Posted on Tuesday 16 August 2016

Ignorance is a state of being uninformed [lack of knowledge]. The word ignorant is an adjective describing a person in the state of being unaware and is often used to describe individuals who deliberately ignore or disregard important information or facts.

    ig·nore (ïg-nôr′)
          To refuse to pay attention to; disregard.

It’s telling that the words ignorance and ignorant come from the verb ignore, implying a chosen version of not knowing. It certainly comes up a lot in matters surrounding clinical trials. For example, the rules for  preregistration or resuls posting on clinicaltrials.gov or preregistration of outcomes as a prerequisite to being considered for publication have been regularly ignored [see the wrong tree…]. Long before we conceived of our RIAT reanalysis of Paxil Study 329, I made a formal request to the Ethics Coimmittee of the American Academy of Child and Adolescent Psychiatry. The committee [and the president-elect] responded, investigated, and told me that the question would be discussed at their yearly meeting. Nothing happened and it was not discussed. I later learned that the editor, Andres Martin, found out and insisted they have no more contact with me [ignored, disregarded] and that was the end of that.

In general, the major organizations [AACAP, APA] have ignored distortion of clinical trial reports in medical journals, including their own official journals when it has been pointed out. In spite of our reanalysis, that paper’s notoriety, and the $3 B settlement, the  Study 329 article still sits in our literature – unretracted. And now, there’s another obvious candidate – the Citalopram trial in children and adolescents called CIT-MD-18. The recent article about that paper reveals how it was actively distorted by the sponsor – Forest Laboratories [see this tawdry era…]:
by Jureidini, Jon N., Amsterdam, Jay, D, and McHenry, Leemon B.
International Journal of Risk & Safety in Medicine, 2016 28[1]:33-43.

OBJECTIVE: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States.
METHODS: Approximately 750 documents from the Celexa and Lexapro Marketing and Sales Practices Litigation: Master Docket 09-MD-2067-[NMG] were deconstructed.
RESULTS: The published article contained efficacy and safety data inconsistent with the protocol criteria. Procedural deviations went unreported imparting statistical significance to the primary outcome, and an implausible effect size was claimed; positive post hoc measures were introduced and negative secondary outcomes were not reported; and adverse events were misleadingly analysed. Manuscript drafts were prepared by company employees and outside ghostwriters with academic researchers solicited as ‘authors’.
CONCLUSION: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety.
The authors wrote the American Journal of Psychiatry where the original article is published requesting a retraction of Wagner et al’s A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents. That letter is in the Background Notes, and it received only this terse, belated reply:
RE: Am J Psychiatry 2004; 161:1079–1083 We are not retracting this article. Robert Freedman MD
In a rational world, one might think that an editor might be embarrassed a bit, but generally be glad to hear about an article that’s as far in left field as this one and look into it – particularly an article he himself had censured in the past for undeclared ghost-writing and omitting a negative european study [see collusion with fiction…]. By the way, throw in its centrality in a pricey legal suit [Drug Maker Forest Pleads Guilty: Will Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations]. But Freedman’s disregarding imperative [We are not retracting this article] is anything but that kind of response – more in the range of a scowl in text.

So the authors appealed to a higher power, Maria A. Oquendo, M.D., President of the American Psychiatric Association. Dr. Oquendo appears to be one of the good guys, able to have a distinguished and successful academic career without the taint of KOL-dom like her predecessor as Chairman at Penn, Dwight Evans [on Senator Grassley’s list of COI violators among other things]. That letter is posted here on this blog [a time for change…], and cosigned by a number of impressive people [and others]. It has been two weeks since it was sent, and there’s been no response yet.

Juriedini et al’s Deconstruction of CIT-MD-18 is substantively different from our Restoring Study 329 article, even though they’re in the same genre. Ours was a reanalysis, and while we were able to access the Raw Data and definitively show it was a negative study, the RIAT format didn’t allow for the subpoenaed emails that expose internal goings on. The CIT-MD-18 Deconstruction brings the corrupt processes out into the light of day as well as showing that this trial was also negative. This paper is important for two reasons: this study was part of the FDA Approved indication in adolescents AND it doesn’t have the negative notoriety of Paxil Study 329. In fact, first author Karen Dineen Wagner used it in her presentation of antidepressant use in kids at the May 2016 APA meeting. So its findings are still very much in use [see what’s it going to take?…].

It’s time for the upper levels of academic psychiatry and journal editors to stop ignoring these corrupt clinical trial reports that literally haunt our literature, moving forward as if none of what happened ever really did happen. They have tainted the reputation of the specialty and the profession in general. These papers sit in the literature like rotten fruit in a barrel and they’re not going to go away. This particular study is unusually influential and must be dealt with. As for the authors, "don’t do the crime if you can’t do the time." I suspect that many of them had no idea what they were signing on to, but that’s no excuse. In the case of Dr. Wagner, the first author [and principal investigator], by her own testimony she neither looked at the whole data set nor checked the statistical analysis [see author·ity…].

So the task before Dr. Oquendo is a big one. Is she going to stick her head in the sand? ignore the obvious? or step up to the plate?…

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