Stanford orthopedic surgeon Eugene Carragee
and his editorial team at the Spine Journal
announced they had examined data that
Medtronic Inc. presented a decade ago to get
approval for the spinal bone graft product
sold as Infuse.
Not only did the team find that evidence for Infuse’s benefits
over existing alternatives for most patients was questionable;
they also discovered in a broad array of published research
that risks of complications (including cancer, male sterility and
other serious side e;ects) appeared to be 10 to 50 times higher
than 13 industry-sponsored studies had shown. And they learned
that authors of the early studies that found no complications
had been paid between $1 million and $23 million annually by
the company for consulting, royalties and other compensation.
Carragee, MD ’82, estimates Medtronic has sold several billion
dollars’ worth of Infuse for uses both approved and “o; label.”
Medtronic issued a statement saying it believed the product
was safe for approved use and gave a $2.5 million grant to Yale
University researchers to review the data. Their analysis is
expected this year.
The financial influence Carragee’s team unearthed makes
this case particularly jarring. Yet the phenomenon of flawed
research is not new. Medical science studies routinely reverse
or cast doubt on previous research that guided physicians’ recommendations on everything from which fat we can safely
slather on our morning mu;n to some of the most invasive and
expensive procedures doctors perform on the human body. No
wonder many people feel less than confident when facing
important health decisions. If it seems that the pace of these
contradictory reports is picking up, it’s not your imagination.
Prompted by soaring health-care costs and increasingly
sophisticated analytical tools, more and more medical treat-
ments are taking their turn under the microscope. One driving
force is John P.A. Ioannidis, chief of the Stanford Prevention
Research Center. He works with colleagues around the globe to
scrutinize treatments that account for huge chunks of the health-
care tab but that are, he says, virtually worthless and sometimes
harmful. Ioannidis says financial influence is one of several factors
that can, deliberately or unintentionally, skew study design and
methodology and undermine the validity of published research
findings. His extensive publications pointing out these prob-
lems are reverberating throughout the scientific community—
and threaten entire medical specialties that have organized them-
selves around big-ticket, but low-value, interventions.
There are many examples of biomedical flip-flops,
but Ioannidis says two are particularly illustrative of the chal-
lenge he and his colleagues face.
For years, doctors monitoring women prescribed hormone
therapy during menopause believed that it protected their
patients from heart disease. However, in the mid-1990s a Women’s Health Initiative study randomly assigned more than
16,000 women to a controlled trial comparing the common hormone treatment—a combination of estrogen and progestin—to
a placebo. Stanford’s Marcia L. Stefanick, PhD ’82, a professor
of medicine, chaired the steering committee and was principal
investigator. The trial was supposed to last eight years but was
stopped in 2002 after five years, when researchers discovered
that the treatment—at the time routinely prescribed to millions
of women—not only failed to o;er any benefit against heart disease but also appeared to correlate with an increase in both
stroke and breast cancer risk.
The other jaw-dropper was the 2007 COURAGE trial exam-
ining patients with stable coronary artery disease, or hardening
of the arteries. It found that a widely performed procedure
