Monday, November 20, 2006

Uh Oh Chuck They Out To Get Us Man: COI

This post (similar to a previous post) centers on a study for risperidone as an add-on to SSRI treatment for depression.

The current post focuses on the failure of some authors to disclose their conflicts of interest. When the advance online publication of the article is examined, the only author listing any financial support is lead author Mark Hyman Rapaport, who lists four grants and a chairmanship. Janssen funded the study according to an earlier abstract version of the study, so it is curious that Rapaport did not list Janssen as a financial supporter. Rapaport was not alone in his failure to disclose. Nemeroff (the last author) and Keller (fifth author) clearly had conflicting interests that should have been declared.

Let’s start with Nemeroff. He is the editor of the journal (Neuropsychopharmacology) in which this article appeared, so he should be familiar with the journal's conflict of interest policy, which states in part: “At the time of submission, each author must disclose any involvement, financial or otherwise, that might potentially bias their work. The information should be listed in the Acknowledgements that appear at the end of the manuscript and noted in the authors’ cover letter.” The policy is pretty clear – so does Nemeroff have a significant conflict of interest in this case?

In the Journal of Clinical Psychiatry Supplement 8 from 2005, the conflicts of interest section mentions that, among Nemeroff’s quite numerous funding sources, Nemeroff has received grant/research support from Janssen, is a consultant for Janssen, and is a member of the speakers bureau for (you guessed it) Janssen, which is the company marketing Risperdal. In the same supplement, which was derived from a “planning roundtable…supported by an educational grant from Janssen Medical Affairs,” Nemeroff penned a review article that reflected favorably upon risperidone, as well as some other drugs. So it’s pretty clear that there was a conflict of interest here – it’s just that editor Nemeroff did not enforce his journal’s policies upon himself. Of course, this is not the first time such behavior has occurred. You can read about a similar failure to enforce editorial policies involving Nemeroff here and here.

But wait, there’s more! Nemeroff actually violated another of his journal’s policies, the one about duplicate publication of data.

On the Neuropsychopharmacology author instructions page, right under Nemeroff’s name as editor of the journal, you can see the following: “Submission is a representation that neither the manuscript nor its data have been previously published (except in abstract) or are currently under consideration for publication.” Nemeroff, in the aforementioned 2005 Journal of Clinical Psychiatry Supplement 8 wrote no less than five paragraphs describing the risperidone add-on study’s data, which was later published in Neuropsychopharmacology. So Neuropsychopharmacology’s editorial policy is that study data should not have been published earlier except in abstract form, but Nemeroff wrote about it for much longer than an abstract in a supplement paid for by Janssen, yet felt free to flout editorial policy regarding prior publication. This, of course, comes in addition to an egregious failure to disclose conflicts of interest.

What is the penalty for such behavior, one might ask? “An accusation that an Editor…has violated the conflict of interest policy shall be referred to the ACNP Ethics Committee for consideration and investigation. The Ethics Committee shall report its findings and recommendations to the Publications Committee and Council for action… an Editor…found guilty of violating the conflict of interest policy is subject to sanction, including forfeiture of the editorship.”

Don’t worry – Nemeroff is one step ahead of the game here – he chose to resign his editorship over the previous scandal involving his pimping of vagus nerve stimulation therapy, which you can feel free to read about here. No, Nemeroff did not state that he was leaving the editor position as a result of the VNS debacle, but the timing seems to reflect more than a coincidence.

To summarize briefly, Nemeroff had a blatant conflict of interest which he did not declare. He is also the editor of the journal in which the article appeared where he did not disclose the COI. In addition, he ignored his journal’s prohibition on prior publication of data. As the editor, he should obviously know much better. Indeed, it is difficult to believe that this was an oversight. It appears that Nemeroff was playing the role of marketer for risperidone as opposed to carrying out his duties as an editor.

How about Martin Keller? In that same 2005 supplement of the Journal of Clinical Psychiatry mentioned above, Keller is listed as having received honoraria from Janssen and as being an advisory board member for Janssen. Keep in mind that whatever work he conducted at the “planning roundtable” upon which the supplement was based was also funded by Janssen. Yet no mention of any financial support from Janssen is provided in the Neuropsychopharmacology article.

Apparently, perhaps due to Nemeroff’s earlier brush with the spotlight regarding his marketing of VNS therapy in the journal in which he edits [an article in which blatant conflicts of interest were not disclosed], the authors thought better of the conflict of interest issue. A corrigendum (correction) is displayed in the November print edition of Neuropsychopharmacology that lists disclosures for Nemeroff, Keller, and Rapaport. But if you are obtaining the article through online access (which is likely true for most people), then you won’t find the correction because it is not included in the pages of the article. Eventually the correction will be picked up on Medline, but many readers will not notice it.

Add the failure to disclose conflicts of interest to the shifting authorship line mentioned earlier and you can see why I am feeling a little skeptical. Of course, given some of Nemeroff’s past ethical issues (here and here), this is not entirely surprising. The last chapter in this tale, regarding the risperidone augmentation study’s data analysis will be told shortly.


Anonymous said...

I've been advised to try .5 of this drug to "boost" the effects of a Celexa / Wellbutrin combination for moderate to severe depression.

Trying to do some research on the efficacy of this approach and possible side effects. I will be awaiting further information and look forward to more entires on your blog.

CL Psych said...

I'm pretty sure there is no evidence on your particular combination of meds. There is really no data that says Risperdal is any better than a sugar pill for depression that I am aware of. I'm not providing medical advice -- just saying what my impression is of the relevant research.

Anonymous said...

Thanks for your comment - I've been trying to find as much information on this drug as possible. I'm not convinced that the benefits outweigh the risks.

In any case, I did appreciate reading your entries.