Wednesday, May 27, 2009

ACCME's Good Courses, Bad Courses--Mystery Solved?

According to an anonymous source, ACCME’s newly proposed “Commercial Support Free CME” did not arise directly from ACCME. Rather, the idea was hatched in response to pressure from the American Board of Medical Specialties, which apparently takes a very dim view of industry-supported CME.

Here’s the background of this increasingly complicated issue.

As I wrote in a prior post, the ACCME has floated the concept of distinguishing two different types of CMEs—a Commercial Support Free CME versus the standard "anything goes" industry-funded CME (see this report
from their March 2009 Board meeting for the details.) This has struck many as a strange idea: the national certifying body presents a refined definition of superior vs. inferior education, but at the same time declares that they would happily accredit inferior education anyway.

The plot got even murkier after the American Medical Association’s Council on Ethical and Judicial Affairs (CEJA) recently released its second effort at defining the ethics of industry funding of medical education. In their first report,
which was released last year, the committee proclaimed that companies should not pay for doctor’s education when those same companies stand to benefit financially from the content of the education. While that made eminently good sense, it angered a subculture of doctors who prefer not to pay for their own education, so the proposal was tabled, and the committee was directed to come up with a more palatable version of medical ethics, which they recently released. This document, like ACCME’s proposal, proposes the same surreal notion of two CMEs: one that is “ethically preferrable” (involving no commercial support) and another that is only “ethically permissable” (funded by drug companies).

Essentially, the world’s premier medical organization is saying that while we should strive for the best ethics, dodgy ethics are also acceptable—at least when a lot of money is at stake.

Well, I finally solved the mystery of the two CMEs. At the heart of this case is neither the ACCME nor the AMA, but rather the American Board of Medical Specialties (ABMS). The ABMS sets the standards for maintenance of specialty board certification. Depending on your specialty, you have to undergo an exam or other evaluation process every few years so that you can continue to call yourself a “Board-Certified” psychiatrist, cardiologist, dermatologist, and so on. Apparently, the ABMS, realizing that industry-funded CME is quickly losing the public's trust, would prefer to no longer allow doctors to submit commercial CME as part of their requirements. But in order to be able to distinguish commercial CME from non-commercial CME, ABMS needed help from the organization that accredits CME, namely, the ACCME. So they asked the ACCME to create a separate Commercial-Free CME designation. ACCME complied, and the result is the proposal and call for comments posted on their website.

I called ABMS to verify they they are the force behind ACCME's proposal, but I was told that this was a "misunderstanding." I then went to my source, who said that ABMS is backtracking because of angry comments from medical societies. Finally, I contacted ACCME to find out if the Commercial Free CME designation was, in fact, prompted by ABMS, and I am still awaiting their response.

Does any of this really matter? Who cares who came up with the idea, or who pressured whom? It matters because we all deserve to know exactly where our major medical organizations stand on issues that are crucial to the public health. And the education of physicians is one of the most crucial issues of all.

Wednesday, May 20, 2009

Med Page Today Interviews Dr. Paul Appelbaum and Me on Industry Relationships

Yesterday, John Gever of Med Page Today interviewed me and Dr. Paul Appelbaum on various topics about the relationship between the pharmaceutical industry and psychiatry, which I have posted above for your viewing pleasure. Dr. Appelbaum is a former president of the APA and is the chairman of the "Ad Hoc Work Group on Relationships Between Psychiatrists and Medical Industries." He and the members of this group have drafted a report with recommendations for how we can clean up our act. While the report has not yet been formally approved by the Board of Trustees and is therefore not public, I can tell you that it contains many of the same elements as the recent Institute of Medicine report, which I described here. Appelbaum's report was discussed in the APA Assembly on Sunday and the review was frankly somewhat mixed. What will happen next is that the Board of Trustees will continue to elicit feedback from the APA membership and will eventually vote on whether to adopt some version of the current report. My prediction is that the current version will be adopted with very few changes, but that's only a prediction (I'm not a member of the Board, just the Assembly).

