Editorial Note: This post has been put together by Peter Goetzsche and David Healy
Dear Dr Goetzsche
“At GSK we firmly believe that making more information available, including clinical study reports and anonymised patient-level data, will enable researchers to study the science behind today’s medicines more closely, to learn more about them and how they can best be used.
For GSK the transparency and access journey [i] started with online clinical trial studies in 2004 and has so far led us to the endorsement of the AllTrials Campaign last year, as well as access to anonymised patient data launched in May 2013. Ultimately this has the potential to improve patient care and drive open innovation.
When patients volunteer to take part in research they have a legitimate expectation that the data will be used to enhance knowledge and improve patient care. Our actions towards transparency are an essential part of meeting those expectations. By being open and accessible we become an even stronger and more trusted partner for society, patients and health care professionals and at the same time improve patient care.
We have been open in describing the steps we have taken. Our initiatives has been acknowledged and welcomed by governments, NGO’s and research institutions.
The recently published report from the Science & Technology Committee in UK, states regarding patient level data: “We recognise the efforts of some members of the pharmaceutical industry, particularly GSK, to increase clinical trial transparency and hope that other companies will act in the same spirit in implementing industry-wide principles for responsible clinical trial data sharing”.[ii]
Our initiatives have been commended by campaign groups as setting a new standard for greater transparency. In response to our commitment to develop a system for access to patient level data, Ben Goldacre, (author of “Bad Pharma” and co-founder of AllTrials) said: “It is a great initiative; I call for it in the book, I hope it happens at GSK, consistently, and I hope it is copied”.[iii]
Similarly, in response to GSK signing up to AllTrials, where the Cochrane Institute is one of the partners, and committing to post CSRs, Tracy Brown from Sense about Science said: “GSK signing up to the campaign is very important, off course, because they are a large global player in clinical research so they have a lot of potentially useful information to share, but also because they are finding a way to put in place the infrastructure needed to do this. Which makes it realistic for others and sets a new standard”.[iv]
In a BMJ article published March 2013, CEO Andrew Witty explained our commitment to transparency[v] and our global position is also reflected in the recent submission of our views as part of the consultation process with respect to EMA’s ‘Policy 0070 on publication and access to clinical-trial data’.
We regret that you find a personal meeting irrelevant and would like to repeat our invitation. In GSK we find dialogue very valuable and ultimately to the benefit of patients, and thus our dialogue should be continued in a face to face meeting either in London or in Copenhagen.
A GSK & AllTrials Coalition?
Here’s that Branded tone again – mentioned in SHIT Happens. A plaintiff note about how the world just doesn’t understand we are the good guys. GlaxoSmithKline (GSK) seem to have bought their own propaganda about being champions of transparency.
As they mention, the House of Commons has rolled over and put its paws in the air so pleased are they – despite being told by GSK that the UK is not a fit place for Pharma to run trials in. No reference here to the recent fines in the USA for $3 Billion against GSK or the fraud action by New York State against GSK in 2004 hinted at above as the kickstart to GSK’s journey to transparency and access.
Worryingly, there almost appears to be a hook-up between AllTrials and GSK. AllTrials have been campaigning to have all trials registered. When GSK endorsed this campaign, Ben Goldacre described it as a “cartwheel moment”.
In fact the idea of registering all trials – and in this sense the start of the journey – is one that Glaxo Wellcome endorsed 15 years ago when Richard Sykes was CEO of the company. GSK then drew back from this commitment, after Glaxo Wellcome merged with SmithKlineBeecham.
The links between GSK and AllTrials have appeared to get even closer recently with Iain Chalmers of AllTrials co-authoring an editorial with Patrick Vaillance of GSK. (The Attitude of Chicks to Trojans and Horses). This editorial pushes trial registration. But it also endorses GSK’s proposal of only releasing some of the material from those trials and then only releasing data in response to a request that contains an analytic plan and even in response to such a request only offering a form of release that actively blocks investigators from having a clear view of what might actually have gone on in the trial.
Transparency GSK-style, like Gangham-style, seems to have gone viral. It went viral went it was a press release with not a shred of policy detail in sight – Won’t get Fooled Again. A case study perhaps for those who think that to get something to go viral needs Jupiter to be in alignment with a cat’s eye in Southern Africa when the wind blows East.
Everyone wanted to hear this message.
The Chalmers-Vaillance editorial justified GSK-style in part by making a case that patient confidentiality was extremely important and that the risks of identification were great. This is a strategy Pharma have deployed from the start of the current Data Access Debate – using the patient group Eurordis to make the case for them (Data Access Wars).
It flies in the face of what the overwhelming majority of people signing consent forms probably intend – which is to make their data available for scrutiny by independent experts. If those of us who have been participants in trials thought some remote risk of a breach of privacy were being used to prevent a disclosure of details that would save someone else’s life but threaten GSK’s profits, most of us would likely be horrified.
It also flies in the face of the original use of consent forms in drug trials – which was solely to establish that you knew you were taking a novel, not-yet-marketed compound. See When Does Yes Mean No.
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?