Friday, August 31, 2007

Uh-Oh Chuck, What About the Disclosure? OR Go Team MAOI!

Introduction: As longtime readers can surmise from the headline, this post is about Dr. Charles Nemeroff. And the Dalai Lama. Let's start from the beginning. Nemeroff was featured in a CME activity on Medscape. To view it, you'll need to complete a free registration at Medscape. For those new to the wonderful world of CME, note that while CME stands for continuing medical education, it is more accurate to refer to it as commercial medical education -- it's paid advertising, dare I say cheerleading. It is rather disheartening that physicians who wish to keep their licenses must sit through a bunch of advertisements as opposed to less biased, more educational forms of training. For more on CME in general, read my earlier posts here and here, or check out Daniel Carlat's excellent work (1, 2, 3, 4, 5 ).

The Present Story: Nemeroff, in the aforementioned CME activity, discusses the transdermal patch for selegiline, a monoamine oxidase inhibitor (MAOI) and how it may serve as a good treatment option for people with depression. Here are a couple of quotes from Nemeroff:

The limited use of oral monoamine oxidase inhibitors (MAOIs) over the past decade or so has been driven largely by physicians' concerns that they might potentiate hypertensive reactions when they interact with tyramine in foods. A new transdermal system is currently available that enables the MAOI to avoid first-pass metabolism by bypassing the gut, thereby reducing the chance of hypertensive reactions caused by tyramine.

The Pande study, which I believe was done when Pande was at Lilly, compared 20 patients with atypical depression treated with fluoxetine and 20 treated with the nonselective irreversible MAOI, phenelzine. Efficacy was about equal. Certainly other data and my own experience would suggest that MAOIs are superior to SSRIs and TCAs [for atypical depression].

A case that is treated successfully (of course) with transdermal selegiline is discussed during the activity in some depth. All's well that ends well. Clearly, the CME activity backs the use of transdermal selegiline. While it discusses some of the risks associated with MAOI treatment, the program states that the transdermal system avoids many of these issues.

Chuck's Conflicts: Nemeroff lists the following disclosures in the CME activity:

Reunette W. Harris Professor and Chairman, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

Disclosure: Grants: AstraZeneca Pharmaceuticals, LP, Bristol-Myers Squibb Company, Forest Laboratories, Janssen Pharmaceutica, National Institute for Mental Health, Pfizer Inc, Wyeth-Ayerst Laboratories, Consultant: Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb Company, Concept Pharmaceuticals, Ltd, Cypress Bioscience, Inc, Cyberonics, Inc, Eli Lilly and Company, Entrepreneur Fund Inc, Forest Laboratories, GlaxoSmithKline, H. Lundbeck A/S, Ingenix i3 DLN, Janssen Pharmaceutica, Otsuka America Pharmaceutical, Inc, Pfizer Inc, Quintiles Transnational Corporation, UCB Pharma, Wyeth-Ayerst Laboratories; Speaker: Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc.; Stockholder—Acadia Pharmaceuticals; Corcept Therapeutics, Inc; Cypress Biosciences; NovaDel Pharma Inc.; Board of Directors: American Psychiatric Institute for Research and Education, NovaDel Pharma Inc, National Foundation for Mental Health

As you can gather, Nemeroff is a busy guy! According to the above, he is a consultant for 18 drug companies and a speaker for four companies. The plot is about to thicken (or, perhaps, sicken) notably...

The Missing Disclosure: Remember how the above CME was all about pushing a newer, safer MAOI drug for depression? Well, it just so happens that Nemeroff is the co-chair of the Scientific Advisory Board for CeNeRx, a company that is developing a (you guessed it) newer, safer MAOI drug for depression! Note that Nemeroff did not mention his position with CeNeRx in his disclosure for the Medscape CME activity. Here's what the CEO of CeNeRx had to say about the MAOI they are testing:

In contrast to other MAO inhibitors, our third generation RIMA series is designed to bind selectively and reversibly, with the goal of significantly reducing the cardiovascular risks and other side effects typically associated with the MAOI class. These safety results, along with the high plasma levels and favorable pharmacokinetics demonstrated in the study, support advancing Tyrima into a multiple dose safety study in late spring.

Note the similarity to what was being said about the MAOI patch in the Medscape CME. Let me put this plainly: Nemeroff stumps for an MAOI in a CME activity, yet does not disclose that he is being paid by a company which also manufactures an MAOI. Can you say "hiding a blatant conflict of interest?"

