CME, Key Opinion Leaders, and Responsibility

Continuing medical education continues to get slammed (1, 2), and somehow the name of Charles Nemeroff keeps finding its way into these incidents. I wrote last week that Nemeroff co-authored a CME piece, on which he failed to disclose a conflict of interest regarding CeNeRx, for whom he co-chairs the scientific advisory board. The conflict of interest that was not disclosed was quite relevant, as the CME article was a cheer piece for MAOI's, and it just so happens that CeNeRx is in the MAOI business.

Daniel Carlat noted that another CME article upon which Nemeroff was an author has been criticized harshly; this one was dissed by one of its own authors. C. Lindsay DeVane, a coauthor, called it "a commercial piece of crap." Let me state this ever-so-clearly: An author called his own article a commercial piece of crap. This should send shivers up and down your spine -- if authors can't even trust the work upon which their name appears, how the hell are physicians supposed to trust it? Taking it a logical step further, how are patients supposed to trust their physicians if M.D.'s are receiving "education" that is "commercial crap."

I should mention that to Nemeroff's credit, on the "crap" article, he discloses an interest in CeNeRx.

What is authorship, anyway? Everyone knows that CME articles are quite often ghostwritten to reflect key marketing points. It's actually fairly comical that a lot (perhaps virtually all?) of the CME litter-ature is written by ghostwriters, and then key opinion leaders such as Nemeroff, DeVane, Keller, et al sign off on them. To be fair, it's not necessarily all that different from clinical trial literature, which is also frequently ghostwritten by industry-friendly writers (1, 2 ).

So we're left with a new definition of "author" on a scientific paper or CME piece:

Author: Someone who stamps his/her name on a paper to lend extra scientific credibility to the marketing of whatever product is discussed most positively in the manuscript. Having read the paper, written the paper, or having anything to do with the paper/study whatsoever is entirely optional.

Time: Some have said that the "authors" of these CME pieces are not to blame because those mean CME outfits send the proofs of the articles to be approved by the authors so quickly that the authors don't have time to review them. That is perhaps the WORST argument I've heard in a while. If that happens to an author once, I can understand...

Perhaps you're a well-meaning scientist who is hoping to provide something of value to educate your colleagues in a CME piece. Great. Then the ghostwriters throw together something that might be described as, um, "a piece of commercial crap," email you the manuscript to approve in 24 hours or else their version stands as the final version. At that point, you have hopefully learned your lesson. If you are repeatedly performing this exercise, lending your name to commercials passing for education, in which your own scientific views are not represented by the CME pieces, then you have nobody to blame but yourself.

Of course, there may be some whose views are accurately represented in CME pieces. Good for them. Have dozens of CME articles under your name, by all means. But, by God, let's not have any more statements like "the article with my name on it does not reflect my own views." I sincerely applaud Dr. DeVane for admitting that the CME article in CNS Spectrums is a joke. Now let's hope that he never finds himself in such a position again. Fool me once, shame on you; fool me twice... The worst forms of CME, which are marketing points covered with a very thin veneer of science, can only exist so long as "key opinion leaders" continue to sign their names on such pieces.

On a final note, I'd like to know if Nemeroff and Preskhorn, the other two authors on the CNS Spectrums piece likewise view the article as "crap" and if they would be willing to disavow themselves of the study. Here's betting they will have not a word to say on the topic.

Also read Pharmalot's great piece on the topic.

Key Opinion Leaders, Continuing Medical Education, and Utter B.S.

Psychiatrist Bernard Carroll has another brilliant post on corrupt, er, continuing medical education (CME) and how the process has been co-opted by various commercial interests. His post a few days ago was certainly great, and in combination with his current post, I officially declare that Bernard Carroll is ON FIRE!

Here's a bit of what he had to say. Commit this paragraph to memory:

Medical journals are not the only compromised medium. Continuing Medical Education (CME) is a second front in the campaign to expand the AAP [atypical antipsychotic] drug market. The standard formula calls for corporate sponsorship channeled through an “unrestricted educational grant” to a medical education communications company (MECC). The MECC employs writers to prepare the “educational content,” and academic KOLs are recruited to deliver this content. The KOLs are chosen for their willingness to be “on message” for the corporate sponsor. If they go “off message” they know they will not be invited back. The talk of “unrestricted grants” is window dressing. The MECC also secures the imprimatur of a nationally accredited CME sponsor, typically an academic institution. The sponsor is paid to certify that the CME program meets the standards of the Accreditation Council on Continuing Medical Education (ACCME). Everybody turns a buck: the MECC and its staff are handsomely paid (CME is now a multi-billion dollar business); the KOLs are generously rewarded with honoraria and perquisites; the academic sponsor is well paid by the MECC; the ACCME receives dues from the academic sponsor; the audience obtains free CME credits rather than having to pay for these required educational experiences; and the corporate sponsor gets what it considers value for its marketing dollar.

Guess what... Charles Nemeroff is also featured -- regular readers will note that his name has appeared on a few occasions on my site. Carroll takes apart a recent CME exercise in which Nemeroff featured information that appears to be false. In fact, I detailed some of the problems with this CME exercise here. Carroll's post has a number of updates. Chances were given for this CME exercise to be redeemed in some form, but misinformation apparently prevailed yet again.

