key opinion leaders: a profession…

Posted on Thursday 2 June 2016

In the last post [key opinion leaders:  an example…], I said of Dr. Thase that "… most of us think of him not in any specific role as an expert professional, but rather as a Professional Expert" – implying that being a KOL is itself is a profession. And it’s the ability to lead the opinion of others that matters, not some particular expertise itself. It was, in fact, around the drug Vortioxetine that I finally started to ponder what being a KOL actually meant. About this time three years ago, I read this in Medscape:
Medscape
by Deborah Brauser
May 20, 2013

The experimental antidepressant Vortioxetine is safe and effective for treating major depressive disorder [MDD], findings from several new phase 3 randomized controlled trials [RCTs] suggest. Three studies of a total of 1545 US patients with MDD showed that those who received 20 mg of Vortioxetine had significantly decreased symptom scores on the Montgomery–Asberg Depression Rating Scale [MADRS] after 8 weeks of treatment compared with those who received matching placebo. However, there was no difference in symptom scores between the 10-mg and the 15-mg dose compared with placebo.

Interestingly, a fourth study conducted in Europe and South Africa with 608 patients showed that both the 15-mg and 20-mg doses of Vortioxetine were associated with significantly lower MADRS scores than placebo. "We wanted to address the correct dose, and across the studies, the 20-mg had the most consistent findings over placebo," principal investigator Madhukar Trivedi, MD, professor of psychiatry at University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News. Dr. Trivedi noted that "it’s very hard to figure out why" the 15-mg dose did well in the European study but not in the US studies, "but this often happens in antidepressant trials"…
I don’t know what it was about that particular day, but instead of following the article’s narrative, all I could see was «We» and «principal investigator Madhukar Trivedi». I felt absolutely sure that he was not the «principal investigator» on this study. And «We»? He hadn’t been any part of «We». He was looking at all of this post hoc – after the fact. I spent an inordinate amount of time looking for any evidence that either Dr. Trivedi or Dr. Thase [presented an earlier APA poster in 2011] had been directly involved in any of these studies ongoing, and it just wasn’t there [see way past time…]. ie:
Planners want KOLs to appear to have done much or all of the important work behind an article, presumably because many readers would be less inclined to give credence to an article that had only pharmaceutical company authors…
Sergio Sismondo
in Corporate Disguises in Medical Science: Dodging the Interest Repertoire

Since then, I’ve just assumed that being a KOL is a profession in and of itself. In this case, the professionals would be Michael Thase, Madhukar Trivedi, and the group that signed on to the review [Schatzberg, A.F., Blier, P., Culpepper, L., Jain, R., Papakostas, G.I., and Thase, M.E. 2014. An Overview of Vortioxetine. Journal of Clinical Psychiatry. 75[12]:1411–1418.]. Today, I decided to look over the 13 RCT articles, the review article, and the meta-analysis funded by the sponsors, Takeda and Lundbeck. Recalling the figures from Cosgrove et al‘s paper, I repeated their compilation of the authors’ COI declarations with the review and meta-analysis included. The 15 articles had 60 by-line author cites spread among 31 authors. 13 of the authors were employees, making up 36 cites. Of the remaining 18 authors, only one didn’t have a financial COI with at least one of the sponsors, so 23/24 of the non-Employee cites had a COI. All 15 articles were ghost-written. And then I read them and looked over Thase and Trivedi’s presentations at the Institute of Medicine and at the FDA hearing.

I’m not totally sure why I did all of that today. I never doubted Cosgrove et al‘s excellent paper. I think I just had to see it for myself, kind of like going to the TMAP Trial in Austin a few years back to make it real. I suppose it’s still hard for me to imagine that smart people like Michael Thase, Madhuklar Trivedi, or all the other Professional KOLs would participate in such foolishness, or that the other tainted authors would sign on to papers written by professional writers being paid to make something look better than it can ever be. But it looks just like it did last time through. Sismondo’s title was well chosen, Corporate Disguises in Medical Science: Dodging the Interest Repertoire.
  1.  
    WDM PhD
    June 4, 2016 | 8:40 AM
     

    I have made a careful study of vortioxetine mentions on web forums for over a year. It does not seem to be tolerable and it does not seem to relieve depression. I conclude that it is a blend of recalled flu shots and expired Gardisil. Any studies that show otherwise are suspect.

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