There are four strands
to this section.
This follows the question of ghost writing of scientific articles.
Ghost writing has probably always happened to some extent. In the
course of the 1980s with the vast increase in the number of company
sponsored satellite symposia and the emergence of a journal supplement
business, ghost writing almost certainly became commoner.
As pharmaceutical corporations reorganised themselves in the 1970s
and 1980s, they outsourced their medical writing into medical writing
agencies. This has the advantage for companies of being able to
get agencies to compete against each other for business, which may
come in the form of a contract for 10 or 20 or 30 articles. Agencies
can potentially compete in areas of cost, but also in terms of access
to the best journals or in terms of attracting a greater proportion
of academic stars as ‘authors’.
Ghost writing has now evolved beyond journal supplements and there
are grounds to think that a significant proportion of the articles
on therapeutics in main stream journals such as JAMA, The New England
Journal of Medicine, the BMJ and the Lancet may be written with
help from medical writing agencies.
In the course of Motus v Pfizer, the lawyers for the plaintiffs,
Baum, Hedlund, Aristei, Guilford and Schiavo turned up a document
produced by Current Medical Directions (CMD), a medical writing
agency based in New York, who appeared to have been working for
Pfizer toward the end of 1998.
This document lists a portfolio of articles on Zoloft (Sertraline),
some of which had already been published and some were still being
written. This document offered us the opportunity to analyse what
proportion the therapeutic literature might be written in a manner
that could be described as non traditional.
We have attempted to do this by seeking out all articles on sertraline
and comparing the previous number of articles published by all authors
in both the CMD and the non CMD series as well as the journal impact
factors in which CMD and non CMD articles had been published and
finally looking at the citation rates of these articles after publication.
These efforts led to a paper -‘Authorships
and Impacts…’ was first sent to the Journal of the American
Medical Association because of their prior interest in this area.
This paper received a series of mixed
The paper was modified in the light of those reviews and sent to
Journal of Psychiatry, where it was reviewed by at least 7 people
The background figures are presented – a list of the impact
factors for CMD journals and authors, citation
rates for CMD articles, as well as a list of non
CMD articles with literature
This second strand in the web site contains a section on missing
In September of 1991
Kahn et al in the American Journal of Psychiatry published an article
giving suicides and suicidal acts in clinical trials of new antipsychotics
submitted to the FDA for licensing purposes. This article lists
suicides and suicidal acts on both new and older antipsychotics
as well as placebo. See Table
1. Aside from a high rate of suicides and suicidal acts on new
antipsychotics compared to placebo, the interest in this paper lies
in the set of missing figures for suicidal acts for Lilly’s antipsychotic
Zyprexa and Astra Zeneca’s Seroquel.
Writing to Lilly and Astra Zeneca brought different responses. Astra
Zeneca supplied the missing data for suicidal acts on Seroquel.
Lilly did not. Scrutinising the material that comes from an FDA
freedom of information request does not give any pointers as to
the numbers of suicidal acts, but it does to show that Zyprexa has
the highest figure for number of suicides in a clinical trial programme
of any current psychotropic drug. It appears that the placebo suicide
listed in Khan for the Zyprexa trials may not have occurred during
treatment with placebo but may in fact have occurred during the
wash-out phase of the trial.
This lack of data led to the following correspondence
with the Minister for Health in the United Kingdom. Ministers
for Health worldwide have no powers to force a pharmaceutical company
to make data public. However they do have some responsibility for
ensuring that patients receiving treatment are able to give informed
This issue remains unresolved nearly two years later, despite written
confirmation from the Department of Health that it needs resolution.
This point links up to
the issue of SSRIs and suicidal behaviour, particularly in children.
In the mid-1990s, Pfizer conducted studies in children with obsessive
compulsive and depressive disorders. The articles resulting from
these studies are included on the CMD list of articles. Of the six
articles listed here, only one makes a clear reference to suicidal
behaviour in one child.
In fact as an Expert Report
prepared for Pfizer on this data reveals there had been at least
six suicidal acts in children taking sertraline.
Studies with Glaxo SmithKline’s Paxil in depressed children reveal
a comparably high rate of suicidal acts on it compared with competitor
antidepressants and placebo (Keller M et al J American Academy Child
& Adolescent Psychiatry 2001, 40, 762-772). In this case the
company defence appears to be that the suicidal behaviour was not
attributed by the investigator to the drug.
However when investigators do attribute causality to the drug in
the case of an adverse event, Glaxo SmithKline and other companies
say that neither these investigators nor even their own company
personnel can attribute causality in this way. That causality can
only be determined by Randomised Controlled Trials. Appling this
logic and sticking strictly to the figures would appear to indicate
that whether or not the investigators believed that Zoloft and Paxil
can make children suicidal, the figures indicate that they can and
possibly do so at a higher rate than occurs in adults.
In addition to the possible ghost authoring of articles (strand
1) and the omission of important safety data (strand 2) there is
a further way in which companies shape what gets published or what
doesn’t get published.
In April 2000 Joseph Glenmullen’s Prozac Backlash was published.