Regarding another of the atypical antipsychotics discussed in this wonderful CME piece, Carroll wrote (in part) the following:

When discussing aripiprazole for nonresponding depression, Dr. Nemeroff once again was economical with the truth. Note that Bristol-Myers Squibb, the marketer of aripiprazole, sponsored this PeerView/UCLA program. To document his claims about aripiprazole, Dr. Nemeroff cited one Abstract from the American Psychiatric Association meeting in May 2007. That does not meet ACCME standards of documentation for learners, most of whom would be unable to access the cited Abstract (not that it would tell them much even if they could). For some reason, Dr. Nemeroff did not inform learners that the complete report of the aripiprazole study had appeared in June 2007 (Berman RM et al. J Clin Psychiatry 2007;68: 843-853), fully 5 months before the CME event went on-line. From that readily available report it is clear that the Number Needed to Treat (NNT) for response with aripiprazole is 10, which compares unfavorably with a NNT of 4 for lithium, the best established augmenting option in placebo-controlled trials. A NNT of 10 means a clinician would need to treat 10 patients with aripiprazole before obtaining one remission that would not have occurred anyway with placebo. That does not constitute compelling clinical benefit. Dr. Nemeroff did not candidly discuss these troubling data. Dr Nemeroff provided his CME audience none of the remission or response data from the published aripiprazole study, though these data were readily available. These omissions of published, highly relevant information signify disrespect for his audience by Dr. Nemeroff, incompetence by the MECC, and failure of due diligence by the accrediting institution, UCLA, to ensure that accurate, balanced information and adequate documentation are provided.

I shall not steal any more of Carroll's thunder. Head over the Health Care Renewal and check it out in full.

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.

Advertising as Education: CME

When physicians become licensed to practice medicine, they must continue to stay informed regarding the wide variety of treatments and procedures available to their patients. To ensure that doctors stay informed, it is required that they receive “continuing medical education,” which theoretically keeps physicians updated about the latest developments in their specialty area. So far, so good. But what, exactly, is continuing medical education (CME)?

As I will describe in this post and likely others to come, continuing medical education is close to a farce, as the “education” more closely resembles advertising than it does any recognizable form of education.

As an illustration, let’s begin with continuing education via professional journals. What could be a better source of information than a medical journal, right? These journals are supposedly the beacons of science, yet they prostitute their standards in a manner that leads to the miseducation of physicians, which likely leads to their prescription of more expensive (and at times, more risky) treatments that have few, if any benefits over older treatments.

Case in Point: Journal of Clinical Psychiatry. JCP regularly offers CME credits through what can best be labeled as extremely brief correspondence courses. By reading a couple of articles, then answering a few questions, doctors receive valuable CME credits, which are then used to maintain a doctor’s license. JCP is far from the only journal which participates in this practice.

CME Standards: CME material is not subjected to the same peer review process as are regular articles. Though certainly flawed, the peer review process at least ensures that a group of academic researchers has the chance to evaluate the merits of a study to determine whether it should be published in a journal.

One of the standards regarding the commercial sponsorship of CME states

The content or format of a CME activity or its related materials must promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest.

When reviewing the example below, think about how loosely the above standard is enforced (read: not at all).

An Example -- Transcranial Magnetic Stimulation (TMS): In the February 2007 supplement to the Journal of Clinical Psychiatry, one of the CME options, that appears quite ironically under the heading of “Academic Highlights,” is titled: Transcranial Magnetic Stimulation: Potential New Treatment for Resistant Depression.

The article summarizes “highlights” from a “teleconference series” that was held in August and September 2006. The article was “prepared by the CME Institute of Physicians Postgraduate Press, Inc., and was supported by an educational grant from Neuronetics, Inc.”

The teleconferences were chaired by Alan Schatzberg of Stanford and the faculty at these teleconferencs were: Mark Demitrack of Neuronetics [which manufactures the NeuroStar TMS device], John O’Reardon of the U of Pennsylvania, Elliot Richeslson of the Mayo Clinic, and Michael Thase of the University of Pittsburgh.

Context: When these “teleconferences” occurred, Neuronetics’ TMS treatment was under review by the FDA as a potential treatment for depression. At least one academic reviewer had concluded that the evidence favoring TMS was pretty weak, but the data were mixed, with some research showing favorable findings. Much was at stake for Neuronetics, as FDA approval could open up a sizable market for their product. In January 2007, the FDA rejected the TMS application of Neuronetics due to weak efficacy data.

Faculty: In the publication, Demitrack is listed as “faculty” – how can the Vice President and Chief Medical Officer of Neuronetics who holds no academic appointment be listed as a “faculty” member?

Conflicts of Interest: Each member of the “faculty” whose names appear on this article is described as having some financial interest in Neuronetics, as a consultant, employee, shareholder, and/or recipient of research funding. Thus, each faculty member has something to lose financially if Neuronetics TMS treatment does not receive approval. Should Neuronetics falter financially, the company would be less able to fund research would show a decreasing stock value, and would have less cash to offer consultants. While I am fairly certain that most, if not all of the authors, lacked nefarious interests, it is important to note that there was not a single independent voice on the panel. In CME articles such as this, however, this is just par for the course.

Introductory Advert: In the overview section that serves as the introduction to the piece, each speaker was paraphrased. Demitrack (Chief Medical Officer of Neuronetics) was paraphrased as saying:

Transcranial magnetic stimulation has shown promise within the device-based platform of interventions because it is an effective, noninvasive procedure; however, at the present time, TMS therapy has not yet received U.S. Food and Drug Administration approval.

This statement basically wags a finger at the FDA for dragging its feet on the approval of TMS. Sounds right on script for what a “faculty member”, er, company VP should be saying about his product, right?

Richelson is paraphrased as saying:

Modulating neurotransmission to specific brain areas through highly focused magnetic pulses (rTMS) may reduce or even eliminate the depressive symptoms associated with specific brain areas.

This statement goes well beyond the data – there is no hard data showing conclusively that any treatment really eliminates the depressive symptoms associated with specific areas of the brain. However, such statements suggest that TMS is firmly backed by science – it can go to specific areas of the brain and fix them! Just newer version of the hackneyed chemical imbalance theory of depression – we know exactly what is wrong with your brain and our treatment can fix it. Same story, different treatment.

