Transparency Is Still A Problem As Big Pharma Struggles With Its Image


http://www.academia.edu/8025839/You_Gain_Respect_in_Drops_But_Can_Lose_It_in_Gallons

http://www.forbes.com/sites/johnlamattina/2015/05/05/transparency-is-still-a-problem-as-big-pharma-struggles-with-its-image/

“Reputation, built on our past, shapes our present and future. A good reputation can open many doors; a bad reputation can close many more. A good reputation generates respect. A bad reputation breeds suspicion.”

Those are not the words of a business consultant or from a television talk show host like Dr. Phil. They are from Ian Read, the CEO of one of the world’s biggest companies, Pfizer PFE -0.7%. In a compelling article that he wrote on February 19th entitled “You Gain Respect in Drops, But Can Lose It in Gallons,” Read correctly talks about the importance of a company’s reputation, particularly in the pharmaceutical industry. But the industry continually stumbles in its efforts. Just last week, Takeda announced that it agreed to pay $2.4 billion in fines to settle lawsuits related to its diabetes drug, Actos. As outlined by Andrew Pollack in the New York Times, this is not a rare event in this industry. Pollack went on to list other large settlements such as the those against Wyeth for the fen-phen diet pills and Merck for Vioxx ($4.85 billion). These type of headlines are definitely in Read’s gallon category.

The industry also suffers from transparency issues on a variety of fronts such as the publication of clinical trial data, hiding or minimization of drug side-effects, and payments to physicians. In terms of the latter, the biopharmaceutical industry has been making progress. Partly due to the Affordable Care Act (ACA) and partly due to their own initiative, companies have begun to make public the payments that they make to doctors. Before the enactment of the ACA, people could go onto the websites of Pfizer, Lilly , and GSK and see all the payments that are being made to doctors and institutions for the work they undertake for these companies. The advent of the ACA has now made it mandatory for all companies to do this via “Open Payment” databases. There was some trepidation as to the potential negative impact that such openness would create. However, as these data rolled out, it became clear that the vast majority of payments to physicians, roughly 80%, are for the discovery and development of new medicines. All payments to doctors are now available, not just for R&D but also those for meals, speaking fees, and consulting. Such transparency did result in concerns voiced by some, including those who believe that physicians should not receive ANY payments from biopharmaceutical companies as these exert undue influence on prescribing practices. However, on balance this transparency eliminated the “behind the curtain” view of company payments to doctors. With the majority of payments being made for critical clinical work, critics have to acknowledge that such payments are indeed justified.

However, as reported last week by the Wall Street Journal’s Ed Silverman, the biopharmaceutical industry seems to be regressing on this issue. In Australia, regulators have approved new rules that require biopharmaceutical companies to disclose all payments made to doctors for speaking and consulting, as well as for travel. However, excluded from the reporting requirements are all payments made for food or beverages given to doctors. The reason given is that ongoing reporting would impose a significant administrative burden on companies. That sort of rationale rings pretty hollow when these payments are routinely reported in the U.S. How can this be an administrative burden in Australia when a system is already in place in a far bigger country? Excluding these payments from reporting practices only serves to breed suspicion.

There is also pushback on aspects of financial disclosure now mandated by the ACA specifically with respect to payments for Continuing Medical Education (CME). These are events designed for doctors to get the latest information about drugs. As again reported by Silverman, Congress now has a draft of the 21st Century Cures bill, designed to jump start medical innovation, that includes a provision that that would eliminate CME payment disclosures now required by the ACA. The problem with doing this is that, again, the perception would be created that the biopharmaceutical industry is hiding these data as these types of events are a way for companies to influence the prescribing habits of the doctors who attend.

So, here’s a suggestion for the biopharmaceutical industry. The trade organizations representing these firms – the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO) – should each issue statements that their members do not agree with the Australian payment position on meals, nor do they agree with creating an ACA exemption for CME payments. Instead, member companies of these organizations will make ALL payments to doctors available in Australia as is done in the U.S. and will NOT support a CME payment exemption in the current form of the 21st Century Cures bill now in the House of Representatives. Will such actions make major headlines? Probably not. But as Ian Read said, “You gain respect in drops”. A few drops would be helpful alleviating the drought suffered in pharma’s reputation.

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GSK: How To Provide Access To Data Without Revealing Anything At All


“The process of using this interface for analysis is unnecessarily maddening and a severe obstruction to the task”..

(1boringoldman-blog- http://1boringoldman.com/index.php/2014/05/25/a-decision-to-reconsider/)


 

 

Does Ben Goldacre really believe that a multi-billion dollar corporation like GSK can’t provide an easier, more technologically advanced, and productive route- for researchers to access their data?

