Medscape News: Diseases for Sale

If you're a physician, you know Medscape. A division of that internet health care behemoth, WebMD, Medscape pounds our inboxes daily with offers of free CME. Much of the CME is industry-sponsored, which is not exactly a news item for most of us. But what you may not be aware of is that Medscape sells its disease-specific "resource centers" to the highest bidder. For example, the ADHD Resource Center is purchased by Shire, the Bipolar Disorder Resource Center is owned by GlaxoSmithKline, and the Pharmacological Management of Pain Resource Center is now the property of Cephalon.

How much do companies pay in order to take control of what doctors learn? Good luck extracting this information from Medscape, but rumor has it that about $500,000 gets you a sort of "base package" which includes four articles. The sponsoring company gets to specify the topics and the authors, of course. There is a menu of extras, so if you really want to saturate the medical mind with your marketing message, you can presumably part with well over a million. And this doesn't include income from the advertising banners that appear to populate each and every web page on the site.

Yes, doctors know Medscape. And Medscape knows money.

From Embarrassment to Scandal: Lilly + APA + The Psychiatrist's Program + Lots and Lots of Money

What began as an embarrassment of Eli Lilly, PV Updates, and PRMS is gradually becoming a full-fledged scandal. The Indianapolis Star picked up the story last weekend (read it here), and psychiatrist David Port, M.D. wrote me a letter alerting me to an expanding crisis of trust in psychiatry. Here is an excerpt:

"Whatever Lilly's justification for sponsoring a course ostensibly to help the psychiatrist to better deal with professional liability risks, I am outraged that PRMS has accepted money from Lilly and has chosen to offer its authority and reputation toward this Lilly effort. PRMS is the American Psychiatric Association-endorsed entity which directs APA members to a selected malpractice insurance agency. PRMS is thus the agency many or most of us psychiatrists turn to for guidance and direction as to liability exposure and malpractice coverage. For PRMS to work for Eli Lilly is a glaring conflict of interest between their psychiatrist clients and a pharmaceutical corporation whose interests do not necessarily coincide with those of the psychiatrists with whom they have a professional relationship. This is analogous to the same law firm representing two individuals opposing one another in a law suit; in that situation we assume that there cannot be fair representation of either client, and we may imagine that the client with an attorney who has more clout in the law firm may well prevail in the action. How can we trust PRMS, or the APA for that matter, to provide us with the best liability support? David Port, M.D."

Yes, it's true. PRMS runs The Psychiatrist's Program, a malpractice carrier that is officially endorsed by the APA.

I know, it can get very confusing. Let's follow the money. Eli Lilly gives the APA at least $1.3 million in 2007 (so far) for industry-supported symposia and fellowships. Lilly then gives PRMS a bunch of money (Lilly refused to tell John Russell at the Indy Star how much) to produce a web-based slide show teaching psychiatrists how to prescribe potentially toxic medications like Zyprexa without being sued. The APA officially endorses PRMS' psychiatry malpractice insurance for its members. Does APA receive any type of kickback for this endorsement? I assume that would be illegal, but who knows?

Look, I get as annoyed by conspiracy theorists as the next guy. But the web of money and influence here is so murky and repugnant that it leaves me wondering what's going on. I officially invite both the APA and PRMS to respond. And I'd love another diplomatic letter from Eli Lilly!

Lilly's Diplomatic Reponse

"Dear Dr. Carlat - We are sorry that you misunderstood the purpose and the message of the risk management program that Lilly supported.

The underlying message of this program is that the best way for psychiatrists – and all physicians – to manage their risk of litigation, happens to be to do what’s also best for their patients – provide good clinical care, be informed, communicate and document the care.

With the barrage of plaintiffs’ lawyer advertising – against Lilly medicines and numerous products made by other pharmaceutical companies – we know that there is misunderstanding and anxiety in the psychiatric community about the risk of litigation and malpractice. For example, Lilly and the National Council for Community Behavioral Healthcare announced in June, 2007, the results of a survey of 400 psychiatrists that showed that more than half had patients who stopped taking antipsychotic medication or reduced their dosages based upon fears raised by law firm advertising. We believe that any information that can help a physician reduce this anxiety and uncertainty will also help return his or her focus to good patient care, which is what is most important.

This program is an attempt to provide helpful, independent, non-product-specific information to psychiatrists to keep the risk of litigation in perspective and to understand what they can appropriately do to reduce that risk.

Initial feedback from psychiatrists who have participated in the program has been overwhelmingly positive.

Please don't hesitate to contact me if you have additional questions.

Marni Lemons
Global Product Communications
Eli Lilly and Company"

What's that in the air? Ahhh, the sweet smell of damage control.

Zyprexa: Lilly Tweaks the Risk

Although Eli Lilly's Zyprexa is an effective antipsychotic, it causes more weight gain, hyperglycemia, hyperlipidemia, and overall metabolic havoc than just about any other medication known to medicine. Because of this, Lilly has been sued by patient groups, and recently settled with 18,000 patients who alleged they were never properly warned about Zyprexa's side effects.

Now Lilly's fighting back. Its weapon: educating doctors about risk management. I recently received this flyer in the mail. Published by PV Updates, a medical education company favored by Lilly, the title of this educational activity is "GET THE FACTS: Understanding Professional Liability Risk Associated with Prescribing Medications." You can watch the slide show here.

Here's the bottom line educational message: You can prescribe whatever medication you want, no matter how toxic, as long as you clearly document your rationale. So go ahead, prescribe Zyprexa--you won't be sued.

This strikes me as one of the more devious drug marketing campaigns in recent memory.

The Generic Drug Witch Hunt

CNS News has already achieved a certain degree of infamy in this blog for its subsidiary, CME Zone, an industry-funded CME factory. In a prior posting, I reviewed one article that masterfully tweaked information on anxiety disorders in order to promote Shwarz Pharma's Niravan, a orally-disintegrating version of Alprazolam (Xanax).

Now, unfortunately, CNS News is back on our radar screen for having commissioned an article bad-mouthing generic medications. You can find it as an insert in the November 2007 issue. The title is "Generic Antiepileptic Drugs: An Update," and the author is Andrew Wilner, M.D., a prominent neurologist with his own website.

Dr. Wilner's article is a biased article against using generic epilepsy drugs. He points out that the FDA allows generics to vary from 80% to 125% of the original drug's bioequivalence. But he ommits the crucial clarification that in actuality, generics vary from brand name by an average of only 3.5%, according to the most recent FDA analysis. He cites surveys of neurologists showing that most of them have seen breakthrough seizures when patients have been switched from brand name to generic formulations. But he fails to discuss how unreliable survey data like this can be. Response rates are low, and the physicians who have seen problems with generics are precisely those who are most likely to respond to a survey about possible generic drug dangers.

Dr. Wilner ends the article with an admission that proof of the dangers of generics is lacking, saying that no definitive study randomizing patients to brand name vs. generic has been done. But in fact, at least two randomized studies have been done. In one, patients randomized to generic carbamazepine had no more breakthrough seizures than patients randomized to a brand-name version. In another, patients on generic Dilantin actually had somewhat higher serum levels than brand name.