Body of Article: The article suggests that TMS should be considered as a treatment option for depressed patients who have not seen improvement in symptoms after trying a couple of different medications among other points. My favorite statement in the article was based on comments from “faculty member" Demitrack:

TMS seems to provide the promise of at least equivalent efficacy and, in some instances, perhaps better efficacy and an improved tolerability profile compared with continued, more complex pharmacotherapy.

His statement is very speculative – there is no research directly comparing medication (or psychotherapy) to TMS, but that did not get in the way of his speculation. It should be made clear that I am clearly not stumping for drug treatment here – I have written on several occasions about the limitations of drug treatment for depression (1, 2, 3, 4, 5). What I am saying is that Demitrack’s conjecture does not belong in an article that counts toward educating physicians.

Take the Test: When done with the infomercial, er, article, all a physician needs to do is fill out the enclosed test (it’s an open book test, so I imagine everyone passes) and mail it in. Physicians can even complete the test online.

Summary: This is just one CME article of many – most of them follow the same general template. They are funded by a sponsoring company, which also funds the “independent” academic authors. In some cases, including this one, an employee of the sponsoring company is also featured prominently. A medical writer may then write up much or all of the article.

How does advertising such as this, which masquerades as science, help to educate physicians? Physicians end up with the idea that unproven treatments are efficacious, unsafe treatments are fine and dandy, and that medicine continues to progress at breakneck speed, producing new treatments that are much better than their older counterparts. And this helps patients… HOW?

The Incredible Vanishing Key Opinion Leader

Charles Nemeroff, former chair of psychiatry at Emory University and key opinion leader extraordinaire has vanished. Not quite vanished from the face of the Earth, but from Medscape CME and now from a Georgia mental health commission. Nemeroff was found to have not disclosed a whole boatload of money he received from Big (and little) Pharma according to an investigation by Senator Charles Grassley. For example, it appears that Nemeroff received about $20,000 in cash from GlaxoSmithKline in one month in exchange for promoting GSK products to his peers.

I have previously written about a number of, um, "interesting" behaviors on the part of Nemeroff, which I recommend you read in order to understand that Nemeroff has, on several occasions, engaged in behavior that certainly appears to have placed the causes of his corporate sponsors over science. Not good for an "independent" researcher.

And now, it seems that Chuck Nemeroff is vanishing. Dr. Bernard Carroll noted that Nemeroff's continuing medical education offerings had vanished from Medscape and offered the following:

Well, good for Medscape. They came in for their share of criticism, here and here, a while back. Now they deserve credit for displaying ethical standards. Meanwhile, we are waiting for another company called CME Outfitters to get the message. Dr. Nemeroff is slated to moderate a raft of new programs for this company in the coming weeks, sponsored by corporations like Pfizer, AstraZeneca, and Ortho-McNeil Janssen. CME Outfitters' logo, after all, is Education with Integrity. Sooner or later the pharmaceutical corporations, like the CME companies, will understand that they are not helping themselves by trotting out a shopworn and sleazy KOL figurehead like Nemeroff for their marketing efforts. And other KOLs who up to now were willing to "wet their beaks" in these CME forums controlled by the Boss of Bosses Nemeroff will now be leery of associating with him.

Well, CME Outfitters is still rolling with Nemeroff. For example, he has an upcoming program called "Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough," which is a scary thought given that he appears to have been pulling data from thin air for a prior CME exercise in which he pimped risperidone as a treatment for refractory depression. Specifically, Nemeroff's presentation claimed that risperidone improved sexual function in a clinical trial, when the published article based on the trial's results said no such thing. In addition, Nemeroff's claim that risperidone had shown efficacy in a short-term study versus placebo for depression was also unsupported. So I'm thinking the upcoming program on antipsychotics for depression might be a fantastic example of marketing beating the crap out of science.

Georgia appointed a commission to address several issues within the public mental health system. They have completed a report. Interestingly...

The final version also does not contain the name of commission member Charles Nemeroff, an Emory psychiatry professor who has been a subject of a U.S. Senate Finance Committee investigation into whether drug company money paid to doctors and academics compromises medical research and scholarship. Nemeroff, an internationally known expert on depression, did not attend recent commission meetings.

But Nemeroff was appointed to the commission with some fanfare. The press release listing Nemeroff's accomplishments is pretty lengthy. The Georgia state legislator who appointed Dr. Nemeroff said, "I am confident that Charles will be an asset to this commission and will serve as a strong advocate for the people of Georgia being served [by] our mental health systems"

Yet Nemeroff was not on the final report. If it weren't for his work on CME Outfitters, I would be worried that we might need to file a missing persons report for Dr. Nemeroff.

Update (12-18-08): The Wall Street Journal Health Blog has two interesting posts on Dr. Nemeroff (1, 2). Read them and feel free to file them under "bizarre."

Advertising as Education: CME Part Deux

I had the good fortune to read the Journal of Clinical Psychiatry supplement which featured Dr. Henry Nasrallah (the author) sneaking in some friendly messages about ziprasidone (Gedon), the antipsychotic from Pfizer that has been dwarfed by its competitors such as Zyprexa, Seroquel, and Risperdal. The piece discusses the findings of the CATIE study, which compared several newer antipsychotics to an older medication, perphenazine, and generally found that the newer and older drugs were of roughly equal effectiveness and that olanzapine had the worst safety profile. I thank an alert reader for passing the article along.

CME Overview: The good news is that physicians can read this article and take a quiz as part of the continuing medical education (CME) that helps them maintain their licenses. The bad news is that these articles are often thinly veiled advertisements for a product or a message that supports a product.