GSK are taking the absolute piss out of Alltrials, the BMJ, the entire scientific and medical community, and the public at large, with their ‘transparency charade’ but most of all they are harming patients -and that is utterly indefensible… the system GSK have in place is obviously a deliberate attempt to block researchers gathering data properly…

 


 

http://1boringoldman.com/index.php/2014/05/25/a-decision-to-reconsider/

 

…as a member of the RIAT team who was granted access to the Data from Paxil Study 329 to do an independent reanalysis by GSK, we’ve now had months of experience working with their “remote desktop” interface as a portal to their information. It is a single windowed multiple document interface, totally self contained that can’t be accessed by any software other than that provided inside the window. Multiple passwords are required multiple times for access, and on some days, one is frequently thrown from the system without warning, necessitating repeated logins. There’s another internal window from SAS that contains the data and allows one to run SAS programs to analyze the data. The data is also provided as text-based CSV files that can be moved outside the internal SAS window and displayed in spreadsheets [Open Office is provided]. The open source statistical program, “R” is also provided. In our case having no-one fluent in SAS procedures and programming, we are using “R” which has the necessary statistical functions. Getting the data into the proper format required by “R” means using multiple spreadsheets – which is very difficult in the cramped space provided – sometimes taking days and involving many “start-overs.” Once the data is analyzed, one can only export non-data containing files with results, and that’s only by application for approval. Using the primitive graphing functions of Open Office or “R’ in the “remote desktop” is very difficult and the graphs can’t be exported. That finally lead us to copy the information for the graphs by hand to get it into the computer proper to create our images. The process of using this interface for analysis is unnecessarily maddening and a severe obstruction to the task.

The original hand written CRFs are provided as PDF documents. In our case, there are some 275 subjects, many with several pdfs, each pdf containing 200+pages. In the interface provided, we can see only one page at a time of the nearly 60,000 pages. Tallying the adverse events from the pdfs is hard enough work, but doing to without being able to make printed copies and referring back and forth is a double nightmare, requiring days of wasted time, and delegation is impossible. Working inside of this little window brings home how important it is to have a workspace that allows simultaneous display of lots of information, and this isn’t it. One of our team has lost one assistant already over this interface. The EMA’s decision to even consider using this kind of interface is at best, ill advised, and a negation of the initial promise of Data Transparency. If I weren’t retired and instead had a job to do, I don’t think I could do it. If I were a graduate student given the task, I might go to the chairman of the department and ask for another major professor. It’s impossible to imagine that anyone contemplating this decision who knows the ins and outs of data analysis has tried it out in this kind of environment. As I said before, it’s like going to sea to see the world in a submarine, looking through a periscope.

I expect the EMA means well, and may think that since the data is available in this system, it should be okay.. But they apparently don’t realize the practical burden that it inflicts on anyone trying to have a serious look at a clinical trial. At the least, I would hope they would sit someone down in front of a computer using such a system so they can see with hands-on what I’m talking about – that I’m not being melodramatic.

From 2006: A Criticism of GSK And Their Transparency Deception : “From optimism to disillusion about commitment to transparency in the medico-industrial complex” by Iain Chalmers


Following up from my post yesterday, titled ‘Ben Goldacre: Wake The Fuck Up” concerning David Healy’s article on his blog titled ‘Fucked’, I think it might be timely to post Iain Chalmers article in the JRSM from 2006, titled :

“From optimism to disillusion about commitment to transparency in the medico-industrial complex”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1484602/

Logo of jrsocmed

J R Soc Med. Jul 2006; 99(7): 337–341.
PMCID: PMC1484602

From optimism to disillusion about commitment to transparency in the medico-industrial complex

In the mid-1970s, I was involved with others in trying to assemble evidence about the effects of care during pregnancy and childbirth. We started by searching Medline to identify reports of controlled trials that we thought might be sufficiently reliable to be taken into account in our analyses; and then searched about 70 journals by hand, page by page, back to the issues published in 1950. We found about 3500 reports of controlled trials and, with help from the World Health Organization, we published the references to these in a classified bibliography in the mid-1980s.1

But then we thought, ‘What about trials that don’t get published? If we don’t take those into account, we might reach biased conclusions’. We knew of anecdotes about researchers who had had disappointing results of trials, and had therefore never made the results public. Furthermore, in an important analysis of controlled trials of treatments for cancer of the ovary published in 1986, an Australian oncologist, John Simes, had shown how failure to publish clinical trials could lead to misleading inferences about the effects of treatments.2 So we wrote to 42 000 obstetricians, paediatricians and other clinicians around the world to try to flush out information about studies that had been done but had never been reported. It was an almost complete waste of time; we published our experience to warn others to think carefully before using the retrospective survey approach we had used in our attempt to deal with publication bias.3

Like John Simes before us, we concluded that a prerequisite for tackling the problem of biased under-reporting of research involved registering controlled trials publicly, at inception, before their results could influence whether or not the world would come to know about them. In 1990, based on a paper I had presented at the 1st Congress on Peer Review in Biomedical Publishing, I published an article with the deliberately provocative title ‘Underreporting research is scientific misconduct’. I suggested that failing to report well-conducted clinical trials was not only scientific misconduct, but also unethical; it broke an implicit contract with the patients who had participated in clinical trials. I reiterated the call for registration of trials at inception.4

As it happens, all the examples of biased under-reporting of controlled trials I gave in that paper referred to non-commercial trials. The drug industry is not very interested in perinatal healthcare, the field in which I was researching at that time, because it does not offer very rich pickings. Ten years before my article was published, however, Elina Hemminki had shown that biased under-publication of studies funded by industry might be a particular cause for concern.5 She compared the study reports submitted by pharmaceutical companies to drug licensing authorities with subsequently published reports of the same studies. From this she found that studies in which the pre-licensing records showed that researchers had looked for adverse effects were less likely to be published than studies in which adverse effects had not been sought.