There have been a number of excellent symposia over the last few days on how to set the right distance between doctors and commercial interests and I'm coming away from this meeting with high optimism that we are really turning a corner in our profession.

Monday, May 18, 2009

Dispatch from the APA Annual Meeting: The "Product Theater"

I'm writing this from the Press Room in the Moscone Convention Center in San Francisco, where the annual meeting of the American Psychiatric Association is being held. On my schedule this morning was a lecture on genetics in psychiatry by Kenneth Kendler, but once I got there a line was snaking its way into the hallway and I was out of luck. So I decided to go to one of Shire's product theaters.

You may recall that recently the APA voted to phase out industry-sponsored symposia (ISS), but they are now allowing companies to hold promotional educational events called product theaters. This one was entitled "Current Perspectives on Diagnostic and Treatment Challenges of ADHD in Adults," and was presented by Robert Lasser, who is Shire's Senior Director of Global Medical Affairs. That's him in the photo.

Overall, he made a fairly balanced pitch for diagnosing more ADHD in adults and for using Vyvanse. He is a psychiatrist, and knew his stuff. It was definitely a soft sell, compared to the experience of being visited by a Shire drug rep.

We heard the usual information (not inaccurate) about 4% of adults having ADHD, about estimates that up to 20% of patients with depression have ADHD. We heard about the ways that ADHD symptoms manifest in adults, like workaholism, possibly due to job inefficiency, frequent changes of life partners, finishing other people's sentences, low frustration tolerance, etc.... Of course, all of these are non-specific symptoms and can be seen in a huge range of other diagnoses and even in people with no psychiatric problems at all, which was something that was not mentioned. On the other hand, would this have been mentioned by a conventional key opinion leader speaking at an ISS? Probably not.

The one thing that bothered me is that, unlike at any of the other symposia, refreshments were served, consisting of a table with coffee, bagels, and muffins. Nothing extravagant, but I can assure you that there was a long line of people feeding themselves, and that this drew people in. It was not as crowded as Kendler's lecture, but then again Kendler is a world famous psychiatrist lecturing on a topic that we hear a lot less about than ADHD.

Thus far, I would say that the product theaters are a success, in that they are transparently promotional and provide a reasonable forum for us to interact at a high level with industry. I'm willing to bet that in New Orleans, they will not be allowed to provide food, because this places them in a privileged position in relation to the other events.

That's all for now--I'll be posting frequently throughout the meeting!

Thursday, May 14, 2009

Akathisia-gate Scandal in Wall Street Journal

Akathisia-gate, Bristol-Myers Squibb's ongoing efforts to distract attention from the major side effect of its blockbuster antipsychotic drug Abilify, has expanded into a scandal that was covered on the front page of today's Wall Street Journal.

Staff writer Shirley Wang profiles Andy Behrman, a man with bipolar disorder who gained notoriety when he published the book Electroboy: A Memoir of Mania. According to the article, representatives of BMS approached Behrman after the book's publication and asked him to do promotional speeches for Abilify, which was about to gain FDA approval for the treatment of mania. He initially signed a contract for $40,000, and eventually made up to $10,000/day.

The problem is, soon after he started taking Abilify, Behrman noticed restless sensations in his legs--akathisia. He said he told his BMS handlers about the side effect, which the company denies. At any rate, apparently the money he was receiving was just too good for him to tell the truth about his side effects, and he continued providing glowing endorsements. He said that the company provided him with talking points, and instructed him to reiterate in his talks that Abilify had no side effects and to avoid mentioning that he was being paid by BMS.

Of course, the company denies any malfeasance, claiming that Behrman requested an exhorbitant $7.5 million for further talks, and that the company refused the offer. The implication is that Behrman is simply a disgruntled former hired gun. We may never know the entire truth of the matter.
But knowing the sordid history of pharmaceutical marketing tactics, I'm giving Behrman the benefit of the doubt here.

