate them withholding inconvenient truths. We haven’t been given any data yet, but you’ll see from the letters from Shannon (James Shannon, Glaxo’s chief medical officer) that the process doesn’t allow them to provide the kind of data we’re requesting.
Pharmalot: And what does he say?
Juredini: In the last letter, he says he’d like to have a phone call about that process and how it might change. I said I‘d like to do this by email, but haven’t heard back. But they have made clear it’s not the kind of information they’ll make available, even though they’re advertising it as open disclosure. It falls short of that.
I’ve done what they’ve requested, which is to put the application on the (new) web site (for data disclosure)… And we’ll do what they request, which is to apply their analytical plan to the data, but we want to go a step further and ensure what’s in the data taggles collected by GSK reflects what was reported by patients to the (Paxil) researchers.
Pharmalot: When did this last exchange occur?
Jureidini: On November 5, he suggested a phone call. On November 8, I wrote back saying thanking him and didn’t think a phone conversation was best way to proceed.
Pharmalot: Why insist on e-mail and not a phone call?
Jureidini: Well, for one thing, I’m representing a team. I’m not an individual functioning alone here. And it’s also partly because part of this process is to document interaction with GSK. Another reason is that I expect that it’s likely Shannon is a more skilled communicator than I am, so it’s more neutral, I think, to communicate in writing.
Unless they can come up with some plausible reason why there are genuine ethical concerns about providing the data, which may satisfy an independent appraisal, then you’d have to suggest there are other reasons why they don’t want us to see it. But we should be clear that GSK hasn’t said no to this request and I don’t want them backed into a corner of being acused of not providing information. I‘m not accusing them of that at all.
But the ability is there. It’s really easy. It’s a small expense to render documents confidential. It’s a question of whether there are more bad things happening that needn’t be hidden. It would be they had something to hide.
Pharmalot: Beyond this one study, what do you expect to accomplish?
Jureidini: There’s some good that can be done here. We can bring to account different parties that failed the community in the process of the publication of the (original) article – the company, the key opinion leaders… And we’re hoping that other people will be interested to make (the same sort of request). It’s an onerous task, but if you form a group, it can be done in the margins of your ordinary working life.
STORY ENDS HERE
FRIDAY, NOVEMBER 15, 2013
BMJ – Hidden Data Putting GlaxoSmithKline to the test over paroxetine
- Peter Doshi, associate editor
Blockbuster antidepressant paroxetine is no stranger to headlines. The drug is now back centre stage as requests for clinical data from one of its trials are testing manufacturer GlaxoSmithKline’s commitment to full transparency, Peter Doshi reports
When the Journal of the American Academy of Child and Adolescent Psychiatry(JAACAP) published study 329 in 2001,1 its editors could have had no idea that the paper would spark a controversy, not only about the use of the antidepressant paroxetine in children but also about secrecy in clinical trials. It is a controversy that rages to this day and that goes to the heart of recent campaigns to gain access to drug companies’ trial data.
By most accounts, GlaxoSmithKline is leading the pack in its efforts to liberate access to its clinical trial data. It was the first major pharmaceutical company to sign up to the international AllTrials petition calling for all trials to be registered with the full methods and the results reported.2 Whereas companies like AbbVie and InterMune have lodged lawsuits aiming to block access to clinical trial data,3 GSK has forged ahead with a new website enabling third party access to deidentified participant level data “because it is the right thing to do, both scientifically and for society.”4 GSK’s website states that five requests have been approved up to 20 September. None have been rejected. One is under review.
But one group’s request for data is testing the limits of GSK’s commitment to full transparency. Jon Jureidini, clinical professor of psychiatry at the University of Adelaide, is leading a team to reanalyse and republish the results of GSK’s study 329—a randomised, double blind, placebo controlled trial of paroxetine for the treatment of depression in adolescents. For over a decade, Jureidini has been critical of how the study was reported in JAACAP in 2001. In 2003, Jureidini and Tonkin wrote toJAACAP: “We believe that the Keller et al study shows evidence of distorted and unbalanced reporting that seems to have evaded the scrutiny of your editorial process.”5 They noted that “on neither of [the study’s two primary outcome] measures did paroxetine differ significantly from placebo”—yet the Keller et al paper concluded that “paroxetine is generally well tolerated and effective for major depression in adolescents.”1
Jureidini was subsequently contracted to provide expert advice as part of a class action lawsuit against GSK in 2004. Through this legal action, some internal company documents were released into the public domain, and Jureidini and colleagues reported that study 329 had an additional six secondary outcomes specified in the protocol.6 Paroxetine was not more effective than placebo on any of these outcomes either.