For the reasons already mentioned, I had had little contact with the pharmaceutical industry while I was a perinatal researcher. In 1992, however, I moved to the UK Cochrane Centre. As the Centre and then the Cochrane Collaboration began to become known to people in industry, representatives of the Association of the British Pharmaceutical Industry asked to meet with me. A delegation came to the UK Cochrane Centre, led by Frank Wells, the medical director of the ABPI. Our discussion lasted for about 3 h, during which I emphasized the openness with which the Cochrane Collaboration did its work: protocols for Cochrane reviews and completed reviews were published in electronic form, and could be criticized publicly, and readily amended if necessary.

After I had explained this, I felt it reasonable to suggest to my ABPI visitors that industry should be more open about its clinical research, because biased under-reporting could harm patients. Encouragingly, Frank Wells subsequently wrote in the preface of a book he had co-authored on fraud and misconduct in medical research: ‘Under-reporting of research is (another) form of misconduct, given that this can lead to seriously misleading recommendations for clinical practice and for new research’.6

The same year that this book was published, Mike Wallace, another member of the ABPI delegation and at that time the chief executive of Schering Healthcare Ltd (the British subsidiary of Schering AG), told me that he realized that biased under-reporting of research was ethically and scientifically indefensible. He felt that unless the pharmaceutical industry started to take an initiative to confront this issue voluntarily it would end up being forced to do so—probably in ways that it would rather not be. Mike Wallace said that he had decided to provide information about all his company’s controlled trials for publication in the Cochrane Controlled Trials Register. I know that he was reprimanded for breaking ranks in this way, in particular, by colleagues from other member companies of the ABPI. I am glad to be able to pay tribute to a senior nonmedical executive in the industry who stepped out of line to do something which he thought was morally correct.

Mike Wallace was not the only person within the British pharmaceutical industry taking steps towards greater openness, however. In particular, David Jackson, medical director of the British holding company of GlaxoWellcome, had persuaded his colleagues in the international parent company that the company should adopt a more open policy. The new policy was announced at the end 1997, and I was pleased to be quoted in the press release welcoming it. The following year, the chief executive of the company, Richard Sykes, wrote a landmark editorial in the BMJ entitled ‘Being a modern pharmaceutical company involves making information available on clinical trials programmes’. He made clear that one reason for Glaxo Wellcome’s new disclosure policy was ‘… to help those undertaking systematic reviews of clinical data and to help reduce the impact of publication bias’.7

GlaxoWellcome implemented the trials registration policy it had announced, and two of the people who were involved—Trevor Gibbs and Elizabeth Wager—later published an account of the challenges this had presented.8 Elizabeth Wager was head of the writers’ group within the company and she convened a group of her colleagues in other companies to agree and then publish guidelines for good publication practice. They noted that ‘… the aim of the guidelines is to ensure that clinical trials sponsored by pharmaceutical companies are published in a responsible and ethical manner. The guidelines cover companies’ responsibilities to endeavour to publish results of all studies’.9,10

Things were stirring among pharmaceutical physicians more widely. In 1998 the Ethics Committee of the Faculty of Pharmaceutical Medicine declared that:

‘Pharmaceutical physicians have a particular ethical responsibility to ensure that the evidence on which doctors should make their prescribing decisions is freely available… the outcome of all clinical trials on a medicine should be reported’.11

Two years later they reiterated the ethical principle: ‘Studies are performed to increase knowledge in some way, and this knowledge should be shared with the wider world. Study findings should be communicated, whatever the outcome, for the benefit of the community at large’.12

Presumably because the ABPI felt that it could not really sit by while one of its major members, GlaxoWellcome, and the Ethics Committee of the Faculty of Pharmaceutical Medicine were showing a moral lead in this way, the Association decided to commend Glaxo Wellcome’s policy to other member companies. I was on the ABPI side of the table at the press conference announcing this policy, and I welcomed it wholeheartedly. In brief, I had become optimistic that the industry really was beginning to address the problems that I had urged should be addressed at our meeting eight years previously. Although the response was not nearly as good as the ABPI had hoped, AstraZeneca, Aventis, MSD, Novartis, Roche, Schering Healthcare and Wyeth did begin registering retrospectively those of their trials that had involved UK patients.

However, these hopeful signs were not sustained during subsequent developments. In the same year that the ABPI announced that it was leading the world in registering clinical trials, Glaxo Wellcome merged with Smith Kline Beecham. Initially, my optimism that the new company would maintain Glaxo Wellcome’s policies on trial registration seemed justified: the new company’s logo had replaced the Glaxo Wellcome logo on the trials register. I wrote to the chief executive of the merged company, Jean-Paul Garnier, to express my pleasure at this. I also mentioned that I was delighted that Elizabeth Wager and her six colleagues in the former. Glaxo Wellcome writing department, and their association with the Good Publication Practice for Pharmaceutical Companies Guidelines, continued to be supported by the new company. I never received a reply to my letter; the company abandoned the trial registration process and abolished its publications departments in the USA and the UK, headed by Elizabeth Wager and Elizabeth Field, respectively—both co-authors of the Good Publication Practice Guidelines for Pharmaceutical Companies.9,10

It was round about that time that increasing amounts of empirical evidence began to confirm doubts about the trustworthiness of research sponsored by industry. As I have noted already, Elina Hemminki had produced evidence of based under-reporting of industry research 20 years earlier: reports of studies submitted in support of new drug licences in which adverse effects had been sought were less likely subsequently to be published.5 A study using similar methods was reported in 2003 by Melander and his colleagues.13 Their paper entitled ‘Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry’ demonstrated result-dependent over-reporting and under-reporting of industry studies of new drugs. They concluded that any attempt to develop treatment recommendations using analyses based only on publicly available data were likely to be based on biased evidence.

