what’s it going to take?…

Posted on Sunday 24 July 2016

At this summer’s American Psychiatric Association meeting, Karen Dineen Wagner, president elect of the American Academy of Child and Adolescent Psychiatry discussed the treatment of depressed children and adolescents, saying:
…only two drugs are approved for use in youth by the Food and Drug Administration [FDA]: fluoxetine for ages 8 to 17 and escitalopram for ages 12 to 17, said Wagner. The youngest age in the clinical trials determines the lower end of the approved age range. So what do you do if an 11-year-old doesn’t respond to fluoxetine? One looks at other trials, she said, even if the FDA has not approved the drugs for pediatric use. For instance, one clinical trial found positive results for citalopram in ages 7 to 17…
She’s referring to a 2004 Citalopram study [in which she was the Principle Investigator and first author]:
by Wagner KD, Robb AS, Findling RL, Jin J, Gutierrez MM, Heydorn WE.
American Journal of Psychiatry. 2004 161[6]:1079-1083.
Meanwhile, based on their recent deconstruction of that same study, Jon Jureidini, Jay Armstrong, and Leemon McHenry were waiting for word from the American Journal of Psychiatry [AJP] editor Robert Freedman about their request that this same article be retracted. Dr. Freedman has now responded by email:
RE: Am J Psychiatry 2004; 161:1079–1083 We are not retracting this article. Robert Freedman MD

Had I read this story in college while I was thinking about what comes next, I wonder if I might have been so disillusioned that I would’ve made other choices? Or later when I was thinking about switching my career direction from Internal Medicine to Psychiatry, would I have made the change? It involves the president of the main organization for child and adolescent psychiatry and the editor of the official journal of the professional organization for all of psychiatry. What if I knew then that this is not just an isolated incident, but rather something more like business as usual? I can’t answer those questions, but I know for sure it would’ve mattered, just like it matters now…

The truth about this article has emerged more slowly than for its cousin Paxil Study 329. Shortly after it was published, people noticed that it had a big error in reporting an effect size [see more Wagner et al]. But in 2009 [shortly after this study was an essential ingredient in FDA Approval for use in adolescents], in a suit alleging off-label marketing, discovery documents revealed it was ghost written, that the listed authors weren’t chosen until the study was over and the article was already drafted. Also, it failed to mention another completed study that was negative [see collusion with fiction…]. That suit was settled for $149M. While the AJP published a stern note, they did not retract the article [see the jewel in the crown…].

Now, in the wake of litigation for yet another legal suit, more internal documents make it abundantly clear that  just about everything about the study was jury-rigged – including the outcome switching mentioned in wonky science…. It’s all detailed in this recent publication by Jureidini et al:
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.

Their difficulties getting this paper published are discussed in the background notes. And in addition to the internal emails, Dr. Wagner’s deposition in the case makes it clear that she never even personally reviewed the data or the statistical analyses that were published under her name [see author·ity…]. So this article is just an advertisement, deceptively written by a drug company [Forest Laboratories], not a science-based report for physicians and their patients.

Why would Dr. Freedman, editor of the AJP, send this hostile email with only six words ["We are not retracting this article"] instead of taking the mountain of information about this article seriously? Why does Dr. Wagner continue to quote this article as clinically meaningful [even promoting off-label use in children] in the face of it being so thoroughly discredited? What’s it going to take to put an end to this kind of irresponsible, deceitful behavior at the upper levels of psychiatry? Whatever it is, it’s way past due…
    Bernard Carroll
    July 24, 2016 | 8:49 PM

    There is an old saying: when you sup with the devil use a long spoon. The sort of thing you describe didn’t happen overnight. But now we are at a point where major medical journals re-cast conflict of interest as laudable synergy. It’s all downhill from there. The term ethical drug company became an oxymoron – or maybe it always was that. And the KOLs like Wagner fell in line the deceptions, which indeed had become business as usual.

