[Ip-health] SCIENCE'S WORST ENEMY: CORPORATE FUNDING

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SCIENCE'S WORST ENEMY: CORPORATE FUNDING



And you thought the Bush administration was bad.



Jennifer Washburn

http://discovermagazine.com/2007/oct/sciences-worst-enemy-private-fundin
g



10.11.2007



In recent years there have been a number of highly visible attacks on
American science, everything from the fundamentalist assault on
evolution to the Bush administration's strong-arming of government
scientists. But for many people who pay close attention to research and
development (R&D), the biggest threat to science has been quietly
occurring under the radar, even though it may be changing the very
foundation of American innovation. The threat is money-specifically, the
decline of government support for science and the growing dominance of
private spending over American research.



The trend is undeniable. In 1965, the federal government financed more
than 60 percent of all R&D in the United States. By 2006, the balance
had flipped, with 65 percent of R&D in this country being funded by
private interests. According to the American Association for the
Advancement of Science, several of the nation's science-driven
agencies-the Environmental Protection Agency (EPA), the Department of
Agriculture, the Department of the Interior, and NASA-have been losing
funding, leading to more "outsourcing" of what were once governmental
science functions. The EPA, for example, recently began conducting the
first nationwide study on the air quality effects of large-scale animal
production. Livestock producers, not taxpayers, are slated to pay for
the study. "The government is clearly increasing its reliance on
industry and forming 'joint ventures' to accomplish research that it is
unable to afford on its own anymore," says Merrill Goozner, a program
director at the Center for Science in the Public Interest, a consumer
advocacy group.



Research universities, too, are rapidly privatizing. Both public and
private institutions now receive a shrinking portion of their overall
funding from government sources. They are looking instead to private
industry and other commercial activities to enhance their funding. Last
summer, an investigation by the San Jose Mercury News found that
one-third of Stanford University's medical school administrators and
department heads now have reported financial conflicts of interest
related to their own research. These included stock options, consulting
fees, and patents.



Is all this truly harmful to science? Some experts argue that corporate
support is actually beneficial because it provides enhanced funding for
R&D, speeds the transfer of new knowledge to industry, and boosts
economic growth. "It isn't enough to create new knowledge," says Richard
Zare, a professor of chemistry at Stanford University. "You need to
transfer that knowledge for the betterment of society. That's why I
don't want to set up this conflict of interest problem to such a
heightened level of hysteria whereby you can't get universities
cooperating with industry."



Even many industry leaders worry that the current mix of private and
public funding is out of balance, however. In 2005, a panel of National
Academies (the National Academy of Sciences, the National Academy of
Engineering, and the Institute of Medicine) that included both industry
and academic members (including Zare) concluded that corporate R&D
"cannot and should not replace federal R&D." (pdf) Norman Augustine, the
panel's chairman and a former CEO at Lockheed Martin, noted that market
pressures have compelled industry to put nearly all its investment into
applied research, not the riskier basic science that drives innovation
10 to 15 years out.



Others fear that if the balance tips too far, the "public interest" side
of the science system-known for its commitment to independence and
objectivity-will atrophy. Earlier this year, former FDA commissioner
Jane Henney remarked that "it's getting much more difficult to get that
pure person with no conflicts at all. . . . The question becomes both
one of disclosure and how much of a conflict you can have and still be
seen as an objective and knowledgeable reviewer of information." More
than half the scientists at the U.S. Fish and Wildlife Service who
responded to a survey conducted by the Union of Concerned Scientists in
2005 agreed that "commercial interests have inappropriately induced the
reversal or withdrawal of scientific conclusions or decisions through
political intervention."



+++



Merrill Goozner argues that the danger runs deeper. "In many precincts
of the scientific enterprise, the needs of industry have become
paramount," he says, turning science into "a contested terrain" where
facts are increasingly contingent on who is funding the research. "The
whole scientific revolution, which was a product of the Enlightenment,
is threatened when you commercialize science," he warns.



