15 Jun 2004 20:23:00 -0700 in article
<[email hidden]> [email hidden] (Zee)
Quoted message said:Please scroll to the end for specifics on the hidden
trials. Please explain to me how it is *they* knew where to
attribute side effects. Are there different rules for
different kinds of studies, or drugs? How is it, we cannot
attribute any causality to statins in trials, but here, we
see Glaxo could, and suppressed negative data from
Seroxat/Paxil trials. Zee
This paroxetine/Seroxat/Paxil case by former SmithKline
Beecham (now GlaxoSmithKline) has been before in the
publicity. It involves even one law suit which
GlaxoSmithKline lost. I guess it sort of started from a
SmithKline Beecham/GlaxoSmithKline sponsored 1995 study
Montgomery SA, Dunner DL, Dunbar GC. Reduction of suicidal
thoughts with paroxetine in comparison with reference
antidepressants and placebo. Eur Neuropsychopharmacol. 1995
Mar;5(1):5-13. PMID: 7613102 [PubMed - indexed for MEDLINE]
<URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retr-
ieve&db=PubMed&list_uids=7613102&dopt=Abstract>
which claimed that paroxetine (a.k.a. Paxil a.k.a. Seroxat)
reduced suicides among depressed people. But the following
articles put the above study in an interesting perspective:
Scandal of scientists who take money for papers
ghostwritten by drug companies Guardian, Thursday February
7, 2002 <URL:http://www.guardian.co.uk/Archive/Article/0,4-
273,4351264,00.html>
"Scientists are accepting large sums of money from drug
companies to put their names to articles endorsing new
medicines that they have not written - a growing
practice that some fear is putting scientific integrity
in jeopardy.
Ghostwriting has become widespread in such areas of
medicine as cardiology and psychiatry, where drugs play
a major role in treatment. Senior doctors, inevitably
very busy, have become willing to "author" papers
written for them by ghostwriters paid by drug companies.
Originally, ghostwriting was confined to medical journal
supplements sponsored by the industry, but it can now be
found in all the major journals in relevant fields. In
some cases, it is alleged, the scientists named as
authors will not have seen the raw data they are writing
about - just tables compiled by company employees. ..."
[...]
The responsibility of scientists for the content of
their papers takes on serious significance in the
context of court cases in the US, where relatives of
people who killed themselves and murdered others while
on SSRIs (selective serotonin reuptake inhibitors) - the
class of drug to which Prozac belongs - claimed the
drugs were responsible. According to David Healy, a
north Wales-based psychopharmacologist who has given
evidence for the families, the companies have relied on
articles apparently authored by scientists who may in
fact have not seen the raw data.
Dr Healy, who had unprecedented access to the data that
the companies keep in their archives, said: "It may well
be that 50% of the articles on drugs in the major
journals across all areas of medicine are not written in
a way that the average person in the street expects them
to be authored."
He cites the case brought last year against the former
SmithKline Beecham (now GlaxoSmithKline) by relatives of
Donald Schell. The court found that the company's best-
selling antidepressant, an SSRI called Seroxat, had
caused Schell to murder his wife, daughter and
granddaughter and commit suicide.
The company's defence was based on scientific papers
which analysed the results of trials comparing Seroxat
with a placebo and found there was no increased risk of
suicide for depressed people on Seroxat. But the raw
data probably does not support that, argues Dr Healy.
Some of the placebo suicides took place while patients
were withdrawing from an older drug. When the figures
are readjusted without these, he says, they show there
is substantially increased risk of suicide on Seroxat.
This raises the question of whether the eminent
scientists whose names were on the papers ever saw the
raw data from the trials - or saw only tables compiled
by company employees, he says. David Dunner, a professor
at the University of Washington, who co-authored one of
the papers in 1995, admits he did not see the raw data.
"I don't know who saw it. I did not," he said. "My role
in the paper was that the data were presented to us and
we analysed it and wrote it up and wrote references."
His co-author Stuart Montgomery, then of St Mary's
hospital medical school in London, declined to answer
calls and emails from the Guardian. The third name on
the paper is that of Geoff Dunbar, a company employee.
The World Health Organisation has expressed concern
about the ties between industry and researchers.
