More and more evidence is suggesting
that medical journals are increasingly
having to retract reports due to fabricated,
erroneous or misleading data from Doctors
and Scientists.
The editors of the
New England Journal of Medicine
this week added another chapter to the
story of disgraced Norwegian researcher
Dr. Jon Sudbo, as they formally retracted
two reports on oral cancer his team published
in the journal in 2001 and 2004.
By his own admission -- issued through
his lawyer earlier this year -- much of
Sudbo's published data was fabricated.
A recent report from an investigative
commission formed by Sudbo's former employers,
the Rikshospitalet-Radiumhospitalet Medical
Center and the University of Oslo, has
since confirmed the fraud. The NEJM
editors based their retraction largely
on the report's findings.
"Given the weight of evidence offered
in the commission's report and the requests
of most of the authors of the articles,
we retract both articles," NEJM
editors Dr. Gregory Curfman, Dr. Jeffrey
Drazen and Stephen Morrissey wrote in
the Nov. 2 issue of the journal.
They noted that all of the two studies'
authors, with the exception of Sudbo,
have agreed with the Oslo commission's
findings and the journal's subsequent
retraction of the article. Sudbo's various
co-authors have been cleared of any wrongdoing.
Both articles focused on patients (typically
long-term tobacco users) who were at high
risk of oral cancer due to the presence
of precancerous white growths in their
mouths or on their tongues known as oral
leukoplakia. Sudbo's April 1, 2004, NEJM
article suggested that a cellular aberration
called "aneuploidy" -- the presence
of disordered cells marked by overabundant
DNA -- might predict which patients would
benefit most from surgical removal of
these white spots.
But the Oslo report found glaring errors
in Sudbo's work. Most notably, they point
out that in the 2004 study, "the
same patient appears several times,"
so the total number of patients listed
is bumped up from 141 to 150.
Even more concerning, "69 of the
141 patients included in the study should
have been excluded because they had been
diagnosed with oral cancer before or at
the same time as the leukoplakia was diagnosed,"
the report's authors noted. "For
these patients, it was not possible to
study the future development of cancer,
since they already had cancer. This error
alone is so serious that the results and
the conclusions are invalid."
In an "Expression of Concern"
published in the journal earlier this
year, the NEJM editors also noted
that, in the 2001 article, two photographs
from a microscope reportedly representing
two different patients at different stages
of precancerous mouth lesions were "in
fact, different magnifications of the
same electromicrograph."
Sudbo also admitted faking data for studies
published in two other leading journals,
The Lancet (a 2005 article linking
over-the-counter pain relievers with lowered
oral cancer risk) and the Journal of
Clinical Oncology (another oral cancer
study, published in 2005). Editors at
those journals also published special
"Expression of Concern" letters
in the following months.
One of the lingering questions is whether
the findings had any negative impact on
cancer patient care. Experts say that,
in the case of the NEJM articles,
the answer is probably "no."
The high-tech molecular test needed to
spot aneuploidy "is a very complex
method, and it's very expensive,"
and so it is out of the reach for most
clinicians who might treat patients at
risk for oral cancer, explained Dr. Deborah
Greenspan, a professor of dentistry and
clinical oral medicine at the University
of California, San Francisco.
Sudbo's findings were also generally
regarded as preliminary, she added. "To
my knowledge, there have not been any
changes in clinical practice, or indeed
in any recommendations, based as a result
of his findings," said Greenspan,
who authored a NEJM "Perspectives"
piece on Sudbo's work when it was published
in 2004.
She said she was "completely surprised"
by the revelation that Sudbo had faked
his data. "I'm always troubled when
we see scientific investigators fake their
results," Greenspan added.
Still, she said, the basic premise behind
the study -- that aneuploidy might help
doctors better tailor treatment for oral
cancer patients -- is still a valid one.
"In fact, as a result of some of
the things he started to do, other people
have become very interested in exploring
aneuploidy," Greenspan noted.
Dr. Len Lichtenfeld, deputy chief medical
officer at the American
Cancer Society, agreed that the
NEJM research "did not gain
a lot of traction" in terms of its
impact on oncological practice. "I
remember commenting at the time years
ago that this kind of approach was 'not
yet ready for primetime,' " he said.
Still, both experts were troubled that
this type of fraud made its way into some
of the world's leading medical journals.
"I can't make a definitive statement
on what happened here," Lichtenfeld
said, "but it appears that, based
on the report, there was a lack of real
oversight and an overabundance of trust
by various investigators as [Sudbo's work]
went forward. This wasn't an isolated,
one-step issue, this was a systemic problem."
Indeed, the Oslo report cites Sudbo's
relative isolation -- he was sole guardian
of the data he claimed to have collected
-- as one reason his fraud went undetected
for so long.
Lichtenfeld did not point any
fingers at the peer-review process at
the NEJM.
"There's really nothing that the
New England Journal could've done
about this," he said. "To have
found this, they would have had to have
gone to every lab, sort through every
piece of information, every approval,
every memo. It's simply not possible."
Karen Pedersen, a spokeswoman for the
journal, said NEJM is limited in
what it can do to minimize the threat.
"Our graphics department is using
PhotoShop to examine figures more carefully,
but this practice only works on certain
types of images and would not have found
the fraudulent images in the Sudbo case,"
she said. "While we continue to work
hard at being vigilant and skeptical,
and have instituted additional safeguards
in how we review images, at this point
there is not an ironclad, foolproof way
to prevent fraud by a single, determined
author."
Lichtenfeld said Sudbo's case, and others
like it, remain very rare and should not
shake the public's trust in medical research
and the journals that publish that research.
"When you have an unfortunate event
like this, it certainly raises questions,"
he said. "But it should not bring
discredit to the thousands of reports
that researchers who are honest and hardworking
put out every year."