Emory neurologist has history of failing to disclose conflicts of interest

My blog last week on Helen Mayberg's talk at the 2010 ScienceWriters conference caused quite a stir. Paul Raeburn, writing in the Knight Science Journalism Tracker, accused me of being wrong on the facts and several commenters defended Mayberg's research in using brain surgery for the treatment of unremitting depression.

Before I get to the gist of Raeburn's accusations, let me just point out that this isn't the first time that Dr. Mayberg, a neurologist at Emory University School of Medicine, has been less than forthcoming about her conflicts of interest. Mayberg was one of the authors on a 2006 paper that touted the effectiveness of a technique known as vagus nerve stimulation (VNS) in patients with treatment-resistant depression. Eight of the authors, including Mayberg, failed to disclose they had consulting ties with Cyberonics, the maker of the device that delivers electrical pulses to the vagus nerve in the neck. (The ninth author was an actual employee of Cyberonics). Because of this egregious failure to disclose, the lead author of the study, Dr. Charles Nemeroff, then chair of psychiatry at Emory, was forced to step down as editor in chief of the journal Neuropsychopharmacology, which published the VNS paper; read about the controversy here. Indeed, Nemeroff, who brought Mayberg to Emory, was forced to step down as chair at Emory last year after a Senate investigation found that he repeatedly failed to disclose to university and NIH officials the millions of dollars he was receiving from drug companies whose products he was touting in research papers and on the lecture circuit; read more about this here.

Mayberg also did not disclose the fact that she was a consultant for Advanced Neuromodulation Systems, a company that holds the patent on her surgical technique for deep brain stimulation, when she co-authored another 2006 article with Nemeroff that reviewed possible brain mechanisms for post traumatic stress disorder and concluded that Paxil might be an effective treatment for PTSD. The study, published in the Journal of Psychiatric Research, was funded by GlaxoSmithKline, the maker of Paxil. While Mayberg wrote about the possible involvement of Brodmann's area 25 in the brain in causing symptoms of PTSD, she did not disclose that she holds a patent for deep brain stimulation of that particular section of the brain or that she was a consultant for the company that is doing clinical trials on her surgical technique.

In my blog last week, I had reported that in her keynote at the Science Writers conference, Mayberg did not disclose that she is still a consultant for ANS, which also goes by the name of St. Jude Medical Inc. She did mention that she had a patent on the technique (which involves implanting electrodes in Area 25) and she referred on one slide to being a consultant for St. Jude Medical. Now, St. Jude Medical is a nonprofit hospital in California and so I (and others in the audience) assumed she was consulting for a nonprofit, not the for-profit company that is doing clinical trials on her patented technique. According to Raeburn who got in touch with Mayberg after I posted my blog, she said that "a review of her slides show that both ANS and St. Jude were disclosed." Now, maybe the good doctor does have a slide with ANS on it, but she did not put it up on the screen Nov. 7 and she did not mention it in her talk.

In my original blog, I also said that her "talk was heavy on anecdotal examples but skimpy on any real evidence of efficacy." She did say she was writing up a paper about her latest results but didn’t disclose much in the way of specifics. After I posted my blog, a reader sent me a summary of Mayberg's most recently published work on deep brain stimulation in UptoDate, a subscription only newsletter. Here it is:

“A case series of 20 patients with major depression unresponsive to more than 4 antidepressants and ECT (17 of the 20 patients) who underwent DBS with subcallosal electrode placement found response and remission rates to be 60 and 35 percent respectively at six months [49].”

A remission rate of 35 percent on 20 patients doesn’t seem that encouraging to me. More to the point, why didn’t Dr. Mayberg share this data with all of us science writers on Nov. 7?

Keynote scientist at ScienceWriters conference dances around the truth

Dr. Helen Mayberg, a neurologist at Emory University, had top billing at the annual Science Writers conference in New Haven Sunday to talk about her work in using deep brain stimulation to treat depression. Nearly 500 writers, editors, public information officers and students listened as she spoke of inserting electrodes into the frontal lobes of chronically depressed patients for whom other treatments (like drugs and ECT) have failed. She spoke with wonder of being able to help "patient after patient" awake from the fog of depression and how for some patients, the difference was like "night and day."

