paxil study 352: plausible deniability…

Posted on Wednesday 5 December 2012

    The kind of ghost-writer we’re talking about is tasked to produce a particular type of illusion. Here are the rules:

  • The article must look and feel like a scientific study using appropriate logic and format.
  • The article must be based on the genuine data set of the study. 
  • The conclusion of the article must confirm the original hypothesis or some acceptable alternative…
  • The data set does not actually support a desirable conclusion [or, perhaps, any conclusion], and specifically doesn’t actually support the conclusion of the article.

    I intentionally left out one of the rules for a ghost-writer of the type being discussed here:

  • Whatever device is used to make the article confirm the original hypothesis or some acceptable alternative, it must have a ready explanation that it was not what it actually was – a trick. This is called PLAUSIBLE DENIABILITY.

Most of us learned about PLAUSIBLE DENIABILITY from the political arena. Karl Rove says, "I did not leak her name" referring to Valerie Plame, the CIA Agent he outed to a reporter to discredit her husband Joseph Wilson. What he actually said to the reporter when he outed Ms. Plame was "Wilson’s wife" [not her actual name]. President Clinton cracked us all up when he stretched the limits of plausibility, "I did not have sex with that woman" [oral sex apparently didn't count as sex in Hope Arkansas]. So, for the ghost-writer, the playing around with numbers needs to be explainable, even if the true authorship is revealed.

In the case of both Paxil Study 329 and Paxil Study 352, the data package went directly to Sally Laden at Scientific Therapeutic Information [STI], was turned by her into a first draft, was edited by GSK, and only then was sent to the KOL who would be among the listed authors. In the case of Study 352, we know that they only saw these later drafts and that the first author, Dr. Charles Nemeroff, was chosen by GSK late in the process and may have never seen the manuscript until time for submission:
The paroxetine 352 bipolar trial: A study in medical ghostwriting
by Jay D. Amsterdam and Leemon B. McHenry
International Journal of Risk & Safety in Medicine 2012 24:221–231.

"… Many of the named authors on the published article had little or no direct involvement in the design, daily conduct, data analysis, or writing of the initial manuscript drafts. In fact, some of the authors were only selected for this role once the ghostwriters began to draft the manuscript from the final study report or a summary provided by GSK. It appears from the available evidence that GSK and STI had originally chosen Dr. Laszlo Gyulai, then Assistant Professor at the University of Pennsylvania, as the paper’s first author. However, Dr. Gyulai was subsequently removed from this position by GSK and replaced by two other authors who were assigned by GSK to the first and second positions on the paper. The evidence also indicates that the final GSK-assigned authors on the published article never reviewed or even saw preliminary drafts of the paper, and only saw the final edited manuscript just prior to final acceptance by the American Journal of Psychiatry."
The point here is that the data presentation [and manipulation] was the work of Sally Laden herself, something she admitted freely in court testifying about Paxil Study 329 [the lesson of Study 329: the authors…]. The job of this kind of ghost-writer is to come up with a way to write the article and stay within the framework of the rules laid down at the beginning of this post – way beyond editorial support or Dr. Nemeroff’s covering lie [following his exercising a PLAUSIBLE DENIABILITY option]:
Nemeroff, the paper’s first author, says that the data used withstood rigorous peer review in a process that sent the paper back to the authors for revisions several times. "Right in the abstract under ‘results’ we report that ‘Differences in overall efficacy among the three groups were not statistically significant’," he says. "I don’t know how much more straightforward we can be than that. "He adds that "with a 2011 magnifying glass, obviously one would have included in the published paper the use of an editorial assistant". Still, he says: "All [STI] did was help collate all the different authors’ comments and help with references. We wrote the paper."
In fact, the PLAUSIBLE DENIABILITY is all through the article, the pieces quoted in the last post spread around in the text. They refute the conclusion, but only the close reader would ferret them all out. To the casual reader, they’re flotsam and jetsam, lost in the words. But they’re all there in case anyone asks, usable for rebuttals such as Dr. Nemeroff’s.

Now, we’re in a position to guess why this article is missing the expected graph of the treatments and placebo over the timeline of the study. There was no separation and that’s clearly stated throughout the article. So why leave it out? In the Protocol, they even say they’re going to show it [last sentence]:

My guess is that if they showed us their advertised graph, they’d be expected to show a similar graph of the High Lithium Strata versus the Low Lithium Strata, the artificial post hoc comparison that they are calling significant, and we’d be able to immediately tell that it’s not a meaningful conclusion. That’s how this kind of ghost-writing works. In Paxil Study 329, they didn’t show us a graph that makes it immediately apparent that a value they base their significance on is an outlier, a spurious value that didn’t characterize the data accurately [our real scientists…]. GSK can easily disprove my speculation by releasing the raw data from Paxil Study 352 like they were forced to do with Paxil Study 329. If I’m wrong, I’ll publish my apology in all capital letters, in bold type.