Jonathan Quick, director of essential drugs and
medicines policy, wrote in the latest WHO Bulletin: "If
clinical trials become a commercial venture in which
self-interest overrules public interest and desire
overrules science, then the social contract which
allows research on human subjects in return for medical
advances is broken.""
UW's Friendly Corporate Ghostwriter by Rick Giombetti How a
UW professor lent his name to drug companies research findings--
without bothering to check whether they were true <URL:http://eatthestate.org/06-
19/UWsFriendlyCorporate.htm> <URL:http://www.drugawareness-
.org/Archives/2ndQtr_2002/record0021.html> <URL:http://www-
.healthyskepticism.org/reports/2002/conflictofinterest%200-
20408.htm>
"Dr. David Dunner of the University of Washington's
Department of Psychiatry admitted he "ghostwrote" an
article that appeared in the March 1995 issue of the
journal European Neuropsychopharmacology (EN) on behalf
of pharmaceutical manufacturer SmithKline-Beecham (which
has since merged with GlaxoWellome to become Glaxo-Smith-
Kline, or GSK). Dunner had purportedly analyzed the data
of clinical studies involving GSK's antidepressant and
anti- anxiety drug Paxil and concluded that it is less
likely to lead to suicidal thoughts than the older
antidepressant imipramine or a placebo(sugar pill).
Dunner never looked at any of the data but he was still
listed as an "author" of the article.
Meanwhile, Dr. David Healy of the University of Wales
Department of Psychological Medicine presented a
different analysis of this same data during the Paxil
trial last year. The family of Wyoming resident Donald
Schell, 60, sued GSK in federal court after Schell shot
his wife, daughter, granddaughter and then himself to
death in 1998 after two days on Paxil. Healy testified
on behalf of the plaintiffs. He argued GSK's internal
records demonstrated that there is a substantially
increased suicide risk for patients put on Paxil. The
jury agreed with the plaintiff's position that Paxil was
primarily responsible for Schell's actions and awarded
them $6.4 million in June of last year. The judge in the
case rejected GSK's challenge of Healy's testimony and
sent them packing to a federal appeals court in Denver
in August. A suicide warning has since been put on the
label for the drug, not here in the United States, but
in Britain, where it is known as Seroxat.
Where did Dunner's stunning admission of having
ghostwritten such an important article appear? In either
of the local dailies the Seattle Times or Post-
Intelligencer? No, not even close. A Seattle resident
would have to purchase a ticket on the next British
Airways flight from SeaTac to London to meet the author
of the article Dunner was quoted in: Sarah Boseley,
health editor of the Guardian. Boseley's February 7
article confirmed what I have suspected all along about
Dunner: he has had little or nothing to do with the
actual research and writing behind many of the articles
where his name, D.L. Dunner, appears.
The current situation in peer-reviewed publication in
academic and clinical medical research is starting to
resemble the Catholic Church's control over publication
of anything in, say, 1300. The pharmaceutical industry
funds most of the research into the crucial Phase III
clinical trials that lead to FDA approval for marketing
drugs (the truth is most of the cost of bringing a drug
onto the market is put up by taxpayers). This gives the
drug companies an enormous amount of influence over
study design and, most crucially, they typically retain
control over study data as proprietary information. The
end result is that it's difficult to find a published
article in peer reviewed medical journals dealing with
clinical drug studies that weren't supported by funding
from the drug's manufacturer. Most medical journals are
now dependent on pharmaceutical industry advertising to
stay in business. This didn't stop 13 prestigious
journals, including the Journal of the American Medical
Association, New England Journal of Medicine, and
Britain's Lancet, from publishing an editorial in
September of last year condemning the conditions put on
researchers by the drug companies as, "draconian for self-
respecting scientists, but many have accepted them
because they know if they do not, the sponsor will find
someone who will." The aim of the journals was to
implement editorial policies to authenticate authorship
of articles.
"The pharmaceutical companies usually retain the right
to withhold the information their researchers find that
they don't want the public to see," said Keith Hoeller,
community college instructor in psychology in Seattle
and editor of Review of Existential Psychiatry and
Psychology (who also brought the Boseley article to the
author's attention). "These kinds of contractual
stipulations also provide researchers with incentives to
find the kind of results the drug companies are looking
for in the studies they fund."