Tuesday, May 12, 2009

The Next Phase in Industry-Funded Medical Education

For those who are shedding tears over the imminent demise of direct industry-funded CME, there is hope. The American Psychiatric Association will allow companies to host "product theaters" at the upcoming annual meeting in San Francisco. I just received the following invitation from Shire. As you can see, the faculty members are Shire employees, and the postcard makes it clear that "this is a promotional event. CME credit will not be available for this session." It's transparent, it's promotional education, and it's honest. I look forward to learning more about their current and upcoming products.

Abilify and the Great Akathisia Cover-up, Part 2

Yesterday, I described a patient who experienced transient severe jitteriness and shakiness on Abilify 5 mg/day. She did not want to discontinue it yet, and as I mentioned, I'll provide an update when I see her next.

Today, I saw a woman in her 30s who has suffered recurrent depression and anxiety for years. I had recently added Wellbutrin SR to her Effexor XR and Klonopin. This seemed to help decrease her crying jags initially, but after a few months she became depressed and hopeless again. She was seeing her therapist regularly, but that wasn't doing the trick. So at her last visit in March, I had her discontinue the Wellbutrin and I added Abilify at 10 mg a day. Today, she said that she stopped the Abilify after 2 weeks, because "I felt like I was having 10 cups of coffee per day." She couldn't sleep, despite taking Ambien 10 mg at night.

Nonetheless, she feels less depressed today because over the couple of months since she stopped the Abilify, she began seeing her therapist more often, up to twice a week. She feels she has more perspective on some of her stressors (an ill father, financial difficulties).

She's doing okay, but this is another case in which the much vaunted Abilify fails as a augmentation for depression, and reveals its true colors as the antipsychotic most likely to cause akathisia. Clearly, starting her at 10 mg was a mistake, and when I use it in the future, I will start at the lowest possible dose, which is 2 mg.

Meanwhile, BMS is funding plenty of CME about using antipsychotics in depression and is making sure to contract with education companies that will hire key opinion leaders who can be depended upon to go easy on Abilify's side effects. For example, here is how Abilify's side effects are discussed by a noted academic in this online symposium created by CME, LLC:

"Adverse event dropouts; you always want to know, How well were these drugs tolerated? And in this first study it was pretty darned good. I mean, it looked very placebo-like in terms of ability to stay on the drug. The data for both studies when they’re put together in the package insert have a dropout rate of about 6% for aripiprazole. So it’s a bit higher than placebo. A lot of restlessness, a lot of akathisia, you know, people sort of a little bit unable to sort of stay still, but they could tolerate the drug. That’s 23%, 25% in the package insert. So some side effects, but overall pretty good tolerability."

Hmmm...."sort of a little bit unable to sort of stay still, but they could tolerate the drug." This is the beauty of industry-funded CME. You're not buying outright deception and therefore a public relations disaster, but you are buying someone who will handle your product's liabilities with kid gloves.

Monday, May 11, 2009

Abilify, the Journal of Clinical Psychiatry, and "Akathisia-gate"

Clin psych has posted this enlightening and relevant article about the efforts of Otsuka and Bristol-Myers Squibb to distract our attention from the major side effect of Abilify, which is akathisia. As he mentions, in the trials leading to Abilify's FDA approval for augmentation of antidepressants (you can watch one of their recent TV commercials here, but do so quickly, before BMS forces YouTube to take it off their site) the rate of akathisia, or extreme and debilitating restlessness, was 25% on Abilify as opposed to 4% in the placebo group.

Here's what Abilify's akathisia looks like outside of the scrubbed fantasy land of hired guns and PR companies. For several years I have treated a woman in her 40s with bipolar disorder who had been fairly stable on Tegretol, an anticonvulsant that is FDA approved for the treatment of manic episodes. But over the last few months, she has become involved in a pyramic marketing scheme and has ended up in serious debt. We both agreed this represented a manic episode, and decided to switch her from Tegretol to another medication, preferably one that did not cause any weight gain. She had not responded well to lithium in the past, Depakote and most of the atypical antipsychotics were out of the question because of their weight gain side effects, so I recommended a trial of Abilify.