But these are all scientific quibbles, and they can reasonably argued in various ways. The most glaring problem is that there is no information about Dr. Wilner's numerous conflicts of interest. Instead, the article is said to be "independently developed by Mcmahon Publishing."

Discovering Dr. Wilner's industry ties is as easy as entering the terms "Wilner and disclosures" in Google. As it turns out, Dr. Wilner has received grants from several makers of anti-epileptic medications, including Shire (maker of Carbatrol), UCB (Keppra), and Novartis (maker of Trileptal). In fact, the first anti-generic survey study reviewed in the article was funded by Shire, and was conducted by none other than....Dr. Wilner!

I was astonished when I discovered this undisclosed conflict, and I wrote Dr. Wilner and the publisher this letter seeking a response. The first response was from the publisher, Donald Pizzi, who said that he had paid Dr. Wilner directly to write the article and that no industry money was involved. Pizzi said that historically, no disclosures are made in his journal, but "eventually" he will add them.

A bit later, Dr. Wilner sent me this letter. He parses the data a bit, engages in what I would consider some artful tweaking, but you can judge it for yourself if you choose to read it. I found it especially interesting that he defends his lack of disclosure by saying: "Regarding disclosures, while I have received grants and honoraria from the pharmaceutical industry in the past, I currently have nothing to disclose." I guess it depends, in the words of a former president, on what "is" is. In December of 2005, Dr. Wilner was funded by UCB pharmaceuticals, and in April of 2006 he helped write this article for a group of industry-funded neurologists, though it's unclear exactly who paid him. Other instances of his pharma funding can be found here and here and here.

Timing aside, the key issue is that Dr. Wilner's article appears to be biased in favor of brand medications, and he has been recently paid by precisely those companies whose profits are threatened by generics. He and the publisher should have disclosed this. If they had, readers would have given little credence to the article. But that would not have made the CNS News drug company advertisers very happy.

By the way, for a more balanced view of generics, visit this post on the Prescription Project's blog, Postscript.

Payback Time: A Counter-Detailing We Will Go

I received many helpful suggestions for how to part with my "dirty thirty." I've decided that the most logical solution is to donate time to "counter-detailing," which is essentially the opposite of giving drug talks. Pioneered as "academic detailing" by Jerry Avorn at Harvard Medical School, counter-detailing involves visiting doctor's offices and teaching about evidence-based medicine. The emphasis is on confronting the latest marketing claims of more expensive me-too medications and alerting doctors to the subtle statistical deceptions so common in pharmaceutical advertising.

Reviewing my Wyeth pay stubs, I can replicate my 2002 March of Shame through local doctor's offices and counter-detail them on my own dime. Anyone who wants a free talk for their organization can contact me at drcarlat@comcast.net. I'll do these until my 30K runs out.

By the way, several physicians at the National Physician's Alliance (NPA) are available for free talks on pharmaceutical industry influence, and they span the specialties, offering counter-detailing on treatments in internal medicine, cardiology, pediatrics, etc.... And join NPA while you're on their site. Unlike the AMA, they will never sell your name to drug companies.

"Return the 30K, You Cheap Thief"

Or so opines one of the commenters on the WSJ Health Blog, where you will find many angry folks calling me a "hypocrite," a "pathetic liar," etc....

I'd be curious to hear opinions about: A. Whether I should return the dirty money; and B. Where it should go if I can bear to part with it?

Other comments that I've received about Dr. Drug Rep:

--"Don't blame Wyeth, blame yourself. Nobody was holding a gun to your head--you chose to take the money." Can't argue with this. The article was, in fact, a long confessional about a series of unethical choices I made every step of the way. I don't blame Wyeth, nor do I blame the pharmaceutical industry in general. I blame the doctors who allow themselves to be complicit and corrupted by the allure of money. And yes, I was there with the worst of them!

--At his excellent blog, Hooked, Howard Brody raises the interesting possibility that Wyeth paid me the 30K as a bribe to get me to prescribe more Effexor in my practice. I'm sure that was one of the motivations, and I received letters from some drug reps indicating that this is standard operating procedure in the industry.

--I've received many letters from people who either are taking Effexor now or had difficulties coming off the drug in the past. While my article may have seemed an indictment of Effexor, it was not meant that way. Effexor is a very effective antidepressant, and I continue to prescribe it in my practice, usually as a second-tier agent. But the hypertension and drug withdrawal risks are real. For a very interesting article profiling one man's struggle with Effexor withdrawal, see Bruce Stutz's article, "Self Nonmedication," also published in the New York Times Magazine.

--Many physicians wrote their own mini-confessionals about giving drug talks. One doctor, also a reformed Effexor speaker, described a teleconference in which Norm Sussman minimized withdrawal problems with Effexor. In response, the doctor had an "ethical lapse" and couldn't help mentioning to the audience that Lexapro might be an easier drug for primary care doctors to prescribe, much to Sussman's annoyance. The writer eventually quit speaking for Wyeth.

--I've also received some shocking marketing stories from drug reps and former drug reps, some of which I'll be sharing in the future as I get permission to do so from the parties involved.

Dr. Drug Rep

To see how I made an extra $30,000 in 2002, click here. The article is published in this Sunday's New York Times Magazine. By the way, the Wyeth-sponsored "Faculty Development Programs" are still being held; a friend tells me he just went to one in Florida.

Antipsychotics for the Masses?

When it comes to antipsychotic medication, it appears that psychiatry has come full circle. The very first antipsychotic, Thorazine, was introduced in 1952, and had originally been considered to be an antihistamine, a bit like Benadryl. Eventually, we understood that it had extraordinary effects on the delusions and hallucinations of schizophrenia.

Over the years, many other antipsychotics have been introduced, and they are all effective at reducing psychotic symptoms, as their name implies. But over the past decade, they have also won FDA approval for treating bipolar disorder. Now, the companies marketing these drugs have their eyes on depression, which represents a far larger potential market than either schizophrenia or bipolar disorder. On November 21, Abilify received FDA approval as an add-on treatment for major depression (see the news item here). This follows closely on the heels of a study published a couple of weeks ago in the Annals of Internal Medicine showing that Risperdal was effective as an adjunctive depression treatment.

How effective are these drugs for depression? Not terribly. The Abilify data, for example, shows a remission rate of 26% vs. 16% for placebo augmentation, meaning that 1 out 10 patients would be expected to respond to an Abilify-induced boosting of their current antidepressant. The design of this study was somewhat manipulated in order to make sure Abilify beat placebo, a fact brought to my attention by this excellent post in Cl Psych. Nonetheless, the Risperdal data are very similar, and I'm convinced that atypicals provide a small antidepressant effect. Enough of an effect to overcome the potential side effects? That's unclear.

What is abundantly clear is that drug companies are going to be pushing both psychiatrists and primary care doctors to think of "antipsychotics" as "antidepressants." Look closely at the data before you buy the message!