As it turns out, Dr. Mayberg left out a few salient details. To begin with, she never mentioned how many depressed patients have actually benefited from this risky surgical technique. She did say that in the initial feasibility study she and colleagues did in 2002 while she was at the University of Toronto, electrodes were surgically implanted in six patients and four out of six "got better and stayed better." She also alluded to a slightly larger study of 20 patients she conducted at Emory in which "patients are achieving remission." But she did not how many patients are actually in remission and for what length of time, or whether the results are statistically significant, only that "we are now writing up the paper for submission." Her talk was heavy on anecdotal examples but skimpy on any real evidence of efficacy.

Of equal concern, Mayberg did not fully disclose the extent of her conflicts of interest. At the beginning of her talk, she mentioned that she held a patent for the technique and that it was now in clinical trials. She also said she was a consultant for St. Jude Medical. Now, St. Jude Medical Center is the name of a well-regarded nonprofit hospital in California and the clear implication (to many of us in the audience) was that she was consulting for a nonprofit hospital. In fact, Mayberg is a consultant for Advanced Neuromodulation Systems, which also goes by the name of St. Jude Medical Inc., a for-profit multinational company that manufactures medical devices and has annual revenues of $4.6 billion.

This is the company that holds the patent for Mayberg's surgical technique and has begun clinical trials to test it. And it has a less than stellar reputation. Last year, the FDA hit St. Jude Medical, otherwise known as ANS, with a stern warning letter alleging that the company had failed to correct known design defects in spinal cord stimulation devices it sells to treat chronic pain. The FDA letter said the manufacture and installation of these devices are not in conformity with good manufacturing practice requirements and called the company to task for failing to respond to previous warnings from FDA inspectors about the devices' defects.

Now maybe St. Jude has cleaned up its act, although as of this afternoon a phone call to its corporate headquarters in St. Paul, Minnesota had not been returned. But if I were a chronically depressed patient being recruited for the company's ongoing clinical trials, I might think twice about participating. And if I had been one of the organizers for the 2010 Science Writers conference, I might have thought twice about inviting Mayberg to speak in the first place.

Alternatives 2010 organizers reverse course on censorship

In the latest twist to the saga of Alternatives 2010, the National Empowerment Center, which organized the conference, has apparently reversed course and restored the original language to Will Hall's workshop -- see my earlier blog about the brouhaha over this.

According to a hot-off-the-presses statement from Dr. Daniel Fisher, the director of the NEC:

"Hall's original workshop title, Coming off Medications: A Harm Reduction Approach. will be restored and we are delighted Will has agreed to come to Alternatives and present on this subject as originally planned."

In his statement, Dr. Fisher, a psychiatrist, also said,

"On behalf of the National Empowerment Center, I wish to apologize to Will Hall and to the consumer/survivor community for the last-minute decision to alter the title of his workshop to remove the reference to coming off medication."

Sanity, it seems, has prevailed.

Mental Health "Alternatives" conference censors a workshop on alternatives

Less than week before the opening of Alternatives 2010, a conference dedicated to promoting alternatives for better mental health care, the organizers did a strange thing: they decided to remove any language about coming off medications from the title and description of a workshop they had approved for the conference months ago. So the workshop's creator, Will Hall, the founder of the Freedom Center, did what he had to do and cancelled his participation in the five-day conference, which starts Wednesday in Anaheim, California.

The organizers of the conference, the National Empowerment Center, a long-time advocacy group for people with mental illness based in Lawrence, MA, say they decided to change the wording of Hall's workshop out of concern for liability issues. "If someone went to the workshop and stopped medication abruptly and had a bad reaction coming off and did something horrible, it would come back to us probably," said Dr. Daniel Fisher, executive director of NEC.