So is private funding a boon or a bane for American science? The answer,
like good science itself, requires looking carefully at how the
phenomenon is playing out in the real world.



Steven Nissen is perhaps the most prominent physician speaking out about
the pharmaceutical industry's growing influence over medical research.
An esteemed cardiologist at the Cleveland Clinic, Nissen has written
more than 300 articles and served as the immediate past president of the
American College of Cardiology. Working in a bustling
academia-affiliated medical center has given Nissen a unique perspective
on the benefits and risks of privatization.



In the past, academic medical investigators strove to maintain
"arm's-length relationships with their corporate sponsors," says Marcia
Angell, a former editor in chief at The New England Journal of Medicine.
That changed with the rise of biotechnology and the passage of landmark
congressional legislation known as the Bayh-Dole Act. Passed in 1980,
the act granted universities and their professors automatic rights to
own and commercialize federally funded research. The goal was to unlock
financial incentives that would speed the pace of American scientific
innovation. Overnight, many of the cultural taboos associated with overt
commercial profiteering on campus began to evaporate.



Nissen believes that interactions between academia and industry are
crucial to the development of new treatments. He also accepts sponsored
research grants from industry, both to test drugs and develop new
treatments, although he tries to limit his personal financial conflicts
of interest by requiring that any other consulting fees and honoraria be
given directly to charity. Still, he is clearly troubled by the threat
that privatization poses to academic autonomy-and to research
objectivity. "We can only make good decisions in science when all of the
information is available for physicians, scientists, and patients to
review," he says. But drug companies are increasingly keeping physicians
and their patients in the dark.



Last year, Nissen grew suspicious about possible health risks associated
with GlaxoSmithKline's top-selling diabetes drug, Avandia. "We requested
access to the original patient-level data," he says, but "we were not
afforded access." Nissen wasn't surprised; for years he has perceived a
growing tendency by the drug industry to suppress negative research
data.



Searching the Internet, Nissen stumbled upon a remarkable cache of data
belonging to Glaxo. His search unearthed 42 Avandia clinical trials-only
15 of which had ever been published. Nissen didn't know it at the time,
but the reason Glaxo's data were just sitting there on the Web was the
outcome of a lawsuit filed by former New York attorney general (and
current governor) Eliot Spitzer in 2004. The lawsuit alleged that Glaxo
had concealed negative trial data associated with its popular
antidepressant drug, Paxil. When the data were properly analyzed, they
showed that children given Paxil were actually two times more likely to
experience suicidal thinking and behavior than children given a placebo,
or sugar pill. When Glaxo settled the suit, it denied having suppressed
data and consented to posting results of all its clinical trials
online-including its data on Avandia.



Nissen knew there were limitations to the public information he had. He
lacked any original patient-level information, and a meta-analysis of
prior drug studies is always less powerful than a large prospective,
randomized clinical trial. This May, however, Nissen felt compelled to
alert doctors and patients to what he had found.



Publishing in The New England Journal of Medicine, Nissen reported that
Avandia raised the risk of heart attacks in patients by 43 percent. The
news made front-page headlines. Two days later, the FDA, which had
already been assessing the health risks of Avandia, imposed its toughest
warning label, the "black box," on the drug, as well as on Actos,
another drug used to treat diabetes.



At a subsequent congressional hearing chaired by Representative Henry
Waxman, it came to light that the FDA had known about Avandia's risks
for some time. Rosemary Johann-Liang, a former FDA drug safety
supervisor, had recommended a black box warning label for Avandia due to
its harmful effects on the heart one year prior to Nissen's publication.
Glaxo's own meta-analysis, presented to the FDA in 2006, showed a 31
percent increased risk of heart attacks. Yet according to Johann-Liang,
"my recommending a heart failure box warning was not well received by my
superiors, and I was told that I would not be overseeing that project."
She was also told to obtain her supervisors' approval before making any
future black box recommendations. After the hearing, the FDA completed
its own meta-analysis of the original patient data and found virtually
the same heart risks Nissen had reported.



