Can we tame the monster?
BMJ 2006; 333 doi: https://doi.org/10.1136/bmj.333.7558.0-f (Published 06 July 2006) Cite this as: BMJ 2006;333:0-fAll rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Sir
After approving SSRI antidepressants in the late 1980s and early
1990s, on the basis of slender evidence of efficacy, the Food and Drug
Administration (FDA) in the United States (US) asserted there was “no
credible evidence” that these drugs could cause violent and suicidal
behaviour in some vulnerable individuals – despite what the evidence
available from the late 1980s indicated. No warning was issued for
prescribers or consumers. The new antidepressant market ballooned to a
$20 billion dollar business.
The US is the biggest profit centre for one of the richest industries
in the world. But there remains for the drug companies a significant
obstacle towards even greater profits: product liability awards. When
drug companies fail to disclose important risks, US courts can award large
sums, and in an effort to keep the risks and their concealment hidden,
settlement costs are now a routine part of doing business on company
ledger sheets.
At someone’s behest – and this is the key point germane to Fiona
Godlee’s question as to whether we can tame the monster (1) - FDA came to
the aid of the pharmaceutical industry by including in a new rule amending
an existing regulation regarding drug labelling, the argument that in the
FDA's view, anyone suing a drug company for failing to disclose a risk
should not be allowed to do so because such a lawsuit is pre-empted by
federal law (2). The argument was that if a drug was sold, that meant it
was approved by the FDA, and that all risks that should be known are in
fact known and disclosed.
In selecting a test case for this legislation, the FDA placed itself
in a position of defending the drug companies against law-suits by people
who claimed they had been harmed by undisclosed risks of antidepressants.
In so doing, they have staked a position that it is illegal to warn
patients about a risk of suicide from antidepressants. This position has
become increasingly untenable as evidence accumulates so that even
GlaxoSmithKline now acknowledges the risk to be present (3). But FDA dug
in and continues to defend its claim even as its scientists protested the
agency’s subjugation of science and public health to political aims (4).
In 2003, the FDA first presented an analysis of suicide from clinical
trials of antidepressants, most of which had been completed a decade
previously (5). Analyses of suicides and suicide attempts in
antidepressants trials had been published previously by others, each
showing that antidepressants increased the risk of suicide. This result
hid for years behind a statistical smokescreen with the claim that the
increased risk of suicide with antidepressants should be disregarded
because it was not “statistically” significant (6). But the FDA, with a
database of more than 40,000 patients in trials from all of the
antidepressant manufacturers, found an increased risk of suicide with
antidepressants that was “statistically significant.” Instead of
concluding that their analysis confirmed the increased risk, which would
necessitate warnings on the drugs and admit the fallacy of their pre-
emption argument (currently being defended in litigation with millions of
dollars hanging in the balance), the FDA concluded that with a few clever
statistical adjustments, all of the increased risk disappeared.
This FDA claim is dubious because in short term randomised drug
trials large amounts of bias sufficient to wipe out a doubling of risk are
unprecedented (6). Indeed, if these trials were so biased, then it would
mean that the studies that formed the scientific basis of FDA approval of
these drugs were seriously flawed. The data present the FDA with a
dilemma: was the FDA decision to approve antidepressants based on biased
evidence, or were the trials valid, in which case so is the “unadjusted”
analysis which shows that antidepressants cause suicide? On these data it
would seem that FDA were faced with the prospect of admitting to a huge
mistake - either the mistake of failing to warn against increased risk of
suicidal behaviour or a mistake in approving antidepressants in the first
place. Fortunately for FDA, this analysis only appeared as an abstract
in a little read journal and their dilemma went unnoticed.
In the meantime, an FDA employee created a scandal by finding that
antidepressants increased suicidal behaviour in paediatric trials, and an
advisory committee recommended a black box, the highest level of warning,
indicating the increased risk for children to all antidepressants. And
one manufacturer, GlaxoSmithKline, admitted that trials in adults showed
an increased risk of suicidal behaviour too. But FDA continues on the
path of denial. This year, they released the “full” publication of their
analysis of suicidal behaviour in trials of antidepressants in adults (7).