"Let's start at 5 mg a day," I said, "then we can increase to 10 mg if we need to."

This was on a Thursday, and over the weekend, she left messages at my office saying that she felt incredibly "shaky," anxious, had insomnia, and just felt all around terrible. She didn't call my emergency coverage, but on Monday I spoke to her and found out that she had in fact increased the Abilify to 10 mg after a couple of days, clearly worsening her akathisia. I recommended she stop it, but she was reluctant, saying she wanted to give it a shot. So I prescribed the tranquilizer Klonopin, and told her to decrease the Abilify dose back to 5 mg. Over the next few days, she became less shaky, and calmer.

Her case is a work in progress, and I'll provide updates in the future. The point here is that this is the side effect that is so common for Abilify, and one that authors paid by BMS chose to play down in a paper apparently written by an employee of Phase V, a medical education company paid for by BMS.

Will my patient ultimately do well on Abilify? I hope so. But it is crucially important for BMS, Otsuka, and their various minions to be accurate about the dangers of the drug, so that doctors can use it appropriately and prevent the kinds of side effects my patient suffered. Publishing an article that was carefully crafted to draw attention away from Abilify's main liability was shameful, and is exactly the kind of deceptive editorial practice that we as a society can no longer tolerate.

Tuesday, May 5, 2009

The Comparative Effectiveness Wars: Three Views from NEJM

Who would have thought that a proposal to funnel $1.1 billion into comparative effectiveness research (CER) would have caused such vicious battles? Battles get this vicious when someone has money to lose, and in this case the biggest losers are those drug companies which depend on me-too drugs for their profits. For them, CER is a stake through the heart.

The current issue of the the New England Journal of Medicine has three articles in its Perspectives section about CER that are well-worth reading if you have the time. (Oddly, the new issue is not yet online, hence the lack of hyperlinks in this posting. Get your act together, Mass Medical Society!)

First, Garber and Tunis put the spotlight on one common argument against CER--that it would somehow stymie efforts to improve personalized medicine. One of the main examples of personalized medicine is using new genetic tests to decide whether specific treatments are likely to work best in specific patients. The authors point out that genomic medicine, as this is sometimes called, has yielded little of clinical use. This is not because the evil insurance companies doen't want to pay for the testing, but because the science has not clearly demonstrated its utility.

I have to agree. In psychiatry, for example, I wrote this article about an ill-fated antipsychotic called iloperidone ("Fanapta") that was being marketed by Vanda Pharmaceuticals as a great advance in personalized medicine. Unfortunately, the company was unable to muster convincing enough data that its genetic testing protocol was truly helpful and the product was rejected by the FDA. Actually, money spent on CER would benefit personalized medicine by helping doctors to decide which genetic tests are valuable, and which are useless.

Next, Jerry Avorn weighs in with a trenchant analysis of how a coalition of pharmaceutical companies and their minions created a series of false debating points which, luckily, have thus far not convinced the Obama administration to scale back the program. Avorn aptly describes the nadir of this debate:

The radio talk-show host Rush Limbaugh then disseminated this message to millions of listeners, warning that once the stimulus bill "computerizes everybody's health record," a new federal bureaucracy "will monitor treatments to make sure your doctor is doing what the federal government deems appropriate."

Actually, CER is all about generating new knowledge to make better medical decisions, and not about denying care. But companies that rely on aggressive marketing rather than creating novel products are threatened by scientific inquiry.

Finally, Naik and Peterson point out that while comparative research is all fine and dandy, without a parallel effort to get doctors to actually use the findings in their practices, the money will be wasted. To quote them: "...a shift is needed from the 'science of recommendation to a science of implementation.'" Wise words indeed.