Medical experts must eliminate money conflicts
By Jerome P. Kassirer
In a society rife with conflicts of interest, disclosure of such conflicts
is usually a good tonic. But in medicine, where decisions on treatment can
have lasting effects, mere disclosure isn't enough.
Patients need advice they can act on without having to calibrate how likely
it is to be biased. Physicians and scientists with financial ties to the
pharmaceutical industry should not just have to disclose conflicts - they
shouldn't be permitted to issue guidelines at all.
But they are permitted, and they do so routinely. The most prominent recent
example of this is how the federal government came up with and then defended
new recommendations on cholesterol levels for individuals with a high risk
of heart disease. It's an enlightening - and depressing - story.
On July 13, the National Cholesterol Education Program (NCEP), part of the
National Institutes of Health, unveiled tougher guidelines for cholesterol
levels - guidelines so stringent that millions of Americans at risk of heart
disease would have to take costly statin drugs to meet the new lower limits.
What the NCEP didn't unveil was that the recommendations had been written by
a panel of doctors, most with financial ties to the pharmaceutical companies
that stood to gain enormously from increased use of cholesterol-lowering
statins.
Critics immediately complained about the hidden financial ties and demanded
disclosure. Within days, the highly respected sponsors of the cholesterol
guidelines - the NIH, the American Heart Association (AHA) and the American
College of Cardiology (ACC) - posted the disclosures on the NCEP's Web site.
The extent of the connections was stunning: Of the nine panel members, six
had each received research grants, speaking honoraria or consulting fees
from at least three and in some cases all five of the manufacturers of
statins.
If all the members with conflicts had recused themselves, only two would
have been left.
That didn't look too good, so another note appeared on the site, explaining
that the panel's draft proposals had been "subjected to multiple layers of
scientific review." "Altogether approximately 90 reviewers scrutinized the
draft," the note said. The message to the public: No need to worry about
pro-industry bias.
The heart association, whose journal Circulation had published the
guidelines, sent an e-mail to its board of directors, its national strategic
team, its communications advisory team and more than 30 prominent physicians
who have worked closely with the organization. It reminded them of the
association's conflict of interest policy, namely that "if in any situation,
a panelist has a current relationship that could unduly influence guidelines
or statements, that individual recuses himself from that aspect of the work
of the writing panel.
"This process ensures that the guidelines are not inappropriately influenced
in any way." (Apparently, none of the panelists felt their drug-company
connections required recusal.)
But patients deciding whether to take these drugs, and physicians deciding
whether to prescribe them, still don't know whether the NCEP panel members
consciously or subconsciously colored their analysis in favor of statin
manufacturers Merck, Novartis, AstraZeneca, Pfizer and Bristol-Myers Squibb.
Cholesterol guidelines have broad impact. They help doctors decide how
aggressively to prescribe drugs. When the guidelines promote greater use of
statins, they also raise the cost of care. And in some cases, statins cause
liver and muscle injury; in rare cases, they have led to kidney failure.
So why did three major organizations choose such a conflicted panel to write
the guidelines? Quite likely the panelists were experts in the field. Most
had helped to write the preceding round of cholesterol guidelines three
years earlier.
Is it imaginable that using conflicted experts is the best way of getting
unadulterated assessments of clinical data? I don't think so. The best
collective decisions arise from diverse and independent views. When
companies with identical interests are underwriting virtually all the
researchers, decision-makers can become susceptible to "groupthink."
Does the review of the guidelines by 90 other leading experts guard against
potential bias? Not really. Many of the reviewers had conflicts of interest,
too. The heart association conceded that in its e-mail, saying: "The best
scientists are asked to speak and provide advice, not only by the NIH and
the AHA, but by industry. Because of this, many of the top scientists on any
issue will likely have received some funding over time from pharmaceutical
companies."
Even if the 90 other scientists had no conflicts, how diligently did they
examine the data or challenge the expert panelists? Was there dissent among
those reviewers? If so, did anyone listen? We don't know.
There certainly is no unanimity of opinion regarding the lower cholesterol
targets. A University of British Columbia group (with no connection to drug
manufacturers) has drawn different conclusions from the same studies.
How could the NCEP have done a better job of coming up with new guidelines?
First, by using physicians without financial ties to statin makers. Second,
by including experts in methods of clinical research. If there aren't enough
non-conflicted physicians for the panel, at least some independent voices
should be mixed in.
Better still, we should dissuade leading physicians from doing nonscientific
work for pharmaceutical makers. Doctors who want to be respected as
independent authorities should not become paid speakers for drug companies
or consult on marketing issues. We should save the prized task of preparing
clinical practice guidelines for experts without such conflicts. Having a
financial conflict is voluntary; physicians can either take it or leave it.
We must convince them to leave it.
If medical organizations continue to use heavily conflicted experts to make
clinical policy, they will erode public confidence. The public needs medical
institutions it can trust for help with decisions it can barely understand.
Jerome P. Kassirer is editor in chief emeritus of the New England Journal of
Medicine and a professor at the Tufts University School of Medicine.