In their latest release, which fails to mention or cite their previous
analysis, the FDA has claimed that the cases of suicide on the new
antidepressants have mysteriously vanished, and with them the previously
reported increased risk. In addition to all the unanswered questions
raised previously, the FDA’s latest story only raises more embarrassing
questions. What happened to the suicides? Why does the FDA now claim to
be unaware of suicides that they previously analysed and of a risk that
even manufacturers have admitted? (8).
The FDA is in a shambles, and there is considerable evidence that
Britain's Medicines and Healthcare Regulatory Agency (MHRA) is not in any
better shape (9). The claims of these regulators in general are now no
more credible than their claims that Vioxx was safe and effective. Given
that these are the bodies that are supposed to tame the monster, the
question posed by Fiona Godlee can only at present be answered in the
negative – unless the answer is that our first step must be to radically
reform these bodies. The key questions otherwise are first who’s bidding
precisely are the regulators now following (are these politicians or
businessmen or who are they?) and second what can we do about that?
1/ Godlee F (2006). Editorial: Can we tame the monster? BMJ 333
2/ Dept. of Health and Human Serv., Docket No. 2000N-1269,
"Requirement of Content and Format of Labeling for Human Prescription Drug
and Biological Products," p. 38 (Jan. 18, 2006).
3/ GlaxoSmithKline. Letter to healthcare professionals, May 2006.
www.gsk.com/media/paroxetine/adult_hcp_letter.pdf (accessed 13/05/2006).
4/ Union of Concerned Scientists survey:
http://www.ucsusa.org/scientific_integrity/interference/fda-scientist-
survey.html).
5/ Hammad TA, Mosholder A, Boehm G, Racoosin JA, Laughren T.
Incidence of suicides in randomized controlled trials of patients with
major depressive disorder. Pharmacoepidemiol Drug Safety 2003;12(suppl
1):S156.
6/ Healy D (2006). Did regulators fail over selective serotonin
reuptake inhibitors. BMJ 333, 92-95.
7/ Hammad TA, Laughren TP, Racoosin JA. Suicide rates in short term
randomised controlled trials of newer antidepressants. J Clinical
Psychopharmacology 2006; 26, 203-207.
8/ Healy D. bmjjournals.com/cgi/eletters/333/7558/92
9/ See correspondence on MHRA’s handling of trial suicide on
www.socialaudit.org.uk/6060116.htm#FOI
Competing interests:
DH has links to all the major pharmaceutical companies and has been an expert witness in legal actions involving antidepressants and suicide
Competing interests: No competing interests
I applaud your call for drugs (and presumably devices) to be
evaluated independently. However, ensuring independent funding of trials
may not be sufficient to ensure their independent implementation.
The people who are most qualified to actually do drug (and device,
for that matter) trials here in the US, and probably in many other
countries, are academic physicians and researchers. The problem is that
conflicts of interest that could threaten their trials' independence are
pervasive in academic medicine.
In the US, the most recent examples of the pervasiveness of such
conflicts appeared in a series of investigative reports on Stanford
University.(1,2) Furthermore, conflicts of interest may affect not only
the academic physicians and researchers who might perform clinical trials,
but also the administrators and executives to whom they report. We have
presented numerous examples of such conflicts of interest on our blog,
Health Care Renewal.(3) The most striking examples include deans of
medical schools, and even the chief executives of universities to whom
medical schools and academic medical centers report, who also sit on the
boards of directors of large health care corporations. Such board
memberships entail not only large salaries and grants of stock options,
but fiduciary duties to those corporations and their stockholders. Some
recent examples from the popular media were: the Chancellor of the
University of California - San Diego, who is also on the boards of Boston
Scientific and Pharmaceutical Product Development;(4) the Dean of the
Medical School at Case-Western Reserve University, who was also briefly on
the board of GlaxoSmithKline;(5) and the President of the University of
Miami, who is also on the board of UnitedHealth Group.(6)
To ensure independent evaluation of drugs (and devices), those performing
clinical studies must not only get indendent funding, but also not have,
or report to leaders with substantial conflicts of interest.
References
1. Jacobs P. How profits, research mix at Stanford. San Jose Mercury
News, July 9, 2006.