Shortly after publication a variety of media outlets received unsolicited
reviews of this book. Attached are a set of reviews sent to Newsday
in New York with a covering letter from Chamberlain
Communications Group and a further set sent to the Boston Globe
from Rasky Baerlein. These
reviews from senior figures in US psychopharmacology echo themes
that were first developed within Lilly in the early 1990s – that
Prozac is one of the most researched drugs ever, that depression
leads to suicide, and that the people likely to suffer following
Prozac Backlash are the depressed people who scared off treatment
go on to kill themselves.
A systematic campaign like this will deter most people from entering
any debate on the possible hazards of antidepressants.
This section gives concrete instances, where it can be certain that
some ghost-writing happened.
A. In 1999 I was approached by the pharmaceutical company, Pierre
Fabre, to participate in a satellite symposium for their antidepressant
Milnacipran at a European College of Neuropsychopharmacology meeting
in London that September. This led to a series
of e-mails. One of these came with a ghost written Healy article
called “Bridging the Gap”.
This was subsequently published with the apparent author as Siegfried
Kasper. It appears in a journal supplement. The manuscript I wrote
for the symposium ‘Antidepressant pharmacotherapy at the crossroads’,
appeared in the same journal supplement. See Kasper
IJP and Healy IJP.
B. In the course of 2000 while I was waiting to move to a position
in the University of Toronto, I had overtures from Sid Kennedy about
involvement in a meeting that had been organised by Wyeth Canada
by CMED, a medical communications
group based in Toronto. This was originally scheduled fro Cancun
in Mexico but was later switched to Laguna Beach in California.
For a variety of reasons I was reluctant to get involved.
While visiting Toronto as participant in symposium celebrating the
75th anniversary of the University Department, in between interviewing
colleagues for positions on the mood and anxiety disorders programme
in the University and other business, Sid Kennedy organised for
me to meet Jack Fava from CMED, who attempted to overcome my reluctance
at being involved. Fava was happy for someone to deputise for me
- Richard Tranter – and was offering to write our article for us..
After returning home and after finding out about the breach of my
contract with the university of Toronto, I approached Richard as
to his willingness to get involved, explaining that a manuscript
would be written for us and that we were going to alter this as
part of an experiment.
This leads into a sequence of e-mails from Jack Fava and Pauling
Lavigne, which are filed under CMED-emails.
The process also led to a series of articles from CMED-original
to CMED-revised and CMED-final.
The meeting in Laguna Beach centred on an article written by Michael
Thase and two Wyeth authors, which appeared in the British Journal
of Psychiatry in 2001. the central claim behind this paper has also
featured in advertisements that Wyeth had been running for Efexor,
which was that unlike other antidepressants, which might get you
better, Efexor got you well. This British Journal of Psychiatry
paper featured prominently in an editorial that subsequently appeared
in The Lancet under the title “How
Tainted has Medicine become?”
Our CMED-revised changed CMED-original in two ways. The two changes
are near the end of the paper. First it introduced some data from
clinical trials on Remeron that were inconvenient for Wyeth’s claims
about Efexor. Remeron (Mirtazapine) was one of the compounds Wyeth
was most concerned about as it had in some respects a comparable
mechanism of action to Efexor.
The second change involved references to the fact that if an antidepressant
did not suit a patient that not only would it neither get you well
not even better but could in fact make you worse to the point of
making you suicidal.
Following CMED-revised the e-mail trace makes it clear that there
was an objection from CMED. The objection was to our introduction
of the material on Remeron.
The next I got to see of this article was after CMED-final had been
submitted to the Journal of Psychiatry and Neuroscience. CMED-final
has removed the reference to suicidality and inserted a reference
to treating anybody who fails to respond with venlafaxine – see
letter June 12th.
This led to a series of e-mails which can be found in the CMED-email
series and letters on July 27th, July 30th, August 13th and August
There was also one phone call, the only phone call I received from
Sid Kennedy following my breach of contract with the University
of Toronto. In this call, Dr Kennedy proposed that I remove my name
from the article given the difficulties I was having and instead
write a commentary, which would reflect some of my concerns. For
a variety of reasons, this proposal had its attractions. This commentary
finally emerged. – see file JpsychNeuro.
In the meantime, the previous article was reviewed and revised on
the basis of these reviews. It was subsequently published in 2002
and is listed there as having been apparently first submitted on
September 10th 2001, and re-submitted following revision on May
15th and accepted on May 24th 2002. This article appears as CMED
Meanwhile my commentary was reviewed and the review suggested that
this piece, which picked up on the issues of possible suicidality,
did not handle this issue in sufficient depth. This led to correspondence
with the editor of the Journal of Psychiatry and Neuroscience, Russell
Joffe, in which a proposal for appoint counterpoint feature was
raised and accepted. See JPN-emails.
This led to a paper on SSRIs and the risk of suicidality – JPCND
Healy. The issues stalled for close to a year. Finally a counterpoint
feature written by Yvon Lapierre appeared (JPN-YLP).
Then both point (JPCNDHealy2)
and counterpoint were sent for review by the Journal. Correspondence
from the Journal had indicated that point and counterpoint would
appear within weeks but this was followed up then by a letter fro
April 9th from Dr Joffe
indicating problems. I responded on April
Also included in this section is the Lancet Editorial on Tainted
Medicine and Point-Counterpoint feature on the question of “Is
Academic Psychiatry for Sale?” involving Michael Thase.
This series of articles meets the BMJ-Lancet article in a Lines
of Evidence article published in Psychotherapy