News reports about prominent academic scientists who failed to disclose their financial relationships with drug and medical device manufacturers—as journal publication policy requires—and who have penned their name to ghostwritten journal reports lead one to conclude that the era of excellence in medical science is a thing of the past.

Medical scientists from prestigious universities, including: Harvard, Stanford, UCLA, Emory, Duke, University of Toronto, Mount Sinai (NYC) Columbia, and the National Institutes of Health, who are generously supported by the public have betrayed public trust and their public responsibility. Operating like thieves under the cover of darkness, prominent academic-based "authorities" in medical specialties have debased academic standards and sold their reputations for cash—mostly to companies that market dubious medical products for questionable “conditions.”

An article published in this, one of psychiatry’s leading journals, purports to review the scientific evidence for the efficacy and safety of a controversial, experimental treatment for depression, called VNS (vagus nerve stimulation). All eight prominent academic psychiatrists whose names are penned to the article, failed to disclose their financial ties to Cyberonics, the manufacturer of this controversial implanted device. [1]

The eight authors are paid members of Cyberonics’ advisory board. The ninth author, an employee of the company, disclosed his company connection in the article.

The principle (first named) author, Dr. Charles B. Nemeroff, is chairman of psychiatry at Emory University. He is also the editor-in-chief of Neuropsychopharmacology, and a past president of ACNP, whom the WSJ identified as "one of the nation’s most prominent psychiatrists." Dr. Nemeroff is also chairman of Cyberonics’ Mechanism of Action Advisory Board. See, Cyberonics Press Release, August 2003:  https://ahrp.org/cms/content/view/293/29/   [2]

The journal incorrectly identifies the authors’ academic affiliations on its website: http://www.nature.com/npp/journal/v31/n7/full/1301082a.html
Their correct identifications are listed in Cyberonics’ August 2003 press release: https://ahrp.org/cms/content/view/293/29/
Dr. Dennis Charney’s affiliation changed since 2003. [3]

When reporters from the WSJ and Bloomberg News questioned the journal’s failure to disclose financial ties of its own editor and those of the other authors, ACNP spokespersons said "a correction will be issued soon." ACNP President, Dr. Kenneth Davis, who is President of Mount Sinai Medical Center (NYC) told Bloomberg News:
“It would be a mistake for you to conclude that there was some malfeasance here because the editor is also the first author and also the head of the advisory group.”

Bloomberg News reports that Dr. Nemeroff offered the following explanation in an e-mail: “As a co-author of the manuscript, I, of course, completely recused myself, from any editorial responsibilities in relation to this submission. All of the authors provided their full financial disclosures.”

Dr. Nemeroff appears to be oblivious to the fact that financial disclosure requirements are not something private between authors and editors—but rather, a requirement for public disclosure.

A Cyberonics Press Release (March 23, 2006) describes Dr. Nemeroff’s role: “identify opportunities”  “new indications”—in a word, market expansion: "The VNS Therapy Mechanism of Action Advisory Board, chaired by Charles B. Nemeroff, M.D., Ph.D., Emory University, is providing expert leadership in the development and implementation of a long-term mechanism of action research plan to identify opportunities to improve the effectiveness of VNS Therapy and prioritize new indications development."

Dr. Nemeroff views VNS as a research tool for expanded uses: "In addition to representing an important novel therapeutic modality, VNS Therapy is a research tool that offers the hope of better understanding and potentially treating a variety of brain diseases. I look forward to working very closely with the other researchers and Cyberonics to execute research initiatives designed to elicit meaningful information regarding the unique mechanism of action of VNS Therapy in TRD," said Dr. Nemeroff.

Cyberonics announced the publication of the favorable “peer reviewed” article in a press release, July 7, 2006: https://ahrp.org/cms/content/view/294/55/

On July 9, it sponsored a symposium, "The Past, Present and Future Therapies for Treatment-Resistant Depression," at the Collegium Internationale Neuro- Psychopharmacologicum (CINP).

