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HMS Beagle Posted February 2, 2001 · Issue 95
OPINION
Something Rotten at the Core of Science?
by David F. Horrobin
Reprinted with permission from Trends in Pharmacological Sciences,
Vol. 22, No. 2, February 2001
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Abstract
A recent U.S. Supreme Court decision and an analysis of the peer
review system substantiate complaints about this fundamental aspect of
scientific research. Far from filtering out junk science, peer review
may be blocking the flow of innovation and corrupting public support
of science.
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The U.S. Supreme Court has recently been wrestling with the issues of
the acceptability and reliability of scientific evidence. In its
judgement in the case of Daubert v. Merrell Dow
(http://caselaw.lp.findlaw.com/scripts/getcase.pl?navby=search&court=US&case=/us/509/579.html),
the court attempted to set guidelines for U.S. judges to follow when
listening to scientific experts. Whether or not findings had been
published in a peer-reviewed journal provided one important
criterion. But in a key caveat, the court emphasized that peer review
might sometimes be flawed, and that therefore this criterion was not
unequivocal evidence of validity or otherwise. A recent analysis of
peer review adds to this controversy by identifying an alarming lack
of correlation between reviewers' recommendations.
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The Supreme Court questioned the authority of peer review.
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Many scientists and lawyers are unhappy about the admission by the top
legal authority in the United States that peer review might in some
circumstances be flawed [1]. David Goodstein
(http://broccoli.caltech.edu/~goodstein/), writing in the Guide to the
Federal Rules of Evidence - one of whose functions is to interpret the
judgement in the case of Daubert - states that "Peer review is one of
the sacred pillars of the scientific edifice" [2]. In public, at
least, almost all scientists would agree. Those who disagree are
almost always dismissed in pejorative terms such as "maverick,"
"failure," and "driven by bitterness."
Peer review is central to the organization of modern science. The
peer-review process for submitted manuscripts is a crucial determinant
of what sees the light of day in a particular journal. Fortunately, it
is less effective in blocking publication completely; there are so
many journals that most even modestly competent studies will be
published provided that the authors are determined enough. The
publication might not be in a prestigious journal, but at least it
will get into print. However, peer review is also the process that
controls access to funding, and here the situation becomes much more
serious. There might often be only two or three realistic sources of
funding for a project, and the networks of reviewers for these sources
are often interacting and interlocking. Failure to pass the
peer-review process might well mean that a project is never
funded. Science bases its presumed authority in the world on the
reliability and objectivity of the evidence that is produced. If the
pronouncements of science are to be greeted with public confidence -
and there is plenty of evidence to suggest that such confidence is low
and eroding - it should be able to demonstrate that peer review, "one
of the sacred pillars of the scientific edifice," is a process that
has been validated objectively as a reliable process for putting a
stamp of approval on work that has been done. Peer review should also
have been validated as a reliable method for making appropriate
choices as to what work should be done. Yet when one looks for that
evidence it is simply not there.
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Why not apply scientific methods to the peer review process?
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For 30 years or so, I and others have been pointing out the
fallibility of peer review and have been calling for much more
openness and objective evaluation of its procedures [3-5]. For the
most part, the scientific establishment, its journals, and its
grant-giving bodies have resisted such open evaluation. They fail to
understand that if a process that is as central to the scientific
endeavor as peer review has no validated experimental base, and if it
consistently refuses open scrutiny, it is not surprising that the
public is increasingly skeptical about the agenda and the conclusions
of science.
Largely because of this antagonism to openness and evaluation, there
is a great lack of good evidence either way concerning the objectivity
and validity of peer review. What evidence there is does not give
confidence but is open to many criticisms. Now, Peter Rothwell and
Christopher Martyn have thrown a bombshell [6]. Their conclusions are
measured and cautious, but there is little doubt that they have
provided solid evidence of something truly rotten at the core of
science.
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Forget the reviewers. Just flip a coin.
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Rothwell and Martyn performed a detailed evaluation
(http://research.bmn.com/medline/search/record?uid=MDLN.20416120) of
the reviews of papers submitted to two neuroscience journals. Each
journal normally sent papers out to two reviewers. Reviews of
abstracts and oral presentations sent to two neuroscience meetings
were also evaluated. One meeting sent its abstracts to 16 reviewers
and the other to 14 reviewers, which provides a good opportunity for
statistical evaluation. Rothwell and Martyn analyzed the correlations
among reviewers' recommendations by analysis of variance. Their report
should be read in full; however, the conclusions are alarmingly
clear. For one journal, the relationships among the reviewers'
opinions were no better than that obtained by chance. For the other
journal, the relationship was only fractionally better. For the
meeting abstracts, the content of the abstract accounted for only
about 10 to 20 percent of the variance in opinion of referees, and
other factors accounted for 80 to 90 percent of the variance.
