the days of faux blockbusters…

Posted on Thursday 5 September 2013

tar·get [tärgt]
     noun
     Something aimed or fired at.
nov·el [nvl]
     adjective.
     Strikingly new, unusual, or different.

I suppose a slang can arise almost anywhere. Until I started nosing around the tangles in psychiatric medications a few years back, I’d never heard these words used as I hear them now, certainly not in tandem – eg a novel target. Maybe they’ve been around forever in the domain of drug development, but they were new to me. At first, I thought targets were the various receptor sites I knew about, but I think  targets are any known or unknown processes where a drug might have an effect. I first heard the word novel used by Dr. Nemeroff in a presentation back when he was at Emory. He used it repeatedly, as if it had some almost mystical meaning. But nowadays, I read it all the time – particularly since the great hue and cry went up that the pharmaceutical companies were pulling out of CNS drug development. Throw in the phrase, me too, and you’ve probably got enough of a vocabulary to pass yourself off as  an insider at a psychopharm meeting. Aside: Who would’ve ever guessed that me too was the opposite of novel?

The thing that got me going on these words was the title of Dr. Hickie’s paper mentioned in that last post [Novel melatonin-based therapies: potential advances in the treatment of major depression]. As Adam mentioned in his comment, Dr. Hickie is well known internationally, and in Australia he’s a star. It’s not surprising that he would be asked to write a review in the Lancet on a subject of interest to him. But it’s beyond surprising that he would lend his name to an article so clearly in the infomercial class that put a positive spin on questionable data. It would seem that the stream of letters protesting the article from impressive international quarters was as predictable as rain. It’s the kind of article that filled our journals earlier – before the extent of the pharmaceutical interference in the psychiatric literature was so well known and before systematic meta-analysis was widely applied. In my speculations about why Hickie or Servier [maker of Agomelatine] would risk a publication like this, I wondered if maybe they thought that the hunger for drugs with a novel target was so great facing a pipeline that was running dry of me too drugs that they could get away with such an article.

Looking back at my own posts after this article was published, I found a timeline I had pieced together in January 2012 [see long overdue…]:

TIMELINE


July 26, 2009:   
Lancet review article submitted for publication
November 5, 2010:   
Hickie speaks at a Servier Masterclass recommending Agomelatine in Depression
April 11, 2011:   
Hickie quoted as part of Servier Press Release when Agomelatine is approved
May 18, 2011:   
Lancet article published online
August 13, 2011:   
Lancet article published in the journal
November 7, 2011:   
US approval effort for Agomelatine abandoned
January 21, 2012:   
Six letters published in the Lancet disputing the claims made by the article

Going over the timeline, I had a further thought. When I look back on what I was writing about at the time this article was submitted, it had nothing to do with psychiatry, psychopharmacology or the pharmaceutical industry. I was a political blogger preoccupied with the ramifications of the Iraq War and the economic crash that came at the end of 2008. I knew about Senator Grassley’s investigations and that the chairman at Emory [my University] had been fired for unreported income, busted along with some other prominent psychiatrists. But I still hadn’t realized that was the tip of an iceberg of corruption that had fingers that reached into the heart of psychiatry and the drug industry.

In June 2009, I had read that a second Emory faculty member, Zach Stowe, had been busted for improprieties [strike two…] and wrote:
I know that this report is particularly disquieting to me, as a faculty member who used to be there full time. And I’d love to find some way to see this as an exception, but this is the second time in one year [Dr. Nemeroff in October 2008]. I sure hope this is the bottom of the barrel…
I still hadn’t figured it out – that this wasn’t just a piece of corruption at one place [that happened to be my former place], this was a specialty-wide [maybe medicine-wide?] collusion between the commercial interests of PHARMA and academic medicine. At that time, I would’ve thought of a pipeline as something coming from Alaska, a hickie as a visible remnant of an adolescent kiss, and the word novel as a noun preceded by "mystery" or "summer beach." And it was also around the time I had begun to volunteer at a local clinic and was seeing the bizarre medical regimens people were on, ordering textbooks to see if they might help me see why [no help, I might add].

I have no idea why there was an almost two year gap between the submission of this article and its initial publication. There are a number of references in the article from 2010 and even a couple from 2011, presumably added during the editing process, but this article was born in an earlier time even if it was only four years ago. So maybe the reason I was thinking that this article was an anachronism, a relic from a former time, is because that’s exactly what it was. It obviously changed over the course of time, but it never escaped the kind of loose science people had gotten away with for years. I know I felt the same thing about the DSM-5 Task Force, that they had set their path in 2002, and were never able to change gears.

Of course that’s no reason for Ian Hickie to sign on to something like this. He should’ve known better in 2009 [or any other time in history]. But still I like my new theory. At the least, it reminds me how far things have moved in a relatively short period of time. Within six months of publication in the Lancet, the journal was publishing six scathing letters:
… and the Lancet Editor, Richard Horton, was publicly tweeting [it’s about time…]:
[1] Tomorrow, we are very heavily criticised for publishing a review on melatonin-based drugs for depression. Biased and overstated, say many.
[2] The bias in this paper is very disturbing – it might be fine to argue your case in a Viewpoint or letter. But…
[3] …this paper purported to be an unbiased review of a new drug class. Peer review improved it, yet not enough.
[4] As troubling is the fact that one author took part in speaking engagements for the company making one of these drugs.
[5] It is this kind of complicity that damages any hopes of a positive partnership between medicine and industry.
Now there’s a definitive meta-analysis published in a prominent journal that leaves little question about the drug’s efficacy [a breath of fresh air…]. Certainly, this is no sign that the problems are solved, but it’s progress. And re-establishing the integrity of the academic journals is a major part of any future solution. The search for novel targets will undoubtedly continue, but at least the days of faux blockbusters may be behind us…
  1.  
    Bernard Carroll
    September 6, 2013 | 1:42 AM
     

    In the early days, infomercial commentaries pumping Pharma products were pretty blatant. As scrutiny increased, we entered an arms race period, in which each side tried to outwit the other. The Hickie review of agomelatine is the apogee of that process. It began with an elaborate review of basic science issues, then segued to the clinical trials, which were not candidly appraised, as my letter to Lancet pointed out. At least the FDA had the good sense not to approve this stupid drug. The current meta-analysis from Corrado Barbui’s group should be the nail in the coffin.

  2.  
    September 6, 2013 | 2:01 PM
     

    We can only hope, Dr. Carroll.

    Unfortunately, history shows those were real blockbusters profit-wise, but faux drugs therapeutic-wise.

  3.  
    wiley
    September 6, 2013 | 3:06 PM
     

    A study at PLOS addressing authorship bias in risk-assessment

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0072484

    There are targets, then there’s targeting. The article I’d really love to read

    http://pss.sagepub.com/content/21/11/1716.short?rss=1&ssource=mfc

    is behind a paywall. Rats.

  4.  
    jamzo
    September 7, 2013 | 1:35 PM
     

    wiley try this link for

    Social Class, Contextualism, and
    Empathic Accuracy
    Michael W. Kraus , Stéphane Côté , and Dacher Keltner

    http://www-2.rotman.utoronto.ca/facBios/file/Kraus%20C%C3%B4t%C3%A9%20Keltner%20PS%20in%20press.pdf

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