Other evidence reported over the past 5 years has demonstrated associations between industry-sponsorship and research results favouring products made by the companies funding the research. As well as biased under-reporting of research, the associations observed may also reflect inappropriate comparison of new products with comparators of existing products in doses too low to be effective or higher than necessary, with consequent higher incidence of adverse effects.1417 Neither of these possible explanations is morally or scientifically defensible. In addition, there is evidence of more subtle forms of industry bias in the way that data are interpreted,18,19 for example, by putting a biased spin on the evidence. The title of a recent report20 says it all: ‘Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head to head comparison studies of second generation anti-psychotics’. One of the five key points emerging from the evidence presented at the 5th Congress on Peer Review in Biomedical Publishing was that ‘… the drug industry is successfully skewing the literature in its favour’.21

By now the public was starting to get interested in these matters. I was asked to write an article about under-reporting of research for the popular weekly journal New Scientist.22 In fact, I had co-authored a piece on the topic in the same journal 8 years previously.23 But now, something happened which made a real difference to the likelihood of the message about publication bias being taken seriously. Eliot Spitzer, the attorney general for New York State, took GlaxoSmithKline to court for withholding information about important possible adverse effects of drugs taken by children for depression.

The company settled out of court for a couple of million dollars, but the charge laid against it had the effect of increasing the pressure to deal with publication bias. It provoked the International Committee of Medical Journal Editors to do what the Committee should have done years earlier. It announced that the authors of any reports of clinical trials that had begun recruitment after the middle of 2005 would have to confirm that the studies had been registered publicly, at inception.

Only then did the drug industry start to try to limit the damage caused by its failure to follow the lead given by Schering Healthcare and Glaxo Wellcome nearly a decade earlier. In a press release issued in June 2004, GlaxoSmithKline announced that it would make the results of all its clinical trials publicly available. The company did not explain how, given that its trials register had been allowed to fall into disrepair, the public would know whether all results were being made available. A BMJeditorialist commented thus:

‘Last month GlaxoSmithKline announced that it would publish summaries of all its clinical trials of a new product once it had been launched. The decision followed news of a lawsuit brought by New York State alleging that the company had concealed the results of paroxetine because they might have spoiled marketing plans. GSK said it had been considering the move for some months. A similar sounding policy was announced by Glaxo Wellcome in 1998, but seems to have been quietly abandoned in 2000 after the merger with SmithKlineBeecham.’24

Industry’s attempts at damage limitation continue. Speaking on the BBC Radio 4 programme In Business on 24 June 2005, Jean-Pierre Garnier said: ‘We have responsibilities beyond those to our shareholders’, and ‘… we must be completely transparent with the public about what we do’. The gap between this statement and an analysis of the records submitted by his company (and other pharmaceutical companies) to the National Institutes of Health trials register25 suggests that GlaxoSmithKline’s understanding of what transparency implies may leave many people disappointed and cynical about the company’s expressed commitment to greater openness.

If GlaxoSmithKline really is committed to the kind of openness the public has come to realise is needed, one might have expected it to have endorsed the Good Publication Practice for Pharmaceutical Companies Guidelines developed by its dismissed former employees and colleagues in other companies.9 It has not. Indeed, at the time of writing, only six pharmaceutical companies have endorsed the guidelines—Aventis, Amgen, LEO Pharma, Otsuka, Serono and 3M Pharmaceuticals.10

The public is beginning to demand stronger sanctions. During 2004 and 2005, the Health Committee of the House of Commons held an enquiry into the influence of the pharmaceutical industry. The Committee drew attention to the problem of biased under-reporting of research and recommended registration of trials at inception.26 Richard Sykes, previously chief executive of Glaxo Wellcome, now rector of Imperial College London, gave oral evidence to the Committee which clearly impressed the members. In its report, the Committee’s recommendations began by noting Richard Sykes’ view that:

‘Today the industry has got a very bad name. That is very unfortunate for an industry that we should look up to and believe in, and that we should be supporting. I think there have to be some big changes.’

On 6 January 2005, the industry announced a global commitment to clinical trial registration and publication. Whether this commitment amounts to the‘big changes’ that Richard Sykes judges are needed is an open question. First, the commitment applies to only a tiny proportion of the clinical trials which should be informing prescribing practices because it is not being applied to trials conducted in the past. Second, there is a continuing flow of empirical evidence of biased reporting and interpretation of industry trials. My judgement is, therefore, that industry’s actions are simply too little and too late to deal with its current reputation for being less than honest with its research—just as Mike Wallace feared might be the case in his conversations with me a decade ago.

Biased under-reporting of research harms and sometimes kills patients, quite apart from the waste of resources that results from this form of scientific and ethical misconduct. In 2004, a former editor of the New England Journal of Medicine published a book entitled The Truth About The Drug Companies: How They Deceive Us and What To Do About It.27. How can we expect the public to trust the pharmaceutical industry and clinical researchers who work with it while we acquiesce in this state of affairs?