Highlights: It is stated that the difference favoring olanzapine (Zyprexa) over ziprasidone in terms of efficacy was not significant after a statistical adjustment (granted, this seems like a legitimate argument). It then mentions that olanzapine had the worst metabolic profile in terms of effects on weight, blood glucose, glycosylated hemoglobin, cholesterol, and triglycerides. It then states “In contrast, patients treated with ziprasidone had the best overall metabolic profile.” It places some numbers in a table regarding the metabolic effects of the various drugs in the CATIE study but provides not a single statistical analysis (or reference to an analysis on CATIE data) backing its assertion that it is significantly better than all other drugs in terms of metabolic profile.

The piece then turns to a secondary phase of the CATIE study, in which patients who discontinued their medications in the first phase of CATIE were assigned to other medications. It mentions olanzapine weight gain then mentions that patients on ziprasidone lost weight. It then discusses weight loss on ziprasidone again, then moves on to ziprasidone being associated with decreases in cholesterol and triglycerides, whereas olanzapine was associated with gains in both of these measures.

In case readers have been sleep-reading through this piece, it then moves to state that “except for clozapine, olanzapine clearly caused the heaviest burden of metabolic side effects. Ziprasidone, on the other hand, was consistently associated with the most benign side effect profile.”

Then, the piece moves to scare the reader about older antipsychotics and their risk of inducing extrapyramidal symptoms [EPS]. “The clinician must carefully decide whether the lower cost of the typical antipsychotic is worth the potential striatal neurotoxicity manifested by acute extrapyramidal side effects and long-term TD [tardive dyskinesia].” Of course, he must be assuming that atypical antipsychotics never or rarely induce EPS, which appears to be wrong and that all older medications induce EPS at the same rate as Haldol, which is likewise incorrect (1, 2).

Overall Message: The bottom line message of the piece is clear. Geodon is safe; Zyprexa is unsafe. Don’t use older meds because they’ll cause EPS – ziprasidone won’t. In fact, Geodon is the safest of the second generation antipsychotics.

Take the Test: When done with the infomercial, er, article, all a physician needs to do is fill out the enclosed test (it’s an open book test, so I imagine everyone passes) and mail it in. Physicians can even complete the test online. [this section was taken directly from an earlier post]

Ghostwriter Watch. Who wrote the article? You tell me – I’m confused. Here’s what is written in the article…

This article is derived from the planning teleconference “Evaluating the Evidence: Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and Beyond,” which was held on May 10, 2006, and was independently developed by the CME Institute of Physicians Postgraduate Press, Inc., and Health and Wellness Education Partners (HWeP) pursuant to an educational grant from Pfizer and addition support from HWP Publishing

Dr. Nasrallah is a consultant for, has received honoraria from, and been on the speakers/advisory boards for Abbott, AstraZeneca, Janssen, Pfizer, and Shire and has received grant/research support from AstraZeneca, Janssen, and Pfizer.

Content development and writing support for this article was provided in part by an independent writer contracted by HWeP: Martin Korn, M.D., a psychiatrist in private practice in New York.

I may be piecing this together wrong, but here goes… Pfizer writes a check to the CME Institute and HWeP. Nasrallah and a few other bigwigs engage in a conference call and are reimbursed (likely quite well) for their time. HWeP hires Martin Korn to write the piece, which then is reviewed, likely in a cursory manner at most, by Dr. Nasrallah. The piece is then reviewed by a member of the CME Advisory Board. These "reviews" appear to be consist of a race to grab the rubber stamp as quickly as possible.

I’m not sure if Pfizer provided the talking points directly to Dr. Korn, but it seems he got the message that Zyprexa and older meds should be slammed while Geodon should come across looking angelic. The CME Institute then stamps their approval and we call all be assured that doctors are being “educated” about the latest and greatest treatments in a purely objective fashion.

Please also feel free to read my earlier piece on CME. I recall seeing Dr. Korn's name on an earlier CME piece similar to this, but I can't seem to track it down.

Don't be confused -- I'm not defending Zyprexa. Geodon appears to be a safer drug than Zyprexa, but this quite thinly veiled advertisement that masquerades as independent education is ludicrous -- how does reading or watching commercials passing for "education" help physicians make better decisions for their patients?

Seroquel for Everything: Off-Label Marketing?

Peter Rost has a trio of documents on his site regarding potential off-label marketing of Seroquel. As you may recall, I promised to track the Seroquel lawsuit saga that I am fairly certain will continue to unfold. Why the lawsuits? Partially due to allegations of off-label marketing. The latest chapter, from Rost's site, is that AZ appears to have sent out a letter to sales representatives asking them to inform doctors about "medical education" events. As you probably know by now, "medical education" is quite often drug company-speak for "advertising." (1, 2, 3 ).

These "medical education" events were available via VHS, DVD, or webcast for doctors to view at their convenience. One event discussed Seroquel use in the young and the elderly, while another focused on Seroquel for bipolar depression prior to Seroquel receiving FDA approval for such an indication. Is that naughty? Yes. Is it illegal off-label marketing? I'm no lawyer, but I bet not.

Why? Well, the medical education was not provided by AZ. No, it was provided through a third party (i3 CME ), which was "supported" by AZ. i3 CME then found some key opinion leaders to provide "education" to their physician peers. The marketing message is laundered through i3 CME so that AZ can say, "We weren't marketing anything off-label -- we're not responsible for what i3 CME did with the program -- i3 CME is independent!"

Yeah, right. Should i3 CME wish to stay in business, they're going to make sure to get pro-AZ speakers and design a program that paints Seroquel in a good light. My favorite part is this snippet from the letter from the AZ CME director to sales reps.

AstraZeneca supported an independent educational activity on October 8, 2006 in the areas of "psychosis and dementia."