Why can't I buy this explanation? Possibly because, as Fisher, who is a psychiatrist himself, also admitted, the last-minute decision had a lot to do with the fact that Hall's workshop offered an alternative to working with psychiatrists and the prevailing biomedical model. "Our concern is that people would do this without working with their psychiatrists," Fisher said in a phone interview.

Ah, there's the rub. What Hall (and the nonprofit Freedom Center) espouse are treatments that don't necessarily depend on psychiatrists and drugs but on alternatives such as yoga, meditation, exercise, nutrition and access to peer-run support groups. I blogged about the Freedom Center and its goals here.

The irony in all of this is that Hall is not anti-medication. While he himself (as a psychiatric survivor -- he was diagnosed with schizoaffective disorder at one point) has been off drugs for 17 years, both the Freedom Center and the workshop he put together for Alternatives 2010 included information about how to continue on drugs, reduce drug utilization or come off medications. Hall is not saying that all mentally ill patients can or should do without their medications; he's just putting out information about possible treatment alternatives to drugs. But that apparently was too much for the psychiatric establishment who pressured the NEC into censoring Hall.

This, by the way, is the same supposedly consumer-driven organization that also rescinded an invitation to speak at its Alternatives conference to Robert Whitaker, author of Mad in America and Anatomy of an Epidemic. Whitaker was restored as a keynote speaker only after mental health advocates raised an outcry.

Sounds to me like Alternatives 2010 is not really about alternatives at all.

GlaxoSmithKline takes a big hit; the story of Avandia and Paxil

I've been experiencing a strong sense of deju vu ever since Gardiner Harris' story in The New York Times earlier this week that GlaxoSmithKline hid negative findings about a bestselling drug and misrepresented data in a clinical trial of the drug. This time, the drug is Avandia for diabetes, and there is evidence that Glaxo not only knew the drug increased the risk of heart attacks in patients and suppressed the data for 11 years. But according to The Times, the company also omitted cases of patients who were taking Avandia and suffered serious heart problems in the trial's tally of adverse events.

Where have we heard this before? As I revealed in Side Effects two years ago, GlaxoSmithKline pulled the same shenanigans with its blockbuster antidepressant, Paxil. Not only did the drug manufacturer suppress negative findings about the safety and effectiveness of Paxil in treating depression in children, but in one of the clinical trials it conducted of Paxil in the mid-90s, there is evidence that researchers actually omitted from the final study results, cases of adolescents who became suicidal after taking the drug. I revealed this pattern of deception in Side Effects and in subsequent blogs here and here.

Side Effects is essentially the story of how the New York State Attorney General's office uncovered GlaxoSmithKline's chicanery and sued the drug company, forcing it to publish the results of all of its clinical trials, negative as well as positive. Which is why it's so good to see one of the players in that 2004 drama -- Eliot Spitzer, who headed the AG's office at the time -- weigh in on the whole saga in Slate today.

The irony is that if Spitzer and his crew had not forced GlaxoSmithKline to post all of the clinical trial data on a public website, Dr. Steven Nissen, a cardiologist with the Cleveland Clinic, would never have been able to gather the data necessary to show, in a groundbreaking 2007 meta-analysis, that Avandia does cause an increase in heart problems. And the company's subterfuge would never have been revealed.

Now, of course, the ball is in the FDA's court. A split advisory panel yesterday recommended that Avandia should either be withdrawn from the market or have sales severely restricted because of its heart risks, according to The Times.

And just today, GlaxoSmithKline announced that that it would take a second-quarter charge of $2.36 billion to settle legal cases involving its drugs, Avandia and Paxil, again according to The New York Times Given that the company has been pocketing enormous profits for both of these blockbluster drugs for more than a decade -- last year alone, it made a total of $8.4 billion -- that's not exactly a ruinous sum. Even so, I'm sure GlaxoSmithKline's stockholders will not be happy with the news.

We can only hope that GSK and all the other drug companies who have practiced similar deceptive tactics over the years are finally getting the point: Crime doesn't pay.