2. Jacobs P. Science critics make issue of financial ties. San Jose
Mercury News, July 10, 2006.
3. http://hcrenewal.blogspot.com/
4. Yang E. UCSD leader also serves as a director on 10 boards. San
Diego Union-Tribune, January 28, 2006.
5. Irving R. GSK recruit helped in legal action against firm.
(London) Times, January 18, 2006.
6. Staff Report. UM's Shalala named in shareholder suit. Miami
Herald, May 23, 2006.
Competing interests:
I own 3200 shares of Elan Corp stock
Competing interests: No competing interests
Editor-in-Chief, BMJ
The basic point that I was seeking to make was that without the
necessary checks and balances afforded by a robust editorial or peer
review process, the BMJ Rapid Response format allows the publication of
potentially misleading information by any party, notwithstanding the
requirement to delcare any competing interests.
To suggest that the BMJ starts from the point that the Authors are
acting in good faith is to miss the point. Surely if there is anything to
be learnt form the position in which the NEJM found itself is that
reliance on the authors of any submission for factual accuracy and balance
is not a sensible option.
J Malde
Competing interests:
None declared
Competing interests: No competing interests
Dr Godlee has provided a good description of the problems that beset
Evidence Based Medicine, namely a corrupt database, which is in danger of
turning Archie Cochrane's admirable vision into a house of cards built on
sand.
Few have focussed on the role that medical journals have played in
this crisis, but Godlee has now added her voice to the concerns about the
role of journals in the murky waters of publication ethics. She refers to
her predecessor, Richard Smith's proposals for radical restructuring of
the way that results of research are more reliably, rapidly and more
transparently disseminated and incorporated into clinical decision making.
Godlee is also correct in urging a firewall between sponsors and the
whole process of creating and disseminating knowledge and product
regulation.
Now Dr Smith has weighed in again as part of a series of articles in
the Journal of the Royal Society of Medicine on restoring integrity to
medical science. His current article (1) provides more detail on the
entangled relations between Merck and the NEJM.
Never afraid to call a spade a spade in the BMJ tradition, Smith
writes "It fits
with the argument that medical journals are an extension of
the marketing arm of pharmaceutical companies and that
the full data of trials should be published not in medical
journals, where an incomplete story is advanced, but on the
web" referring to his own startling essay in his current journal, last
year (2). This joins a growing chorus of disillusionment in traditional
publishing as a component of epistemiology (3-5). The reader may notice a
pattern here, namely that former editors are almost unanimous in voicing
concerns about the commercialisation of science and medicine. The
encouraging factor is that Horton (Lancet) and Godlee (BMJ) are preaching
from the pulpit, not the churchyard.
It is time that the chorus was turned into definitive action. The
Ottawa Statement (6) and the World Health Organization (WHO) statement on
the new standard in clinical trial registration (7) enables this to now
move forward with a comprehensive and systematic method for knowledge
management independent of sponsors. However it is going to take
organisations with the scope of WHO and the World Association of Medical
Editors to build on all this groundwork and create a new system which
fully exploits the technological resources that have already transformed
publishing. There can be no turning back or excuses for further delay.
References:
1. Smith R. Lapses at the New England Journal of Medicine JRSM 2006
vol 99 August http://www.rsmpress.co.uk/0607JRSMSmith.pdf
2. Smith R. Medical jourmnals are an extension of the marketing arm
of pharmaceutical companies PLoS 2005 May 2:e138 2005
http://medicine.plosjournals.org/perlserv/?request=get-
document&doi=10.1371/journal.pmed.0020138
3. Horton R. The dawn of McScience. New York Rev Books 2004 51(4):
7–9
4. Angell M. The truth about drug companies: How they deceive us and
what to do about it. New York: Random House 2005. 336 p.
5. Kassirer JP. On the take: How medicine's complicity with big
business can endanger your health. New York: Oxford University Press. 2004
251 p.
6. Ottawa Statement on Trial Registration.
http://ottawagroup.ohri.ca/
7. Sim I, Chan AW, Gülmezoglu AM, Evans T, Pang T Clinical trial
registration: transparency is the watchword. Lancet 2006 May 20 367(923):
1631-1633
Competing interests:
Have published on the need for greater integrity and transparency in science.