So if AZ supported an "independent" educational activity, doesn't that make the activity, um, not independent? Give me a break. For more on the Seroquel for everything saga, please read prior posts here and here.

Zyprexa and Key Opinion Leaders

Since the Zyprexa trial is ongoing in Alaska, I thought I should return to the wonderful world of Zyprexa. I encourage readers to follow the Zyprexa coverage at Furious Seasons, Pharmalot, and PharmaGossip. Today, I will discuss the link between key opinion leaders and the marketing of Zyprexa. To preface, a coveted Golden Goblet Nomination could be handed out to several individuals based on their involvement in Zyprexa marketing...

In March 2000, Zyprexa received FDA approval for treatment of manic episodes. One document laid out the multipronged marketing maneuvers that Lilly utilized to move Zyprexa shortly after its approval. Some of the details of this document have been well-covered in a terrific piece of investigative journalism at Furious Seasons. This post will provide some coverage of the link between Zyprexa and the key opinion leaders who helped popularize the drug across the nation.

Once approved for bipolar disorder, Lilly utilized several tactics to market Zyprexa for bipolar disorder, including a satellite conference beamed to about 6000 physicians, and 8000 treatment team members in 1000 facilities. The faculty providing this educational service included many of the big names in academic psychiatry, including Paul Keck, Jan Fawcett, Hagop Akiskal, and Alan Schatzberg.

Alan Schatzberg, you say? Yes, the same Alan Schatzberg who is set to become president of the American Psychiatric Association. Some have been less than pleased with his election as APA president, considering his background as a physician-marketer, a key opinion leader with large conflicts of interest. The same Alan Schatzberg who has been involved in marketing passing itself off as continuing medical education.

Lilly also bankrolled dinner meetings, anticipated to draw 150-400 physicians per sitting. Dr. Schatzberg was also listed as a speaker for such dinners. One mental health service provider was impressed enough with receiving such excellent medical education that you can find it on his CV.

In the document outlining Zypexa's big marketing launch, Paul Keck's name appears in the following contexts:

• Satellite symposium provider
• Trainer of "local speakers." I believe this means he would train local physicians in various markets to then discuss Zyprexa with their colleagues.
• Faculty for bipolar weekend symposia
• Faculty for audio conferences
  
• Faculty for a satellite CME workshop
• Faculty for "dissemination of Bipolar information to 30,000 customers"
• Faculty on a "closed symposium" resulting in a CME newsletter and a CME audiotape, both of which were mailed to 30,000 individuals
• Author of two journal supplement articles

Paul Keck was also a member of a task force chartered by the American Psychiatric Association that served to revise the organization's guidelines to provide a more favorable view of atypical antipsychotics (including Zyprexa) in the treatment of bipolar disorder. No conflict of interest there, eh?

Keck said in a 2002 interview that:

"Often," Keck said, "patients with bipolar disorder require complex treatment regimens to manage all phases of their illness, creating a compliance challenge for patients and a management challenge for clinicians. These studies suggest that physicians may be able to use olanzapine as a foundation to simplify patients’ treatment regimens, and the combination of olanzapine and fluoxetine could be an effective treatment choice

It is likely that Keck was not performing all of his "educational" functions for Lilly in exchange for lollipops. He was likely receiving a healthy dose of cold, hard cash. Yet in the article, nothing is written about his financial links to Lilly. Keck has also appeared in press releases saying nice things about Symbyax (fluoxetine/olanzapine combination).

To be fair, Keck has also stumped for Pfizer's Geodon in press releases. Oh, and he also said nice things about Abilify in a press release. I suppose that if one is going to be a true key opinion leader, a real mover and shaker, one should be prepared to say nice things about whatever new drug is released, since each new drug naturally represents an "important" treatment option. Keck, like Alan Schatzberg and Charles Nemeroff, is also currently listed as a member of the clinical advisory board for Neuroscience CME, a for-profit entity awash in drug industry money. Dr. Daniel Carlat has previously written that the "educational" content produced by this organization is biased, and I find that easy to believe. It's not hard to find examples of poorly done industry-funded CME. In fact, you might be interested in reading about a CME activity in which Nemeroff seems to have pulled data out of thin air.

In sum, the usual fun and games were in play when Zyprexa was initially being pushed for bipolar disorder. Some of the biggest names in psychiatry left their fingerprints all over the marketing of Zyprexa and one of these key opinion leaders recently won the presidential election for the American Psychiatric Association. I suppose, then, that American psychiatrists are generally either unaware of conflicts of interest or don't care about them.

The beautiful thing about being a key opinion leader is that one's name recognition is huge. Among psychiatrists, I bet that Schatzberg's name is better known than that of Bill Clinton, since Schatzberg's byline appears on journal supplements and CME so frequently. That can't hurt when running for president of the national professional organization. I will be very interested to see how Schatzberg handles questions about conflicts of interest and drug industry influence on his profession. Don't be expecting any major efforts at reform in the near future.

Advertising as Education: Carlat Hits Home Run

Daniel Carlat is the chief of the Carlat Report, a newsletter which provides CME credits for physicians and is (gasp) sometimes critical of the drug industry and its marketing practices.

Carlat has an op-ed in the New York Times where he presents several examples of how drug companies, in the name of education, have misled physicians. I'd like to summarize what he wrote, but he really said it best. Please check it out. It covers a lot of important material in relatively few words. He also has a simple solution -- any CME paid for by drug companies should not count for educational credit for physicians. I couldn't agree more!

As y'all know, I am highly critical of current CME practices, which allow physicians to maintain their medical licenses based upon their soaking up sugarcoated drug company advertising which masquerades as education. For examples, please read an earlier post on a pro-Geodon piece and a puff piece pushing transcranial magnetic stimulation for depression. I am very pleased that the Times ran Carlat's piece.