Luvox CR: Let the Marketing Battles Begin

My Luvox CR posting from this past Monday somehow made its way quickly to the upper echelons of Jazz Pharmaceuticals. Lloyd Davies, the Director of Finance of the company (at least that's his title in this recent industry training event), responded to my early review of Jazz's new product with the following email:

(November 21, 2007)
"I just read your blog. There are a few factual inaccuracies that you might want to correct. 1) It's Luvox CR not SR; 2) The product has not actually been approved yet - presumably why the adverts do not mention the product; 3) Luvox CR is a once a day formulation as opposed to the old product which was twice a day. Therefore the half life might be different right? 4) I am guessing that it is "comorbid" not "comorbic" which is not a word that exists.If you want people to pay attention to what you say you should at least get your facts straight. Perhaps quality would be better than quantity. Lloyd"

I think that my response was civil, but you can be the judge:

November 21, 2007
"Mr. Davies,
Thank you for your corrections, which I have already fixed. However, regarding the half life, my understanding is that CR formulations do not change the actual half-life of the molecules upon with they are based. The major relevant example would be Effexor vs. Effexor XR. The sustained release version is advantageous because it produces fewer GI side effects, but there is no evidence that I am aware of that XR causes fewer discontinuation side effects. Regarding the relationship between half lives and once a day vs. twice daily dosing, this is a non-issue for most psychiatrists. Both Cymbalta and nefazodone are short half life antidepressants that are typically dosed once-daily with no evidence of therapeutic disadvantages. Perhaps Jazz has conducted head to head studies of Luvox vs. Luvox CR--if so, the results would be informative.
Best, Danny Carlat"

I haven't heard back yet from Mr. Davies. I'm guessing that some folks higher up in the company are mulling over the best response, from a marketing perspective. I'd also hazard a guess that the CEO is none-too-pleased with Mr. Davies' e-mail to me. Somehow, I doubt that his message was vetted through media relations at Jazz. But I could be wrong!

Nature Journal Publishes Major Article on Biased Medical Education

A few months ago, Jim Giles, a science writer for the New Scientist and Nature, called me out of the blue to ask about my opinions on drug industry-funded CME. I gave him my usual earful, and mentioned a preliminary study on CME bias that I presented at the American Psychiatric Association meeting two years ago. He asked to see the raw data, meaning the ghost-written CME articles, and it impressed me that he took this level of interest. The result is this article published in this week's issue of Nature.

The bottom line is that in 14/15 articles I reviewed, the sponsored drug received the highest number of favorable mentions. That may not be terribly surprising, but it is evidence of commercial bias, which is not allowed by ACCME standards of commercial support.

Giles is right that the instrument I used, called the Commercial Bias Inventory (CBI), has not been tested for reliability, but I'm now working with two psychiatrist colleagues, Ingrid Li at Tufts and Robert Kelley at Cornell, to validate the CBI. Once it's validated, we're going to blindly rate a number of CME articles and report our findings. If anyone else out there is interested in collaborating with us in this research, let me know (drcarlat@comcast.net).

Luvox CR and All That (Yawn) Jazz

Jazz Pharmaceuticals is running two-page spreads in the psychiatric journals advertising...well, it's hard to figure out what. The headline reads: "Anxiety disorders often present first, before other comorbid conditions." Then there are two blurbs, one about social anxiety disorder (SAD), and the other about obsessive compulsive disorder (OCD). No drug is mentioned.

So you have to google Jazz Pharmaceuticals and social anxiety disorder to find out that Jazz bought the rights from Solvay to market a "new" product, Luvox CR. According to press releases, it is close to FDA-approval for both SAD and OCD and will be released sometime in the first quarter of 2008. What a bummer--not that we have to wait, but that it is being foisted on us at all.

Luvox is another SSRI, and actually the first ever used by psychiatrists, having been approved in 1984 for the treatment of OCD. It has very little going for it. Its half-life is about 15 hours, and it causes more drug-drug interactions than any other SSRI. Before, Luvox was a pretty useless drug; come next year, we'll have a pretty useless drug that lasts even longer than the original.

Jazz Pharmaceutical's advertising slogan is "Innovation that performs." With Luvox CR, there's precious little innovation, and the only performance is a level of marketing chutzpah that is guaranteed to turn off prescribers.

Some Great Blogs to Peruse

Nice to have some good news to report--namely, that I've added three great blogs to my blogroll.

1. The Psych Central Blog by John Grohol. John is a great psychologist and web expert who I know personally. While I've known about his famous Psych Central website for a long time, I only just started reading his blog. He's been posting at a furious pace (unlike me) and everything he writes is interesting and fresh. I'm not really sure how he does it, I just know I'm jealous.

2. PostScript, the new blog by Kate Peterson and The Prescription Project. These are more or less weekly postings covering the world of excessive drug industry influence in medicine. They are thorough, informative, and beautifully written. These are not rants pounded out in the middle of the night, unlike some blogs I know!

3. Hooked: Ethics, Medicine, and Pharma, by Howard Brody. Dr. Brody is an ethics expert and author of the book Hooked, which argues eloquently that we physicians need to reclaim our integrity. Don't blame Pharma, people, it's up to us!

How Money Doth Breed CME Niches!

First, my apologies for the sparsity of posts lately--I ran behind on some newsletter work and I have to keep my subscribers happy.

I just received a flyer from an outfit called "CME Peer Review" (look them up on the web here), a new company which has wormed its way into a brand new niche in the commercial CME world--"independent content validation."

This is NOT their marketing copy, but it might as well be:

THE PROBLEM: OK, you're making money hand over fist by providing drug company-sponsored "medical education" (nudge-nudge, wink-wink). It's a sweet gig, getting million-dollar grants to hire medical writers to scribble out pseudo-newsletters. Donald-me-no-Trumps, these are FAT profit margins...and all yours! So what's the problem? A new "regulatory environment," that's what. Suddenly, everyone from the New England Journal of Medicine to the Senate Finance Committee is whining about "conflict of interest" and "commercial bias." Haven't they read Nietzche?! You are beyond such fairy tales as truth and morality, but in order to maintain your uber status, you must play the game.

THE SOLUTION: At CME Peer-and Jeer Review, our "turn-key system helps you ensure your CE activities are valid, aligned with the public interest and compliant with regulatory guidance and accreditation standards" (that's lifted verbatim from their actual marketing copy!). Got an article sponsored by Pfizer pushing more docs to prescribe Geodon? Choose from our "ever-expanding independent network of reviewers" to find just the shill to give your article the seal of approval. Don't worry, we have a patented system of laundering our reviewers--they're spic and spam and ready to deploy our CME SCRUB DOWN (TM) process for your CME activity.

CLIENT TESTIMONIALS:

"We encountered a difficult situation in which management had already spent the sponsor's grant on a $100,000 rehab of his office shower. Then, at the last minute, we found out the activity was hopelessly biased. We called CME Peer-and-Jeer Review and our problems were solved--what a quick turn-around! Thanks, guys!"

"Your team found an issue in one of our activities--it was subtly promoting a competitor's drug! By helping to bring the activity back in line with the sponsor's agenda, you helped us secure double our original grant for next year. We feel so much more confident about our income stream, thanks to you."

CME Peer-and-Jeer Review: Your CME SCRUB DOWN specialists!

Skirting CME Regulations in Real Time: Watch it Here!

Because the Senate Finance Committee concluded that the commercially-funded CME system is broken, the ACCME issued new policies intended to create thicker firewalls between industry and medical education. In a prior post, I "translated" these new policies into language mere mortals can understand. Now, in a new article in Medical Marketing and Media, we can see how commercial sponsors are already finding ways to avoid real changes.