Paroxetine was a blockbuster antidepressant, known by its trade names Paxil in the United States and Seroxat in the United Kingdom, and was widely prescribed “off label” for use in children and adolescents. The drug came under heightened attention in the early 2000s, after a decade of rising antidepressant use among youths,7 over concerns about a link between paroxetine and suicidality in children.
In 2003, the UK Committee on Safety of Medicines recommended that paroxetine not be used in children and adolescents for the treatment of depressive illness because of concerns about an increased risk of self harm and potentially suicidal behaviour. And in 2004, the US Food and Drug placed a boxed warning, its most serious type of warning, on all antidepressants, stating that they increase the risk of suicidal thinking and suicidal behaviour in these age groups.8
In 2012, GSK agreed to pay $3bn (£2bn; €2.4bn) in a fraud settlement with the United States government. In a statement connected with the lawsuit, the Department of Justice declared that “the centerpiece of GSK’s efforts to market Paxil for childhood depression was the GSK funded Study 329,” about which the published JAACAP“article distorted the study results and gave the false impression that the study’s findings were primarily positive, when they were, in fact, primarily negative.”9
Jureidini and colleagues have led a long campaign to compel the journal to correct or retract the article, which was authored by both academics and GSK employees.10Earlier this year, Jureidini presented GSK’s chief executive, Andrew Witty, with a final plea to help correct the scientific record. “Your corporation has so far failed to take responsibility for a published report that has harmed young patients who were prescribed paroxetine on the basis of this misleading article. As the CEO of GSK, you have the opportunity to correct the scientific record. I respectfully urge you to do so,” Jureidini wrote (see data supplement on bmj.com ).
But GSK defended the integrity of the 2001 publication. “GSK does not agree that the article is false, fraudulent or misleading,” John E Kraus, head of medical governance, wrote to Jureidini.
Jureidini has responded by assembling a team to reanalyse and republish study 329. In July they publicly declared their intention to produce a new journal report of study 329, written in accordance with the BMJ endorsed restoring invisible and abandoned trials (RIAT) initiative, which calls for third party authors to publish or republish unpublished and misreported clinical trials.11 The team’s starting place is a trove of over 6000 pages from a previously internal clinical study report written by SmithKline Beecham in 1998 that was forced into the public domain as a condition of a consent order GlaxoSmithKline agreed to in the settlement of a 2004 lawsuit with the New York State Attorney General.12 (SmithKline Beecham and Glaxo Wellcome merged in 2000 forming GSK.) The pages include a report of the trial, the study protocol, statistical analysis plan, blank case report forms, and numerous data tables, which Jureidini’s team will use for its analysis.
But GSK’s public posting of its internal report on study 329 is incomplete, lacking an unknown number of pages containing original case report forms from Appendix H. Jureidini and colleagues have therefore asked GSK for access to the deidentified case report forms and the corresponding deidentified electronic participant level data, “so that we can restore the publication of trial 329 in a fair, complete and publicly transparent way.”
“With regard to the electronic database,” James Shannon, GSK’s chief medical officer, wrote to Jureidini on 11 October, “I would ask that you do indeed submit an analysis plan via the website and sign a data sharing agreement.” Jureidini had initially rejected submitting an analysis plan arguing that “such a plan is irrelevant when restoring a publication where our primary focus is the original analysis plan drawn up and implemented by your own statisticians.” Nonetheless, Jureidini complied, and submitted an analysis plan—mostly a direct copy and paste from the protocol contained in the company’s 1998 clinical study report—placing GSK’s independent review panel in the unusual position of refereeing the appropriateness of the manufacturer’s own analysis plan.
As for the case report forms, GSK initially rejected Jureidini’s request, explaining, “We do not publicly disclose Case Report Forms (CRFs) and we do not provide them to other researchers. Complete CRFs are available to regulatory authorities for audit and for them to assure the integrity of the data sets and CSRs.” However, last week the company suggested a phone call with Jureidini, “to explore with you how we can help with this.”
COMMITMENT TO TRANSPARENCY
GSK’s wavering responses contrast with the many upbeat public proclamations by its executives about the company’s commitment to transparency. “Increasing transparency about our research is a critical area we’ve been pursuing at GlaxoSmithKline for almost a decade,” Shannon wrote in a September editorial in theHuffington Post.13 “We’ve also launched a new website allowing scientists to request access to the very detailed, anonymised patient-level data sitting behind the results of our clinical trials. This will mean independent researchers, with a fresh perspective, can conduct further research which could advance medical science and improve patient care.”
