"Glaxo and its transparency commitment
By Ed Silverman
For the past year, GlaxoSmithKline has vowed to usher in a new era of transparency by creating a system to disclose detailed clinical trial data. This widely publicized move has been hailed by many critics of the pharmaceutical industry who have accused drug makers of deliberately concealing vital information that should be accessible to others in order to confirm safety and effectiveness.
Now, though, a group of researchers is putting the drug maker to the test by requesting detailed data for an infamous study of its Paxil antidepressant, but are squabbling with the drug maker over information being sought. In the process, the dispute is raising questions about whether Glaxo complied with a 2004 consent order with the New York State Attorney General to publicly disclose the Paxil trial data.
At issue is data for Study 329. Glaxo participated in preparing, publishing, and distributing what U.S. authorities called a misleading medical journal article because the results reported that a Paxil clinical trial demonstrated efficacy in treating depression in patients under age 18, when the study actually failed to make the case. The trial missed its endpoints and also figured in a ghostwriting controversy.
For more than a decade, the study has haunted Glaxo after it became known that suicide risks in what was one of the best-selling antidepressants had been minimized. The episode, which led Glaxo to the 2004 consent order, factored into the $3 billion settlement with the U.S. Department of Justice last year for illegal promotion and pricing activities. For its part, Glaxo maintains it has fully complied with the order.
However, a loose-knit group of researchers led by Jon Jureidini, a child psychiatrist at the Womens and Childrens Hospital in Adelaide, Australia, and a professor in psychiatry and pediatrics at the University of Adelaide, is haggling with Glaxo over certain data referred to in the consent order. They maintain the drug maker has balked at their request and raised questions about its commitment to releasing data.
The tussle underscores the ongoing tension over the extent to which certain data notably, anonymous patient-level data can or should be released. Recently, a group that includes academics and consultants some of whom are affiliated with the Multi-Regional Clinical Trials Center at Harvard University suggested an independent panel should be created. And in a recent essay in The Lancet, Glaxo R&D chief Patrick Vallance and Iain Chalmers one of the founders of the Cochrane Collaboration argue that open access to this detailed data poses many risks.
But according to the researchers, Glaxo is using this as a smokescreen. The company has come up with the perfect way to appear to be transparent while making actual access to data close to impossible, David Healy, a psychiatry professor at Bangor University in Wales and frequent industry critic who wrote Let Them Eat Prozac a book about the marketing of antidepressants tells us. The group has been writing to (Glaxo CEO) Andrew Witty et al and getting nowhere really.
The researchers plan to provide the correspondence with Glaxo to BMJ, one of the sponsors of the AllTrials campaign that was launched earlier this year to prod drug makers into releasing trial data. In their view, public pressure is needed to convince drug makers to release clinical trial data. For instance, Roche agreed to release data for the companys Tamiflu treatment after its correspondence with researchers was published in BMJ.
I dont think its a coincidence that the only two pharmaceutical companies which have got a policy on access to previously confidential trial data are Roche and GSK. In my mind, this shows the power of the media and academia, BMJ and the Cochrane group if used in a responsible and balanced way, says Tom Jefferson, an epidemiologist with the Cochrane Collaboration, who tussled with Roche and is advising the researchers who are seeking Study 329 data. The BMJ is a can opener it exposed this to the world.
By publicizing the dispute, the researchers hope to demonstrate that Glaxo is failing to live up to its commitments. Jureidini, by the way, also sought to have Journal of the American Academy of Child and Adolescent Psychiatry, which published Study 329 in 2001, disavow the study and issue a retraction, but the journal has repeatedly refused to do so.
Although the researchers have not yet released the details of their correspondence with Glaxo, one issue they have raised, and which some describe as central to the dispute, is the extent to which the drug maker is making all data available in accordance with the consent order. And this apparently hinges on the definitions of various terms used to describe the requirements Glaxo must follow.
For instance, page 7 of the order says, beginning in February 2005, Glaxo must provide public access to the clinical study reports of Paxil as a treatment for major depressive disorder in the pediatric population for a 10-year period. An attached document defines clinical study report as including all data. And data is defined as all the results and outcome measurements obtained from a clinical study.
The researchers note the page on the Glaxo Website housing 329 Study data lists several appendices, but one Appendix H is just four pages and lists only patient identification numbers found in case report forms for patients who experienced serious adverse events that led to withdrawal from the trial. This information was reported to regulators. One page has a table with the intent-to-treat population.
The researchers are questioning whether this omission violates the 2004 consent order. They point out that Glaxo has already redacted certain information that was contained in the other appendices that are publicly posted, and believe that the drug maker should do the same for Appendix H, rather than, essentially, not post any of the information.
We asked the New York State Attorney General whether this constituted a violation and a spokeswoman would not address the specifics raised by the researchers, but tells us that the office is continually monitoring compliance and, in this instance, continues to monitor the Glaxo consent order. She adds that researchers are free to file complaints if they believe a violation has occurred.
For its part, Glaxo maintains that its newly launched Website contains the necessary data for the researchers to analyze Study 329, although the site does not publicly disclose case report forms, which are the files that were used to collect data from each patient, because these contain information (such as names) that can readily identify the patients concerned, a Glaxo spokeswoman explains.
And she adds that the press release from the New York Attorney General, which contains links to the consent order and related documents, refers only to the clinical trial register. And the CTR, she explains, posts only summaries and nothing with the level of detail that is found clinical study reports or clinical report forms.
The clinical study reports for Study 329 already are posted on our Website; the data that Study 329 was set up to obtain is contained in the CSRs and the associated appendices posted on our website; and the anonymized patient-level data is available through the online system we launched in May, the spokeswoman writes us.
As you know, any request to that site is reviewed by a panel at arms length from GSK and researchers who have a legitimate trial question and protocol, and commit to publishing their results, are likely to be granted access to the anonymized electronic data they request, she continues. We believe that with the information already available on our website and if he submits a request through our online system to access the patient-level data, Prof. Jureidini will have what he needs to complete his new analysis.? We have fulfilled our commitment to public access by posting on our website the Clinical Study Reports and associated Appendices which contain the results and outcome measurements from the studies. For access to anonymized patient level data in an electronic, analyzable database, we require a research proposal to be submitted which is reviewed by an Independent Review Panel. Where approved, access is provided in a secure website, she concludes.
In other words, a great deal of parsing is under way. And much of this hinges on the understandings that occurred at the time the consent order was reached, as well as the extent to which Glaxo can or should provide redacted information referring to patient-level data.
Posted: December 2013 "