Just one more comment about this kind of ghost-writing. It’s hard work, fulfilling the requirements of all those rules. One has to run the numbers all kinds of different ways until you find something you can use. Then you have to figure out how to present it as credible. Then you have to jury rig what’s omitted and included all the while insuring PLAUSIBLE DENIABILITY. It’s hard not to leave behind signs of all that activity. This article has something that might be such a sign. In the quote from the Protocol above, it says, "… no data are carried forward to estimate missing data points." And yet in the Results Database on the site, the headings for the Data Tables say:

LOCF stands for Last Observation Carried Forward, which has nothing to do with the table as it’s presented. I’d speculate that’s left over from some former use of the table as they searched for something of significance. Who knows? It’s sure an odd heading for the table as it is now, particularly with them saying they weren’t going to do that in the Protocol.

So why bother to get all paranoid and dissect this 11 year old article looking for chinks? Well, for one thing, the first two authors are Chairmen of respected psychiatry departments. For another, it’s published in America’s top psychiatry journal. The main author didn’t have anything to do with writing it and lied about that to Nature. It’s supposed to be a peer-reviewed journal and yet the facts to refute the conclusions given in this and the last post are peppered throughout the article for any close reader to see. And it is way too carefully crafted to be anything other than a planned deception. How’s that for starters?
  1.  
    Bernard Carroll
    December 6, 2012 | 3:04 AM
     

    The authors had to submit 3 times before this report was accepted by American Journal of Psychiatry. One would like to see how the reviews shaped the drafts of the manuscripts. Before we believe Nemeroff’s statement to Nature that “We wrote the paper” one would want to see hard evidence of his input from the beginning. STI and GSK must have that information, as well as the reviews from the journal, so why will they not disclose it?

    If memory serves, the Associate Editor of American Journal of Psychiatry who handled the review of this report was Jack Gorman, MD. He is now disgraced, but in 2001 he was a well known crony of Nemeroff.

    The published report says it came “From the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.” Oh, really? Was this ghost written publication used to burnish the publications record of Dr. Nemeroff’s department? That would be a joke. How he may choose to misrepresent matters on his own CV is one thing, but I doubt the Emory administration is happy about receiving credit for this compromised article.

    The published report lists no fewer than 20 collaborating study sites. These sites recruited only 112 patients into the Intent to Treat cohort… over 5+ years… that’s approximately 1 case per year per study site. And still after 5 years the study was underpowered! Um, what does that say about the engagement of the investigators? And if they were not engaged, what does that say about the likely quality of the data? No wonder GSK decided to bring in STI – these academic turkeys from Nemeroff on down could not be relied upon to get their act together. It almost makes one want to feel sorry for GSK.

    Is this an instance of the much defended essential academic collaborations with industry, without which the pipeline will run dry? Or was GSK ripped off by these academic entrepreneurs? Either way, no essential advance resulted from this deeply flawed project that was executed by the finest KOLs money could buy.

  2.  
    December 6, 2012 | 8:00 AM
     

    I wasn’t aware of the Jack Gorman connection but it sure makes sense. He was more that a crony, he was on the GSK payroll. I culled the 2001 projects from a list of Scientific Therapeutic Information [STI] projects with SKB/GSK. They were doing a brisk business that year:

    STI GSK Projects 2001

    Quite a line-up! There’s Nemeroff and Schatzbergs Handbook, a Social Phobia Trial by Liebovitz et al in the Journal of Clinical Psychiatry, Paxil Study 329 by Martin Keller et al, and Paxil Study 352 by Nemeroff et al for starters. Then there are various projects for the Anxiety Disorders Association of America, a group specifically pushing Paxil for Social Anxiety and GAD [everyone listed here was involved with the ADAA]. Before his fall from grace, Dr. Jack Gorman was an active KOL for GSK/Paxil pushing Paxil for GAD [Disorders Made to Order]. Also listed: Karen Wagner, an author on Study 329, and Mark Rapaport, current chairman at Emory. And then there was training for the GSK Speaker’s Bureau.

    Kind of hard to imagine…

  3.  
    December 6, 2012 | 9:05 PM
     

    The GSK clubhouse!

    As I recall, “plausible deniability” was coined to describe the firewall around Reagan protecting him from blame in the Iran-Contra scheme.

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