Study 329: The Data
The text below reproduces the latest page from the Study329.org site. The links mentioned here will become live on the site once Restoring Study 329 is published late Wednesday – early Thursday next week.
In 2004 as part of the resolution of a fraud action taken by New York State, GlaxoSmithKline agreed to post the data from all their studies on the Company Website. They posted lengthy Clinical Study Reports (CSRs) for all the pediatric antidepressant studies (Paxil). They also posted shorter Summary Reports on Avandia and other drugs.
There are two CSRs for Study 329, one for the Acute Phase (528 pages) and one for the Continuation Phase (264 pages).
Clinical Study Report 329: Acute Phase.
Clinical Study Report 329: Continuation Phase.
In January 2012, Peter Doshi noticed that the CSRs for Study 329 referred to a number of Appendices (A to H), but that these were not present. He wrote to New York State’s Attorney General’s Office who contacted GSK. GSK agreed to post Appendices A – G, but Appendix H was posted without content.
Appendix A: Protocol & Related Material (952 pages).
Appendix B: Patient Data Listings (640 pages).
Appendix C: Efficacy (660 pages).
Appendix D: Adverse Events (224 pages).
Appendix E: Vital Signs (89 pages).
Appendix F: Laboratory Values (856 pages).
Appendix G: CRF Tabulations by Patient (2073 pages).
Appendix H: [Empty Shell]
The original coding used by GSK was from an obscure, inaccessible coding dictionary. The Study 329 RIAT Team believed that a more modern and widely-used coding system was more appropriate, and so they re-coded all the adverse events.
Originally, GSK posted all Appendices as PDF documents. Eventually, with the exception of Appendix H, GSK did provide the data in electronic form to the team. For the harms of treatment, we had already created our own “live” spreadsheets which contain both GSK’s codes and the RIAT team coding side by side. These can be downloaded and analyzed. Having the data available is important for debating the meaning of observations, challenging approaches taken and spotting errors.
The most difficult challenge lay in getting access to the data in Appendix H. Appendix H contains the individual patient level data in the form of Clinical / Case Report Forms (CRFs). There are roughly 77,000 pages – between 200-300 pages for each of 273 patients. The correspondence with GSK between December 2013 and March 2014 reveals the negotiations that took place to get access to this data. Click here to view the correspondence.
The Adverse Harms Data Spreadsheet re-created by the 329 RIAT Team contains material from Appendix H which gave rise to adverse events not listed in the original Appendix D. To make the data usable, the Study 329 RIAT Team had to create Excel Spreadsheets and re-enter the data.
GSK also granted access “for audit purposes” to Appendix H, the CRFs. Even though all patient names and details were redacted, this access was not in the form of a PDF. It was through a “periscope” – a remote access portal that reached into GSK and allowed Joanna Le Noury to scrutinize the 77,000 pages individually without being able to print or download them. She had to make manual notations for each document.
We used the R environment for statistical computing and graphics for this Study. Under our data access agreement with GSK, we cannot post the data. Consequently, the RIAT team is unable to provide direct access to this data. However, the full efficacy data is available in a PDF format. (See Appendix B, C, & D above)
Click here for our Harms Data Spreadsheet.
Click here for our Patient Demographics Withdrawal Reasons Spreadsheet.
Click here to view the basic form use for the files imported into R for the analysis, followed by the code for the calculations.
Click here for the Data Sharing Agreement between GSK and RIAT.
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David,
re: ” Appendix H contains the individual patient level data in the form of Clinical / Case Report Forms (CRFs).”
Are there sign off notations on each of these CRFs? Is the credential of each reporter known?
What is the level of expertise required by the reporter who reviewed and evaluated the significance of the adverse effects recorded in Appendix H?
The “periscope” you describe as the remote access portal to Appendix H bears a strong resemblance to the restricted access policies imposed by the Juvenile Court here in Boston, with regard to medical records, secured by court order at the request of attorneys representing the family of a young patient who had been declared a “ward of the state,”
Attorneys can view the records in a monitored room in the court house for a prescribed period of time. Attorneys are allowed only legal pads and pens– no electronic devices, for making notations. To further impede this vital process, it is common practice for the medical records to be shuffled out of sequence, then stuffed into as many uncoded boxes as needed to contain up to a year’s worth of medical records. Apparently, there is no law, or established legal guidelines that prohibit such blatant attempts to impede the review process of confidential documents. Institutions who are under scrutiny must take a certain amount of delight in knowing everything == literally everything they can get away with!
The”” here “” links are not working at my end……
Amazing the lengths they will go to to hide the truth, I wonder how many documents have been rewritten, before being supplied?
the links will be active on Thursday
DH
Oh. I thought you were just trying to give readers first-hand experience at the frustration of not being able to access data.
Looking forward to reading on Thursday.
And thanks for all you’ve put into this.
It will be very interesting to see this..
If GSK’s periscope is their idea of transparency, then surely they should go back to the drawing board with Ben Goldacre and Alltrials?..
Transparency is supposed to give easy access to information not obstruct it..
Well done on managing to achieve a re-interpretation of this Paxil (Seroxat) study despite these major road blocks…
Shelley’s (full) interview with Mina Dulcan is priceless, nae golden!
Well done David for cutting through the lies, somehow the word lies feels impudent,it doesn’t cover the magnitude of what is being done.
Can anyone tell me if Stewart Hosie MP is worth going to with a claim just asking on behalf of a good friend.
Angus
Yeah, all this is very positive, and by the sound of it it will show pretty much the opposite of the original publication.
Now I wish for some unity.
Unity behind this team of Healy, Nardo, le Noury and the others.
From who? Well, anyone who wants future (and past) studies to have access to the full raw data.
Let academics argue over conclusions made from raw data, not over marketing-spun Words in “abstracts” or “conclusions”.
And if something isn’t “safe and efficacious”, do not ever bring it Close to any human recipent!
I really hope this wakes up some doctors from the lies they are being told. It’s enough already
Thank you and your colleagues’ for your relentless pursuit of the whole truth. If this was the way Paxil clinical trial outcomes were handled in the past, was that what gave drug companies tacit approval (freedom from repercussions) to put other similar iterations of these drugs on the market? Is there no end to this? No day of reckoning? No way to compensate people for their destroyed lives? Why is Effexor still on the market? Why is Abilify marketed as a booster drug when the never, ever to begin with antidepressants’ ability to deaden emotions would wear off? Why, why, why?
Thank you for everything you and your colleagues have done. For not giving up and pursuing the truth.