Wednesday, November 10, 2010

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.

14 comments:

David Dobbs said...

Hi Alison. I can't speak to the issue of any consultant relationship Mayberg might have with ANS/St. Jude (I didn't know of one), but regarding the issue of results from more than the first 6 Toronto patients, there is actually a paper describing 20 in all. That shows pretty strong rates of improvement in all 20 patients, roughly similar to those found in the first 6 (which are part of the 20).

If I remember correctly, Mayberg actually did mention this study in her keynote and had a slide on it. But as it was soon followed by her discussion of the still-unpublished results of the still-in-the-works Emory study, which also has about 20 patients (different than those in the Toronto study), it might have been easy, at the keynote, to confuse the two and think she reported results in the talk (or otherwise) on only 6 patients. But indeed there is published data on 20, and I believe she mentioned and showed a slide on it in the talk. In any case, an abstract of that 2008 paper can be found here:

http://journals.lww.com/jonmd/Abstract/2008/05000/Neuropsychological_Impact_of_Cg25_Deep_Brain.7.aspx

The PDF here:

http://www.societyns.org/runn/2008/278-Subcallosal%20cingulate%20gyrus%20deep%20brain.pdf

As you know, I introduced Mayberg, as I have written about her work a couple of times. As you also know, I feel extremely strongly that researchers should report all conflicts of interest and have written about failures to do so many times. If Mayberg has neglected to do so here, she should correct the record. She has, however, disclosed the patent she shares with Toronto surgeon Andres Lozano on the procedure (not the stimulator), and she has taken pains at other times to pay cash for stimulators rather than have arrangements with the manufacturers.

My overall impression of Mayberg, having spent several hours with her on several occasions over the last 5 years and written on her work, is that she is an unusually diligent, careful, and ethical researcher who is keenly aware of the dangers of conflicts-of-interest. If she failed to disclose a consultancy with ANS (much obliged if you can provide the link/data on that, so I'm not in the dark), then she obviously made a mistake. But, again, my own impression, based on everything I know now, is that Mayberg works with high ethical standards, including regarding conflicts-of-interest and disclosures; that any failure to disclose at the talk was anomalous and uncharacteristic of her, as I know her; and that it was not a mistake to invite her to speak. (I had no part in that decision, but asked to introduce her when I learned she had been invited).

Readers interested in an earlier look at her work might be interested in my article on her in the Times Magazine a few years back; it's at http://www.nytimes.com/2006/04/02/magazine/02depression.html?ei=5070&en=a5747de019ee30a5&ex=1170651600&pagewanted=all

Hope that helps.

Paul Raeburn said...

Alison,

I’m the person who invited Mayberg, so I should respond.

You’re correct, of course, to be on the lookout for conflicts and lack of transparency. But in my view, you have gone a bit too far, establishing a standard that would prevent a lot of interesting research from ever being presented at the science writers’ meeting.

You say she left out “a few salient details” about her work. As she noted, much of the work is so far unpublished, and so she gave us an overview—not the kind of detailed analysis that we would expect after a paper has been published. In my view, she was cautious about the potential of the work, and did not propose it as a miracle cure. For our group, I think it’s best to encourage speakers to discuss unpublished work with as much detail as they can, rather than limiting them to published work, which they can describe in greater detail. I think this audience understands the difference and is unlikely to be hoodwinked.

As to conflict of interest, she noted—as you observed—that she has patents in this area and said she was partnering on a clinical trial. Indeed, the web is full of clips describing the partnership. I didn’t make the assumption, as you say you did, that this was a non-profit venture. When I hear people talk about patents, I assume they are going to make money. You might have raised the point at the session by asking a question about her corporate ties.

You make some good points, and I, for one, am glad to know more about St. Jude’s. I wonder who you think is a solid device-maker that might have been a better choice? They all seem pretty dicey to me. (Need I say “Medtronic”?)

I trust the science-writers—like you—to be on the lookout for trouble. Indeed, posts like yours are why I feel comfortable inviting people who are doing interesting work, because I know that if there is reason to be skeptical, you, or someone, is likely to find it.

I welcome the comments. I did think twice before inviting her—as I always do. And I think she was an excellent choice.

And I’d be happy to hear your suggestions of whom we should invite next year.

Cheers.

Peter said...

Hi Alison et al.

Just wanted to point out in Mayberg's favor that she has been an active participant in the discussion of the ethical aspects of DBS as both a research area and potential therapy, a valuable contribution in a realm that is inevitably evaluated in the light of the rather sorry history of psychosurgery, etc.

See, e.g., Rabins et al., Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought. Arch Gen Psychiatry 66: 931-937, 2009.

Pete

Pete

Alison Bass said...

David:

Here's the link to the disclosure about Dr. Mayberg's consulting work with Advanced Neuromodulation Systems (aka St. Jude Medical Inc.); it was very easy to find on google:

http://books.google.com/books?id=Xx7iNGdV25IC&pg=PR27&lpg=PR27&dq=Helen+mayberg+patent&source=bl&ots=Usc5zm9hLA&sig=72KcWtIhYUoPi7E4iyenGpBMr8o&hl=en&ei=w_jaTJGQNsH-8Abw1K20CQ&sa=X&oi=book_result&ct=result&resnum=6&ved=0CD8Q6AEwBQ#v=onepage&q=Helen%20mayberg%20patent&f=false

Alison Bass said...