John Mack noted that the Drug Wonks blog (predictably) came to the rescue of Big Pharma by calling Carlat's piece "hysterical." Of course, Robert Goldberg (the Drug Wonks author in question) provided no evidence -- he also said

Oh, and if I were Carlat, I would drop the characterization "Unbiased" from the description of his expensive newsletter. He is as biased as anyone. Anyone who calls his colleagues money launderers is biased.

Oh gee, we're all biased, so who knows what's right? It's all so relativistic. Please. I think that many pharma bloggers (including myself), have marshaled sufficient evidence to indicate that Big Pharma has often placed marketing well ahead of patient benefit. For documentation, um, start reading a bunch of posts on this and similar sites. Yes, we're all biased to one extent or another -- that's why we should stick to facts rather than label industry critics as "hysterical" or worse. And the facts indicate that CME needs reform. Call me hysterical if you want.

Hat Tip: Furious Seasons

Big Pharma: Less Cash Toward Misinforming Doctors?

According to John Mack at the ever-thoughtful Pharma Marketing Blog:

“2005 marks the second consecutive year of decreased growth in commercial support of continuing medical education (CME) by the pharmaceutical industry, according to the 2005 annual report of the Accreditation Council for Continuing Medical Education (ACCME), which collects this data from accredited CME providers.”

Why would these big supporters of infomercials, er, "education" do such a thing? John thought:

“This could be in reaction to calls from the medical community that medical schools stop accepting "free gifts" from pharmaceutical companies and that grants for CME from pharma be contributed to a general fund rather than to individual physicians. We could be witnessing payback by the pharma industry.”

There’s more on his site, which I encourage you to check out here. Go directly to his post on CME here.

Links to articles and abstracts that justify my skepticism toward the accuracy of medical education provided by Big Pharma can be found here, here, and here.

Editorial Support, CME, and the Primary Care Companion

By now, everyone who has been paying attention should know that a journal article which lists "editorial support" is an article that was ghostwritten. Yet the average reader of these articles is apparently uninformed enough to not care. Why else would so many articles get published which feature "editorial support provided by [insert name of ghostwriter here]." One my my favorite journals, under the "so bad, it's good" category, is the Primary Care Companion to the Journal of Clinical Psychiatry. Good articles certainly make their way into the journal, perhaps by accident, but the journal can always be counted on to provide a steady supply of utter garbage.

Here's the acknowledgements section from one recent piece in the journal: "Editorial support was provided by George Rogan, MSc, Phase Five Communications Inc, New York, New York. Mr. Rogan reports no other financial affiliations relevant to the subject of this article." And in case you're wondering, "Funding for editorial support was provided by Bristol-Myers Squibb." If you've somehow guessed that this is an advertorial for Abilify, you win. Other ghostwritten pieces of fluff paid for by BMS include an article discussing the safety profile of Abilify in depression. It states that "In conclusion, this post hoc analysis extends previous findings demonstrating that aripiprazole is safe and generally well tolerated as an augmentation strategy to standard ADT in patients with MDD with a history of an inadequate response to antidepressant medication." But Abilify caused akathisia in a quarter of patients - I think that's a problem.

But wait... there's more. An article based on data from two trials, which showed (allegedly) that Seroquel improves anxiety in patients with bipolar disorder. This piece also acknowledges that it was ghostwritten. And we know that AstraZeneca, manufacturer of Seroquel, has cooked the books on Seroquel in the past. Feel free to look through the journal every month and have a giggle at some of the ridiculous pieces that make their way into print.

CME

You can get your continuing medical education (CME) from the Primary Care Companion as well. One particularly awesome piece of medical wisdom pimped Abilify educated physicians about the best ways to manage resistant depression. This one is a beauty. It was supported by cash from BMS, which features prominently in the "treat aggressively" message of the piece. The article features none other than Michael Thase as the leading discussant. The same guy who was the leading author on a paper which allegedly showed the wonders of Abilify for depression - despite the pesky fact that patients said it didn't work.

Back to the CME.. Thase starts off by stating that only a third of patients achieve remission of depressive symptoms during treatment. Given that Abilify is being marketed for treatment-resistant depression, this is a perfect way to start off this infomercial educational piece. He adds that failure to achieve remission increases the risk of suicide and puts people at risk for more depression, worse psychiatric outcomes, and all sorts of other bad things. So we better get rid of all symptoms of depression. Thase suggests that clinicians should closely monitor patients to see if their symptoms are remitting.

In particular, "Relying on the global statement “I’m definitely better” from the patient overlooks persistent, minor, or residual symptoms. Dr Thase recommended using a standardized symptom assessment measure and keeping track of the patient’s levels of symptom burden." So even if the patient says he or she is much better, don't believe it. Have the patient fill out rating scales and if any symptoms at any level are present, keep treating. In Thase's words, "If the current treatment is well tolerated and the individual has made significant symptom improvement but is still experiencing residual symptoms, then it may be necessary to adjust the treatment dose, add another medication, or combine pharmacotherapy and psychotherapy." Note that adding psychotherapy comes after adding another medication.

Then a series of other objective, expert psychiatrists chime in. Dr. Gaynes offers his wisdom, which includes "Dr Gaynes concluded that incomplete remission requires aggressive identification and management." Don't be afraid - be aggressive. The unspoken message: Hey, using an antipsychotic like Abilify for depression may seem freakin' crazy. But don't worry, you need to be aggressive. Dr. Trivedi then comments about using rating scales to measure side effects. I don't have much to say about his section, but things get worse momentarily...