Competing interests: No competing interests
Yes it is the answer and yes it is feasible. I've been thinking the
same thing for a long time now. It would guarantee the appearance of a lot
more 'negative' results in the public domain, not necessarily fascinating
reading but important nonetheless.
Going one step further, I believe drug companies should not be
allowed to promote their products directly but should again contribute to
a central fund which would provide independent academic detailers. Of
course, if a new drug is any good it will promote itself.
Competing interests:
None declared
Competing interests: No competing interests
An excellent article.
Some dismiss proposals to isolate medical research and medical
researchers from drug company money as "unrealistic".
In my view, however, your sequestration proposal is feasible and
deserves to be seriously considered, along with other alternatives
designed to achieve the same end or goal.
Such alternatives are outlined in a paper I published recently:
“Biomedical Conflicts of Interest: a defence of the sequestration thesis”,
Journal of Medical Ethics 2004; 30:8-24.
Professor Arthur Schafer
Director, Centre for Professional and Applied Ethics
University of Manitoba
Competing interests:
None declared
Competing interests: No competing interests
Regarding fact checking in responses
We haven't got the resources to check that references cited in
responses or articles elsewhere in the journal say what the authors claim
they say.
Nor can we ascertain whether the cited references are a fair
representation of the literature or whether they're just those that suit
the author's case. Our starting position is that authors are acting in
good faith. (Nevertheless, we ask all authors to declare any competing
interests, and we make these disclosures public.)
Anyone who believes that an author isn't giving a fair representation
of the issues is free to make this point - which we believe is one of the
important functions of rapid responses.
To be useful, however, such concerns would need to be expressed in
more specific terms than "some contentious points worthy of further
scrutiny."
Competing interests:
The author is editor-in-chief of bmj.com and partially responsible for its policies
Competing interests: No competing interests
Six years ago I was a Banker without a care in the world. Then my
eldest son,
Ellis, died from vCJD and by invitation from MRC (and Sir Iain Chalmers in
particular) I became deeply involved as a professional amateur lay person
on
several projects.
I am continualy surprised by articles such as this because what is
suggested is
such common sense that I am astounded it doesnt happen already. Imagine
your
Insurance Salesman being allowed to self regulate. It happened in the past
and
we are still paying the cost.
I do not underestimate how challenging it is to "manage" the world of
Health but
there are some basic principles that should be embedded - and the editors
suggestion is just one.
Its not in the least bit radical - its obvious
Competing interests:
I am employed by DH and MRC as
Co Chair of a clinical trial and am
also Chair of the Development
Group of james Lind Alliance
Competing interests: No competing interests
Indeed, the solution must be in the same line of thought proposed by
Godlee. External evaluations of pharmaceutical products should be
imperative. The problem is that even the regulatory agencies come to fail
in their goalkeeping, as was exemplified by the Faxon case reviewed in the
BMJ by Tanne (1), where the FDA continued to sponsor research from a
proven fraudulent investigator. The monster is free, but the tamers might
not be valiant enough to stand aloof to this challenge.
1. Tanne, JH:FDA limits research of former AHA president for submitting
false information BMJ, Dec 2002; 325: 1377 ;
doi:10.1136/bmj.325.7377.1377/a
Competing interests:
None declared
Competing interests: No competing interests
Journals Must Exercise Their Authority as Gatekeepers
The harm done by journals’ failure to protect the integrity of
science can hardly be overstated. If physicians can’t rely on the unbiased
objectivity of journal reports—they cannot practice evidence-based
clinically responsible medicine. Changes are needed to restore
credibility to the medical literature.
December, 2005: an editor of The New England Journal of Medicine
(NEJM) acknowledged under oath that although editors knew of three
unreported Vioxx deaths in the VIGOR-Vioxx study, [1] but decided not to
inform physicians. That acknowledgement, five years after publication,
was reported by Forbes, [2] then The Wall Street Journal (WSJ) [3] sending
shock waves—but did it change journal policies?