Dr. Bernard Carroll, the retired chairman of the department of psychiatry at Duke University, who is a member of the ACNP, put it bluntly:
     “This is about as classic an example as you’ll ever find of conflict of interest and manipulation by thought leaders who are beholden to corporations.”  “This article is a piece of a slick, skillfully coordinated PR campaign directed by the corporation.”

Indeed the acknowledgment that Sally Laden provided "editorial support in developing early drafts of this manuscript," raises questions about the article’s authorship. The article failed to disclose her relationship to Cyberonics which the WSJ reports:  Ms Laden is "a professional medical writer hired by Cyberonics to compile the review with materials from its advisory board meetings."  

She claims, "This was not a ghostwritten project. I was just a facilitator." (Bloomberg News, below).  If this is not a ghostwritten piece, how are ghostwritten articles defined? If those credited as “authorities” in their field cannot be expected to compile, analyze, and explain their conclusions about the safety and efficacy of treatments they endorse; what is their scientific contribution? Is it the norm and practice among editors-in-chief-of peer reviewed journals to pen their name to the work of a commercial copy writer? Or is this practice unique to psychiatric journals?
 
VNS is one among several examples of hucksterism in psychiatry—a capital venture exploration which is essentially a gamble not backed by any scientific evidence.
Others include: deep brain stimulation (DBS, which is described as “delicate but brutal”) See: https://ahrp.org/cms/content/view/129/28/
and transcranial magnetic stimulation (TMS) see:   http://www.ists.unibe.ch/TMS%20concensus.pdf

The FDA process that approved VNS was a demonstration of the debasement of scientific standards in FDA decision-making: Advisory committee members who voted to recommend approval abandoned logic, much as the followers of cults:  "The feeling was that anything that gives these people hope is potentially worthwhile."

FDA administrators overruled the objections of its medical officers. A devastating report issued by Senator Charles Grassley documents the VNS approval spectacle.  See:  http://finance.senate.gov/press/Gpress/02_2006%20report.pdf
 
Today’s acknowledgement by the editor of the Journal of the Medical Association that she has been snookered once again, this time, by six authors of a study linking severe migraines to heart attacks in women (published in the current issue of JAMA), underscores and confirms that academic medicine suffers from an epidemic of corruption. Failure to protect the integrity of medicine—and the public health interest—rests not merely with industry, but more importantly the responsibility is shared by academic research centers and journals. Neither have done anything to enforce financial disclosure policies or to establish meaningful penalties such as would deter violators.

Only two journal editors (that we know of) have taken meaningful steps to stem the tide of tainted scientific objectivity by the proliferation of industry-manipulated reports in medical journals: The Journal, Environmental Health Perspectives, added penalties to its disclosure policy in 2004 barring publication for 3 years to authors who fail to disclose financial conflicts. And in December 2005, the Journal of Thoractic and Cardiovascular Surgery announced it would similarly ban authors who fail to comply with disclosure requirements

None has taken steps to cleanse the literature of tainted reports, reviews, and editorials.  So much for self-policing.

This opens the door for a demand for legislation mandating financial disclosure by any scientist who receives government grant support.

References:

1. Charles B Nemeroff, Helen S Mayberg, Scott E Krahl, James McNamara, Alan Frazer, Thomas R Henry, Mark S George, Dennis S Charney and Stephen K Brannan.  VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms  Neuropsychopharmacology (July, 2006) 31, 1345–1355. published online 19 April 2006. http://www.nature.com/npp/journal/v31/n7/full/1301082a.html

2. See Cyberonics Press Release, August 13, 2003 at: https://ahrp.org/cms/content/view/293/29/

3. § Dennis Charney, M.D., Dean for Academic and Scientific Affairs for Mount Sinai School of Medicine, and Senior Vice President for Health Sciences of The Mount Sinai Medical Center. [Formerly, Chief, Mood and Anxiety Disorder Research Program, NIMH Chief, Experimental Therapeutics and Pathophysiology Branch, NIMH]

Contact: Vera Hassner Sharav
veracare@ahrp.org

 
http://online.wsj.com/article/SB115322997681109756.htm l
Wall Street Journal
Medical Reviews Face Criticism Over Lapses
By DAVID ARMSTRONG
July 19, 2006; Page B1

Charles Nemeroff, one of the nation’s most prominent psychiatrists, edits the journal Neuropsychopharmacology, which this month favorably reviewed a controversial new treatment for depression.

