Six not-so-simple steps toward protecting people from dangerous drugs

Over the past two years there has been a steady diet of books and media reports about the disturbing influence the pharmaceutical industry has on medical research and doctors' prescribing patterns. Not a week goes by without a new report on the marketing muscle of the industry and the pervasive ties between the industry and the doctors upon whom we rely for supposedly objective medical advice.

A recent addition to this growing body of literature is The Risks of Prescription Drugs, which explains why the number of Americans taking prescription drugs has soared 72 percent in the last decade, with the result that an estimated 46 million Americans suffer from adverse side effects and 2.2 million are hospitalized every year. The book is co-written by five health policy experts and for the most part coalesces what has been written about in other places, including Marcia Angell's The Truth about Drug Companies, Jerome Kassirer's On the Take, Howard Brody's Hooked, Melody Petersen's Our Daily Meds, Peter Conrad's The Medicalization of Society and Side Effects, along with many newspaper reports.

However, The Risks of Prescription Drugs, published by Columbia University Press, does two things particularly well. First, it explains in a clear concise fashion why, despite the fact most new drugs offer little or additional benefit over existing meds, so many doctors prescribe these new drugs, exposing patients to serious side effects and adding billions in wasted costs to an already overburdened health care system.

Second, in the final chapter, the book offers comprehensive solutions to the problem, such as:

* Prohibit direct to consumer advertising by drug companies (because advertising to patients conveys inherently commercialized, biased information). Read more about this here.
* Create a stronger more independent Food and Drug Administration by more fully funding this federal agency so that it is no longer reliant on drug company user fees. (As reported in Side Effects, drug company money now accounts more than half of the FDA's entire drug-review budget.
* Change FDA policy so that new drugs are tested against existing drugs rather than against a placebo or sugar pill. (Right now, most drugs only need to show they are more effective than a placebo to win FDA approval).
* Reduce the commercial influence on doctors. While some medical schools such as Harvard have enacted strict policies prohibiting doctors from accepting free gifts, lunches and lucrative consulting and speaking deals from drug companies, too many others continue to allow such conflicts, all of which have been shown to bias doctors' judgment as researchers and clinicians).
* Get Big Pharma out of medical education. The Carlat Psychiatry blog makes a persuasive, ongoing case for why drug companies should not be allowed to fund continuing medical education.
* Limit the prescribing of unapproved uses of drugs, since such off-label uses are responsible for many of the adverse side effects seen in patients. See more about this here and here.
* Create and fund a new federal institute of medical science that can run clinical trials of new medications free of the drug industry's commercial interests. This institute could also be charged with doing objective research that compares the effectiveness of new products with existing drugs. As reported here, in the economic stimulus bill passed last year, President Obama included $1.1 billion for just this kind of comparative effectiveness research, but that should only be the beginning of a much larger, more comprehensive effort).

While all of these solutions are crucial if we want to improve our health care system and protect the public from dangerous and unnecessary drugs, the reality is that they will require the kind of political will that is in short supply on Capital Hill these days. That doesn't mean, however, that we should stop working toward such reforms. If anything, books like The Risk of Prescription Drugs are more important than ever -- in getting the truth out.

Mount Holyoke journalism class gains real-world experience

At the risk of tooting my own horn, I thought I'd post this video that was produced by Mount Holyoke College about the multimedia journalism class I teach there and our collaboration with the local newspaper, The Daily Hampshire Gazette. The video talks about how Mount Holyoke students are gaining real world journalism experience and helping a local newspaper gain a bigger footprint in its own community.

Government oversight agency calls on NIH to ban ghost-writing

Much has been written about the insidious practice of ghost-writing in medical research in this and other blogs and news articles. Even Dr. Francis Collins, the director of the National Institutes of Health (NIH), expressed dismay over the problem in a C-SPAN interview last year, calling it a threat to the "integrity of science." So far, however, not much has been done to curb such abuses.

In an open letter to the NIH yesterday, the Project on Government Oversight dialed up the pressure on Collins and the NIH by calling attention to several particularly egregious examples of ghost-writing. In the first, two psychiatrists, Dr. Charles Nemeroff and Dr. Alan Schatzberg, (whose ties to the pharmaceutical industry and conflicts of interest have been well-publicized) signed their names to a psychiatric textbook for primary care physicians that was in fact ghost-written by a contractor for SmithKline Beecham, now known as GlaxoSmithKline. As Duff Wilson reports in The New York Times, not only did SmithKline pay for the contractor to develop the outline and text for the two named authors but in emails obtained by PGO and the Times, the contractor also said it planned to show drafts and page proofs of the book to the drug company for sign off and final approval. Yet such company control was never disclosed in the textbook, which doesn't come as any particular surprise, since Nemeroff and Schatzberg have a history of failing to fully disclose their ties to the drug industry; see here.

Another ghostwriting example that the Program on Government Oversight highlights in its letter to NIH is one that I exposed in Side Effects: that a study of Paxil, spearheaded by Dr. Martin Keller, then chief of psychiatry at Brown University, was in fact ghost-written by the same contractor that ghost-wrote the psychiatric textbook mentioned above. According to documents that I obtained and posted here, this particular clinical trial, known as study 329, was skewed to downplay the suicidal risks of Paxil in adolescents and to make the drug seem more effective than it really was. According to email correspondence obtained by a law firm suing Glaxo, the contractor also sent this study to the drug company for final approval before it was published. In Side Effects, I quote an employee of Brown's department of psychiatry saying, “Everybody knew we had to keep [SmithKline] happy and give them the results they wanted."

While Keller has stepped down as chair of psychiatry at Brown, he remains a full professor there and is still receiving lucrative NIH grants. As the PGO letter notes, "Currently, [Keller] is the primary investigator on two NIH grants, with funding in 2010 of $1,341,493. Over the last five years, the NIH has given Dr. Keller $7 million in grants."

This is unacceptable. Keller has been accused of manipulating scientific data not only in my book but in scientific journals as well; see here and here. It's high time that the NIH stepped up to the plate and did as the Project on Government Oversight asked: "implement new policies that will require institutions to ban ghostwriting and make NIH funding contingent upon periodic certification from institutions that ghostwriting is strictly prohibited..."

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.