Fighting for lower drug prices, or how to counteract Big Pharma's lobbying

At a recent talk I gave on health care, the question came up: why isn't our government negotiating with the pharmaceutical industry to lower drug prices in the US? My audience was a group of sharp-minded Mount Holyoke College alumni, and almost all of them were on some kind of prescription medicine. While private health plans (which insure most working Americans) don't have the clout to negotiate more reasonable drug pricing, the US government, which funds Medicare and Medicaid, does. Yet it doesn't use it, unlike in Canada and many European countries, where the government ensures low drug prices through tough-minded negotiations.

Why? The reason is glaringly obvious: Congress won't give the Department of Health and Human Services (HHS) the authority to negotiate lower drug prices because too many of its members are in bed with the industry. That's why HHS was expressly prohibited from negotiating lower drug prices in the Medicare Part D legislation enacted during the Bush administration.

One has only to look at the list of top industry spending on campaign contributions and lobbying in Washington to understand. This past year, the pharmaceutical/health products industry headed the list of industries spending millions of dollars to sway the opinion of Congressional and executive policy makers, according to Center for Responsive Politics, a nonpartisan, nonprofit research organization that tracks money in U.S. politics. This industry, which includes big pharma, biotech and the medical device industry, spent $263 million in 2009, ahead of the second (business associations), the third (oil and gas -- gee, could this be why BP was allowed to drill without the proper environmental review?) and the fourth highest (insurance companies) industry spenders.

It's difficult for individual consumers to have much of a voice in the face of such well-oiled (forgive the pun) special interests. But it doesn't hurt to try. So I will repeat what I told the Mount Holyoke crowd: Pick up the phone or write a letter/email to your Congressional representatives telling them that you want Congress to pass a law giving HHS the power to negotiate lower drug prices for Medicare and Medicaid (and while you're at it, ask for a ban on direct to consumer advertising too).

But don't stop there. Organize a town meeting with your Congressional representative or a mass street protest in Washington. If Americans devoted an iota of the time and energy to drug pricing reform that they shower on their favorite sports team, just think what this country could accomplish!

Why statins should not be widely prescribed, or the difference between relative and absolute risk

In The New York Times yesterday, Duff Wilson did a great job of explaining why many medical experts question the growing use of cholesterol-lowering statins in people without heart problems. He reported on new studies showing the risks of otherwise healthy people taking statins, and he exposed the huge conflict of interest by the scientist who led the study that enabled AstraZeneca to win FDA approval for marketing its statin, Crestor, to people without heart problems. (The scientist, Dr. Paul Ridker, a cardiologist at Harvard and Brigham and Women's Hospital, receives lucrative royalties on the test used in the study to determine whether people without visible heart problems might benefit from Crestor, There is much dispute over whether test itself, which measures an elevated level of inflammation in the body, indicates underlying heart problems).

Wilson also performed another estimable service: he highlighted the difference between relative risk and absolute risk. Relative risk is the statistical difference in outcome between a control group and a group taking an active drug in a study, whereas absolute risk is the actual number of people who might actually benefit from the drug. Most randomized clinical trials only report relative risk, which often inflates the benefits of the drug being studied.

So, as Wilson explained:

The rate of heart attacks, for example, was 0.37 percent, or 68 patients out of 8,901 who took a sugar pill. Among the Crestor patients it was 0.17 percent, or 31 patients. That 55 percent relative difference between the two groups translates to only 0.2 percentage points in absolute terms — or 2 people out of 1,000.

And then he goes on to put the difference into even clearer context:

Stated another way, 500 people would need to be treated with Crestor for a year to avoid one usually survivable heart attack. "That’s statistically significant but not clinically significant,” said Dr. Steven W. Seiden, a cardiologist in Rockville Centre, N.Y., who is one of many practicing cardiologists closely following the issue.

Well done, Duff!

On another note, I just wanted to let readers know that I am taking a hiatus from weekly blogging. I may still wade in now and then to blog about a timely issue (when I can't resist), but it's time to turn my attention to another project.