But yesterday, the journal said it plans to publish a correction because it failed to cite the ties of the article’s eight academic authors to the company that makes the treatment, including the article’s lead author: Dr. Nemeroff.

The journal’s nondisclosure of the financial ties of its own editor as well as those of the other authors highlights the failure of many respected medical journals to identify relationships between academic researchers and medical companies that may benefit from positive research reports. A spate of recent lapses is prompting calls for more journals to ban offending authors from publication. In addition, medical schools are being urged to regulate relationships between their researchers and industry more closely.

Last week, the Journal of the American Medical Association published a correction indicating that seven authors of a February paper on depression during pregnancy failed to reveal they were paid by the makers of antidepressants. It was the third such incident at JAMA this year.

"If journals are going to have ethical standards and if those ethical standards are going to mean anything, there has to be sanctions associated with them," says Sheldon Krimsky, a Tufts University professor who has studied conflict-of-interest policies of medical journals. Most policies require authors to report financial ties, but don’t include any punishment if they fail to do so.

The science journal Environmental Health Perspectives added penalties to its disclosure policy in 2004 after several authors failed to note industry relationships. The new policy calls for a three-year ban on publication for authors who willfully fail to disclose financial links. In addition, the journal said it would retract studies if it determined that the unreported conflicts would have prompted it to initially reject the manuscript.

Last December, the Journal of Thoracic and Cardiovascular Surgery said it would start to ban for "some period of time" authors who fail to disclose conflicts. The journal’s editor said the common remedy for disclosure failures — a published correction — doesn’t go far enough.

Most journal editors, however, are reluctant to ban authors, partly out of concern these researchers will shop their work to a different publication. The editor in chief of JAMA, Catherine DeAngelis, takes another approach. She asks medical school deans employing the researchers to investigate. She says sanctions, which she didn’t specify, have resulted against authors each time she has asked for such an investigation.

Jerome P. Kassirer, a former editor of the New England Journal of Medicine, says medical schools need "more stringent policies" limiting financial relationships between researchers and industry. "These faculty members are just up to their ears in financial conflicts and academic medical centers are just not doing anything about it," he says.

In the latest case, Neuropsychopharmacology published a review of a new treatment for depression in which a small device is implanted in the chest to deliver mild electrical pulses to the vagus nerve in the neck. The Food and Drug Administration approved the device, made by Cyberonics Inc. of Houston, for use in treating depression last year. The authors conclude that vagus nerve stimulation is "a promising and well-tolerated intervention that is effective in a subset of patients with treatment-resistant depression." (See the review article1.)

Concerns about the treatment have been raised elsewhere. In congressional testimony this year, U.S. Sen. Charles Grassley (R., Iowa) said FDA reviewers opposed use of the device for depression because Cyberonics didn’t demonstrate reasonable assurances of safety and effectiveness.

Of the nine authors of the review, eight are academic researchers who serve as consultants to the company, according to Ronnie Wilkins, executive director of the American College of Neuropsychopharmacology, which publishes Neuropsychopharmacology. The ninth author is an employee of Cyberonics, which was reported in the review article.

Mr. Wilkins says the academic authors revealed their relationships with the company in disclosure forms required by the journal. However, he says the authors didn’t report the financial ties in the manuscript submitted to the journal as required. He says the journal is reviewing its procedures "to prevent similar omissions in the future," and a correction will be issued soon.

Dr. Nemeroff, chairman of psychiatry and behavioral sciences at the Emory University School of Medicine, says there was "no intent whatsoever on my part or any of my co-authors to hide the fact we were working in collaboration with Cyberonics."