The article profiles Bruce Bellande, Ph.D., president of CME Enterprise. Dr. Bellande bemoans that he and his parent organization, Deborah Wood Associates, have to demonstrate that they are meaningfully "separate." Deborah Wood Associates began as a medical education communication company, but has expanded into a 100-employee strong marketing consultation firm for the pharmaceutical industry. In order to show ACCME that CME Enterprise is now separate from Deborah Wood Associates, Bellande moved his staff into "new quarters" (read: Time for everyone to pick up your laptops and move down the hall!) and he had to create a trail of paperwork proving that a firewall exists. This included an organizational chart, some disclosure forms, and a few other documents that he likely had on his computer because ACCME has always required these for accreditation. He fired it off to Murray Kopelow, CEO of ACCME, and received this letter back, saying, essentially, that the firewall requirements were satisfied.

If you go right now to the Deborah Wood Associates website, you can see just how strict ACCME's new firewall policies are. This site is geared toward pharmaceutical companies wanting to sell their products, and their techniques couldn't be clearer: "See how we achieve optimal results through two dedicated groups: CME Enterprise and Avant Healthcare Marketing."

This rice paper firewall makes a mockery of ACCME's new policies. It's astonishing that Kopelow has signed off on CME Enterprise.

What's Wrong with DTC Ads?

According to the Wall St. Journal's Health Blog, John Edwards is calling for a two year post-approval ban on direct-to-consumer drug ads. Having stayed up for the past several nights watching my team win the World Series, I have certainly received an excessive dose of DTC ads for the likes of Cialis, Flomax, and Lipitor (is anybody else creeped out by Jarvik as he cocks his head and bats his baby blue eyes?) And, yes, I get that DTC's encourage consumers to ask their doctors to prescribe the newest and most expensive meds.

But banning them doesn't make sense. Why? For one, it's one of the only arenas where drug companies advertise their products with full disclosure. Everybody knows it's an expensive ad paid for by the company. There's no pseudo-legitimate journal or medical education company pretending to be a scientific article, when in reality it's a paid advertisement.

Second, they do serve an educational function for consumers, if biased. There are a lot of guys out there urinating very frequently who would not consider this a potentially treatable issue if they hadn't seen those irksome Flomax commercials, the ones featuring the sports-crazed baby boomers who get to hang out in their kayaks longer without having to run into the woods--all because they're taking their Flomax. Sure, viewers are going to run to their doctors and ask for Flomax my name, but it's up to the docs to decide which drug is best. And meanwhile, some men will find out they have early prostate cancer (rather than benign prostatic hyperplasia) and might get their lives saved in the bargain.

I say let the companies have their DTC ads, and use the extra money they gain from increased sales to fund a government-administered pool of money to pay for unsponsored continuing medical education. This will save the health care system much more money in the long run.

Takeda's Clinical Symposia: It's all about Rozerem

Today's New York Times has a nice piece by Stephanie Saul on sleeping pills, entitled "Sleep Drugs Found only Mildly Effective, but Wildly Popular." She covers a recent NIH-funded report which concludes that sleeping pills "reduced the average time to go to sleep 12.8 minutes compared with fake pills, and increased total sleep time 11.4 minutes." Saul focuses particularly on Rozerem, which has been heavily promoted in direct-to-consumer ads, and yet was found by NIH to be one of the less effective pills. To quote Saul: "Consider that it costs about $3.50 a pill; gets you to sleep 7 to 16 minutes faster than a placebo, or fake pill; and increases total sleep time 11 to 19 minutes."

I am not anti-sleeping pill by any means. I prescribe plenty of them, and sometimes take them myself. They certainly work. But I am not convinced that the brand-name pills are worth their higher prices. I prescribe plenty of trazodone, temazepam, and diazepam for sleep, as well as generic Ambien (zolpidem). Occasionally I'll go to pricey Ambien CR for patients who like Ambien but who wake too early in the morning.

I have had a grand total of one patient respond to Takeda's Rozerem. Nonetheless. The journal Clinical Symposia, in a recent edition sent free to all physicians, likes Rozerem so much that it highlights the melotonin receptors on the picture of the brain on the cover (see above). That seemed odd to me, since this was an issue on insomnia for primary care physicians, and Rozerem is hardly the drug that PCPs would or should turn to first when treating insomnia. Once I flipped it over, the mystery was solved, as this entire issue was sponsored by Takeda. In addition, the first author, Gary Richardson, M.D., is a prominent Takeda speaker. See, for example, this website, "SleepJournalClub.org," chaired by Richardson, funded by Takeda, and providing CME credit for reading journal articles on insomnia. I suggest you click on "archived events" and scan through the 11 articles posted thus far. I went through this exercise in an effort to determine whether the articles chosen were biased either in favor of Rozerem or against its competitors. Here's what I found:

1. Effects of NG2-73 On Sleep Onset, Quality and Next Day Function In a Transient Insomnia Study. A clinical study of a new compound, NG2-73, manufactured by Neurogen, which acts as a partial GABA agonist. Does not promote Rozerem.

2. A Review of the Evidence for the Efficacy and Safety of Trazodone in Insomnia. A review of trazodone concluding that it has little supporting evidence as a hypnotic and that is has significant side effects. Promotes Rozerem by trashing its main generic competitor.

3. Highlights from APSS (a sleep conference) 2007. Reviews a study showing that Ambien causes the elderly to be shaky on their feet, and refers to Takeda-funded studies (read abstracts here) showing that Rozerem does not have this liability. Promotes Rozerem.

4. The Brain’s Master Circadian Clock: Implications and Opportunities for Therapy of Sleep Disorders. Emphasizes the importance of the melatonin system in insomnia. Promotes Rozerem.

5. Safety of Ramelteon in Individuals With Mild to Moderate Obstructive Sleep Apnea. Need I say more? Promotes Rozerem.

6. Combined Therapeutics for Insomnia: Should our First Approach be Behavioral or Pharmacological? Unsponsored paper on therapy vs. meds for insomnia. Does not promote Rozerem.

7. Tiagabine Enhances Slow Wave Sleep and Sleep Maintenance in Primary Insomnia. Promotes Tiagabine.

8. Influence of Pharmacokinetic Profiles on Safety and Efficacy of Hypnotic Medications. Funded by Sanofi, maker of Ambien CR, this article is strongly and cleverly promotional of Ambien CR.

9. The Management of Insomnia: From Herbals to Hypnotics. While this is a review of all sleeping pills, it ends with several extraordinarily positive statements about Rozerem (eg., "The selective melatonin receptor agonist ramelteon represents the first major advance in the treatment of insomniain more than 40 years.") Promotes Rozerem.

10. Insomnia and Hypnotic Use, Recorded in the Minimum Data Set, as Predictors of Falls and Hip Fractures in Michigan Nursing Homes. Study showing that hypnotics do not increase the risk of nursing home fractures; rather, insomnia does. While this is not specifically promotional of Rozerem, this fits in well with Takeda's promotion of Rozerem as being safer than Ambien for the elderly. Promotes Rozerem.