These appalling figures will not be surprising to critics of peer
review, but they give solid substance to what these critics have been
saying. The core system by which the scientific community allots
prestige (in terms of oral presentations at major meetings and
publication in major journals) and funding is a non-validated charade
whose processes generate results little better than does chance. Given
the fact that most reviewers are likely to be mainstream and broadly
supportive of the existing organization of the scientific enterprise,
it would not be surprising if the likelihood of support for truly
innovative research was considerably less than that provided by
chance.
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Objective evaluation of grant proposals is a high priority.
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Scientists frequently become very angry about the public's rejection
of the conclusions of the scientific process. However, the Rothwell
and Martyn findings, coming on top of so much other evidence, suggest
that the public might be right in groping its way to a conclusion that
there is something rotten in the state of science. Public support can
only erode further if science does not put its house in order and
begin a real attempt to develop validated processes for the
distribution of publication rights, credit for completed work, and
funds for new work. Funding is the most important issue that most
urgently requires opening up to rigorous research and objective
evaluation.
What relevance does this have for pharmacology and pharmaceuticals?
Despite enormous amounts of hype and optimistic puffery,
pharmaceutical research is actually failing [[50]7]. The annual number
of new chemical entities submitted for approval is steadily falling in
spite of the enthusiasm for techniques such as combinatorial
chemistry, high-throughput screening, and pharmacogenomics. The drive
to merge pharmaceutical companies is driven by failure, and not by
success.
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The peer review process may be stifling innovation.
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Could the peer-review processes in both academia and industry have
destroyed rather than promoted innovation? In my own field of
psychopharmacology, could it be that peer review has ensured that in
depression and schizophrenia, we are still largely pursuing themes
that were initiated in the 1950s? Could peer review explain the fact
that in both diseases the efficacy of modern drugs is no better than
those compounds developed in 1950? Even in terms of side-effects,
where the differences between old and new drugs are much hyped, modern
research has failed substantially. Is it really a success that 27 of
every 100 patients taking the selective 5-HT reuptake inhibitors stop
treatment within six weeks compared with the 30 of every 100 who take
a 1950s tricyclic antidepressant compound? The Rothwell-Martyn
bombshell is a wake-up call to the cozy establishments who run
science. If science is to have any credibility - and also if it is to
be successful - the peer-review process must be put on a much sounder
and properly validated basis or scrapped altogether.
David F. Horrobin
(http://news.bmn.com/hmsbeagle/current/about/contrib#horrobin), a
longtime critic of anonymous peer review. heads Laxdale Ltd., which
develops novel treatments for psychiatric disorders. In 1972 he
founded Medical Hypotheses
(http://www.harcourt-international.com/journals/mehy/default.cfm), the
only journal fully devoted to discussion of ideas in medicine.
Endlinks
http://www.ama-assn.org/public/peer/7_15_98/toc.htm International
Congress on Biomedical Peer Review and Scientific Publication -
articles and abstracts from the third congress, held in 1997. The
fourth congress (http://www.ama-assn.org/public/peer/peerhome.htm)
will be held in September 2001.
http://www.nap.edu/books/0309071275/html/99.html Peer-Review Practices
at EPA - a section of the 2000 NAS report Strengthening Science at the
U.S. Environmental Protection Agency: Research-Management and
Peer-Review Practices, which discusses the strengths and limitations
of the process.
http://www.nap.edu/issues/16.3/p_brosnan.htm Can Peer Review Help
Resolve Natural Resource Conflicts? - suggests that a modified form of
peer review could be useful in policy-related decisions.
http://www.willyancey.com/evidence.htm Evidence and Expert Testimony -
includes many online references for scientific evidence.
http://www.law.depaul.edu/criminalscience/peerreview/peerreview.html
Peer Review Articles - an annotated bibliography covering scientific
peer review and its relevance to judicial proceedings.
Related HMS Beagle Articles:
* Top Ten Reasons Against Peer Review
* (http://news.bmn.com/hmsbeagle/86/xcursion/topten) and Top Ten
* Reasons For Peer Review
* (http://news.bmn.com/hmsbeagle/84/xcursion/topten) - arguments both
* humorous and serious.
* Anatomy of a Rejection
* (http://news.bmn.com/hmsbeagle/48/labres/adapt.htm) - strategies for
* improving the outcome of the peer review process.
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