Is this the perfect storm of corruption? ACNP Journal Review VNS

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.”

The Wall Street Journal and Bloomberg News report about a case involving
Neuropsychopharmacology, the official journal of the American College of
Neuropsychopharmacology (ACNP) that will likely go down in history as
psychiatry’s Watergate.

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:
http://www.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: http://www.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: http://www.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: http://www.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:
http://www.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.html
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.com4

~~~~~~~~~~
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
Copyright 2006 Dow Jones & Company, Inc. All Rights Reserved 
 
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