11. Relative Abuse Liability of Hypnotic Drugs: A Conceptual Framework and Algorithm for Differentiating Among Compounds. This article, sponsored by Takeda, is essentially a prolonged advertisement for Rozerem, highlighting its main advantage: lack of abuse liability. Promotes Rozerem.

Conclusion? In my analysis (certainly biased by my heightened sensitivity to underlying promotional agendas), 7 out of 11 articles in this Takeda-sponsored CME program are promotional of Rozerem.

Mais bien sur, you say. Why else would Takeda pay Richardson and colleagues to chair this journal club? If they didn't choose articles that made Takeda happy, these physicians would be "missing their dreams" of fat honoraria checks!

A Pharma Mule Show and Tell

Clin psych just dropped me a note requesting that I scan in the documents that I described yesterday. These were the industry-funded CME activities that poor Primary Psychiatry has to schlep around like the abused but well-paid mule that it is.

I tried scanning them right into this blog but Blogger gave me too much technical grief. So I have posted them all at Google Docs. Just click on the relevant links to go directly to the artwork.


1. Here's the DVD funded by i3CME and Bristol-Myers Squibb in which they paid three of the foremost experts in schizophrenia to say nothing about Abilify's propensity to cause akathisia/activation.

2. Here is Stephen Stahl's Cephalon-sponsored newsletter, "Wake up!", which awards 1.25 hours of CME credit to encourage you to detect more patients with "excessive sleepiness" and to prescribe Provigil.

3. Here is a larger version of the actual journal (also pictured above) with its Eli Lilly overwrap advertising a nonsense telesession about bipolar disorder.

4. Finally, here is the first page of the Michael Clark "Cymbalta Synergy" article including the erroneous financial disclosure.

Good old show and tell. I haven't had this much fun since kindergarten!

Primary Psychiatry: Pharma's New Mule

Granted, everyone’s entitled to make a buck, medical publishers included. This almost always involves doing some advertising for drug companies. There’s nothing inherently wrong with this, as long as the advertising doesn’t infiltrate the content of the articles. This firewall between marketing and editorial content is crucial, and some journals are very good at maintaining this separation—journals such as Lancet and New England Journal of Medicine come to mind.

And then, on the other hand, there is Primary Psychiatry.

The September issue of Primary Psychiatry is the encapsulation of the worst of the worst of what might be called "greed journalism." Rather than serving as a medical journal, Primary Psychiatry has become a mule for various sponsoring pharmaceutical companies, heaving promotional CME programs into our offices. An almost exquisite example of journal as marketing vehicle, the September issue is the very Mona Lisa of CME corruption.

It arrived in my office “polybagged” with three industry-funded educational activities. Polybagging entails wrapping the journal in plastic wrap and throwing in stuff that drug companies want you to see. The September issue contains:

1. A DVD funded by Bristol-Myers Squibb, coyly entitled, Akathisia: Problem of History and Concern of Today. BMS markets Abilify, widely acknowledged as the atypical most likely to cause akathisia—an inconvenient truth for BMS, because this drives down Abilify’s market share. Thus, BMS paid i3CME (you remember them--the producers of the great Lindsey DeVane fiasco) to find speakers who would play down this liability, and they got exactly what they paid for in these Three CME-usketeers: Prakash Masand, Naveed Iqbal, and Tim Lambert. Abilfy’s association with akathisia is conveniently not mentioned by any of these key opinion leaders. Instead, we hear that Risperidal, Zyprexa, Clozapine, and even Seroquel (!) can cause it. If you can stomach watching this biased presentation, you'll quickly discover that its promotional message is: (1) Akathisia is more common with first generation antipsychotics; (2) There’s no real difference between the atypicals; (3) It’s often caused by SSRIs rather than atypicals; (4) Don't worry, prescribe Abilify.

2. The second prize is a newsletter called “Wake up!”, produced by Steven Stahl and funded by Cephalon. An 8-page advertisement for Provigil, it contains articles written by a Who’s Who panel of industry-funded psychiatrists, including Wallace Mendelson, famous for his ghost-written trazodone-bashing article in the Journal of Clinical Psychiatry (2005;66:469-476; see my New York Times op-ed on his work for Sepracor here). For those who don’t know, Stephen Stahl, founder of the company Neuroscience Education Institute, is one of the more industry-conflicted psychiatrists in the profession, right up there with Charles Nemeroff. The “wake up!” newsletter oozes Cephalon and Provigil, with exhortations to diagnose more people with "excessive sleepiness" and to treat them with Provigil and other meds. Cephalon pays Stahl tens of thousands to say good things about Provigil, and then pays Primary Psychiatry even more to mule the newsletter to 60,000 physicians.

3. Finally, the actual journal is covered with an overwrap advertisement for an Eli Lilly-sponsored educational event on bipolar disorder. No, I didn't spend any more of my precious time enduring that telesession. I'm assuming it will argue that patients with bipolar disorder are at a higher risk for diabetes regardless of which medication they use, so don't worry about slamming them with Zyprexa.

The "Pharmatorial" content doesn’t end with the plastic goody bag. Inside the journal, synergizing nicely with a three-page ad for Lilly’s Cymbalta, is an entire section on pain in psychiatry, including an article on "Psychopharmacology of Chronic Pain." The author, Michael R. Clark of Johns Hopkins, is listed as having “no affiliation with or financial interest in any organization that may pose a conflict of interest.” This fib can be checked out by going to Google and typing in “Michael Clark, M.D. and disclosures.” The first page of results shows that Dr. Clark has been the course director of two CME conferences on pain management this year, supported by educational grants from Lilly, King Pharmaceuticals, and Cephalon.

It isn't easy being a mule. But the money helps.

The AMA, Pharma Gifts, and the Power of 8

This Thursday I will be joining several colleagues in testifying at the Massachusetts State House in support of a bill to tame the cost of medical care in the state (read a fact sheet from Health Care For All here). One portion of the bill will ban most drug company gifts to doctors. The thinking here is that when we receive gifts from reps, such as textbooks or free dinners or lunches, we inevitably feel that we owe the rep something in return. That's just human nature.

What we give the rep in return varies widely. Sometimes, it's just increased access--more frequent visits with us, an extra few minutes of shmoozing, etc.... This works for the rep, since more access equals more time to sell their product.

More insidiously, the pay-back is choosing to prescribe their product over an alternative drug that may be much cheaper. This happens to us all, even to an industry skeptic such as myself. For example, not too long ago, my Ambien CR rep gave me a pamphlet with a selection of free books, and against my better judgment I took her up on it. It was a book on the brain by John Ratey.

Several days after her visit, one of my patients came in complaining of insomnia which had not responded to several hypnotics. He had tried Ambien, Sonata, and Benadryl, but was unable to sleep through the night. Usually, in these situations, I would offer trazodone, which has a long enough half life to last most patients all night long. But something in me made me think about my Ambien CR rep, who had left the office saying, "I hope you'll give Ambien CR a try." I prescribed Ambien CR. As it turned out, this worked no better than regular Ambien, and he ended up on trazodone.

The fact is that pharmaceutical gifting is an effective marketing technique, as much as physicians deny that their medical opinions can be swayed by such small dispensations.