The Dalai Lama: Nemeroff is appearing with His Holiness the Dalai Lama for a presentation on depression at Emory University. Thankfully, Nemeroff is not scheduled to speak about MAOI's. He is actually scheduled to speak about the relationship between early life experience and depression, about which the research is quite interesting and important. However, given the history of Nemeroff's scientifically questionable behavior (read a summary here, which has links to more detailed stories), it strikes me as strange that he'll be presenting alongside the Dalai Lama.

Golden Goblet: Does this earn Nemeroff a nomination for a Golden Goblet ? I believe so.

Thursday, August 30, 2007

Comment Wars

I recently posted about Dr. Rita Pal, who is under investigation by the General Medical Council in the UK. There have now been 67 comments written regarding the post, and I suspect the number will continue to rise. Anonymous commenters have made several posts challenging the veracity of Dr. Pal's assertion that she is being investigated for the ludicrous charge of linking to a "secret" document from her blog. Other comments have attacked Dr. Pal from other angles. Dr. Pal has refuted the allegations of the anonymous commenters vigorously. My original post is here and more in-depth reporting can be found at Furious Seasons and the Scientific Misconduct Blog, as well as at the Register, where the story was initially reported.

I've not been very impressed with some comments, such as the one that simply accused Dr. Pal of being "borderline." I've got a pretty open comment policy (obviously), but if we're going to post comments, let's make them something other than name calling. Some of the posts have been regarding the Lisa Blakemore-Brown issue, on which my original opinion remains unchanged.

Monday, August 27, 2007

The Crime of Linking

Both Philip Dawdy and Aubrey Blumsohn (and others) have described the tale of Dr. Rita Pal, who committed the apparently serious offense of linking to a document on her website, lost her job (coincidence?) and is being further investigated by the General Medical Council. The linked document was the transcript of the case of Lisa Blakemore Brown, a British psychologist who was accused of misconduct. Feel free to read my tirade about the ludicrousness of how Blakemore Brown has been persecuted (1, 2).

The real killer here is that Pal's fitness to practice medicine is being questioned because she linked to a document that had not a thing to do with patient confidentiality and is entirely unrelated to Pal's fitness to practice medicine. Perhaps someone can explain how linking to a document makes one unfit to practice medicine...

Oh, did I mention that Dr. Pal has a blog where she frequently criticizes the British National Health Service? What a great way to silence a critic -- trump up a patently ridiculously charge in an attempt to crush her career.

Please read Dawdy's and Blumsohn's posts to get the whole story.

Update: A reader has posted a comment challenging the veracity of this story. I'm quite interested in seeing other comments on this topic as well...

Friday, August 17, 2007

Amateur Sleuthing

The Wiki Scanner story is simply irresistible. Pharmalot let us know that AstraZeneca had changed the Wikipedia entry for Seroquel (story via the Times of London). Read more at Wired and Forbes. But, why wait around for a journalist to break the story when you can do it yourself? The Wiki Scanner site is a wonderful tool for amateur sleuths such as myself. Wanna see which companies made changes to Wikipedia entries? Here's just one example: Edelman PR made a change to the Wikipedia for Celecoxib (Celebrex) and for Viagra.

I'm far too short on time to continue this exercise, but I encourage all of you to hit the Wiki Scanner site and see what you can find.

Thursday, August 16, 2007

Hats Off to a Troublemaker

The winner of the Sunshine Troublemaker of the Week: Ben Hansen. Yes, the same Ben Hansen who has been digging up records regarding antipsychotic use in Michigan and the same Ben Hansen whose website you can check out here. Keep up the good work, Ben!

Tuesday, August 14, 2007

When to Say Sorry?

In a recent post, Daniel Carlat apologized to Charles Nemeroff for nicknaming him "Bling Bling" in a prior post. So what? Who cares? Well, I think we need to take a look at what behavior requires an apology and what does not. I'm not saying I have the answers, but I think the issue is quite important.

Let's look at some documented issues regarding Nemeroff:

ARISE-RD 1: Nemeroff was an author on a study (called ARISE-RD) examining the use of risperidone as an antidepressant. The study results did not demonstrate that the drug worked, especially after the authors issued a correction indicating that one of the findings in the published version of the study was incorrect (oops -- sorry that we mentioned that the drug worked; we screwed up -- it really did not work).

ARISE-RD 2: The study results were clearly not reported in full, leaving open the possibility that unfavorable data for risperidone was simply swept under the rug.