Transparency is “at the core of how we work,” Shannon explains. “People have asked me, ‘what if a new side effect comes to light for one of your medicines? Or what if a scientist discovers that you made a mistake in your research?’ My answer back is ‘why wouldn’t we want that to happen? Isn’t it better that we know? There is always the potential for us to find a better way to do things.’”13
Last month, Witty took it one step further in a television interview with the US Fox News. “We’re not simply going to publish data on trials still to come, but we’re going to go back, and we’re going to publish all the data for all the trials that have been done since the company was formed.”14
Witty’s phrase “all the data” sounds straightforward, but the company’s 11 October response to Jureidini implied that “all the data” would not include case report forms from study 329—or, it would seem, any other study. Nor, it seems, is GSK going to “publish” any of the deidentified patient level data on its new website, if “publish” means to make something public and freely accessible.
A more careful reading of GSK’s stance is that it believes in what it calls a “closed-access system,”4 in which only approved researchers are permitted to query (but not download) data in preapproved ways. To gain access to GSK’s participant level data, requestors must first submit and have their analysis plan approved by an “independent review panel” and sign a data sharing agreement. A sample agreement posted on GSK’s website indicates that researchers are expected to run only preapproved analyses: “GSK and Researcher agree that GSK will provide the Researcher with access to patient level data from the GSK-sponsored clinical studies listed in Exhibit A for the sole purpose of analysis according to Researcher’s approved research plan (the “Analysis”) attached as Exhibit B and for no other purpose.”15
GSK suggests that such a system is necessary to protect the privacy of research participants. It is not enough to simply remove personally identifiable information from the participant level dataset. “It may be possible to combine deidentified data with other information to identify individuals. To minimize any such risk, our approach will be to provide access to anonymous patient-level data on a password-protected website that has controls in place to prevent data from being downloaded or transferred.”4
This concern is underscored in an editorial, published in the Lancet, coauthored by Patrick Vallance, GSK president of pharmaceuticals research and development, and Iain Chalmers, one of the founders of the Cochrane Collaboration and now coordinator of the James Lind Initiative.16 They write that “the protection of privacy is vital in IPD [individual participant data] analyses,” but point out that the process of deidentification can be carried out so thoroughly as to render the scientific value of the data useless. Deidentify the data insufficiently, and trial participants may be re-identified, violating their privacy. Vallance and Chalmers posit that a “controlled system” of restricted access offers a possible solution to the reidentification problem.16
It is therefore unsurprising that GSK initially refused Jureidini and colleagues access to the case report forms on grounds of protecting the privacy of trial participants. “The content of Appendix H is not posted on our website because it contains information (such as names) that can be used to readily identify the patients concerned.”
But Jureidini and company are challenging GSK. “As a group we do not accept your argument about patient confidentiality . . . The blank case report forms (CRFs) in the Clinical Study Reports (CSRs) make it clear that the only patient identifiers in any CRF not contained in the CSRs were initials. Redacting initials is the work of minutes.” Jureidini adds that reidentification of patients “is not our intention. We think anyone in our group attempting to do this would do significant damage to the data access cause. We are happy to sign agreements that there will be no effort to identify anyone and that the de-identified CRFs will not be shared with anyone outside the 329 group, with access limited to two to three designated individuals within our group.”
Jureidini also questioned GSK’s commitment to its patients: “noting the concern you expressed in your letter for the wellbeing of patients who participate in clinical trials, can we enquire as to GSK’s follow-up of patients who were in Study 329? For instance, were those who became suicidal or violent on Paxil subsequently advised of the possible role of the drug in their dangerous and distressing feelings/actions and counselled that it may be better for them to avoid SSRIs [selective serotonin reuptake inhibitors] in future?”
Perhaps most concerning, Jureidini explained to GSK that his team has concerns about how some of the adverse event data were reported in the 1998 clinical study report and therefore needs the additional requested data.
Recently, GSK has softened its position and seems willing to discuss the possibility of rethinking its previous position. “I recognize, however, that you believe you need to see the CRFs and I would like to explore with you how we can help with this,” Shannon wrote. “Please could we arrange a telephone call to discuss this more fully and agree a way forward?”
Jureidini has declined the telephone call, and requested keeping the interactions by email. “I would be grateful if you could indicate what in your opinion is the safest way of getting all CRFs from study to me, suitably de-identified, but otherwise complete with narrative elements intact.”