Dr. Papakostas then checks in. "A meta-analysis of randomized, double-blind, placebo controlled studies found that augmentation of various antidepressants with the atypical antipsychotic agents olanzapine, risperidone, and quetiapine was more efficacious than adjunctive placebo therapy. In addition, Dr Papakostas noted that the atypical antipsychotic aripiprazole was recently approved by the US Food and Drug Administration (FDA) for use as an adjunctive therapy to antidepressants in MDD. Augmenting with atypical antipsychotics has so far been the best studied strategy for managing treatment-resistant depression, said Dr Papakostas." Dr. P was the coauthor of a meta-analysis that provided "considerable evidence" regarding the wonders of antipsychotic therapy for depression. The only problem was that the analysis actually did not find convincing evidence that the drugs were particularly effective, which I discussed in December 2009.

Next comes Dr. Shelton. Time to be aggressive, again: "Thus, said Dr Shelton, the long-term management of depression should be viewed in the context of acute treatment and the need for early aggressive management to get the patient as well as possible." Be aggressive by adding Abilify to the antidepressant regimen. If not, your patient won't achieve full remission and will suffer needlessly... "Dr Shelton advised clinicians to be aggressive in treatment and stay active over time, asking themselves if everything has
honestly been done to help the patient." Psychotherapy is given a brief mention in this section, but let's face it -- most physicians think of "be aggressive" as upping the dosage and/or adding medications - not as "let's be aggressive by adding psychotherapy."

Then there's the exam at the end. Write up your answers, mail them in, and get your medical education credit. Here's one of the questions...
3. Scores on both patient- and clinician-rated scales found that Ms B is still experiencing residual depressive symptoms. You optimize her current SSRI dose, which produces some improvement. She has not reported any problems with side effects. What course of action to improve her outcome has the most comprehensive efficacy data?
a. Increase the dose of her current SSRI again
b. Augment her current SSRI with another SSRI
c. Switch her to a serotonin-norepinephrine reuptake inhibitor
d. Augment her current SSRI with an atypical antipsychotic

If you guessed that D is the correct answer, you're one step closer to CME credit. And one step closer to writing a prescription for Abilify despite the fact that it is as likely to induce akathisia as to induce remission of depressive symptoms. Or that its advantage over placebo is small on several measures and nonexistent on a patient-rated measure of depression. But D is still the "correct" answer.



The offending educational piece is cited below:
Thase, M., Gaynes, B., Papakostas, G., Shelton, R., & Trivedi, M. (2009). Tackling Partial Response to Depression Treatment The Primary Care Companion to The Journal of Clinical Psychiatry, 11 (4), 155-162 DOI: 10.4088/PCC.8133ah3c

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.

Key Opinion Leaders, Osteoporosis, Vioxx, Psychiatry, Science, and Patients

Remember Richard Eastell? To summarize briefly, he is a professor at Sheffield University who was lead author on a publication that showed positive results for the osteoporosis drug Actonel. One problem: the data did not actually provide good news for Actonel. In a key graph in the published paper, 40% of patient data was missing. Now that's an interesting form of science: Just eliminate the pesky 40% of the data that don't go along with your hypothesis and POOF!, you get exactly the results you are looking for. An excellent writeup of the situation can be seen in Jennifer Washburn's excellent piece in Slate. Making the plot more interesting, Eastell did not have the raw data; Procter & Gamble's (Actonel's sponsor) statisticians were in charge of the analysis. Hence the missing 40% of the data, which helped to cast Actonel in a more positive light. Read more on the topic here. When all data are included, the analysis does not support Actonel's marketing points. Eastell signed off on the original (misleading) paper saying that he had seen all of the data, which was, of course not true.

I noted in October 2006 that Eastell was chairing a session on osteoporosis, one that charged a hefty registration fee. The website promoting the session at the time mentioned: "This course is suitable for pharmaceutical industry personnel from clinical through to marketing disciplines." I suppose that Eastell is a key opinion leader in his field. Being willing to put one's name on a paper where the key graph knocks out 40% of the data is a good step toward becoming an influential academic these days. I suppose Eastell could at least claim ignorance, since he was unfamiliar with the underlying data.

In psychiatry, Charles Nemeroff, a key opinion leader, put his name on a continuing medical education presentation in which the data don't match with the published article that was based on the same data set. In the CME presentation, the medication (risperidone) outperformed placebo, although the published report indicated that risperidone did not beat a placebo, and in the CME presentation, risperidone was claimed to improve sexual functioning, which was never mentioned in the published article.

Eastell and a colleague recently received a roughly $7.5 million grant. Good for them. I've got nothing against the guy personally; I just find it interesting that he is getting rewarded nicely despite the whole Actonel fiasco. And I've only described a wee bit of that strange saga. The Scientific Misconduct Blog has much, much more. Like the part where he told Blumsohn to stop bothering Procter & Gamble about the data because P & G was a good source of income for the university. I've got no problem with excellence being rewarded. Perhaps Eastell has done many excellent things. However, during the P &G/Actonel fiasco, Eastell was willing to let the sponsors push him around, even if science was being bastardized in the process. Their money meant more than good science. And if patients took Actonel thinking that it was more effective than it actually was, who cares -- they're not the ones providing the research funding, right?

Think about this for a second. Many people have been up in arms about the recently unveiled Vioxx ghostwriting scandal. For a fantastic take on the scandal, see Health Care Renewal or Hooked. Briefly, Merck and its associated medical writers wrote manuscripts that said nice things about Vioxx. Then academic authors/key opinion leaders were found to review the papers and stick their names on as lead authors. Mind you, "reviewing" the papers often meant simply meant making minimal edits, if even putting in that much effort. Did they see the data? They saw tables and figures provided by Merck, but did they see the raw data? In most cases, apparently not. Doesn't that make them information launderers? They take industry data, and clean it up with their academic reputation. Oh, Dr. So-and-So is at Sheffield or Emory or Harvard... -- he must have made sure that the sponsoring drug company is portraying the data accurately. A veneer of credibility. And an extra publication for the key opinion leader, which makes the KOL that much more important in the academic world where publication envy runs rampant.