ARISE-RD 3: The study was published in a journal of which Nemeroff was the editor. Strangely, he did not report that he had a financial conflict of interest in the study, though the journal requires such relationships to be disclosed.

ARISE-RD 4: Authorship was switched around, leading one to wonder if the authorship line was an accurate reflection of who contributed significantly to the study or if it included an effort to stamp on the names of several "key opinion leaders" in order to improve the study's marketing value (1, 2 ).

I strongly encourage readers to read the linked posts above in order to plumb the depths to which this study appeared to be flawed. But there's more...

VNS: In his role of journal editor, Nemeroff again failed to disclose relevant conflicts of interest regarding a study that appeared in his journal and upon which he was an author. Read more on that tale here and here.

Mifepristone/RU-486: Nemeroff wrote an article reviewing various treatments. One treatment he mentioned was mifepristone (Corlux/RU-486). Nemeroff serves in a paid advisory role to Corcept, maker of the drug. He concluded, based upon incredibly weak evidence, in the review, that mifepristone was "very effective" in treating psychotic depression.

Lithium patch: In the same review article as mentioned above, Nemeroff mentioned that the lithium patch improved tolerability and compliance. So the patch made patients stick with treatment better and lowered the side effect burden. Oh, and Nemeroff did not cite a single source to back up these claims. Um, the entire point of a review article is to make claims and back them with sources. Nemeroff holds the patent for the lithium patch, by the way.

David Healy: According to some sources (not entirely confirmed, though I believe it), Nemeroff was part of the effort to get David Healy ousted from his position at the Univeristy of Toronto. It's a long story, worth reading about here and here. As readers of my site know, I have cited Healy's work here many times due to his close knowledge of data regarding psychiatric medications (particularly SSRI's) -- he's a good scientist with, in my mind, a very strong conscience. If Nemeroff was involved in getting Healy's position rescinded, then I say shame on him.

CME and Dr. Nemeroff: Dr. Nemeroff, like many key opinion leaders, is willing to set his name on journal supplement papers which are then used for continuing medical education. Daniel Carlat has a great post about a recent CME activity, upon which Nemeroff was an author, that seemed to magically transform unfounded ideas into "science" by just adding a sprinkling of money from the sponsor, Bristol Myers Squibb. Kinda made me think of a Chia Pet for some reason. Suh-Suh-Suh-Science! to the tune of Chuh-Chuh-Chuh-Chia!

So looking at the above list of items involving Nemeroff, I ask readers: Is it okay to nickname someone "Bling Bling" or to nominate someone for a Golden Goblet award? Please chime in with a comment to let me know. Is it acceptable sarcasm or is it character assassination, or something else?

The Point: I'm not in favor of name calling, nor am I in favor of being a jerk. But where does one draw the line? Where is the line drawn between acceptable reporting on controversial and important issues and being a bully? Over at the Drug Wonks blog, there are several posts that take aim at Steve Nissen and others, often using a nastier tone than nicknaming people "Bling Bling." Plenty of mudslinging occurs in blogs and in the "old media" -- watch most of the talking heads on so-called cable "news" networks and see what I mean. How often, and to what degree, is someone allowed to use sarcasm before it becomes rude and bullying? Part of writing is entertaining one's audience, and let's face it -- sarcasm can be very entertaining. How is a blogger to be entertaining, stick to the facts, and bring important information to readers without crossing the line into being offensive? I don't know. Perhaps you do -- again, leave a comment and see if you can shed light on this issue.

Friday, August 10, 2007

Prescribing Multiple Antipsychotics, Eh?

The Last Psychiatrist has a highly impressive (and hilarious) post on why prescribing multiple antipsychotics to the same person is not such a hot idea. I strongly encourage everyone to read it as soon as humanly possible.

Is Wyeth's Psychiatric Ship Sinking?

Wyeth's attempt at an antipsychotic (bifeprunox) was rejected by the FDA today. Liz Spikol has a post on the topic that I found immensely entertaining. Daniel Carlat points out why the drug was rejected -- because it does not work very well. Yes, some doses showed a bit of improvement over placebo, yet bifeprunox did not impress when tried head-to-head against risperidone or olanzapine. Adding this drug to an already crowded antipsychotic market would seemingly do little for people with schizophrenia but would help Wyeth, which is looking a little desperate these days considering it has little to replace its flagship antidepressant Effexor.

What about Pristiq, the "son of Effexor," -- well, that ain't looking so promising (1, 2, 3). Good luck, Wyeth. It appears you're going to need it!