“RESPONSIBLE” DATA SHARING
Jureidini’s quest to access the complete participant level data for study 329 highlights some of the anxieties surrounding disclosure of clinical trial data.
Looming large are concerns about misuse of data. “We believe that there are public health risks if the proposed analyses are not scientifically robust and give rise to erroneous concerns about safety or false hopes of a potential benefit for patients,” GSK has declared.4 This fear of misleading analyses is embodied in an adjective gaining popularity among discussions over data sharing: “responsible.” The Institute of Medicine has named its ongoing consensus study on the topic “Strategies for Responsible Sharing of Clinical Trial Data” and a recent essay in the New England Journal of Medicine entitled Preparing for Responsible Sharing of Clinical Trial Data, warns that “poor-quality analyses can harm rather than advance public health, it must ensure responsible use of data.”17
IRONY OF STUDY 329
There is a certain irony in the story of study 329 and its 2001 publication in JAACAP. In a letter to Jureidini, GSK explained that the JAACAP publication “was subjected to peer review on three occasions” and “accurately reflects the honestly-held views of the clinical investigator authors.” But a more pertinent question is whether the published article accurately reflects the trial.
In their most recent letter to GSK, Jureidini and his colleagues reiterate their need for the study 329 case report forms and their intention to analyse study 329 “following the original analytic plan.” As such, Jureidini’s team’s efforts to independently analyse and publish the results of study 329 can be viewed as perhaps the most “responsible” of all analyses—and one that it seems may yet overturn the JAACAP publication that GSK continues to defend.
Story of study 329
1994-98: SmithKline Beecham conducts study 329, a study of 275 adolescents with depression
24 November 1998: Date of SmithKline Beecham’s internal clinical study report for study 329, which was made public by the 2004 consent order
July 2001: Keller et al publish study 329 in the Journal of the American Academy of Child and Adolescent Psychiatry1
26 August 2004: GSK signs consent order with the New York State Attorney General, agreeing to pay $2.5m and publicly post clinical study reports for GSK sponsored trials of paroxetine in children and adolescents
2 July 2012: US Department of Justice announced that GSK “agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices”18
26 April 2013: Jureidini writes to GSK chief executive requesting his help in retracting the Keller et al JAACAP article
3 May 2013: GSK responds that “GSK does not agree that the article is false, fraudulent or misleading”
13 June 2013: BMJ publishes the restoring abandoned and invisible trials (RIAT) declaration11
25 June 2013: GSK expresses support for RIAT, stating that “by making the Clinical Study Reports available we are very happy for others to publish on the records if they wish to and if journals consider the work to be of scientific merit”
15 July 2013: Jureidini publicly announces his team’s intent to republish study 329 in accordance with the RIAT initiative
28 October 2013: Jureidini and colleagues formally submit a request for deidentified electronic participant level data through GSK’s website. The result of their request is pending review by GSK’s independent review panel
Cite this as: BMJ 2013;347:f6754
Competing interests: I have read and understood the BMJ policy on declaration of interests and declare the following interests: I am the first author of the RIAT declaration, which was co-authored by David Healy, who is part of Jureidini’s team. I am providing the Jureidini team with unpaid advice on the RIAT process. I am also a member of a Cochrane review of neuraminidase inhibitors that is based in part on clinical study reports provided by GSK for zanamivir. I initiated an inquiry in 2012 that resulted in an additional 38 781 pages from the clinical study reports of study 329 and eight other studies to be publicly posted on GSK’s website.
Provenance and peer review: Commissioned; not externally peer reviewed.
- ↵Kmietowicz Z. GSK backs campaign for disclosure of trial data. BMJ2013;346:f819.
- ↵Hawkes N. Industry and drug regulators disagree on which data should remain confidential. BMJ2013;347f5390.
- ↵Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Saf Med2008;20:73-81.
- ↵Zito JM, Safer DJ, dosReis S, Gardner JF, Soeken K, Boles M, et al. Rising prevalence of antidepressants among US youths. Pediatrics2002;109:721-7.
- ↵United States ex rel. Greg Thorpe, et al v. GlaxoSmithKline plc, and GlaxoSmithKline llc. United States’ complaint. C.A. No. 11-10398-RWZ. 2011 www.justice.gov/opa/documents/gsk/us-complaint.pdf.
- ↵Newman M. The rules of retraction. BMJ2010;341:c6985.