Jan Vandenbroucke has noted how science as an errordetecting process simply ceases to exist in these circumstances:

‘In all scientific debates all sides always have their own biases: we have no other way to look at data but to interpret them. However, in usual clinical or epidemiologic research, studies are repeated by others, in different settings and by different means, looking for biases, flaws, and ways of remedying them, endlessly arguing whether the biases are remedied or not. That is the essence of open scientific debate and criticism, which is the only guarantee for progress. That is no longer possible with pharmaceutical products because the monopoly of the pharmaceutical industry of studies of its own products leads to persistently one-sided studies that can no longer be questioned by studies from other sides. Moreover, the one-sidedness cannot be seen from the public record, that is the published papers. Without the possibility of open debate, science simply ceases to exist’.28

Careful thought needs to be given to this analysis by governments, public and charitable organizations, and individuals who promote research collaboration with industry while remaining silent about the unethical and unscientific behaviours alluded to above. As I have made clear, biased reporting and lack of transparency is not limited to commercially-sponsored research; but the empirical evidence makes clear that it is a particularly noticeable problem in that sphere. Those who collaborate with industry need to be clear that their acquiescence in these forms of scientific misconduct inevitably casts doubt on their integrity, as reflected in the title of a book by another former editor of the New England Journal of Medicine—On The Take: How Medicine’s Complicity With Big Business Can Endanger Your Health.29 The responsibilities of doctors should be unambiguously to their patients. Yet some clinician researchers (with plenty of encouragement from government and the institutions with which they are associated) appear to have become so seduced by the financial rewards resulting from collusion with industry’s agenda and practices that they have forgotten this most fundamental of their professional duties. Indeed, that is the most depressing cause of my optimism of a decade ago becoming disillusionment today.

A few weeks before finalizing a draft of this essay for submission to the Journal of the Royal Society of Medicine I was invited by Richard Tiner, medical director of the ABPI, to address a meeting of 60 or so members of medical departments of member companies on the topic of ‘clinical trial transparency’. In response I suggested that, rather than give a talk, it might be a more useful to pre-circulate the above text so that it could be discussed at the meeting, and Dr Tiner accepted this proposal.

It came as a bit of a surprise to me that there was no serious challenge to the facts I had assembled to explain why my earlier optimism had turned to disillusion. This may have been partly because it was clear that I have tried to work with industry over the past decade to increase transparency, and to commend publicly the positive steps that some individuals, companies and the ABPI had taken in that direction. Instead of giving me the rough ride that I had been expecting, participants at the meeting asked me for suggestions about what could be done to deal with the bad reputation to which Richard Sykes had referred in his evidence to the Health Committee of the House of Commons.

Although I made one or two off the cuff suggestions at the meeting, I realized that I needed to add to this essay some suggestions for steps that might go some way to increasing confidence in the scientific integrity of the industry. So, in conclusion, here are three practical suggestions:

  1. All pharmaceutical companies should join Aventis, Amgen, LEO Pharma, Otsuka, Serono and 3M Pharmaceuticals in publicly endorsing the Good Publication Practice Guidelines for Pharmaceutical Companies9,10
  2. Industry as a whole should put in place mechanisms for promoting and monitoring adherence to these guidelines, thus making clear to the public that it regards under-reporting of research as just as serious a form of scientific misconduct as fabrication of data
  3. Industry should voluntarily take steps that go beyond the minimum currently being required for clinical trial registration,30 for example, by publishing full protocols at the inception of all randomized trials.

 

I hope that I may be able to write another essay in 5 years’ time entitled ‘From disillusion to optimism about the scientific integrity of the pharmaceutical industry and the people collaborating with it.’

Notes

Acknowledgments I am grateful to Richard Sykes, Richard Tiner, Elizabeth Wager, Mike Wallace, Frank Wells, Jan Vandenbroucke, and participants at the ABPI meeting held at BMA House on 28 February 2006, for helping me to ensure that this account is accurate.

Competing interests None declared.

Note Listen to an audio interview with Iain Chalmers on [http://www.jrsm.org]

References

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29. Kassirer J. On The Take: How Medicine’s Complicity With Big Business Can Endanger Your Health. New York: Oxford University Press, 2004
30. Sim I, Chan A-W, Gülmezogğlu AM, Evans T, Pang T. Clinical trial registration: transparency is the watchword. Lancet 2006;367: 1631-3 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press
Iain Chalmers

The Great Glaxo Transparency Swindle… Prof. David Healy says ‘now is the time of greatest peril’…


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http://davidhealy.org/welcome-to-troy/#comments

Trojan Horse

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

Neil1Neil2

 For more on The Ben Goldacre/GSK/Data Debacle See My Previous Posts Here:
https://truthman30.wordpress.com/tag/ben-goldacre/
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Hey Mr. Ben Goldacre, Can You Ask Your GSK Buddy (Rob Frost) About Seroxat Suicides?


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http://www.alltrials.net/2014/alltrials-campaign-video-coming-soon/

AllTrials campaign video coming soon

27th January 2014

In the year since the launch of the AllTrials campaign over 63,000 people have signed the petition and 445 organisations have joined up; MEPs told us that our supporters’ input shaped the new European clinical trials law; and companies, research funders and regulators are having serious discussions about how to implement necessary changes to increase transparency.

This is great progress, but transparency in clinical trials is a global issue and to effect a major and lasting change the campaign has to have success internationally. There are people around the world who want to build the campaign in their own country and we want to help them by producing material they can use.