Our increasingly embarrassing American Medical Association (AMA) touts its policy on the ethics of accepting pharmaceutical gifts. Recently, they accepted over $600,000 in pharmaceutical money in order to help advertise their guidelines to doctors. In a nutshell, the policy is: no gift over $100 in value, and any gift must be related to medical care or medical education. Here, as in most of AMA's policies, the emphasis is on making no waves and maintaining the status quo, since this allows docs to get their textbooks, stethoscopes, and nice dinner programs, as long as the dinners are modest. (By the way, the AMA defines "modest" dinners as those meals that physicians would ordinarily pay for themselves, which leaves plenty of room for largesse).

The AMA guidelines become farcical at times. For example, not only is it acceptable to accept a nice dinner out by industry, but it is also acceptable to be offered an array of $100 gifts as an inducement to attend the dinner. But here's where AMA draws the line: physicians can be offered no more than eight different gifts to choose from. Here, verbatim, is the relevant section:

"(i) May companies invite physicians to a dinner with a speaker and offer them a large number of gifts from which to choose one?
In general, the greater the freedom of choice given to the physician, the more the offer seems like cash. A large number of gifts presented to physicians who attend a dinner would therefore be inappropriate.
There is no precise way of deciding an appropriate upper limit on the amount of choice that is acceptable. However, it is important that a specific limit be chosen to ensure clarity in the guidelines. A limit of eight has been chosen because it permits flexibility but prevents undue freedom of choice. Each of the choices must have a value to the physicians of no more than $100."

We don't need gifts from drug reps, nor do we need the biased "education" they provide during their visits. Let's stop pretending that gifts are anything other than influence-peddling.

DeVane Mounts Defense of his CNS Spectrums Article

Lindsay DeVane, the Medical University of South Carolina professor who had described this article in CNS Spectrums as "commercial crap," is now defending said crap from its detractors.

Possibly responding to this letter just published in Psychiatric News, in which Harvard psychiatrist Alan Stone advocates officially "shaming" unethical colleagues who participate in ghost-writing, Dr. DeVane sent me the following e-mail:

"Dear Dr. Carlat, I am writing to say there should be no doubt about the integrity of the CNS Spectrums publication as an i3 CME certified activity. In particular, my unflattering characterizations of the CNS Spectrums article reflect the inherent limitations in providing practicing clinicians with fundamental descriptions of complicated issues. The initial draft of the article that was eventually published was written directly from the transcripts of the live CME televised broadcast last December and was not ghost-written. All three co-authors were heavily involved in multiple edits before agreement was reached on a final manuscript. Although my opinion is that antidepressant drug-drug interactions of major clinical significance are rare events, we all know that interactions can occur and the need for such awareness was a theme in the broadcast and article. My Neuropsychopharmacology commentary allowed a more complete discussion of some scientific issues, but there should be no question about the integrity of the CNS Spectrums publication as a CME activity. Lindsay DeVane."

I can only assume that Dr. DeVane must have been severely pressured by multiple parties to change his tune. You can read his earlier, and very different take, on the article in my prior posting here. At that time, Dr. DeVane called the first draft of the article a “ridicuous text… parts of it were inaccurate, simplistic, and [contained] over-generalizations.” The fact that he is now saying that this article was "written directly from transcripts of the live CME televised broadcast" is not exactly an endorsement of that Hawaiian event, which was funded by Bristol-Myers Squibb.

And although he is now saying that "all three co-authors were heavily involved in multiple edits before agreement was reached on a final manuscript," in his earlier letter, he stated, "I haven't even read the CNS piece, but from what you say, I probably shouldn't as it's likely embarassing. Please ignore it for purposes of interpreting my researchand views."

By the way, the founder of CNS Spectrums, James LaRossa, who knows all the players involved in this scandal quite well (in fact, he now publishes a different journal with both Nemeroff and DeVane on the masthead), said of the CNS Spectrums piece, "I am willing to bet dollars to doughnuts that Nemeroff never saw proofs of the article either."

As La Rossa commented further, "In truth, the CME business has become rotten to the core." I couldn't agree more.

Prescription Data Mining: A Transparent (-ly absurd) Defense by Verispan

The arguments in favor of that latest manipulative marketing technique, prescription data-mining, come in many different hues of speciousness. I recommend you visit this excellent page on the National Physician's Alliance website to learn more.

Today, however (on a tip from PharmaGossip), I read the most absurd argument in its defense yet, reported in yesterday's Philadelphia Inquirer. The reporter, Karl Stark, quoted Jody Fisher, Verispan's vice president of product management, as saying: "Doctors are trying to create a special right of privacy. I can certainly appreciate where they're coming from. But the way the world is going is toward increased transparency of information."

"Transparency of information"! What a wonderful Web 2.0 buzz phrase!

Here's what, Jody: Let's hold hands and use that argument together on the pharmaceutical companies who are refusing to reveal their payments to doctors. And while were at it, let's extend your cutting edge concept into other areas of commerce as well. For example, groceries stores can combine customer's credit card information with their bar-coded food item data to create a goldmine of "transparent" marketing information for Kraft and Proctor & Gamble. I can't wait for the smiling cereal reps to detail me. "Mr. Carlat, I was wondering if you would consider purchasing more Great Grains Selects? We have new head-to-head data comparing it to Smart Start...."

If you haven't heard about prescription data-mining yet, here's a short course. When I was a hired gun speaker for Wyeth back in 2002, drug reps would book me speaking gigs at primary care doctor's offices. My job was simple: say whatever I possibly could to get doctors to prescribe more Effexor XR.

Before each of these "Lunch 'n Learns," as they are called, the rep would fax me a little cheat sheet about the doctor we'd be visiting. This sheet spelled out exactly how many prescriptions for which antidepressants this doctor was writing. Doctors who wrote too much Celexa and Zoloft, and not enough Effexor, were crucial "targets," and I was implicitly encouraged to give these misguided doctors a particularly hard sell.

How did the reps get such detailed information? Since the 1990s, drug companies, pharmacy information companies (such as Verispan and IMS) and the AMA have been collaborating in packaging doctor's prescription information and using it to help companies more efficiently sell their drugs. Companies like Verispan buy prescription info from local pharmacies, then they purchase identifying data on all us doctors from the AMA (which makes over $40 million a year by leasing out its physician Masterfile), and finally they turn around and sell the whole package to the highest-bidding drug companies.

Most readers of this blog have probably already heard about this latest piece slime-marketing, but doesn't it make you slightly nauseous to contemplate it again? It does for me.

Well, the word about this practice has finally hit the media, and many doctors, particularly members of the vibrant new physician's organization, National Physician's Alliance , are outraged (I know, this is the second plug I've given them in this posting; here's the subliminal message: JOIN THEM INSTEAD OF THE AMA). So far, three states, New Hampshire, Maine, and Vermont, have passed legislation curtailing the practice. However, the well-funded pharmacy information companies are planning to sue each and every state that limits prescripion data-mining. They've already succeeded in persuading a New Hampshire judge to strike down the law.

Don't worry, people. The good guys are gonna win on this one--I guarantee it!

