November 26

Negative Research Results–Mostly Concealed in Journals_SharonBegley, WSJ

A recent engaging column by Sharon Begley, Wall Street Journal (below), underscores the importance of publishing both the positive and negative scientific findings.

Whether the research involves new patented drugs that are claimed to be superior to existing (cheaper) ones; or claims of genetic markers of disease (interpreted as "risk" factors), or claims of statistical relationships are promoted as "evidence" of a cause / effect relationship-discerning whether the claims are spurious or confirmed by subsequent trials can only be ascertained by making the full body of controlled test findings publicly available.

In medicine, failure to do so casts doubt on the safety and efficacy of treatments as well as undermining the integrity of the scientific literature.  Scientific journals are supposed to protect the integrity of science–but don't.  As is the case with most deficient practices in medical research and practice-there is an unacknowledged financial motive.

"Why are scientists coy about publishing negative data? In some cases, says Dr. Kern, withholding them keeps rivals doing studies that rest on an erroneous premise, thus clearing the field for the team that knows that, say, gene A doesn't really cause disease B.  Which goes to show that in scientific journals, no less than in supermarket tabloids, you can't believe everything you read — or shouldn't."

Several new journals are attempting to set the record straight by publishing negative research results that mainstream journals fail to publish. 
They are: The Journal of Spurious Correlations; Journal of Negative Results in Biomedicine, the Journal of Negative Observations in Genetic Oncology-the courageous editors are to be applauded.

Contact: Vera Hassner Sharav


New Journals Bet
'Negative Results' Save Time, Money
Sharon Begley
September 15, 2006; Page B1

In ancient Greece, sailors who survived shipwrecks had their portraits
displayed in a temple on Samothrace as a testament to the power of Neptune.
When Diagoras of Melos was told that this proved that the gods insert
themselves into the lives of men, he answered, "but where are they painted
that are drowned?"

Today, showing only the rescued sailors would be called publication bias,
the tendency of scientists to report findings that support some point
(Neptune rescues sailors) but to bury examples (drowned sailors) that
undercut it. It has existed for years, most seriously in the failure to
publish studies that cast doubt on the safety or efficacy of new drugs.

Now, guardians of scientific probity are fighting back. A handful of
journals that publish only negative results are gaining traction, and new
ones are on the drawing boards.
"You hear stories about negative studies getting stuck in a file drawer, but
rigorous analyses also support the suspicion that journals are biased in
favor of positive studies," says David Lehrer of the University of Helsinki,
who is spearheading the new Journal of Spurious Correlations.

"Positive" means those showing that some intervention had an effect, that
some gene is linked to a disease — or, more broadly, that one thing is
connected to another in a way that can't be explained by random chance. A
1999 analysis found that the percentage of positive studies in some fields
routinely tops 90%. That is statistically implausible, suggesting that
negative results are being deep-sixed. As a result, "what we read in the
journals may bear only the slightest resemblance" to reality, concluded Lee
Sigelman of George Washington University.

Example: In the 1990s, publication bias gave the impression of a link
between oral contraceptives and cervical cancer. In fact, a 2000 analysis
concluded, studies finding no link were seldom published, with the result
that a survey of the literature led to "a spurious statistical connection."

Keeping a lid on negative results wastes time and money. In the 1980s,
experiments claimed that an antibody called Rap-5 latches onto a
cancer-related protein called Ras, exclusively. Scientists using Rap-5 then
reported the presence of Ras in all sorts of human tumors, notes Scott Kern
of Johns Hopkins University. That suggested that Ras is behind many cancers.

Oops. The antibody actually grabs other molecules, too. What scientists
thought was Ras alone was a stew of compounds. In part because the glitch
was published in obscure journals, researchers continued to use Rap-5 and
reach erroneous conclusions, says Dr. Kern.

"If the negative results had been published earlier, scientists would have
saved a lot of time and money," adds Bjorn Olsen of Harvard Medical School,
a founding editor, with Christian Pfeffer, of the Journal of Negative
Results in Biomedicine. After a slow start in 2002, that journal is
receiving more and better papers, says Dr. Olsen. One found that, contrary
to other reports, the relative length of the bones of a woman's index finger
and ring finger may not be related to her exposure to testosterone in utero.
Another found that a molecule called PYY doesn't have a big influence on
body weight; another, that variations in a gene that earlier studies had
associated with obesity in mice and in American and Spanish women isn't
linked to obesity in French men or women.

That may sound like the set-up for a joke, but studies that dispute
connections between a gene and a disease are among the most important
negative results in biomedicine. They undercut the simplistic idea that
genes inevitably cause some condition, and show instead that how a gene acts
depends on the so-called genetic background — all of your DNA — which
affects how individual genes are activated and quieted. But you seldom see
such negative results in top journals.

Hence, Dr. Olsen's journal, which is full of studies disputing reported
links between gene variations and disease. The Sod1 gene and inherited forms
of Lou Gehrig's disease? Probably not. MTHFR and the age at which Huntington
disease strikes? Uh-uh. PINK-1 and late-onset Parkinson's disease? No.
Hopefully, each of these reports kept researchers, including those at drug
companies, from wasting time looking for ways to repair the consequences of
the supposed genetic association. But it isn't clear that any would have
been published without the new journal.

Questionable correlations between a gene and cancer are the bread-and-butter
of NOGO, the Journal of Negative Observations in Genetic Oncology, which Dr.
Kern edits. "Fully half [of discoveries] of novel mutations in tumors, we
found, were not confirmed in the subsequent literature," he says. "You
expect to see follow-ups if the claims held up, so the fact that we didn't
casts doubt on the original claim. But that wasn't explicitly reported."

Why are scientists coy about publishing negative data? In some cases, says
Dr. Kern, withholding them keeps rivals doing studies that rest on an
erroneous premise, thus clearing the field for the team that knows that,
say, gene A doesn't really cause disease B.
Which goes to show that in scientific journals, no less than in supermarket
tabloids, you can't believe everything you read — or shouldn't.

. Email me at

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