    “There are many fine points to medical ethics, and some difficult puzzles, but the most rudimentary morality is the line between the guardian and commercial (traditions). It’s as crucial that physicians understand it as it is that lawyers recognize that when they go into guardian service they can’t morally also be in service to clients seeking to influence legislation or regulatory decisions.” [Jane Jacobs. Systems of Survival, Random House 1992]

    donald klein
    July 25, 2016 | 4:21 AM

    The issue is, “what will it take ?” Currently critiques
    of scientific and KOL distortions re pharmacotherapy seem limited to our small group-the names of comment providers are quite familiar. That isn’t sufficient to raise enough public concern. Also it gets buried under conventional wisdom propaganda.
    Is there was some way to compare the impact of various groups that ,on a science basis , are against the conventional wisdom ,like
    dawkins re evolution,critchen re atheism,Trials re trial transparency. Sure have left some out.
    They are doing a better job in getting to the public than our discussions— which boils down to media coverage. .
    So should we learn from them, imitate, attempt to form united fronts or what?
    (The idea of public blogs ,perhaps limited to more than 26 words and a conclusion , seems one possibility but may be ineffective).
    That needs a different discussion if we are to get past our quite correct critiques. That may be what it takes.

    July 25, 2016 | 11:29 AM


    A very thought provoking comment. Something all of us need think about.

    July 26, 2016 | 3:25 AM

    Well, I had a punk rock song about dysthymia accepted for an exhibit at the Whitney museum in New York.

    I wrote to AllTrials and asked if I could donate a small percentage of CD sales to them. Till Bruckner and the crew listened to the song, and said it was fine, gave me a copy of the logo to use and everything.

    Wish I could get AllTrials mentioned in the actual exhibit somehow– maybe it’s possible. The show opens in a couple of days, I’ll see what it’s like when I’m out there. Hopefully, I can get the logo uploaded to the page of CD Baby that will be selling the song– maybe bring a little new traffic to the AllTrials website anyway.

    The “public” per se will probably not care– at least for now– as Donald says. But the artists and rockers and punks and queers and the warrior therapists and social workers– they might.

    berit bryn jensen
    July 27, 2016 | 8:36 AM

    What will it take? Never give up. We shall overcome some day… Unsustainable systems, huge systems of snake-oil sellers shall fail and fall when the affected and concerned citizens keep on challenging their myth of easy fixes to life’s complexities and suffering. I stayed up last night to watch an American documentary about the Hillsborough disaster in Sheffield in 1989, when 96 people were crushed to death and 766 were injured. Official cowardice, prejudice, bias, blame and lies blotting out the truth until quite recently. institutionalized injustice, institutionalized complacency and downright fraudulent massaging of facts reported correctly by ordinary police witnessing unfolding tradegies, while their boss crumbled and froze and did not issue the orders necessary to stop the carnage by concerted police action. Lies put the blame on the victims, mostly young soccer fans from Liverpool, children of ordinary working folks. Perseverance in the face of all this by the bereaved, their support group and solidarity brought 30.000 to the 20th yearly commemoration. Google and watch. I sat transfixed listening to the voices of victims and to professor Phil Scraton, whose book Hillsborough: The Truth I’ll read for more lessons. We are up against similarly institutionalized corruption and injustice, enormous losses in lives, health and wellbeing. Do keep up the good work, dr Nardo, and thanks!

    July 27, 2016 | 11:46 PM

    Mastery of the media is a critical element. After all, the dominance of the pharmaceutical industry is not due to their superior products, but to their expertise in getting a particular message out to the public. They are aided by the vast sums of money they can spend, but huge amounts of money are not essential. Look at the media profile of “Occupy Wall Street” or “Black Lives Matter” or any other group willing to organize, and make a noise about a deep injustice in our society. If we organize, and if we tell the public why they need to be concerned about the profound level of misinformation given to them and their physicians, and what they can do about it, why, then we might have a societal change on our hands.

    July 28, 2016 | 1:51 PM

    1bom, Hope you find it of interest to comment on this:
    The part on the limitations of clinical trials is particularly interesting.

    James OBrien, M.D.
    July 28, 2016 | 1:52 PM

    The science is either good or bad.

    It should have nothing to do with politics, except that the APA is hyperpolitical.

    The APA or AACAP is not the government, no one has to join or pay dues, but many have been brainwashed that they do.

    Asking the establishment to change is a waste of time. The APA is run by log-rolling joiners. The solution is to form a better organization, like the psychologists did.

    I get why the entrenched act the way they do, what I don’t understand is the seal clapping obsequiousness of the rank and file who throw hard earned cash and praise at them.

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