We launched an appeal for donations in October 2013 to make a short campaign video that gathers together the voices of patients, doctors, campaigners and pharmaceutical companies. You helped us reach our target and we’ve started filming with Rob Frost, Policy Director from the Chief Medical Officers office at GSK; Dr Ben Goldacre, doctor and author; Richard Stephens, cancer patient and trial participant; and Síle Lane, who manages campaigns at Sense about Science and runs AllTrials.

We hope the video will be ready in a few weeks and will be subtitled in many languages to maximise its reach.  Thank you to everyone who kindly fundraised for us or donated money to the appeal. We hope you will share the video with your contacts and networks when it’s launched and help us spread the word far and wide.

Here’s a sneak preview from behind the scenes:

Ben GoldacreBen Goldacre explains why doctors must have access to all trial results

Sile Lane Síle Lane talks about the importance of publishing all trials, past and present

The team from Red Banana Ltd with Richard Stephens and Sile LaneThe team from Red Banana Ltd with Síle and Richard Stephens
after relating his own experiences with clinical trials

Rob Frost

Rob Frost explains why GSK joined AllTrials and the importance of transparancy

The Flaws In Ben Goldacre’s ‘Evidence Based Medicine’ Transparency Agenda


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). 

Dr David Healy explains how they do this in an interview here:

“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.

See here: http://seroxatsecrets.wordpress.com/2009/12/30/the-seroxat-paxil-pil-over-the-years-ch-ch-ch-changes/

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 here:

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

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…?

The answer is nothing happened to Glaxo – nothing at all.”

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?

Ben Says:

“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?”

Indeed, that would be (fairly) unfair..
However, I’m not the only one to express such cynicism about GSK and their promises of transparency, see the following comments from this article about GSK’s promises..

“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”..

jmz, MD

02/25/13

“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

03/02/13

“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..”

 

GSK Transparency Has Yet To Materialize


GSK have received a lot of good press over the past year for their promises of transparency and access to data. They received particularly glowing praise by Ben Goldacre (author of Bad Pharma). However, no real transparency has actually occurred. Even if GSK did fulfill their promises- for Seroxat users and ex-Seroxat users- damaged by the drug- this will be of no use-whatsoever because GSK said they will only be giving (controlled) access to data post-2000 therefore that leaves out Seroxat data (and data for many other dangerous/dubious GSK drugs). So much for transparency!…

Good PR though..

http://www.pharmalive.com/more-drugmakers-to-join-glaxo-effort-to-disclose-trial-data

To what extent the Glaxo effort will take hold remains to be seen. Nisen says the drugmaker has, so far, received 10 proposals and about 100 inquiries for data. Already, though, Glaxo has encountered criticism. For one, there is concern that its independent panel, which was established to review data requests, is not fully independent, if only because one member previously worked as a consultant to the drugmaker (see this). Glaxo has refused such assertions.

Separately, the drugmaker is haggling with a group of researchers who want clinical study reports for an infamous study of its Paxil antidepressant. They maintain Glaxo has balked at the request and has raised doubts about its commitment to releasing data. In the process, the dispute has raised questions about whether Glaxo complied with a 2004 consent order with the New York State Attorney General to publicly disclose the Paxil trial data (more here).

 

Are Ben Goldacre and AllTrials Being Manipulated By GSK?


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.)” 

http://1boringoldman.com/index.php/2013/07/28/a-closing-argument/

a closing argument…

Posted on Sunday 28 July 2013

I’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 results
The Guardian
by Ian Sample
21 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 Details
eye·for·pharma

Market Access

by Craig Sharp
Jul 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 steps

A. 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:
      1. Mobilising patient groups to express concern about the risk to public health by non-scientific re-use of data.
      2. Engaging with scientific associations to shape the industry commitment for data sharing, and to discuss concerns about re-use of data.
      3. Work with other business sectors that are also concerned about release of trade secrets and commercially confidential data.
      4. 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:
      1. No process outlined to discuss CCI in CSRs prior to release.
      2. Raw data: unenforceable controls to ensure robust and scientifically credible secondary analyses.
      3. Requirement for anonymised raw data to be supplied at submission negates EMA’s responsibility for release of PP information.
      4. Publication of CSRs from withdrawn or unsuccessful submissions could undermine future commercial viability of product.
      5. 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…
  1.  
    July 28, 2013 | 8:11 PM
     

    Let’s hear it for enactments.

  2.  
    July 29, 2013 | 4:52 AM
     

    Great job Mickey. :)

  3.  
    berit bj
    July 29, 2013 | 7:05 AM
     

    Excellent exposure! As expected by this biased mom, as foretold by George Orwell.

    “Advocacy” they call it, lobbying the European Council and scores of big-business-friendly politicians, media, bureaucrats, big-pharma-sponsored consumer groups NAMI with sister EUFAMI..

  4.  
    Johanna
    July 29, 2013 | 7:11 PM
     

    I ran across this joint statement on “responsible” data-sharing practices from PhRMA and its European cousin EFPIA. It is a real piece of poop, of course … we will share data only with “responsible” parties in a “responsible” format. In other words, we are committed to telling you everything we think you need to know. Trust us.

    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.)

    So I hope they ask GSK: Are you standing behind this Orwellian piece of poop issued by your trade associations? If not, please stand up and say so. And if so, what the heck does it mean that you also “endorse” AllTrials?

  5.  
    a-non
    July 30, 2013 | 3:27 PM
     

    Is COI limited to pharma only?

