Superfluous Medical Studies Called Into Question
- From: "Cowboy" <msbuckaroo@xxxxxxxxxxx>
- Date: 2 Jan 2006 03:35:53 -0800
http://www.washingtonpost.com/wp-dyn/content/article/2006/01/01/AR2006010100749.html
Superfluous Medical Studies Called Into Question
By David Brown
Washington Post Staff Writer
Monday, January 2, 2006; Page A06
In medical research, nobody is convinced by a single experiment.
A finding has to be reproducible to be believable. Only if different
scientists in different places do the same study and get the same
outcomes can physicians have confidence the finding is actually true.
Only then is it ready to be put into clinical practice.
Nevertheless, one of medicine's most overlooked problems is the fact
that some questions keep being asked over and over. Repeated tests of
the same diagnostic study or treatment are a waste -- of time and
money, and of volunteers' trust and self-sacrifice. Unnecessary
clinical trials may also cost lives.
All this is leading some experts to ask a new question: "What part of
'yes' don't doctors understand?"
Two papers dramatically illustrated this problem last year and may have
helped nudge the medical establishment toward doing something about it.
One article examined 18 years of research on aprotinin, a drug used to
reduce bleeding during heart surgery. The other looked at studies on
the relationship between a baby's sleeping position and sudden infant
death syndrome. Both concluded that research on these subjects went on
long after the answers were known -- namely, that aprotinin worked and
that babies sleeping on their backs were less likely to die of SIDS.
The odyssey of aprotinin, which is derived from the lung tissue of
cows, was recounted in the journal Clinical Trials.
Dean Fergusson and his colleagues at the Ottawa Health Research
Institute found 64 randomized, controlled trials -- the most
authoritative type of study -- on the use of aprotinin in heart
surgery. They were done in half a dozen countries over 18 years,
starting in 1987.
Two-thirds were little more than variations on each other. And nearly
all showed the same thing: Patients who received aprotinin during
surgery bled less. They had only one-third the chance of needing a
blood transfusion of patients who did not get the drug.
What was surprising was that this advantage was clear by June 1992,
after the 12th of the 64 studies. If researchers after that time had
familiarized themselves with previous studies -- and especially if they
had analyzed summaries of those studies, called "meta-analyses" -- they
might not have considered it necessary to run their own.
But it appears that very few of them studied closely what had been
published previously about aprotinin. On average each new paper listed
only one-fifth of the previous studies in its references. Only two
research teams mentioned the two published "overviews" of aprotinin
research, one from 1994 and the other from 1997. Both of them
demonstrated the unquestionable advantage of giving the drug.
In all 64 studies, the patients were randomly assigned to get aprotinin
or a placebo. In general, mortality did not differ between the two
groups. But some of the patients receiving a placebo had bleeding and
needed transfusions that they might have avoided had they been given
aprotinin.
Being given a placebo long after aprotinin's value had been proved
probably did not cost lives. The same cannot be said of medicine's
failure to pay attention to studies of infant sleep position.
Last April, in the International Journal of Epidemiology, Ruth Gilbert
of the Institute of Child Health in London examined 40 studies of SIDS
and sleep position going back to 1965.
Gilbert found that if researchers had pooled the results of the oldest
studies and analyzed them, they might have gotten a big hint by 1970
that putting babies to sleep on their stomachs raised the risk of SIDS.
Instead, that observation did not become convincing until the late
1980s.
Researchers now know that sleeping on the stomach raises the risk of
SIDS sevenfold. That realization led to "Back to Sleep" campaigns in
Britain in 1991 and in the United States in 1994.
Between 1970 and the unveiling of that advice, 11,000 British infants
-- who might have survived if sleeping on the back had been the norm --
died of SIDS. In the United States, Europe and Australia, "at least
50,000 excess deaths were attributable to harmful health advice,"
Gilbert and her colleagues wrote.
The problem is evident even in research on the highest-profile
diseases.
In 1992, Joseph Lau, then at the Department of Veterans Affairs
hospital in Boston and now at Tufts University, published a paper that
has become a classic in epidemiology. He examined 33 clinical trials of
streptokinase, a drug that dissolves clots in the coronary arteries of
people having heart attacks.
The trials were conducted from 1959 to 1988. Lau conducted a
"cumulative meta-analysis" of the results. This is done by adding each
trial's patients and their outcomes to all the preceding ones. The
result was a running scorecard of streptokinase's performance.
Lau determined that by the end of the eighth trial in 1973, the
evidence was clear that heart attack patients who got streptokinase had
25 percent lower death rates than those who did not. That conclusion,
and the percentage, did not budge while 34,542 more patients were
enrolled in 25 more trials of streptokinase over the next 15 years.
There are lots of reasons this kind of thing happens.
In many of the aprotinin studies, the researchers tested the drug in
subgroups of patients or altered variables to see if outcomes changed.
The drug is very expensive, so they tried different doses. Sometimes
they added it to the blood in the heart-lung machine; sometimes they
injected it directly into the patient. Some studies examined not only
aprotinin's effects on bleeding, but also on the function of artery
bypasses to restore blood flow to the heart muscle.
Additionally, surgical culture and practices differ somewhat from
country to country, and apparently surgeons in some nations felt they
needed to study the drug themselves before adopting its use.
Even given these justifications, however, there was much repetition.
Two studies of aprotinin's effects on patients taking aspirin were
published in 1994, another in 1998, and another in 2000. All showed the
same thing: Aprotinin worked for those patients, too.
The reason for the plethora of SIDS studies was different. The evidence
that stomach-sleeping was hazardous arose from observational studies,
which are inherently less authoritative than controlled trials where
people are randomly assigned to do one thing or another. It takes more
observational studies to persuade doctors to change something as
important as advice to new parents.
The number of unnecessary studies that occur is an open question.
Nobody requires that medical scientists review previous research to
make sure the question they are asking has not already been answered.
This may change, though.
The Lancet, a British journal, announced last summer that it will
require that authors submitting papers show they performed a
meta-analysis of previous research or consulted an existing one.
"In 10 years we are going to look back on this time, and we won't
believe this wasn't done as a matter of course," said Steven N.
Goodman, a physician and biostatistician at Johns Hopkins University
who edits Clinical Trials.
The current state of affairs, in his opinion, is indefensible.
When a patient volunteers for a randomized clinical trial, he or she
strikes an implicit bargain with the researcher. The patient may
benefit, but even if he does not, others will. That is because the
study will produce new knowledge. But if the question is already
settled, then the patient's sacrifice and altruism are for naught.
"In the ethical world, two things need to be considered -- harms and
wrongs," Goodman said. "People in unnecessary trials are sometimes
harmed, but I would say they are always wronged. And in the world of
clinical research, wrongs are almost worse than harms."
.
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