Drug profits infect medical studies By Abramson LATimes 1-7-06

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From the Los Angeles Times

Drug profits infect medical studies

By Abramson

JOHN ABRAMSON, a clinical instructor at Harvard Medical School, is

author of " Overdosed America " (Harper, 2004). He is a consultant

to attorneys of patients who took Vioxx and are suing Merck.

January 7, 2006

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Vioxx, now withdrawn.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 & 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

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.