He also says the identification of one author as a Cyberonics employee as well as a notation that the report was supported by a Cyberonics grant made clear the review was connected to the company. Dr. Nemeroff says he serves on two Cyberonics advisory boards but declined to say how much he was paid. Mr. Wilkins says Dr. Nemeroff recused himself from the editing and peer review. He was shown an edited version before it was published.

The article acknowledges Sally Laden for "editorial support in developing early drafts of this manuscript," without citing her ties to Cyberonics. Ms. Laden, a professional medical writer hired by Cyberonics to help compile the review, said the company provided her with materials from its advisory board meetings. Ms. Laden says she prepared the first draft of the review piece, which then went through many revisions based on edits and suggestions by the listed authors. All the authors were involved in preparing the final version, she says.

A Cyberonics spokeswoman declined to comment. The company issued a press release this month announcing publication of the review. The press release quoted Dr. Nemeroff as saying, "It is clear VNS therapy is a promising treatment." His consulting work was not mentioned. The company also ordered 10,000 reprints of the article.

Write to David Armstrong at david.armstrong@wsj.com

~~~~~~~~~~
Bloomberg News
Medical Journal to Correct Cyberonics Device Article
2006-07-18 15:32 (New York)
By Rob Waters

     July 18 (Bloomberg) — The medical journal Neuropsychopharmacology will correct a review of Cyberonics Inc.’s depression-treatment device to disclose that scientists who wrote the article had financial ties to the company.
     The links to Houston-based Cyberonics involve eight of the authors of this month’s article. Failing to report the connections violated the journal’s policy, said Kenneth Davis, president of the Nashville, Tennessee-based American College of Neuropsychopharmacology, the journal’s publisher, in an interview yesterday.

     “All those relationships were disclosed” to the journal before publication, Davis said. The omission was an error on the part of the editors, not the authors, he said. The correction will appear on the group’s Web site and in a future issue of the journal, he said.
     Earlier this month, an article in the Journal of the American Medical Association failed to report financial links between researchers on antidepressants and the makers of the drugs. The journal last week said it would strengthen its conflicts-of-interest disclosure policy.
    The Neuropsychopharmacology article didn’t state that eight of the nine authors are also paid members of a scientific advisory committee for Cyberonics. The ninth scientist is an employee of the company, which was disclosed. The Wall Street Journal reported the journal’s plan to correct the article today in its on-line edition.

                        Epilepsy Treatment
     The Cyberonics machine was designed to treat epilepsy by applying electrical stimulation to a nerve that runs through the abdomen and heart to the brain, helping to regulate both organs.  In their article, the scientists called the device `a promising and well-tolerated intervention” for people with depression who aren’t helped by other treatments.
     U.S. regulators approved the Cyberonics device to treat depression in July 2005, over the objections of “more than 20”  Food and Drug Administration scientists, according to a report by investigators from the Senate Finance Committee.

                        `Classic Example’
     “This is about as classic an example as you’ll ever find of conflict of interest and manipulation by thought leaders who are beholden to corporations,” said Bernard Carroll, a member of the neuropsychopharmacology group who is the retired chairman of the department of psychiatry at Duke University, in a July 16 telephone interview.
     The plan to issue a correction notwithstanding, Carroll criticized the article for mixing “credible basic science” with the “marketing message” of the company. “This article is a piece of a slick, skillfully coordinated PR campaign directed by the corporation,” he said.
     A request for an interview with Cyberonics Chief Executive Officer Skip Cummins was referred to the journal. Company spokesman Dana Conti said Cyberonics wouldn’t have any additional comment.
     The study’s principal author, Charles B. Nemeroff, is also chairman of the Cyberonics advisory board and is the editor-in-chief of the journal itself. He declined to be interviewed.     “As a co-author of the manuscript, I, of course, completely recused myself, from any editorial responsibilities in relation to this submission,” wrote Nemeroff, who is chairman of the psychiatry department at Emory University in Atlanta, in an e-mail. “All of the authors provided their full financial disclosures.”
    Davis, the organization’s president, said he wasn’t sure how the mistake was made. He said Nemeroff wasn’t to blame.

                           Earlier Case
     “It would be a mistake for you to conclude that there was some malfeasance here because the editor is also the first author and also the head of the advisory group,” Davis said.
     Duke’s Carroll and Robert Rubin, now a professor of psychiatry at the University of California, Los Angeles, in 2003 said Nemeroff failed to disclose financial interests in depression treatments mentioned in a review he wrote for the journal Nature Neuroscience, including his ownership of a patent on one product.
     Carroll and Rubin wrote to the editors of Nature Neuroscience, which, like Neuropsychopharmacology, is owned by the Nature Publishing Group. Their letter and an article in the New York Times prompted the Nature journals to change their policy and require that all authors of reviews disclose all their financial ties to products they are writing about.

–Editor: Simison

To contact the reporter on this story:
Rob Waters in San Francisco at (1) (415) 743-3549 or rwaters5@bloomberg.net.

To contact the editor responsible for this story:
Robert Simison at (1) (202) 624-1812 or rsimison@bloomberg.net.
~~~~~~~~~~~~~~~~
http://online.wsj.com/article/SB115322997681109756.html    
THE WALL STREET JOURNAL    
Medical Journal to Issue Correction On Review of Depression Treatment
By DAVID ARMSTRONG
July 18, 2006 11:43 a.m.