May 2, 2006: The New York Times (NYT) reported: “Virtually every
major scientific and medical journal has been humbled recently by
publishing findings that are later discredited." [4]
July 12: Just when Dr. Fiona Godlee’s editorial was posted, [6] the editor
of the Journal of the American Medical Association (JAMA) acknowledged
publishing two reports whose authors failed to disclose their financial
ties to drug manufacturers. [7] [8] The reported findings provided a
rationale for increased use of psychoactive drugs by women—even during
pregnancy.
Less than a week later, the FDA issued two public health advisories
warning about evidence of additional lethal risks linked to antidepressant
drugs: persistent pulmonary hypertension in newborn infants whose mothers
took antidepressants during pregnancy, [9]
http://www.fda.gov/cder/drug/advisory/SSRI_PPHN200607.htm
and serotonin syndrome when taken with migraine medications. [10]
http://www.fda.gov/cder/drug/advisory/SSRI_SS200607.htm
These contradictions raise questions about the credibility of not
only these two JAMA reports, but also the medical journals that clinicians
rely on for guidance in their medical practice. JAMA editor, Dr.
Catherine DeAngeles told the WSJ (which broke the news) that she was
“misled.” [11] When questioned by the Chicago Tribune, she snapped: "I
don't give people lie detector tests. I am not the FBI." [12]
Do physician /authors and journals bear no moral, professional, or public
responsibility when they publish misleading information resulting in
preventable deaths?
July 19: the WSJ exposed the “perfect storm,” involving coalescing
conflicts of interest violations. [13] All eight prominent academic
psychiatrists whose names are penned to a report in the official journal
of the American College of Neuropsychopharmacolgy (ACNP), failed to
disclose that they are paid members of the advisory board of Cyberonics,
[14] the manufacturer of VNS (vagus nerve stimulation), an experimental
surgically implanted device for the treatment of depression. The ninth
author, an employee of the company, disclosed his company connection in
the article. The report in Neuropsychopharmacology [15] purports to review
the scientific evidence for the efficacy and safety of VNS. Its
controversial approval “despite strong objection by FDA’s review team,”
was severely criticized in a Congressional report. [16]
The principle author, Dr. Charles B. Nemeroff, "one of the nation's
most prominent psychiatrists" [13] is chairman of psychiatry at Emory
University, a past president of ACNP, the editor-in-chief of
Neuropsychopharmacology, and chairman of Cyberonics' Mechanism of Action
Advisory Board. [14] An editorial in the NYT [17] described these industry
ties as “particularly incestuous.” “It is hard to know whether to be more
upset at the journal's failure to disclose these ties or at its decision
to let such interested parties serve as authors in the first place.” The
Times notes that “Early drafts of the article were prepared by a
professional writer hired by the company.” In other words, the paper was
crafted not by the authors but by a “professional writer” hired by the
sponsor.
Since the 1990s editors have known (or should have) that industry’s
influence was penetrating journals not only directly (through advertising)
but indirectly—by planting favorable reports often written by
professional ghostwriters but “authored” by influential leaders in their
field. [18] Academic scientists traded their influence for cash, penning
their names to biased, ghostwritten reports of trials they did not
conduct, and whose source data they did not analyze. [19] Others,
constrained by contractual publication restriction agreements with the
sponsoring company, published fraudulent reports based on partial data
findings.[20] As two thirds of medical research is now sponsored by
industry, [21] the most influential (“high impact”) medical journals have
become accomplices, camouflaging the commercial nature of industry
promotional reports. [22]
Journals’ failure to take measures to stop this growing malaise
provided a shield for corrupt practices that have undermined the integrity
of science and the journals themselves. Dr. Richard Horton, editor of The
Lancet, calls medical journals “information laundering operations.” [23]
The magnitude of industry’s corrupting influence has put the credibility
of the entire academic literature reporting the safety and efficacy of
(psychotropic) drugs under a dark cloud. [24]
June 2004: New York State Attorney General, Elliott Spitzer, charged
GlaxoSmithKline with fraud for concealing negative data from its pediatric
Paxil trials, [25] citing as evidence the dichotomy between published
journal reports about and company documents refuting those claimed
findings. [26] Only then did drug companies and their accomplices in
academia wake up to the fact that their illegitimate practices constitute
fraud and are subject to prosecution. May 2006: GlaxoSmithKline reversed
years of denial, acknowledging a six-fold increased suicide risk in adults
linked to its antidepressant, paroxetine (Paxil)—thereby discrediting the
entire Paxil literature. [5]
Writing about the SSRI antidepressants, Dr. Jonathan Leo observes:
[27]
“Doctors accepted these drugs and prescribed them so willingly not because
they were given free pens, free dinners, or even free trips. They put
their trust in the drugs because they were backed by papers that were:
written by professors at the major academic medical centers; approved by
peer reviewers; published in the major medical journals; cited in review
articles; discussed at meetings; defended by the ACNP…You can hardly fault
the average physician for putting faith in them.”