"It would be a simple matter to say that the data is
inherently unscientific while it remains proprietary,"
said David Healy. "There is no other branch of science
in which the raw data remains inaccessible to
investigators generally and indeed essentially to the
public." We can all see what happened when the clinical
data in the Paxil trials became a scientific matter in a
court case last year. This tells us that there may be
something to what many critics of the marketing of
psychiatric drugs during the '90s suspected all along:
The public has been fed a self-serving party line about
the efficacy and safety of Paxil, Prozac, Zoloft, and
all of the other newer antidepressant drugs.
Actually Dunner is anything but friendly and
approachable on the topics being reviewed in this
article. Dunner won't talk to me about what he knows
about the side effects of the newer antidepressant
drugs and his conflicts of interest with the
pharmaceutical industry. I don't mind Healy's
willingness to discuss these matters with me. It's just
that I help pay Dunner's salary and help fund his
department every time I pay Washington state's
regressive sales tax. None of this is a problem in the
area of financial conflict of interest, though, as I
have recently received copies of Dunner's honoraria and
conflict of interest records from the UW.
Here is a brief summary. Since July of 1997 and up until
the end of last year, Dunner made at least 80 requests
for outside professional work for compensation including
33 lectures sponsored by various pharmaceutical
companies, 14 for various universities and 11 on behalf
of various professional societies and other
organizations. No exact dollar amount is ever given on
any of the records I have obtained. He also spends at
least a few days every year as a "reviewer" for various
peer-reviewed academic journals.
Dunner's record also includes eight statements of
significant financial interest. The most significant
with regard to the Paxil clinical trial data is a
disclosure he made in 1998. The disclosure was made
regarding an application for a clinical trial dealing
with Paxil in which Dunner would serve as an
investigator at his Center for Anxiety and Depression.
His Confidential Statement to the Vice Provost for
Research states, "My involvement with SmithKlineBeecham
(the pre-Glaxo merger owner of Paxil) involves being a
member of the international advisory board related to
paroxetine (Paxil)." In other words, Dunner's name
appeared in the EN article not as an independent
scientist but most likely as a part-time employee of the
manufacturer of Paxil. This conflict of interest is not
mentioned in the EN article.
Here is Dunner in his own words in Boseley's Guardian
article: "I don't know who saw it (the Paxil clinical
trial data). I did not. My role in the paper was that
the data were presented to us and we analyzed it and
wrote it up and wrote references." Dunner's co-author
Stuart Montgomery, then of St. Mary's hospital medical
school in London, declined comment for the Guardian
article. His other co- author is Geoff Dunbar, a company
employee (Dunbar's status as a SmithKline employee was
mention in the EN article).
Healy figures about half of all articles appearing in
medical journals today are ghostwritten jobs by
pharmaceutical companies. What this tells us is that
we should regard much of what we read in the published
medical literature with a level of suspicion similar
to that of a citizen of the former Soviet Union
reading Pravda. In other words, take with a grain of
salt any published article stating "studies show that
drug X is a safer and more effective treatment than
drug Y and placebo."
The lack of candor most of the psychiatric profession
and the pharmaceutical industry has about these heavily
marketed drugs has potentially deadly consequences for
the patients taking them. According to Healy, "The
evidence from across the board from all the companies
producing SSRI's (i.e., Prozac, Zoloft, Paxil, etc.) is
that their drugs can make 1 in 20 of us agitated to the
extent that we drop out of trials." Healy figures that
at least 250,000 people worldwide have attempted
suicide because of Prozac alone and 25,000 have
succeeded. That sounds like a huge number, but if you
put 50,000,000 people on the drug, at least 2,500,000
will become extremely agitated. If ten percent of that
population attempts suicide because of the extreme
agitation, that gives you 250,000. If ten percent of
that population succeeds in carrying out their suicide
attempt, you end up with 25,000 dead bodies. Put
another 100 million people on Zoloft (comedian Phil
Hartman's wife Brynn), Paxil, Luvox (Eric Harris, one
of the Columbine High School shooters), and the other
more potent newer antidepressants and you might have
another 50,000 dead bodies.