BOSTON — A review of a new depression treatment published in a medical journal failed to disclose that the authors are consultants to the company that sells the treatment.
An official of the medical society that publishes the journal Neuropsychopharmacology says a correction will be issued soon.

The review piece in this month’s Neuropsychopharmacology comes to favorable conclusions about the treatment, called vagus nerve stimulation. The treatment involves the implanting of a small device just under the skin. Electrodes attached to the device are wrapped around the vagus nerve in the neck. The Food and Drug Administration approved the treatment for use in depression last year.

Of the nine authors, eight are academic researchers who are consultants for Cyberonics Inc., which makes the vagus nerve device. The ninth author is an employee of the company, which was disclosed.

In the conclusions of the review article, the authors write that vagus nerve stimulation is "a promising and well-tolerated intervention that is effective in a subset of patients with treatment-resistant depression." (See the review article <http://www.nature.com/npp/journal/v31/n7/full/1301082a.html> 1.)

Ronnie Wilkins, the executive director of the medical society that publishes Neuropsychopharmacology, says that the consulting arrangements should have been disclosed and that a correction will be published as soon as possible. He says the authors did report their financial relationships with the company in forms they are required to fill out as part of the publication process. However, he says the consulting information was not included in the manuscript of the review piece as required.

The first author of the article, Charles B. Nemeroff of Emory University, is also the editor of Neuropsychopharmacology. Mr. Wilkins says Dr. Nemeroff recused himself from the editing of the review. Dr. Nemeroff, however, did see an edited version of the review article before it was published, Mr. Wilkins says.

Dr. Nemeroff, chairman of the department of psychiatry and behavioral sciences at the Emory school of medicine, did not respond to telephone messages left at his office.

While the acknowledgements section of the review article says "preparation of this report was supported by an unrestricted educational grant from Cyberonics Inc.," it does not disclose that the academic authors are company consultants. The acknowledgements also thank Sally Laden for "editorial support in developing early drafts of this manuscript."

Ms. Laden is a professional medical writer who was hired by Cyberonics to help compile the review article. She said the company provided her with materials from the company’s advisory board meetings to help draft the review article. Ms. Laden said she prepared the first draft of the review piece which then went through many revisions based on edits and suggestions by the listed authors. All of the authors were involved in preparing the final version of the review article, she said.

"This was not a ghostwritten project," Ms. Laden said. "I was just a facilitator."

Ms. Laden declined to say how much she was paid by the company for her work. A Cyberonics spokeswoman said the company would have no comment on the review article.

Write to David Armstrong at david.armstrong@wsj.com4
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