A Danish review (2006) of head to head studies of so-called atypical
antipsychotics found that in 90% (of 33 studies) outcomes favored the
sponsor’s drug. “This pattern resulted in contradictory conclusions across
studies when the findings of studies of the same drugs but with different
sponsors were compared.” [28]
Clearly major journals have not taken meaningful steps to protect the
integrity of the scientific literature, or to cleanse it of discredited
reports, or to ensure that biased findings are not published in the
future. Academic medicine is tainted because its gatekeepers, the
journals, not only turned a blind eye; they joined in the desecration of
the scientific foundation of medicine for a 70% profit return from
reprints of “favorable” industry-sponsored reports. The NEJM reportedly
made $697,000 from VIGOR reprints. [3]
Dr. Goldee’s call for a separation between drug producers and
evaluators is both valid and justified, but journals must exercise their
authority as gatekeepers if the integrity of science and safety in
medicine is to be restored. A few suggestions:
1. Require authors to submit protocol and raw data to substantiate
reported findings;
2. Post the protocols and data on a website so that independent analysis
is possible;
3. Require authors’ to declare details of ties to the sponsor, indicating
the nature of those ties (e.g., consultant, speaker, investment; stock
option; advisory board, grant recipient);
4. Require detailed disclosure of author’s contribution to the report:
specify who wrote the first draft, and whether any “professional writers”
were involved;
5. Publish only reports by authors who have control over the data and
control over what is published;
6. Enforce publication policy; adopt penalties for violators barring them
for 3 years.
Vera Hassner Sharav
President, Alliance for Human Research Protection (AHRP)
veracare@ahrp.org
References:
1. Bombardier C., Laine L., Burgos-Vargas R., Davis B., Day R.,
Ferraz M. B., Hawkey C. J., Hochberg M. C., Kvien T. K., Schnitzer T. J.,
Weaver A., Reicin A., Shapiro D. Comparison of upper gastrointestinal
toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.
N Engl J Med 2000;343:1520-1528.
2. Langreth, R and Herper, M. Merck’s Deleted Data, Forbes, December
8, 2005 http://www.forbes.com/home/sciencesandmedicine/2005/12/08/merck-
vioxx-lawsuits_cx_mh_1208vioxx.html.
3. Amstrong, D. Bitter Pill: How the New England Journal Missed
Warning Signs on Vioxx: Waited Years To Report Flaws in Article That
Praised Pain Drug The Wall Street Journal, May 15, 2006; Page A1.
http://online.wsj.com/article/SB114765430315252591.html
4. Altman, L. For Science's Gatekeepers, a Credibility Gap, The New
York Times May 2, 2006.
http://www.nytimes.com/2006/05/02/health/02docs.html?
5. See: GSK. Briefing. Paroxetine Adult Suicidality Analysis. April
5, 2006: http://www.gsk.com/media/paroxetine_adult.htm; GSK. Letter to
healthcare professionals: “Clinical worsening and suicide risk” May 2006:
http://www.gsk.com/media/paroxetine/mi_letter.pdf.
6. Godlee, F. Editor’s Choice: Can we tame the monster? BMJ 2006;
333:
7. Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera
AC, Suri R, Burt VK, Hendrick V, Reminick AM, Loughead A, Vitonis AF,
Stowe ZN. Relapse of major depression during pregnancy in women who
maintain or discontinue antidepressant treatment. JAMA. 2006 Feb
1;295(5):499-507.
8. Kurth, T, Gaziano, MJ, Cook, NR, Logroscino, G, Diener, HC Buring,
JE. Migraine and Risk of Cardiovascular Disease in Women JAMA.