"The fact that (pharmaceutical) companies have chosen to
market them as antidepressants rather than agents of
agitation is a business decision rather than a
scientific matter," said Healy. Yes, business has been
great for the companies manufacturing these
"antidepressant" drugs. The sale of these drugs is now a
$10 billion-per-year industry. However, the outcomes for
the patients put on these drugs have not necessarily
been great. The four dead members of the Schell family
are testimony to this fact. GSK's line in the Paxil
trial that their drug didn't have enough time to "help"
Donald Schell follows no coherent logic. What GSK is
saying is that Schell needed to stay on the drug in his
agitated state, and his dose possibly needed to be
increased, a common occurrence in psychiatric practice.
Increase the patient's dose and you get an even more
agitated individual. You still end up with the deaths of
three generations of Schells in Gillette, Wyoming on
February 13, 1998, with Paxil as the suspected culprit,
no matter what kind of semantic games GSK wishes to
engage in with this case.
How much longer is David Dunner going to remain silent
about the record of harm these "antidepressant" drugs
have caused? How many articles in Dunner's publication
record were ghostwritten? How much longer are the Times
and P-I going to quote Dunner as an unbiased expert on
mental health issues?"
Revealed: how drug firms 'hoodwink' medical journals
Pharmaceutical giants hire ghostwriters to produce articles
- then put doctors' names on them Antony Barnett, public
affairs editor The Observer, Sunday December 7, 2003 <URL:h-
ttp://observer.guardian.co.uk/uk_news/story/0,6903,1101680,-
00.html> <URL:http://observer.guardian.co.uk/print/0,3858,4813867-
102285,00.html>
"Hundreds of articles in medical journals claiming to be
written by academics or doctors have been penned by
ghostwriters in the pay of drug companies, an Observer
inquiry reveals.
The journals, bibles of the profession, have huge
influence on which drugs doctors prescribe and the
treatment hospitals provide. But The Observer has
uncovered evidence that many articles written by so-
called independent academics may have been penned by
writers working for agencies which receive huge sums
from drug companies to plug their products.
Estimates suggest that almost half of all articles
published in journals are by ghostwriters. While doctors
who have put their names to the papers can be paid
handsomely for 'lending' their reputations, the
ghostwriters remain hidden. They, and the involvement of
the pharmaceutical firms, are rarely revealed.
These papers endorsing certain drugs are paraded in
front of GPs as independent research to persuade them to
prescribe the drugs.
In February the New England Journal of Medicine was
forced to retract an article published last year by
doctors from Imperial College in London and the National
Heart Institute on treating a type of heart problem. It
emerged that several of the listed authors had little or
nothing to do with the research. The deception was
revealed only when German cardiologist Dr Hubert
Seggewiss, one of the eight listed authors, called the
editor of the journal to say he had never seen any
version of the paper.
An article published last February in the Journal of
Alimentary Pharmacology , which specialises in stomach
disorders, involved a medical writer working for drug
giant AstraZeneca - a fact that was not revealed by
the author.
The article, by a German doctor, acknowledged the
'contribution' of Dr Madeline Frame, but did not admit
that she was a senior medical writer for AstraZeneca.
The article essentially supported the use of a drug
called Omeprazole - which is manufactured by AstraZeneca
- for gastric ulcers, despite suggestions that it gave
rise to more adverse reactions than similar drugs.
Few within the industry are brave enough to break cover.
However, Susanna Rees, an editorial assistant with a
medical writing agency until 2002, was so concerned
about what she witnessed that she posted a letter on the
British Medical Journal website.
'Medical writing agencies go to great lengths to
disguise the fact that the papers they ghostwrite and
submit to journals and conferences are ghostwritten on
behalf of pharmaceutical companies and not by the named
authors,' she wrote. 'There is a relatively high success
rate for ghostwritten submissions - not outstanding, but
consistent.'
Rees said part of her job had been to ensure that any
article that was submitted electronically would give no
clues as to the origin of the research.
