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Sep. 27, 2004. 01:00 AM

Cracking down on medical trials

Doctors need to have unbiased data on effectiveness of new drugs, says
medical ethicist Arthur Schafer

North Americans consume a lot of pills: pills for high blood pressure,
low libido, high cholesterol, acid reflux, arthritic pain, and
depression.

We take prodigious quantities of pills because our doctors have been
persuaded and have, in turn, persuaded us, that these pills work.

Doctors get their information about what works and what doesn't from a
variety of sources, including what they were taught 20 years ago at
medical school and what they were told last night by a paid consultant
of some drug company after a fancy-free dinner.

Doctors are expected, however, to base their treatment recommendations
upon the best scientific evidence available in the leading medical
journals. We are supposed to be living in the era of "evidence-based
medicine."

Unfortunately, when your doctor consults the medical journals she will
likely discover only a thin slice of the relevant evidence, namely, the
slice that makes new drugs look good. Those clinical trials which show
the new drugs to be no more effective than older cheaper drugs are
seldom submitted to the journals; hence, they remain unpublished and
inaccessible to your doctor.

Here's an example. Let's say that 20 studies have been done of a new
class of drug for high blood pressure. Now, suppose that of those 20
studies, six are positive (favourable to the new drug) and 14 are
negative (showing that the drugs have dangerous side effects or work
less well than older drugs).

One might naïvely think that this would be the end of the story. The
new class of drugs would be consigned to the scrap heap of medical
research, and the hunt would continue for a better, more effective
treatment.

Suppose, however, that as a direct or indirect result of drug company
influence, 12 of the negative studies are not published, while every
positive study is published. Physicians who then attempt
conscientiously to review the literature would find six positive but
only two negative studies.

Since four out of six published studies seem to demonstrate that the
new drug works well, drug company reps then spread the good word ­
along with quantities of free samples ­ to the medical community. The
new drug is hailed as a medical breakthrough and rapidly becomes part
of standard therapy.

This phenomenon of suppressing negative results is known formally as
"publication bias." More colloquially, it's known as "the file drawer
effect," because negative studies are hidden away in a company's file
drawer.

If the much-touted movement towards "evidence-based medicine" is to
mean anything, then physicians need unbiased data on the clinical
effectiveness, toxicity, convenience and cost of new drugs compared
with available alternatives.

The pharmaceutical industry claims that when it sponsors drug trials
the resulting data become its commercial property, to publish or to
suppress as it sees fit. Critics argue that it's vital for doctors and
patients to know the bad as well as the good news about new drugs in
order to make proper health decisions.

Happily, rescue from this alarming situation is at hand. The
International Committee of Medical Journal Editors (ICMJE) has just
announced that in future it will refuse to publish the results of any
clinical trial if that trial was not recorded at its outset in a
publicly accessible registry.

The editors hope to compel drug companies to disclose all the data from
the trials they sponsor. Publication bias would thus be eliminated.

For many years, health advocates have been warning that the current
state of medical research isn't proper science so much as marketing
through censorship or self-censorship. What seems finally to have
spurred the medical journal editors into action was a lawsuit, brought
by New York State Attorney-General Elliot Spitzer against the British
pharmaceutical company GlaxoSmithKline.

The company was successfully marketing its anti-depressant Paxil for
use by children and young people, even though the evidence from some of
the clinical trials ­ which it refused to make public ­ indicated
both that Paxil was no more effective than placebo AND that Paxil
increased the suicidal tendencies of depressed children.

GlaxoSmithKline has not admitted wrongdoing, but it has agreed to pay a
multi-million dollar settlement. It has also agreed, as have some other
drug companies, that it will, in future, post more complete trial
results on its website.

The ICMJE, however, is not impressed by the companies' deathbed
repentance. As one editor asks: "Why would you put the fox in charge of
the hen house?"

Perhaps it's time for governments, including Canada's, to compel
companies by law to register all their results online in a
not-for-profit database.

The next important step will be to tackle the bias that comes from
having so many of our leading hospitals, universities and researchers
sponsored by the pharmaceutical industry.

When your grandmother told you "he who pays the piper calls the tune"
she knew whereof she spoke. If we want public science in the public
interest we must pay for it with public funds, as we used to do before
the trend towards "partnerships" with industry took hold.

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Arthur Schafer is a professor and director of the Centre for
Professional and Applied Ethics at the University of Manitoba.