2006;296:283-291.
9. FDA advisory: Pulmonary Hypertensionion:
http://www.fda.gov/cder/drug/advisory/SSRI_PPHN200607.htm
10. FDA Advisory: Serotonin Syndrome:
http://www.fda.gov/cder/drug/advisory/SSRI_SS200607.htm
11. Armstrong, D, Drug Interactions: Financial Ties to Industry Cloud
Major Depression Study, WSJ. July 11, 2006; Page A1
http://online.wsj.com/article/SB115257995935002947.html
12. Japsen, B. and Dow Jones News Wires, Journal tightens rules for
authors: Doctors must disclose conflicts of interest, Chicago Tribune,
July 12, 2006, http://www.chicagotribune.com/business/chi-
0607120198jul12,1,1635801.story?coll=chi-business-hed
13. Armstrong, D Medical Reviews Face Criticism Over Lapses, WSJ.
July 19, 2006; B1 http://online.wsj.com/article/SB115322997681109756.html
14. Nemeroff, CB, Mayberg, HS, Krahl, SE, McNamara, J, Frazer, A,
Henry, TR, George, MS, Charney, DS, and Brannan, SK. 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
15. Senator Charles Grassley. Review Of The FDA’s Approval Process
For The Vagus Nerve Stimulation Therapy System For Treatment-Resistant
Depression. Staff Report.
http://finance.senate.gov/press/Gpress/02_2006%20report.pdf
16. See: Cyberonics Press Release, August 13, 2003 at:
http://www.ahrp.org/cms/content/view/293/29
17. Our Conflicted Medical Journals, NYT, Editorial, July 23, 2006
http://www.nytimes.com/2006/07/23/opinion/23sun2.html?
18. Flanagin, A; Carey, LA, Fontanarosa, PB, Phillips, SG, Pace,
BP, Lundberg, GD, Rennie, D. Prevalence of Articles With Honorary Authors
and Ghost Authors in Peer-Reviewed Medical Journals. JAMA. 1998;280:222-
224.
19. Kaufman, A and Julien, A. Scientists helped industry to push
diet drug. Hartford Courant, April 10, 2000, p. A-1; A8; Peterson, M.
Madison Ave. Has Growing Role In the Business of Drug Research, NYT,
November 22, 2002, A-1.
20. Chan, AW, Hróbjartsson, A, Haahr, MT, Gøtzsche, PC, Altman, DG.
Empirical Evidence for Selective Reporting of Outcomes in Randomized
Trials, JAMA 2004;291:2457-2465; Gøtzsche, PC, Hróbjartsson, A, Johansen,
HK, Haahr, MT, Altman, DG, Chan, AW. Constraints on Publication Rights
in Industry-Initiated Clinical Trials, JAMA 2006;295:1645-1646.
21. Egger M, Bartlett C, Juni, P. Are randomised controlled trials in
the BMJ different? BMJ. 2001 Nov 24;323(7323):1253-4.
22. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical
industry sponsorship and research outcome and quality: systematic review.
BMJ 2003; 326: 1167-70.
23. Horton, R. “The Dawn of McScience,” New York Review of Books,
March 11, 2004;
Smith R. “Medical Journals an extension of the marketing arm of drug
companies,”
24. Healy, D and Cattell, D. Interface between authorship, industry
and science in the domain of therapeutics, British Journal of Psychiatry
(2003);183:22–27.
25. NYS Attorney General Press Release:
http://www.ahrp.org/infomail/04/06/02.php
26. GSK memo details concealment strategy, 1998:
http://www.ahrp.org/risks/SSRI0204/GSKpaxil/index.php
27. Leo, J. The SSRI Trials in Children: Disturbing Implications for
Academic Medicine Ethical Human Psychology and Psychiatry, Volume 8,
Number 1, Spring 2006
28. Heres S Davis J, Maino K, Jetzinger E, Kissling W, Leucht S. Why
olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine
beats olanzapine: an exploratory analysis of head-to-head comparison
studies of second-generation antipsychotics. Am J Psychiatry. 2006
Feb;163(2):185-94.
Competing interests:
None declared
Competing interests: No competing interests