'One standard procedure I have used states that before a
paper is submitted to a journal electronically or on
disc, the editorial assistant must open the file
properties of the Word document manuscript and remove
the names of the medical writing agency or agency
ghostwriter or pharmaceutical company and replace these
with the name and institution of the person who has been
invited by the pharmaceutical drug company (or the
agency acting on its behalf) to be named as lead author,
but who may have had no actual input into the paper,'
she wrote.
When contacted, Rees declined to give any details. 'I
signed a confidentiality agreement and am unable to
comment,' she said.
A medical writer who has worked for a number of agencies
did not want to be identified for fear he would not get
any work again.
'It is true that sometimes a drug company will pay a
medical writer to write a review article supporting a
particular drug,' he said. 'This will mean using all
published information to write an article explaining the
benefits of a particular treatment.
'A recognised doctor will then be found to put his or
her name to it and it will be submitted to a journal
without anybody knowing that a ghostwriter or a drug
company is behind it. I agree this is probably
unethical, but all the firms are at it.'
One field where ghostwriting is becoming an increasing
problem is psychiatry.
Dr David Healy, of the University of Wales, was doing
research on the possible dangers of anti-depressants,
when a drug manufacturer's representative emailed him
with an offer of help.
The email, seen by The Observer, said: 'In order to
reduce your workload to a minimum, we have had our
ghostwriter produce a first draft based on your
published work. I attach it here.'
The article was a 12-page review paper ready to be
presented at an forthcoming conference. Healy's name
appeared as the sole author, even though he had never
seen a single word of it before. But he was unhappy with
the glowing review of the drug in question, so he
suggested some changes.
The company replied, saying he had missed some
'commercially important' points. In the end, the
ghostwritten paper appeared at the conference and in a
psychiatric journal in its original form - under another
doctor's name.
Healy says such deception is becoming more frequent. 'I
believe 50 per cent of articles on drugs in the major
medical journals are not written in a way that the
average person would expect them to be... the evidence I
have seen would suggest there are grounds to think a
significant proportion of the articles in journals such
as the New England Journal of Medicine, the British
Medical Journal and the Lancet may be written with help
from medical writing agencies,' he said. 'They are no
more than infomercials paid for by drug firms.'
In the United States a legal case brought against drug
firm Pfizer turned up internal company documents showing
that it employed a New York medical writing agency. One
document analyses articles about the anti-depressant
Zoloft. Some of the articles lacked only one thing: a
doctor's name. In the margin the agency had put the
initials TBD, which Healy assumes means 'to be
determined'.
Dr Richard Smith, editor of the British Journal of
Medicine, admitted ghostwriting was a 'very big
problem'.
'We are being hoodwinked by the drug companies. The
articles come in with doctors' names on them and we
often find some of them have little or no idea about
what they have written,' he said.
'When we find out, we reject the paper, but it is very
difficult. In a sense, we have brought it on ourselves
by insisting that any involvement by a drug company
should be made explicit. They have just found ways to
get round this and go undercover.'"
References to some studies by Healy et al.:
Healy D, Whitaker C. Antidepressants and suicide: risk-
benefit conundrums. J Psychiatry Neurosci. 2003 Sep;28(5):331-
7.<URL:http://www.cma.ca/cma/staticContent/HTML/N0/l2/jpn/vol-
28/issue-5/pdf/pg331.pdf> <URL:http://www.ncbi.nlm.nih.gov/-
entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14517576-
&dopt=Abstract> ( <URL:http://www.biopsychiatry.com/suicides-