- ↵Doshi P, Dickersin K, Healy D, Vedula SS, Jefferson T. Restoring invisible and abandoned trials: a call for people to publish the findings. BMJ2013;346:f2865.
- ↵Civil Action No 04-V-5304 MGC. People of the State of New York against GlaxoSmithKline, plc and SmithKline Beecham Corporation. Consent order & judgment. 2004. www.ag.ny.gov/sites/default/files/press-releases/archived/aug26a_04_attach1.pdf.
- ↵Shannon J. Unlocking access to clinical trial data— what are we afraid of? Huffington Post2013 Sep 9. www.huffingtonpost.co.uk/james-shannon/clinical-trial-data_b_3859734.html.
- ↵GlaxoSmithKline CEO on increasing transparency of clinical trials. Fox Business2013 Oct 10, http://video.foxbusiness.com/v/2735629915001/glaxosmithkline-ceo-on-increasing-transparency-of-clinical-trials/.
- ↵GlaxoSmithKline. Data sharing agreement. https://clinicalstudydata.gsk.com/Documents/DATA-SHARING-AGREEMENT.pdf.
- ↵US Department of Justice. GlaxoSmithKline to plead guilty and pay $3 billion to resolve fraud allegations and failure to report safety data. 2012. www.justice.gov/opa/pr/2012/July/12-civ-842.html.
From Dr David Healy’s blog (for full article see link)
The Moral High Ground?
GSK are claiming the moral high ground of concern for patient welfare. Have they in the process managed to co-opt groups from the House of Commons to AllTrials who might otherwise hold them to account?
Study 329 is GSK’s most famous clinical trial. In this a large number of children became suicidal on paroxetine. Antidepressants like paroxetine – thanks to Study 329 but not thanks to GSK – now come with a Black Box Warning that they may cause suicide.
Study 329 was worth roughly $1 Billion to GSK. It enabled the company to get six months patent extension on Paxil-Seroxat.
The children who became suicidal on Paxil in Study 329 are more likely than others to become suicidal again if exposed to another SSRI.
Against this background:
- What should a company genuinely concerned about the welfare of patients who have done so much for the welfare of the company (participating in this trial without payment) do at this point?
- Should GSK’s concern about patient welfare extend to informing the subjects in Study 329 of the link between their treatment and their problems and future risks they may run?
- Andrew – have you contemplated the possibility that if you don’t inform those affected you are in fact still to this day making suicide more likely for some of those affected?
- Has GSK – or any pharmaceutical company – ever gone back to any of the subjects enrolled in any of its trials to explain to them what might have happened to them and the role their drug might have played in what happened? Please send known examples.
- Would explaining to people how their injury arose not be a more telling indicator of concern for patients than an effort to keep identifiers out of the public domain?
- What would the patients who have participated in clinical trials think was the more important indicator of genuine company concern?
- What do Flaminia Macchia and Eurordis think would be the most appropriate indicator of genuine company concern?
Following a legal action taken by New York State in 2004, GSK agreed to post Clinical Study Reports (CSRs) for their pediatric Paxil trials and other trials on the company website along with further details of their Avandia and other trials on the company website.
Any good investigative journalist could likely identify each of the children who became suicidal on paroxetine from the CSRs available on GSK’s website. Pretty well the only additional details that the patient level data that the company refuses to release contains are the patients’ initials. These could easily be redacted. This raises the question as to why GSK are so resistant to making the original case report forms (CRFs) available?
The only obvious other details that the CRFs contain not found in the CSRs are adverse effects. Its clear from looking at the CSRs, there are a very large number of mismatches (several hundred) between what the CSRs show and the CRFs are likely to contain.
There is a team attempting to rewrite Study 329 according to the RIAT process. See Reading the Riat Act . The difficulties they are having in getting data out of GSK have been covered by Ed Silverman of Pharmalot.
1boringoldman has also covered this ground and the apparent growing links between GSK and AllTrials, and how GSK are using their model of transparency to block access to the data.
Because there is a mismatch between the CSRs and CRFs, the Study 329 RIATers are at a point where they require the raw data – the CRFs. GSK refuses to hand over the CRFs.
What would the now 35-year-old or so children who participated in Study 329 think should happen at this point?
If you are a small player in the scheme of things, you may know just how the world should work but will never get a chance to implement any of your ideas. If you go into coalition with a bigger power you may get to implement policies you have always supported but have no chance to see brought into being. Or perhaps you can temper policies your partners might want to put in place that you disagree with.
What do AllTrials think should happen at this point?