Publisher of Psychopharmacology Bulletin Weighs in on CME issues

James M. La Rossa Jr. built a medical publishing empire and knows a thing or two about industry-funded CME. He founded CNS Spectrums and Primary Psychiatry in 1997, and sold them to its current publisher in 2003. Aside from publishing the journals T.E.N. and Mental Fitness, he recently rescued the journal Psychopharmacology Bulletin from oblivion by buying it from NIMH, which wanted to get out of the medical journal business. He got out of the commercial CME business in 2001 because he couldn't stand what it was becoming.
I spoke with La Rossa, who had commented on a recent posting on unsavory CME manipulation.

Dr. Carlat: As publisher of various psychiatric journals, you could have made a ton of money publishing commercial CME articles. Why didn't you?

La Rossa: First of all, I am in media, which I love. I did not want to be in the CME business. Going from venue to venue to put on the exact same CME programs -what I refer to as the dog-and-pony show-had no attraction for me. I gave up a potential law career to be a journalist and publisher. The most important job of any publisher is to influence a field of interest, make your publications an indispensible part of that field, and, most importantly, play the game while keeping your third party credibility. Once you lose that independence, it is next to impossible to regain it.

Dr. Carlat: Do you think it’s possible for publishers take industry money for CME material in an ethical way?

La Rossa: I don’t think so. In my experience, the publisher inevitably becomes nothing more than an agent of the sponsoring pharmaceutical company. Rather than producing true medical education content, they are customizing intellectual material for pharmaceutical companies. While there is nothing inherently wrong with this, where it gets sticky is when the publication runs the customized project as a CME activity in the journal, which automatically implies that the project is sanctioned by the journal's editors, board of advisors, etc.

Dr. Carlat: The scale of the CME enterprise has certainly mushroomed over the past several years. Why?

La Rossa: Several reasons. First, of course, is that people began to see how much money there was to be made, and that has attracted many companies in itself. But another driver of this enormous CME problem can be traced back to about 5 years ago when the APA began to get very aggressive about retaining exclusive rights to any and all symposia. What they were doing was trying to prevent sponsors and/or outside CME companies from profiting off of these symposia. These companies responded by inviting the APA speakers to a hotel near the meeting, for example, to give the same talk. They changed the title, said it was in "conjunction with the APA meeting," or language like that. In other words, as the APA tightened controls to the dissemination of CME materials to psychiatrists, a CME free-for-all started as private content providers started coming out of the woodwork. It sounds like I am putting most of the blame at the APA's door, which is unfair. Universities-who view CME as a profit center-are getting in on the action as well. But I do think that the APA should stick to what they do best: Make excellent journals and books. Isn't that the very heart and soul of psychiatry?

Author Calls his own CNS Spectrums Article “Ridiculous, Inaccurate, Simplistic”

C. Lindsay DeVane, a Professor of Psychiatry and an author of an ACCME-accredited article published in the journal CNS Spectrums has termed his article a “piece of commercial crap,” and said he had not read the final version before it was published, according to an e-mail he sent to this writer (read his e-mail here).

DeVane, who is Professor of Psychiatry and Behavioral Sciences and Vice Chair for Research at the Medical University of South Carolina, is one of three authors listed for an “Expert Roundtable Supplement” published with the May 2007 issue of CNS Spectrums. The supplement was accredited and produced by i3 CME, a medical education company owned by Ingenix, and was funded by Bristol-Myers Squibb.

Responding in an e-mail to questions I had about the accuracy of the article (read this e-mail here), Dr. DeVane said that he had originally been approached by Dr. Charles Nemeroff to participate in a videotaped discussion to be held at a psychiatric meeting in Hawaii. The discussion was to be funded by Bristol-Myers Squibb, which recently released the antidepressant patch, EMSAM. DeVane initially declined Dr. Nemeroff’s invitation, saying that he did not want to participate in a “circus debate for the sake of selling CME time.” However, he eventually changed his mind and participated in a discussion of antidepressant drug-drug interactions with Nemeroff and Sheldon Preskorn, another high-profile academician who often consults and speaks for drug companies.

After the broadcast, the CME company, i3 CME, presented DeVane with an article based on the discussion, apparently ghost-written by a medical writer hired by the company. DeVane called this a “ridicuous text… parts of it were inaccurate, simplistic, and [contained] over-generalizations.” It is not clear whether DeVane insisted that editorial changes be made. He had not read the final version, and advised that the article be ignored “for purposes of interpreting my research and views.”

The controversy involves a seemingly arcane topic in psychopharmacology, the issue of how drugs interact with other drugs in the bloodstream. In an earlier article in a different journal, published without pharmaceutical funding, Dr. DeVane had argued that these drug-drug interactions were rarely significant when prescribing antidepressants. According to DeVane’s e-mail, that article “represents my summary of the field and opinions.”

The CNS Spectrums article, however, claims that these interactions are often significant when certain antidepressants are used. The article also points out that EMSAM, the drug made by the article’s sponsor, has the advantage of not sharing these drug interaction liabilities. If DeVane’s earlier statements had been used as the basis for the article, then EMSAM could not have been claimed to have this competitive advantage.

In response to inquiries about the discrepancies in DeVane’s earlier article and the newer article, CNS Spectrums and i3 CME did not comment on specifics, but denied any irregularities regarding the planning or writing of the article. According to their written statement, “the faculty [referring to Nemeroff, Preskorn, and DeVane] remains comfortable with the positions they have taken in this CME activity….”

File article under: Corruption in High Places

ACCME's "New" Policies, Translated

On 8/24, ACCME announced 7 new policies that will go into effect as of January 1, 2008. Some of these were probably motivated by the Senate Finance Committee's critical report, but I assume that these don’t represent ACCME's definitive response (or at least I desperately hope not!). You can read the new policies yourself here, but unless you have been through an application for accreditation, as I have, don’t expect to understand what is being said. I’ve taken the liberty of translating each of their impenetrable pronouncements below, along with some commentary along the way.

New Policy # 1: If you make an agreement to provide a CME activity for a drug company, make sure to sign the document. Huh? This is new? It's a little bit alarming that this needs to be spelled out.

New Policy # 2: Drug companies are no longer allowed to tell you how to produce the CME they sponsor. Okay, I guess this is an admission that, in fact, companies had been able to directly influence CME content for all these years. I’m shocked, just shocked.

New Policy # 3: If you produce a web-based CME program, you can no longer conveniently leave off the fact that it is industry-sponsored from the first few web pages, as many providers were doing. This was a rather slimy way of roping doctors into an activity before they realized that it was just another promotional fluff piece. Thus, this policy enhances disclosure. Problem is, disclosure by itself does nothing to prevent promotional content. It only provides the illusion of objectivity.

New Policy # 4: Drug companies can’t put links to CME programs on their websites. This allows providers to more effectively hide the fact that you are about to watch a drug ad in the guise of education. Bad idea.

New Policy # 5: You know all that pesky disclosure stuff that we’ve always required you to do? Well, now we’re serious. You really have to do it. And this is a new policy…how???