ssri.htm> )
Healy D. Lines of evidence on the risks of suicide with
selective serotonin reuptake inhibitors. Psychother
Psychosom. 2003 Mar-Apr;72(2):71-9. Review <URL:http://www.-
ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&l-
ist_uids=12601224&dopt=Abstract>
More articles about Ghostwriting:
Ghostwriting: Page 1 CBC - Marketplace - Canada's
Investigative Consumer Program <URL:http://www.cbc.ca/consu-
mers/market/files/health/ghostwriting/index.html>
Ghostwriting: Page 2 CBC - Marketplace - Canada's
Investigative Consumer Program <URL:http://www.cbc.ca/consu-
mers/market/files/health/ghostwriting/index2.html>
Ghostwriting - the basics CBC - Marketplace - Canada's
Investigative Consumer Program <URL:http://www.cbc.ca/consu-
mers/market/files/health/ghostwriting/faq.html>
Ghostwriting - Links & Resources CBC - Marketplace -
Canada's Investigative Consumer Program <URL:http://www.cbc-
.ca/consumers/market/files/health/ghostwriting/links.html>
Madison Ave. Plays Growing Role in Drug Research By MELODY
PETERSEN from New York Times, 22 November 2002
<URL:http://www.biopsychiatry.com/bigpharma/bigpharma.html>
Transcript - Science for Sale? <URL:http://www.pbs.org/now/-
printable/transcript_scienceforsale_print.html>
Larkin M. Whose article is it anyway? Lancet. 1999 Jul
10;354(9173):136. <URL:http://www.thelancet.com/journal/vol-
354/iss9173/full/llan.354.9173.news.3708.1>
Bennett DM, Taylor DM. Unethical practices in authorship of
scientific papers. Emerg Med (Fremantle). 2003 Jun;15(3):263-
70. <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=-
Retrieve&db=PubMed&list_uids=12786648&dopt=Abstract>
Bevan JC. Ethical behaviour of authors in biomedical
journalism. Ann R Coll Physicians Surg Can. 2002 Mar;35(2):81-
5. <URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R-
etrieve&db=PubMed&list_uids=12755122&dopt=Abstract>
Riis P. Scientific dishonesty: European reflections. J Clin
Pathol. 2001 Jan;54(1):4-6. <URL:http://www.ncbi.nlm.nih.go-
v/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=112717-
87&dopt=Abstract>
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 Jul 15;280(3):222-4. <URL:http://jama.ama-
assn.org/cgi/content/full/280/3/222>
Mowatt G, Shirran L, Grimshaw JM, Rennie D, Flanagin A, Yank
V, MacLennan G, Gotzsche PC, Bero LA. Prevalence of honorary
and ghost authorship in Cochrane reviews. JAMA. 2002 Jun 5;287(21):2769-
71. <URL:http://jama.ama-
assn.org/cgi/content/full/287/21/2769>
Foregone conclusions Richard Smith The Guardian, Wednesday
January 14, 2004 <URL:http://www.guardian.co.uk/analysis/st-
ory/0,3604,1122568,00.html> <URL:http://www.guardian.co.uk/print/0,3858,4835656-
103674,00.html>
HARLOT plc: an amalgamation of the world's two oldest
professions David L Sackett, Andrew D Oxman BMJ 2003;327:1442-
1445, doi:10.1136/bmj.327.7429.1442 [ <URL:http://bmj.bmjjo-
urnals.com/cgi/content/full/327/7429/1442>
News reports about Paxil/Seroxat/paroxetine:
Seroxat safety advice to be changed BBC News, Monday, 9
June, 2003
<URL:http://news.bbc.co.uk/2/hi/health/2975844.stm>
Children 'should not take Seroxat' BBC News, Tuesday, 10
June, 2003
<URL:http://news.bbc.co.uk/2/hi/health/2976498.stm>
Scientist in rethink over drug link to suicide Sarah
Boseley, health editor Wednesday October 1, 2003 The
Guardian <URL:http://society.guardian.co.uk/mentalhealth/st-
ory/0,8150,1052979,00.html>
Child warning on anti-depressants BBC News, Wednesday, 10
December, 2003
<URL:http://news.bbc.co.uk/2/hi/health/3306327.stm>
Britain issues warning on hazards of kids' taking
antidepressants FDA conducting its own study of risks
Shankar Vedantam, Washington Post San Fransisco Chronicle,
Thursday, December 11, 2003 <URL:http://www.sfgate.com/cgi-
bin/article.cgi?file=/c/a/2003/12/11/MNG2I3KPIC1.DTL>
Britain says kids shouldn't be prescribed antidepressants By
Jason Cato The Herald (Published December 11‚ 2003) <URL:http://www.heraldonline.com/local/story/3121752p-
2827015c.html>
British Ignite Debate in U.S. on Drugs and Suicide NY Times,
December 16, 2003, Tuesday <URL:http://www.nytimes.com/2003-
/12/16/health/psychology/16SUIC.html>
--
Matti Narkia
