Orig. posted to another group:

Medical Journals Are an Extension of the Marketing Arm of
Pharmaceutical Companies
Richard Smith
Richard Smith is Chief Executive of UnitedHealth Europe, London, United
Kingdom. E-mail: richardswsm...@yahoo.co.uk
Competing Interests: RS was an editor for the BMJ for 25 years. For the
last 13 of those years, he was the editor and chief executive of the
BMJ Publishing Group, responsible for the profits of not only the BMJ
but of the whole group, which published some 25 other journals. He
stepped down in July 2004. He is now a member of the board of the
Public Library of Science, a position for which he is not paid.
Published: May 17, 2005
DOI: 10.1371/journal.pmed.0020138
Copyright: © 2005 Richard Smith. This is an open-access article
distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited.
Citation: Smith R (2005) Medical Journals Are an Extension of the
Marketing Arm of Pharmaceutical Companies. PLoS Med 2(5): e138

"Journals have devolved into information laundering operations for
the pharmaceutical industry", wrote Richard Horton, editor of the
Lancet, in March 2004 [1]. In the same year, Marcia Angell, former
editor of the New England Journal of Medicine, lambasted the industry
for becoming "primarily a marketing machine" and co-opting "every
institution that might stand in its way" [2]. Medical journals were
conspicuously absent from her list of co-opted institutions, but she
and Horton are not the only editors who have become increasingly queasy
about the power and influence of the industry. Jerry Kassirer, another
former editor of the New England Journal of Medicine, argues that the
industry has deflected the moral compasses of many physicians [3], and
the editors of PLoS Medicine have declared that they will not become
"part of the cycle of dependency...between journals and the
pharmaceutical industry" [4]. Something is clearly up.
The Problem: Less to Do with Advertising, More to Do with Sponsored
Trials
The most conspicuous example of medical journals' dependence on the
pharmaceutical industry is the substantial income from advertising, but
this is, I suggest, the least corrupting form of dependence. The
advertisements may often be misleading [5,6] and the profits worth
millions, but the advertisements are there for all to see and
criticise. Doctors may not be as uninfluenced by the advertisements as
they would like to believe, but in every sphere, the public is used to
discounting the claims of advertisers.
The much bigger problem lies with the original studies, particularly
the clinical trials, published by journals. Far from discounting these,
readers see randomised controlled trials as one of the highest forms of
evidence. A large trial published in a major journal has the journal's
stamp of approval (unlike the advertising), will be distributed around
the world, and may well receive global media coverage, particularly if
promoted simultaneously by press releases from both the journal and the
expensive public-relations firm hired by the pharmaceutical company
that sponsored the trial. For a drug company, a favourable trial is
worth thousands of pages of advertising, which is why a company will
sometimes spend upwards of a million dollars on reprints of the trial
for worldwide distribution. The doctors receiving the reprints may not
read them, but they will be impressed by the name of the journal from
which they come. The quality of the journal will bless the quality of
the drug.