In response to my blog today about Helen Mayberg's research, an alert reader sent me this summary of the latest research on deep brain stimulation in depression, published in UptoDate, a subscription only online newsletter:

"There is preliminary evidence that some patients with treatment-resistant depression may benefit from DBS. The optimal site of electrode placement for treatment of major depression is unclear, with studies targeting either the ventral capsule/ventral striatum (VC/VS) or the subcallosal white matter. 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]. Adverse effects included infection (5), generalized seizure (1), and headache or pain at the implant site (4). Response and remission rates of 40 and 20 percent respectively at six months with VC/VS electrode placement were reported in another group of 15 patients with refractory depression [50]. Adverse events, affecting 6 patients, included pain at implant site, lead fracture, increased depression or suicidality, and syncope."

The results so far do not look very encouraging.

David Dobbs said...

Alison,

Two things:

1. Thanks for the link. I know how to use Google. I didn't use it earlier as I was struggling to write and send that comment while I was on a plane's dreadfully slow wifi.

2. On the results you cite in your most recent comment: Mayberg's trial was the one at the subcallosal white matter (Area 25). I'm not trying to sell Mayberg's work but to put the results in perspective. The 20 patients had failed to respond to anything else, including ECT as well as extensive attmepts at talk therapy. They were catastropically and in some cases almost catatonically depressed.

The experimental treatment -- which Mayberg repeatedly stresses is just that -- significantly relieved depression in 60% of them and outright eliminated it (by standard depression scores) in 40%. Those people, some of whom I met, got their lives back. In return, some experienced, passingly, the side-effects you mentioned: infection (5), generalized seizure (1), and headache or pain at the implant site (4). I believe that in all cases, those were fairly quickly controlled, and unlike drug therapy, they did not last, while the relief from depression did.

That actually seems pretty encouraging to me -- and certainly did to the patients who got well.

pj1280 said...

David Dobbs wrote:

"...she is an unusually diligent, careful, and ethical researcher ..."

It's a sad reflection on these times when a researcher's diligence, care, and ethics are described as "unusual."

cap said...

As a patient treated by Dr. Mayberg for several years, it has not been my experience to witness her "dance" around any truths as far as her communicating to me all possibilities as a part of having the deep brain stimulation surgery for TRD

From 1st visit to evaluate dbs an option option from both sides,I would without doubt say she leaned to the side of caution &emphasized the potential complications & wthe facts of the procedure not having enough history at that to lead me to believe the surgery was anything other than experimental.

This being said, I would point that my frame of mind had become cynical, guarded, yet realistic as to the potential to trust fully healthcare in general. Seeking help with the horrific symptoms of depression and all involved re treatment as well as the financial/insurance issues involved begging for my insurance carrier to cover what was stated in policy. In addition, my former career was with a large healthcare organization (NO relation at all to the organization Dr. Mayberg and her colleagues represent) which provided the basis motivation of much current healthcare legislation as it pretains to physcian's ownership in various apects of healthcare for fear of conflict of interest.
my trust is not something that is automatic by any means. Quite the contrary, it is something that makes me evaluate in some cases, to much, what I am told.

Despite my nature, I have to say in all honesty, Dr. Mayberg has never given me ANY reason to doubt her dedication and very obvious passion to succeed in progressing medicine to a point where futur Understanding how someone who has not experienced the dibilitating effects of the constant psychic pain amplified in one's head cannot really understand, or even believe in the symptoms experiencing, makes the appreciation of someone who does "get it" (Dr. Mayberg) that much more appreciated as a provider of care. She "gets it" so clearly.. I think her understanding of just how torturous existence it can be provides much fuel to her diligent, relentless pursuit of answers. Her awareness of the total impact of the illness to the patient as well as the understanding just how devasting in total the illness is the patients family and complete life circumstances is something I think is vital the team of whoever progresses treatment options. Many times I've left an interaction with her regarding treatment, feeling as if this work is somewhat like a child to her, or her "baby" that she she needs to nuture and progress.

I was not at the conference, but from your description, it just didn't make any sense as to this being the person I've experienced. Her "cautious" explanations I have always heard as being almost overly cautious, certainly not vague selling based upon no specifics. You are the writer, and this is not my background, but what jumped out to me is that where there are specifics that are not available for public communication as of yet, would mean that whatever study is involved has limitations as to what can and can't be made public yet???

As for my experience with the actual dbs surgery, it is almost unbelievable despite being there as the patient experiencing, what I know resulted from the stimulation. Prior to surgery people addressed me as if I would be nervous, but for me there was nothing in terms of fear that existed as everything so paled to the mental anguish. To be in that state and then experience that it was no longer there upon things tried in surgery is still shocking to me. It was so not like what I think people may think...not a high, up, elevated, happy in the least. It was that the pain left, and calm was experienced. I realize each person is different and this does not always happen this profoundly, but as a person who has experienced this in my being, makes me feel the need to communicate how my experience so in my gut makes me feel they are very on track with vital information to find a solution.

Paul Raeburn said...

Mayberg says you're wrong on the facts in your post. See my reporting on her views.

Jim said...

For those who want to hear more about the procedure and hear from Mayberg herself, we did the first feature on her work at the University of Toronto. Here's an MP3 file of that feature from CBC Quirks & Quarks:

http://www.cbc.ca/quirks/media/2005-2006/mp3/qq-2006-01-21.mp3

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Louis Bush said...

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Louis Bush said...

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