This system is not exactly set up to benefit patient outcomes, is it?

Doing Some Digging

Some good material is coming. Unfortunately, it involves the same old people doing the same old tricks. But the scandal factor is reasonably high, so I assure that regular readers will not be disappointed.

In the meantime, check out another hot, hot psych blog: The MacGuffin. This fellow anonymous mental health blogger hates bad science. We're peas in a pod that way. And he's willing to diss research on both psychotherapy and meds. Dripping with sarcasm and with a sharp eye for spotting scientific shortcomings, I wholeheartedly encourage all readers to add the site to your list of faves.

Also, Danny Carlat is continuing to get into scrums with the CME industry and it's fun to read about.

Furious Seasons updates us on the FDA and child bipolar disorder.

As per usual, the Scientific Misconduct Blog has items related to scientific misconduct. Questions surrounding the behavior of a so-called regulatory agency and drug safety are brought to the fore yet again.

Findings from my latest investigations will hopefully be unveiled soon. Stay tuned!

Another Key Opinion Leader Contradicts Himself

It appears that Lindsay DeVane, who called his own continuing medical education article (appearing in CNS Spectrums) a "commercial piece of crap" has retracted his story (via the excellent Carlat Psychiatry Blog). Apparently, his take on the former "crap" piece has now changed to "there should be no question about the integrity of the CNS Spectrums publication as a CME activity" The article went from, in his own words, a "ridiculous text" to an article that reflects "the inherent limitations in providing practicing clinicians with fundamental descriptions of complicated issues." Is he implying that practicing clinicians lack the intellectual fortitude to understand "complicated issues," so he had to dumb it down to meet their limited capacity? Perhaps there is another interpretation.

He also changed his tune to "all three co-authors were heavily involved in multiple edits before agreement was reached on a final manuscript" from stating originally that he had not actually read the manuscript. That is quite a change indeed. One can only wonder which individuals pressed DeVane to change his story. Here's what I don't understand. DeVane has been in the game for a long time. Does he really have that much to lose by pointing out the joke that it today's continuing medical education system? I want to know who spoke with him and how he was persuaded to change his mind. This is such a ridiculous turnaround in stories that it makes Larry Craig look like a straight shooter. I am 99.9% doubtful that DeVane would have changed his story without significant influence from others. Drs. Charles Nemeroff and Sheldon Preskorn were the coauthors. I can't help but wonder if one or both of them took exception to DeVane's labeling of the piece as "crap" and read him the riot act. Does DeVane not realize that this turnaround in story is farcical?

Read the full story here. Two further glittering examples of continuing medical education in psychiatry gone awry can be read here and here. To see another key opinion leader contradict himself, go here.

Key Opinion Leader Provides False Information in Psychiatry CME

Just when I thought it was safe to stop writing about the ARISE-RD study, which was an attempt to demonstrate the efficacy of risperidone (Risperdal) for depression, even more evidence of misleading salesmanship regarding the study surfaces. Feel free to read six prior posts regarding the study, described in a bit more detail here.

Here's the rub. Dr. Charles Nemeroff is the presenter for this continuing medical education activity entitled Add On Atypical Antipsychotics Efficacious in Short Term for Unipolar Depression. This post concerns slides 5, 6, and 9, which reference the aforementioned ARISE-RD study, which examined the use of risperidone as an add-on to citalopram (Celexa) in treating depression. The full presentation is available for your examination.

Slide 6 reads in part:

• Global Impressions of Sexual Functioning scores improved significantly in men and women (p < .02) with RIS augmentation.
• RIS may ameliorate sexual dysfunction associated with SSRIs.

There is a reference to a published study in Neuropsychopharmacology at the bottom of the slide. The kicker: The published study contains no mention of improved sexual functioning on risperidone. This is called lying. Remember, Nemeroff was an author on the study published in Neuropsychopharmacology; he'd know if sexual functioning was referenced in his article, so there is no pleading ignorance on his part.

Slide 9 reads in part:

• Augmentation options for treatment-refractory depression include adjunctive atypical antipsychotics.
  -Controlled studies: short term efficacy with OLZ, ARI, RIS [risperidone]

This is a baldfaced falsehood. The study took people who had not responded to citalopram treatment, then added risperidone to the mix. There was no placebo control during this phase. So it was not a controlled study and should not be referred to as a controlled study in Nemeroff's presentation.

In fact, here is what the lead author (Mark Rapaport) of the ARISE-RD study had to say about its results in a letter to the editor (currently in press):

The paper repeatedly states in Abstract, Methods and in Discussion that continuation of risperidone augmentation therapy was not more beneficial than placebo, and hence the working hypothesis was disproven...

I would like to thank the reviewers and the editors of Neuropsychopharmacology for having the courage to allow us to publish this negative finding.

Compare and contrast: Nemeroff's presentation indicates that the study was a controlled trial showing that risperidone was more effective than placebo. The lead author admits that the study was a "negative finding" and that risperidone was "not more beneficial than placebo."

To summarize, Nemeroff did the following:

• Claimed that a peer-reviewed study showed risperidone improved sexual functioning, when the effects of treatment on sexual functioning were not even mentioned in the paper.
• Claimed that the study showed risperidone to demonstrate efficacy over placebo, which it in fact did not.
  

This is what passes for education for physicians. Being lied to about study results is how physicians receive continuing medical education to keep them abreast of the latest research findings so that they can better serve their patients. If you are not disgusted, you are not paying attention. It is far from reassuring that this incident involves one of the biggest names in academic psychiatry.