Fortunately from the point of view of the companies funding these
trials-but unfortunately for the credibility of the journals who
publish them-these trials rarely produce results that are
unfavourable to the companies' products [7,8]. Paula Rochon and others
examined in 1994 all the trials funded by manufacturers of nonsteroidal
anti-inflammatory drugs for arthritis that they could find [7]. They
found 56 trials, and not one of the published trials presented results
that were unfavourable to the company that sponsored the trial. Every
trial showed the company's drug to be as good as or better than the
comparison treatment.
By 2003 it was possible to do a systematic review of 30 studies
comparing the outcomes of studies funded by the pharmaceutical industry
with those of studies funded from other sources [8]. Some 16 of the
studies looked at clinical trials or meta-analyses, and 13 had outcomes
favourable to the sponsoring companies. Overall, studies funded by a
company were four times more likely to have results favourable to the
company than studies funded from other sources. In the case of the five
studies that looked at economic evaluations, the results were
favourable to the sponsoring company in every case.
The evidence is strong that companies are getting the results they
want, and this is especially worrisome because between two-thirds and
three-quarters of the trials published in the major journals-Annals
of Internal Medicine, JAMA, Lancet, and New England Journal of
Medicine-are funded by the industry [9]. For the BMJ, it's only
one-third-partly, perhaps, because the journal has less influence
than the others in North America, which is responsible for half of all
the revenue of drug companies, and partly because the journal publishes
more cluster-randomised trials (which are usually not drug trials) [9].
Why Do Pharmaceutical Companies Get the Results They Want?
Why are pharmaceutical companies getting the results they want? Why are
the peer-review systems of journals not noticing what seem to be biased
results? The systematic review of 2003 looked at the technical quality
of the studies funded by the industry and found that it was as
good-and often better-than that of studies funded by others [8].
This is not surprising as the companies have huge resources and are
very familiar with conducting trials to the highest standards.
The companies seem to get the results they want not by fiddling the
results, which would be far too crude and possibly detectable by peer
review, but rather by asking the "right" questions-and there are
many ways to do this [10]. Some of the methods for achieving favourable
results are listed in the Sidebar, but there are many ways to hugely
increase the chance of producing favourable results, and there are many
hired guns who will think up new ways and stay one jump ahead of peer
reviewers.
Then, various publishing strategies are available to ensure maximum
exposure of positive results. Companies have resorted to trying to
suppress negative studies [11,12], but this is a crude strategy-and
one that should rarely be necessary if the company is asking the
"right" questions. A much better strategy is to publish positive
results more than once, often in supplements to journals, which are
highly profitable to the publishers and shown to be of dubious quality
[13,14]. Companies will usually conduct multicentre trials, and there
is huge scope for publishing different results from different centres
at different times in different journals. It's also possible to combine
the results from different centres in multiple combinations.
These strategies have been exposed in the cases of risperidone [15] and
odansetron [16], but it's a huge amount of work to discover how many
trials are truly independent and how many are simply the same results
being published more than once. And usually it's impossible to tell
from the published studies: it's necessary to go back to the authors
and get data on individual patients.
Peer Review Doesn't Solve the Problem
Journal editors are becoming increasingly aware of how they are being
manipulated and are fighting back [17,18], but I must confess that it
took me almost a quarter of a century editing for the BMJ to wake up to
what was happening. Editors work by considering the studies submitted
to them. They ask the authors to send them any related studies, but
editors have no other mechanism to know what other unpublished studies
exist. It's hard even to know about related studies that are published,
and it may be impossible to tell that studies are describing results
from some of the same patients. Editors may thus be peer reviewing one
piece of a gigantic and clever marketing jigsaw-and the piece they
have is likely to be of high technical quality. It will probably pass
peer review, a process that research has anyway shown to be an
ineffective lottery prone to bias and abuse [19].
Furthermore, the editors are likely to favour randomised trials. Many
journals publish few such trials and would like to publish more: they
are, as I've said, a superior form of evidence. The trials are also
likely to be clinically interesting. Other reasons for publishing are
less worthy. Publishers know that pharmaceutical companies will often
purchase thousands of dollars' worth of reprints, and the profit margin
on reprints is likely to be 70%. Editors, too, know that publishing
such studies is highly profitable, and editors are increasingly
responsible for the budgets of their journals and for producing a
profit for the owners. Many owners-including academic
societies-depend on profits from their journals. An editor may thus
face a frighteningly stark conflict of interest: publish a trial that
will bring US$100 000 of profit or meet the end-of-year budget by
firing an editor.
Journals Should Critique Trials, Not Publish Them
How might we prevent journals from being an extension of the marketing
arm of pharmaceutical companies in publishing trials that favour their
products? Editors can review protocols, insist on trials being
registered, demand that the role of sponsors be made transparent, and
decline to publish trials unless researchers control the decision to
publish [17,18]. I doubt, however, that these steps will make much
difference. Something more fundamental is needed.
Firstly, we need more public funding of trials, particularly of large
head-to-head trials of all the treatments available for treating a
condition. Secondly, journals should perhaps stop publishing trials.
Instead, the protocols and results should be made available on
regulated Web sites. Only such a radical step, I think, will stop
journals from being beholden to companies. Instead of publishing
trials, journals could concentrate on critically describing them.
Acknowledgments
This article is based on a talk that Richard Smith gave at the Medical
Society of London in October 2004 when receiving the HealthWatch Award
for 2004. The speech is reported in the January 2005 HealthWatch
newsletter [20]. The article overlaps to a small extent with an article
published in the BMJ [21].

Examples of Methods for Pharmaceutical Companies to Get the Results
They Want from Clinical Trials
Conduct a trial of your drug against a treatment known to be inferior.
Trial your drugs against too low a dose of a competitor drug.
Conduct a trial of your drug against too high a dose of a competitor
drug (making your drug seem less toxic).
Conduct trials that are too small to show differences from competitor
drugs.
Use multiple endpoints in the trial and select for publication those
that give favourable results.
Do multicentre trials and select for publication results from centres
that are favourable.
Conduct subgroup analyses and select for publication those that are
favourable.
Present results that are most likely to impress-for example,
reduction in relative rather than absolute risk.
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