The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
PUBLICATION
&
CITATION BIAS IN FAVOR OF INDUSTRY-FUNDED RESEARCH?
In
last week’s
column (www.doctorwascher.com/Archives/9-21-08.htm),
I raised the issue of potential biases being introduced into the
publication of
clinical research studies when the manufacturer of a drug or medical
device
provides funding for such research projects.
Multiple previous assessments have reported that
industry-sponsored
studies far more frequently come to favorable conclusions regarding the
products
manufactured by their sponsors than similar studies (including other
studies
that have evaluated the very same devices and drugs) that have been
funded by
government or non-industry philanthropic sources.
Moreover, manuscripts from studies that
report “positive” findings (i.e., studies that report a beneficial
effect of a
treatment being studied) are more likely to be published in leading
medical
journals than similar studies with “negative” conclusions. Interestingly, this
“positive publishing bias”
has been confirmed for submitted manuscripts irrespective of the
source, or
sources, of research funding utilized to conduct these clinical
research
studies.
Now,
a newly
published research paper in the journal Circulation
adds further objective evidence that the increasingly common trend of
conducting clinical research with industry dollars significantly
improves the
likelihood that such research will be accepted for publication in the
most prestigious
medical journals, and that such studies will also receive far more
widespread
distribution in the world’s medical literature than comparable studies
underwritten by government and non-industry philanthropic sources.
This
study, which
was conducted at Harvard University,
assessed all
303 cardiovascular medicine clinical research trials that were
published
between 2000 and 2005 in the world’s three most prestigious medical
journals:
the Journal of the American Medical
Association, the New England
Journal
of Medicine, and The Lancet.
Specifically, the
authors tabulated all of the
citations associated with these 303 research studies, annually, from
2000 through
2006 (citations are those references that are published in other
research
papers, and that refer back to the original study being cited).
The
results of
this study were eye-opening, and potentially very worrisome. The median (midpoint) number
of citations per
year for research trials funded entirely
by for-profit industry sponsors was 46, while the median number of
citations per
year for studies jointly funded by for-profit and
not-for-profit sponsors was 37. More
strikingly, compared to the median of 46
citations per year for purely industry-sponsored studies, the median
number of
citations per year for published research studies funded solely by
government
grants was a meager 29.
When
the authors
of this study then looked specifically at those cardiovascular medicine
research studies that found the new treatments to be better
than standard treatments, the bias against
studies not sponsored by for-profit industry sources became
even more dramatic. The
median number of
citations per year for the for-profit industry-sponsored “positive”
research
studies was 52, while similar research studies that were funded by
government
and other not-for-profit sources managed only 25 citations per year in
the world’s
published medical literature!
As
if the data
presented so far wasn’t provocative enough in suggesting that
industry-sponsored “positive” research studies get a much larger share
of the limelight
in the world’s medical literature (i.e., compared with
non-industry-sponsored
research), when the authors of this newly published analysis then
looked at the
number of citations per year being reported for “negative” studies that
identified a worse outcome with the
new treatments being studied, the results, once again, strongly
suggested that a
powerful publishing and citation bias exists in favor of
industry-sponsored “positive”
research studies. Among
those clinical
research studies that identified a worse
outcome associated with new treatments, the median number of citations
per year
was 33 for industry-sponsored “negative” trials and 41 citations per
year for the
“negative” studies that were funded by not-for-profit sources.
All
of the above
biases in favor of for-profit industry-sponsored clinical research
studies, and
against government-sponsored studies, held true even when the same
clinical issues
and treatments were being addressed by both types of studies, and even
when
both types of studies were published back-to-back in the very same
journal!
Perhaps
you are
not surprised by these findings, or perhaps, on the other hand, you may
wonder
what these apparent publication and citation biases have to do with the
price
of tea in China (or, say, with the way that Medicine is practiced by
the
doctors who care for you and your loved ones…)?
In fact, these biases, which continue to strongly favor
the publication
and citation of research underwritten by for-profit companies (and
whose
products are being assessed in these very same studies), can indeed
have a
profound impact on how your doctor may choose to treat you and his or
her other
patients.
Like
most doctors
these days, I try to ensure that my clinical practice guidelines for
various
diseases follow an evidence-based approach. That
is to say, I rely heavily upon recently published
research studies, and particularly those studies that have been
published in
the world’s most prestigious medical journals, to inform me about the
safest
and most effective way to treat the illnesses that patients come to see
me
about. Thus, if
these exalted sources of
cutting-edge clinical research information are preferentially
publishing
clinical research studies that are underwritten by the very same
companies that
manufacture the drug or device being studied, while at the same time
they are
apparently declining to publish similar research studies that have been
funded
by unbiased governmental funding sources, then I, and with most other
doctors, become
far more likely to recommend treatments that are being underwritten by
the very
drug or device companies (and who are clearly not unbiased) that
manufacture
and market the same treatments being evaluated in these studies.
Unfortunately,
clinical researchers, and their academic institutions, are under
enormous
pressure to accept research funding from the deep pockets of for-profit
industry
sponsors. Because
of a continuing
decline in the availability of government-based funding for clinical
research (and
especially for the younger generation of clinical researchers who may
not
already have an elaborate history of previous government grants), many
researchers find themselves between the proverbial rock and a hard
place. In the end,
many clinical researchers end up
making rather Faustian deals with industry sponsors because they cannot
find
alternative (non-profit) sources of funding.
Although the precise impact of these publication and
citation biases on
the quality and cost of medical care is difficult to measure, multiple
drugs
and medical devices have recently been taken off the market by the FDA
due to belated
findings of severe, and even lethal, side effects associated with
treatments
that were originally lauded within industry-sponsored clinical research
trials,
and which, after being published in some of the world’s most exalted
medical
journals, were then expeditiously approved for marketing by the FDA.
Despite
recent efforts
of the editorial boards of many of these same prestigious journals to
demand, from
all researchers, full disclosure with respect to their funding sources,
the
deck still remains stacked against the publication and citation of
important
clinical research that has been conducted with funding from government
agencies
and non-industry not-for-profit philanthropists, and most especially
for those
studies concluding that a new treatment is inferior to existing (and
often less
expensive) treatments. The
best way to
rectify this pernicious and potentially harmful source of bias is quite
simple: provide
qualified researchers with
adequate sources of government-based funding to allow them to conduct
meaningful clinical research studies.
Government-based
sources of funding could also be further supplemented by not-for-profit
philanthropic organizations that are able to prove that they have no
potential conflicts
of interest with regards to the treatments being evaluated, and that
will agree
to completely abstain from attempting to influence the conduct of the
research,
the interpretation of the resulting data, the composition of the
study’s
manuscript, and the submission of the manuscript to specific medical
journals.
In
addition to
all of these initiatives, the editorial boards of all
medical journals need to come together and jointly agree to
eliminate their continuing biases in favor of industry-sponsored
studies, as
well as their ongoing biases against otherwise high quality research
studies
that reach negative conclusions about the treatments that they are
assessing. It is
only in this way that we can reduce the
risk of skewing the world’s published medical literature in ways that
are very likely
to drive up both the risks and costs associated with providing medical
care in
our already over-burdened and under-funded healthcare system.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