    “OPINION: Health service researchers – are we blind to our own conflicts of interest?” Healthy Debate July 3, 2013 by

    Andreas Laupacis

    “It might be worthwhile articulating different degrees of conflict of interest. One scheme might go as follows, in order of increasing conflict of interest: 1) receipt of only operating funds to conduct the research from the payor, 2) receipt of personal salary or consulting fees, 3) receipt of funds for a research group or institute, so many individuals are dependent upon those funds for all or part of their salary and/or projects, and 4) potential to derive entrepreneurial profits in partnership with the payor. An important point here is that, except for the fourth conflict, the others pertain to both industry and the public sector.”

    http://healthydebate.ca/opinions/health-service-researchers-are-we-blind-to-our-own-conflicts-of-interest

 

 

GSK’s Seroxat Files: What are they hiding?…


Birth Defects, Suicide, Aggression, Withdrawal? …What other Seroxat side effects have GSK concealed in their clinical trial cupboards? 

http://davidhealy.org/gsks-manifesto-voyeurs-of-the-world-unite/

GSK’s Manifesto: Voyeurs of the World Unite!

October 9, 2013 3 Comments

Editorial Note: There is a widespread impression that the pharmaceutical industry are split on the issue of access to clinical trial data with the bad guys like AbbVie taking legal actions to block access and the good guys like GSK in favor of transparency. An editorial like this one from GSK’s James Shannon in the Huffington Post on September 3rd might support such impressions. See Neal Parker Avoiding Adverse Events.

Nothing could be further from the truth. A recent House of Commons report on Clinical Trials in the UK, which entols the supreme virtues of GSK at every possible turn, contains the following summary recommendation:

“We are not in favor of placing anonymized individual patient-level data (IPD) in the public domain in an unrestricted manner…  specific individuals should be provided with controlled access to IPD through carefully managed and secure “safe havens”. Access should be facilitated by an independent gatekeeper responsible for ensuring that the data … makes a useful contribution to scientific understanding”.

This is GSK’s preferred way to deny access to the data written into a House of Commons recommendation. In practice, as outlined in April Fool in HarlowGSK are offering an opportunity for voyeurism rather than the full-bodied engagement with the data that is science.

Several researchers are at present attempting to write up GSK’s most famous ever clinical trial – Study 329, a study of Paxil given to children, that led to charges of fraud from New York State and contributed to GSK’s recent $3Billion dollar fine. Despite an undertaking given to the Courts to make the data from this study available, GSK are currently refusing to do so – requiring investigators instead to apply through their “safe haven” which seems exquisitely designed to make it impossible to establish what the data actually shows. See Reading the RIAT Act. This is a space to watch.

You’d never guess at GSK’s stonewalling tactics from James Shannon’s editorial below. This editorial suggests the company is supremely confident it has successfully pulled the wool over the eyes of academics and politicians – as suggested last April Fool’s Day – See April Fool in Harlow.

___________________________________________________________________________________________

Unlocking Access to Clinical Trial Data – what are we afraid of?  James Shannon, GlaxoSmithKline’s Chief Medical Officer. Huffington Post 03/09/2013 Today thousands of people all over the world will take part in clinical trials. Why do they volunteer, willingly sacrifice their time and in some cases experience discomfort and inconvenience? Of course there is the hope that perhaps they can benefit from the medicine under the microscope. But they also do it to contribute something to the wider population – the hope that they can play their part in developing new medicines for diseases like cancer or Alzheimer’s disease that we are still trying to tackle. And I think they expect something else – when that trial is over, regardless of whether it results in a new medicine on the pharmacy shelves, they expect that the data gathered – their contribution – will be used to help others, to drive forward discovery through the scientific community learning from research already undertaken. In recent months the words ‘data transparency’ have found their way into our vernacular, with calls for pharmaceutical companies to be more transparent about their research and to publish results from all their clinical trials. The pharmaceutical industry has been the source of a great many advances and there are many people in the world today living longer, healthier lives because of the medicines researched and developed by the industry. But despite this, it is an industry which still draws criticism and concern. Historically, being open and transparent aren’t traits the industry has been famed for. We haven’t always done a good enough job to be transparent so that people trust and feel proud of how we operate and what we achieve. Increasing transparency about our research is a critical area we’ve been pursuing at GlaxoSmithKline for almost a decade. In 2004 we launched an online study register which means visitors to our website can see any trial that we are running or are about to start. We also post every set of results here, regardless of whether they are positive or negative. Since then we’ve taken more action to increase the information we share, culminating this year with our commitment to disclose detailed reports of our studies and support for the AllTrials campaign, led by Sense about Science and British doctor, Ben Goldacre. 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. It’s inevitable that some will still worry that we are hiding something. Honestly, we’re not. GSK is not alone in its drive to increase transparency, as we have seen from the growing support for the likes of the AllTrials campaign. It is obviously for others to decide the approach they take in this space but it is certainly an issue that has captured the attention of not just pharmaceutical companies but academic and public institutions carrying out research. So what could we possibly be afraid of? Concerns have been raised about greater transparency introducing a competitive disadvantage. We don’t see it. 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.” We still need new treatments to tackle diseases and there are still many scientific unknowns that stand in the way of us developing those treatments. Who knows? Perhaps increased transparency in clinical research and the sharing of knowledge and data will help solve some of our trickiest scientific questions. We hear from scientists that making more information available will be incredibly helpful – it will enable them to study the science behind today’s medicines more closely, combine data from different studies and look at how medicines can best be used. Ultimately this has the potential to improve patient care, which can only be a good thing. There is more to be done. All those carrying out clinical research, whether they are companies like GSK, academic institutions or other research organisations, have a role to play in ensuring information from their clinical trials is made publicly available. There is also a clear need for a broad, independent system to be created where researchers can access data from any trial from multiple companies and organisations. We want a truly independent organisation from the public or charity sector to take on the oversight of this and make it a reality as soon as possible. There is a lot to be gained by having that transparency at the core of how we work. I think science, society and, most importantly, patients, will be better for it. [As for scientists we figure they’ll get by looking]. –