New Policy # 6: We’ve changed our official definition of “commercial interest.” But don’t worry, after listening to the concerns of all the for-profit Medical Education Communication Companies, we’ve made certain that our new definition won’t disrupt business as usual. The crux here is that a “commercial interest” is not allowed to produce CME. As you can imagine, any redefinition of commercial interest generates high anxiety among MECCs. To the rest of the world, any company that makes all of their income by taking grants from drug companies and producing education that relates to their products, would be defined as a “commercial interest.” But somehow, ACCME has tweaked, massaged, nay, Shiatsued language as we know it to ensure that MECC’s remain blissfully non-commercial. This way, they can continue to make loads of money!

New Policy # 7: If you teach a CME activity, you can get two hours of CME credit for every hour of credit you teach. Excellent! That nets me 24 extra CME credits per year for writing The Carlat Psychiatry Report! Now this is policy I can get behind.

Bottom-line: The status quo finds ever more elaborate ways of maintaining the status quo.

CNS Spectrums Responds, Sort of....

On July 26, I sent CNS Spectrums a formal letter-to-the-editor outlining, in more genteel terms, the concerns about their commercially biased supplement on drug-drug interactions that I posted early this week here. I just received their response. It is the bland denial of wrongdoing that one might expect. There is no mention of Dr. DeVane's mysterious sea-change in his opinions about the clinical relevance of drug-drug interactions in EMSAM's competitors. Cheer up, truth fans. There is much more to this drama than meets the eye. Stay tuned.

August 14, 2007

Daniel Carlat, M.D.
Assistant Clinical Professor of Psychiatry
Tufts University School of Medicine
Editor-in-Chief
The Carlat Psychiatry Report
42 Pleasant Street
P.O. Box 626
Newburyport MA 01950

Dear Dr. Carlat:

We have had the opportunity to review your Letter to the Editor dated Thursday, July 26, 2007 regarding the Expert Roundtable Supplement “Antidepressant Drug-Drug Interactions: Clinical Relevance and Risk Management,” by Drs. Nemeroff, Preskorn, and DeVane.

We have forwarded your concerns to the faculty members, reviewed the activity planning and independent peer review processes, and examined the participant evaluations that have been received to date. Our findings include the following:

• The faculty remains comfortable with the positions they have taken in this CME activity, both in their presentations as well as how the question and answer section of the activity was addressed.
• Our independent review processes — both for MBL Communications and i3 CME — established that there was no concern of commercial bias with either the live activity or the subsequent enduring supplement.
• Evaluation reports show that 91% of the participants believe this supplement activity to be “objective,balanced and of scientific rigor”.

The ACCME’s Standards for Commercial Support were strictly adhered to and all decisions for this activity were made free of the control of the commercial interest. This includes the identification of the need, the determination of the educational objectives, the selection and the presentation of the content, and the identification of the persons that were in a position to control the content presented during the CME activity. In addition, the disclosure of commercial support was provided to the participants prior to the beginning of the activity as well as all relevant financial relationships of those planning members who had control over the content.

We would also like to note that the question and answer session is live and i3 CME has no influence on questions received from the audience. For many this is a rare opportunity to speak with the experts and questions received are not always directly related to the content.

Given the above information, it is our position that certifying this activity for AMA PRA Category I CreditTM is appropriate. Both our organizations have done due diligence in ensuring that this activity meets the standards for a certified medical education activity.

Sincerely,

Sandra T. Weaver, MS, Vice President, CME Program Development, Compliance Officer, I3CME

Darren L. Brodeur,, CEO & Publisher, MBL Communications, Inc., Publishers of CNS Spectrums, Primary Psychiatry, and Psychiatry Weekly

CNS Spectrums: "A Piece of Commercial C__p"

No, that's not Carlat getting nasty and personal again. Those are the words of one of the most well-recognized names in American psychiatry, an academic of impeccable credentials who is involved in the industry-CME charade and is getting sick of it (insert the letters "r" and "a" to complete the headline--the spelled-out version was offensive to some). He will remain anonymous.

Why is he saying such terrible things about CNS Spectrums? He is referring to one of the most corrupt CME activities to hit the stands in a long time, and believe me, it takes a lot to impress this reporter.

The article in question can be found in the May 2007 Supplement to CNS Spectrums, entitled, “Antidepressant Drug-Drug Interactions: Clinical Relevance and Risk Management,” (Nemeroff CB, Preskorn SH, DeVane LC, CNS Spect 12:5 (Suppl 7) May 2007).

According to my source, this sham article was originally a televised roundtable which was adapted by medical writers to form the basis for an industry-supported supplement. The CME company in question is i3 CME, which, my source said, wrote a "ridiculous text...parts of it were inaccurate, simplistic, and had overgeneralizations."

And yet, it was published anyway, and is accredited by the ACCME for 1 hour of Category 1 PRA credit.

The details of the science are a bit murky. But the short version is the Bristol-Myers Squibb, maker of the newly approved antidepressant EMSAM (transdermal selegiline patch), commissioned the article to convince doctors that EMSAM is safe to prescribe, even though it is an MAOI, which can produce fatal interactions with other drugs and with certain foods containing the amino acid tyramine. In order to deflect attention from this liability, the article dwells primarily on a drug-drug interaction in which EMSAM is safe: interactions involving the liver's P-450 enzyme system. Indeed, EMSAM neither inhibits nor induces these enzymes, meaning that it won't affect the levels of other medications that are metabolized in the liver.

Of course, this is an "advantage" only if drug-drug interactions are problematic for other antidepressants. The article works hard to make the case that two SSRIs, Prozac (fluoxetine) and Paxil (paroxetine), are dangerous medications because of drug-drug interactions: "To put these numbers in perspective, fluoxetine and paroxetine at 20 mg/day produce approximately a 500% increase in the AUC of CYP2D6 dependent drugs" (see page 6).

But this opinion directly contradicts what one of the authors recently wrote in a non-commercially funded article published in the journal Neuropsychopharmacology, at that time edited by Dr. Nemeroff, who happens to be the first author of the CNS Spectrums piece. According to my source, Dr. Nemeroff spearheaded this CNS Spectrums EMSAM advertisement "for the sake of selling CME time."

At any rate, in that earlier unfunded article, Dr. DeVane, the third author of the CNS Spectrums piece, wrote: "Dr. Preskorn and Dr. Werder's commentary is confusing because it frequently fails to distinguish between verifiable statements and personal opinion, includes dubious extrapolations of data (eg 'lowest effective dose of fluoxetine and paroxetine produces approximately a 500% increase in the plasma concentration of co-prescribed [CYP2D6] drugs')" (Neuropsychopharmacology 31:1594-1604, 2006).

With a sprinkling of industry money, an opinion that was once a "dubious extrapolation of data" becomes a fact. While I'm no fan of industry-funded CME, in this case there was a silver lining: old foes (Dr. DeVane and Dr. Preskorn) were reunited.

By the way, I have nothing against EMSAM, but I rarely prescribe it because most patients don't want to have to hassle with wearing a patch. Generally, if I want to prescribe an MAOI, I'll prescribe oral Parnate or Nardil.

In the CNS Spectrums parallel universe, however, patients appear to be yearning for a patch. The article ends with the following promotional comment by Dr. Nemeroff: “I have had more and more patients say to me, “I really think that I would like to try selegiline transdermal system. I do not like taking pills.”

Carlat Blog Verdict: CNS Spectrums: The very definition of a "throwaway" journal.