(from: www.commondreams.org/views06/0107-28.htm)

Published on Saturday, January 7, 2006 by the Los Angeles Times
Drug Profits Infect Medical Studies
by John Abramson

Several of our most venerated scientific journals have recently been
besmirched by allegations of scientific misconduct. Shocking? We should be
just as shocked as Inspector Renault when he discovered gambling at Rick's
Cafe in Casablanca.

First, the New England Journal of Medicine made public its concerns about
crucial data having been withheld from its 2000 report on a study
sponsored by Merck exaggerating the safety of its blockbuster drug Vioxx,
now withdrawn. Then the lead author of a seminal article published in the
journal Science reporting the creation of viable stem cells from cloned
human embryos admitted he falsified results and resigned his academic post
in disgrace.

This week brings the news that a Johnson & Johnson subsidiary failed to
include the deaths of two patients in a clinical trial of its new drug for
heart failure, Natrecor, in an article published in the Journal of
Emergency Medicine.

Why shouldn't we be surprised? Because over the last 25 years, clinical
research has been largely privatized. Three-quarters of the clinical
studies published in the three most respected medical journals (the New
England Journal of Medicine, the Journal of the American Medical Assn. and
the Lancet) are now commercially funded. As a result, our medical
knowledge grows not in the direction that best improves our health but
toward corporate profits, the way that plants grow toward sunlight.

This wasn't always so. Before 1980, most medical studies were publicly
funded, and most academic researchers scorned industry support. Now,
however, the vast majority of clinical trials are commercially funded, and
with the financial stakes so high, there is mounting evidence of
individual scientists and corporations manipulating their findings.

Even our most trusted journals are dependent on drug-company money. Drug
makers don't just buy advertising in their pages. According to Richard
Horton, editor of the Lancet, they also pay up to $1.75 million for
reprints of articles favorable to their drugs, which sales reps then hand
out to doctors.

And many journal articles are biased in favor of their sponsors' products.
A 2003 report in the Journal of the American Medical Assn. found that
clinical studies funded by drug companies are three times more likely to
conclude that the sponsor's drug is the treatment of choice, compared to
studies of the same drug that were not commercially funded. (This study of
the effects of commercial bias, by the way, was funded by Danish research
institutions.) The disturbing conclusion is that most of the evidence in
what doctors believe to be "evidence-based medicine" is more infomercial
than dispassionate science.

It's vital to protect the integrity of our medical knowledge. But the
current peer review system alone can't do the job. The journals, and the
peer reviewers they rely on, are in the untenable position of having to
trust that corporate sponsors have accurately and completely reported
their findings. At present, journal editors and peer reviewers typically
are not allowed unrestricted access to the data from commercially
sponsored research. Amazingly, many drug company-funded researchers who
write the articles are also not allowed access to all of the data the
company has collected.

There is no better cautionary tale than the unwarranted success of Vioxx.
Greater safety was the only reason for doctors to have prescribed Vioxx,
given that it provided no better relief of arthritis symptoms or pain and
cost up to 10 times more than the older anti-inflammatory drug, naproxen
(sold without a prescription as Aleve). But Merck's own study clearly
showed that Vioxx was more dangerous than naproxen overall and caused
significantly more heart attacks, blood clots and strokes — whether or not
the patient had a previous history of cardiovascular disease.

So why did American doctors prescribe $7 billion worth of Vioxx after
Merck and the Food and Drug Administration knew all this?

Because the New England Journal article that ostensibly reported the
results of Merck's study didn't even mention either the cardiovascular or
the overall dangers of Vioxx. Instead, it reported only selective data on
heart attacks and strokes, allowing Merck to claim that Vioxx wasn't a
risk to people without a history of these problems.

The Journal's editors are now accusing Merck of withholding critical data.
Shame on Merck. But shame on the Journal too for not insisting that the
article include a discussion of the most important complications. Doctors
were left with the impression that Vioxx was safer than naproxen when
exactly the opposite was true.

The Journal again misled its readers in 2001, when one of its influential
review articles dismissed the dangers of Vioxx as perhaps reflecting "the
play of chance." This article was published seven months after FDA
reviewers' concerns and Merck's own research data, which documented the
dangers, had been posted on the FDA's website. Worse, the Journal violated
its own policy prohibiting scientists with conflicts of interest from
writing review articles. (Both authors had financial ties to Merck.) That
the Journal disclosed those ties mitigates neither its ethical breach nor
the consequences of its repeated understatement of the risks of Vioxx.

This is hardly an academic argument. According to an article in the
Lancet, based on Merck's own data Vioxx probably caused between 88,000 and
144,000 cases of serious heart disease.

The stem cell and Natrecor debacles offer further evidence that the
problem is not just individual bad actors or occasional lapses of
scientific integrity by drug makers. It's that even the most prestigious
journals are unable to perform the quality control that doctors take for
granted.

Sadly, the evidence shows that it's time for the journals to change their
policies from trust to "trust, but verify." They should introduce a new
standard requiring an independent audit of the accuracy and completeness
of research reports before they are sent out for peer review. These
scientific auditors should be statisticians and medical experts who are
completely free of conflicts of interest and are given unfettered access
to the data.

The journals will rightfully claim they cannot afford to pay for such
scientific oversight. But the lack of oversight is even more costly.
Americans waste billions each year on drugs of dubious value. Until we
find a way to fund quality controls on published research, the cost of our
medical care will continue to soar and our health will suffer.

John Abramson, a clinical instructor at Harvard Medical School, is author
of "Overdosed America" (HarperCollins, 2004). He is a consultant to
attorneys of patients who took Vioxx and are suing Merck.

© 2006 Los Angeles Times

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