See more at: http://davidhealy.org/gsks-manifesto-voyeurs-of-the-world-unite/#sthash.XBXbvrGb.dpuf

– See more at: http://davidhealy.org/gsks-manifesto-voyeurs-of-the-world-unite/#sthash.XBXbvrGb.dpuf

Glaxo Transparency… Plus Conflict of Interest Of Course…


http://www.pharmalive.com/glaxo-and-transparency-one-panel-member-has-a-conflict

Seven months after promising to release clinical trial data, GlaxoSmithKline has created an online system for researchers to request access to patient-level data and released the names of a group of experts who will review requests from outsider researchers seeking to examine trial data. The drugmaker maintains the effort will make it possible for outside scientists to study Glaxo data and develop their own findings about safety and effectiveness (back story).

However, one member of the panel – which is described as independent and will be tasked with reviewing data requests – has previously worked as a consultant to the drugmaker. Brian Strom, a professor of public health and preventive medicine, and also a professor of biostatistics and epidemiology of the University of Pennsylvania, received $5,500 last year, according to the ProPublica database (see the data here).

“That’s the challenge when individual companies set up their own review panels,” says a Glaxo spokewoman. “We won’t have influence over the panel decisions. We’ve said it won’t be perfect first time out, but the important thing is to be transparent about it… We’re trying to make this attempt to put this effort forward. Maybe this can accelerate the discussion about what is the right system.” She added that Glaxo wants to retain an independent third party to eventually oversee this system and, at that point, the panel may be superceded or even dissolved.

[UPDATE: Strom writes us this: “My role on the committee is completely independent. GSK does not have any say in our decisions…. The story here is someone in industry is looking to do it right. I’m an academic. I gave them advice about what this should include. This is a major scientific advance. There are big things that can come out of here, especially if other companies join… The fact that I did consulting in the past is not news… Our choices are going to be independent… I’m independent. My funding comes from an academic center… You can’t say go to industry and say get the best people in the industry and then criticize them when they do.”]

As noted previously, the move comes after years of controversy over the extent to which drugmakers disclose clinical trial data. The pharmaceutical industry has long been criticized for failing to fully make underlying patient-level data available to others who seek to verify results. Drugmakers have insisted the data is proprietary, but critics have said the reluctance to disclose such information can be a red herring for hiding unflattering results that may limit sales.

The debate has factored into numerous scandals in which drugmakers have been accused of withholding important information about side effects. Glaxo, in particular, was cited for such behavior with its Avandia drug, which figured prominently in a $3 billion settlement the drugmaker reached last year with the US Department of Justice for a number of infractions.

The feds claimed that, between 2001 and 2007, Glaxo failed to include certain safety data about Avandia in reports to the FDA. The missing info included data from post-marketing studies, as well as data about two studies undertaken in response to European regulatory concerns about cardiovascular safety. Glaxo (GSK) agreed to plead guilty to failing to report data to the FDA and to pay a $242.6 million criminal fine (see this).

In agreeing to disclose data, Glaxo also has been at odds with two industry trade groups. Three months ago, the drugmaker publicly supported the AllTrials campaign in its quest to have patient-level data released, a move that PhRMA and the Association of the British Pharmaceutical Industry have opposed (read more here).

Only one other drugmaker has taken any similar steps. Last month, Roche said it would make available data from all 74 clinical trials for its Tamiflu treatment to a team of Cochrane Collaboration researchers. That came after the drugmaker agreed to widen access more generally for clinical trial information for its medicines in response to increased pressure from academics and a widely publicized online petition (back story).

As for Glaxo, the drugmaker plans to list trials on a new web site once a medicine has been approved by regulators or terminated from development and the study has been accepted for publication. Studies that do not progress to publication will also be included. The site already includes global studies conducted since 2007. Over the next two years, global studies going back to the formation of GSK in December 2000 will be added. In addition, all studies starting in or after 2013 will be included, the drugmaker says.

The system would be run by an independent third party that would be responsible for appointing and overseeing a review panel to assess research proposals. “We are the first organization to develop a system for sharing detailed clinical data in this way. Now we want to see this initiative transition to a broader independent model that brings together data from multiple organizations,” says Glaxo pharma R&D president Patrick Vallance in a statement.

He did not offer a specific timeline for retaining a third party to run the initiative. For now, the members of the independent review panel – in addition to Strom – include Marc Buyse, an associate professor of biostatistics, Hasselt University Belgium and founder of the International Drug Development Institute; Bartha Maria Knoppers, who heads the Center of Genomics and Policy at McGill University; and John Hughes, the patient and public involvement member of the UK Clinical Research.