Faked Data's Influence on Medical Practice

Science depends upon accuracy and honesty. All too often these days, we tend to assume that scientific researchers are impeccably honest. Unfortunately, the image of the objective scientist toiling away in the lab looking for the truth is not always accurate. There is too much money influencing research these days. The following article taken from Scientific American is a clear case in point.


A Medical Madoff: Anesthesiologist Faked Data in 21 Studies
A pioneering anesthesiologist has been implicated in a massive
research fraud that has altered the way millions of patients are
treated for pain during and after orthopedic surgeries

By Brendan Borrell

Over the past 12 years, anesthesiologist Scott Reuben revolutionized
the way physicians provide pain relief to patients undergoing
orthopedic surgery for everything from torn ligaments to worn-out
hips. Now, the profession is in shambles after an investigation
revealed that at least 21 of Reuben's papers were pure fiction, and
that the pain drugs he touted in them may have slowed postoperative
healing.

"We are talking about millions of patients worldwide, where
postoperative pain management has been affected by the research
findings of Dr. Reuben," says Steven Shafer, editor in chief of the
journal Anesthesia & Analgesia, which published 10 of Reuben's
fraudulent papers.

Paul White, another editor at the journal, estimates that Reuben's
studies led to the sale of billions of dollars worth of the
potentially dangerous drugs known as COX2 inhibitors, Pfizer's
Celebrex (celecoxib) and Merck's Vioxx (rofecoxib), for applications
whose therapeutic benefits are now in question. Reuben was a member of
Pfizer's speaker's bureau and received five independent research
grants from the company. The editors do not believe patients were
significantly harmed by the short-term use of these COX2 inhibitors
for pain management but they say it's possible the therapy may have
prolonged recovery periods.

Baystate Medical Center in Springfield, Mass., began investigating
Reuben's findings last May after its chief academic officer, Hal
Jenson, discovered during a routine audit that Reuben had not received
approval from the hospital's review board to conduct two of his
studies. Reuben "violated the trust of Baystate, the community and
science," Jenson says. The story of the investigation was first
reported by Anesthesiology News late last month.

Reuben, 50, has been stripped of his research and educational duties
and has been on medical leave since May. He received his medical
degree from the State University of New York at Buffalo School of
Medicine & Biomedical Sciences in 1985 and did his residency at the
Mount Sinai Medical Center in New York City. In 1991, he joined
Baystate, which serves as the western campus for Tufts University
School of Medicine, and has worked as a staff anesthesiologist and the
director of acute pain management.

His lawyer, Ingrid Martin of Dwyer & Collora, LLP, in Boston, told
ScientificAmerican.com that Reuben has cooperated with the
investigation and that he "deeply regrets that all of this happened."
She added that "with the [investigating] committee's guidance, he is
taking steps to ensure this never happens again." She declined to
answer any further questions, and Reuben did not respond to an e-mail
request for comment.

Beginning in 2000, Reuben, in his now-discredited research, attempted
to convince orthopedic surgeons to shift from the first generation of
nonsteroidal anti-inflammatory drugs (NSAIDs) to the newer,
proprietary COX2 inhibitors, such as Vioxx, Celebrex, and Pfizer's
Bextra (valdecoxib). He claimed that using such drugs in combination
with the Pfizer anticonvulsant Neurontin (gabapentin), and later
Lyrica (pregabalin), prior to and during surgery could be effective in
decreasing postoperative pain and reduce the use of addictive
painkillers, such as morphine, during recovery. A 2007 editorial in
Anesthesia & Analgesia stated that Reuben had been at the "forefront
of redesigning pain management protocols" through his "carefully
planned" and "meticulously documented" studies.

Many orthopedic surgeons, however, were slow to adopt COX2 inhibitors
due to animal studies that showed short-term use might hinder bone
healing. Then, in 2004, Vioxx and Bextra were pulled from the market
because of their link to an increased risk of heart attacks and
strokes, leaving Pfizer's Celebrex as the only COX2 inhibitor
available. Celebrex sales plunged 40 percent after a study that same
year suggesting that it, too, posed a heart attack risk. Despite this,
Reuben continued to present "findings" in research funded by Pfizer
that trumpeted Celebrex's alleged benefits and downplayed its
potential negative side effects.

He apparently hoped to erase doubts by persuading orthopedic surgeons
to co-author papers with him based on his bogus data. In 2005 he and
Evan Ekman, an orthopedic surgeon at Southern Orthopaedic Sports
Medicine in Columbia, S.C., published a study on the use of Celebrex
to control pain in back surgery patients. "The short-term
administration of celecoxib," they wrote in the paper published in The
Journal of Bone and Joint Surgery, "results in no significant
deleterious effect on bone or ligament healing or cardiovascular
outcomes."

Three years later, Reuben's career would begin to unravel as Ekman
began to suspect foul play. In addition to collaborating with Reuben
on the now-retracted Celebrex study, Ekman agreed to review a Reuben
manuscript on surgery on the anterior cruciate ligament (ACL) in the
knee. But when he asked the anesthesiologist for the name of the
orthopedic surgeon on the study, Reuben ceased communication with him.

Then, last year, Ekman was invited by Pfizer to give a talk. While
there, he was handed a version of the very manuscript Reuben had asked
him to review, which had subsequently been published in Anesthesia &
Analgesia. To his surprise, and horror, he was listed as a co-author:
Reuben had forged his signature on the submission form, Ekman says.

By then, Editor in Chief Shafer had already put several Reuben
manuscripts on hold after learning that Baystate had initiated a probe
into the validity of his research. The investigation later identified
21 articles based on patient data that had been partially or
completely doctored. Although Pfizer funded Reuben's research between
2002 and 2007, Baystate has no records of those payments and says that
the research funds could have been paid directly to Reuben. Such an
arrangement would be "highly unusual," Shafer notes. "It's just a
little frustrating," Baystate spokesperson Jane Albert says. "I don't
know how many dollars went to Dr. Reuben or his group."

Pfizer spokesperson Sally Beatty insists the grants were properly
disbursed to Baystate in accordance with Pfizer policy. "Pfizer is not
familiar with the records retention policies of Baystate Medical
Center," she says, "However, independent investigator-initiated
research grant agreements were executed between Pfizer and Baystate
Medical Center." Beatty was unable to provide information on the
dollar amount of the grants, but editor White says they typically
range between $10,000 to $100,000.

The question is: Why did it take 12 years before a "routine audit"
revealed Reuben's widespread data fabrication? "Baystate publishes
about 200 [studies] every year, and of those [articles], the audit
rate might only be 5 percent," Baystate's Jenson says, acknowledging
that ultimately "Baystate is responsible" for making sure that
research done there is properly conducted and reported. He says that
the hospital has been trying to strengthen its oversight program over
"the past few years" and that it is in the process of applying for
accreditation from the Association for the Accreditation of Human
Research Protection Programs (AAHRPP) in Washington, D.C., which
provides an independent evaluation of an organization's ethical
standards and oversight. The lack of accreditation is not unusual
because the nonprofit program was not established until 2001 and only
recently has grown to include 159 hospitals, academic institutions and
other organizations.

In hindsight, Anesthesia & Analgesia editors Shafer and White admit
that it should have been a "red flag" that Reuben's studies were
consistently favorable to the drugs he studied. White, who has also
received drug company educational grants, says that such funding comes
with "subtle pressure" to give the companies the results they want.
For now, at least, neither the drug companies nor Reuben's co-authors
are officially sharing in the blame, but that's expected to change.
"There's a lot of responsibility to pass around," White says, "It's
all being focused on Scott Reuben, but the reality is there are many
other responsible parties."

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