Nevertheless, Nissen found himself under attack, often by people with
explicit financial ties to the drug industry. His challengers have
included Valentin Fuster, who wrote a critique of Nissen's work in
Nature Clinical Practice Cardiovascular Medicine. Fuster receives Glaxo
funding and serves as the chairman of Glaxo's Research and Education
Foundation. Peter Pitts wrote a stinging attack on Nissen in The
Washington Times; he is a senior vice president at the PR firm Manning
Selvage & Lee, which represents Big Pharma, including Glaxo. Douglas
Arbesfeld, a senior communications consultant at the FDA, disparaged
Nissen in a biting e-mail to the media. He formerly worked as a
spokesman for Johnson & Johnson.



Press reports over the last 15 years detail how whistle-blowers inside
academia and within the FDA who have attempted to expose drug-research
and safety issues have been pressured. Some were threatened with legal
action, others punished by their superiors and discredited. "Whenever
we've raised safety questions about drugs," Nissen says, "there's always
been a reaction like this. Exactly the same thing happened in 2001 when
we published a manuscript that suggested that Vioxx might be causing
excess heart attacks." Nissen was coauthor of one of the first studies
on the dangers of Vioxx. Three years later, Merck pulled the drug from
the market. By that time, one FDA analyst estimates, the drug had
contributed to up to 139,000 heart attacks. (A Merck representative
states that the paper from which the estimate of 139,000 was derived had
"serious limitations" and did not necessarily reflect the views of the
FDA.)



Experiences like these have bolstered Nissen's position that the
independent research system needs to be protected and preserved. "I
think having independent physicians leading the study and analyzing the
data is the best way to protect against biases in the reporting of
results." But increasingly, he says, the pharmaceutical industry is
farming out its clinical trials to for-profit entities, known as
contract research organizations. Independent academic investigators are
getting shut out.



The numbers bear Nissen out. Big Pharma now finances approximately 70
percent of the nation's clinical drug research. In the past, most of
this sponsored-research money went to academic medical centers; today an
estimated 75 percent flows to for-profit contract research firms.



Even when academic physicians are involved, often they don't enjoy
anything close to true research independence, Nissen says: "Academic
physicians are still involved in the leadership of the study, but not
fundamentally in the design of the study, or in the key aspects of the
execution of the study." Often, he notes, the industry sponsor will
prevent the academic investigator from performing any independent
analysis of the complete raw data related to his or her research. "The
physician gets a printout of the main results," Nissen says, "but the
actual analysis itself is done by statisticians within the companies."



+++



The whole scientific revolution, which was a product of the
Enlightenment, is threatened when you commercialize science.



In 2001, the editors of 12 leading medical journals, including The New
England Journal of Medicine and The Lancet, expressed their shock at
what was happening to independent scientific inquiry. Many of these
journals implemented new policies requiring authors to sign a statement
verifying that they had unfettered access to the complete trial data,
took full responsibility for the conduct of the trial, and controlled
the decision to publish.



But cases of commercial influence continue to surface, often making
headlines, prompting some editors, like Drummond Rennie, an editor at
The Journal of the American Medical Association, to sound defeated: "You
know, if people lie to us, all we can do is reveal that lies were told
afterwards-and usually they're lying on their way to the bank."



Like medical researchers, university professors have long collaborated
with private industry. In recent years, though, the nature and scope of
these relationships have changed dramatically. The University of
California system is a prime example.



Lisa Bero, a pharmacologist and health policy researcher at the
University of California at San Francisco (UCSF), has immersed herself
in studying the relationship between industry-funded science and
research quality. She also chairs the internal UCSF committee that
reviews professors' financial conflicts of interest. "Corporate money is
certainly moving into academia," Bero says. "And now we have all these
new models of funding. I mean, before, it used to be just the
investigator who goes out and gets an industry grant. Now entire
departments are being funded by one company."



Early this year, BP (formerly British Petroleum) announced it was
signing the largest proposed academia-industry research alliance in U.S.
history: a 10-year, $500 million agreement with UC Berkeley, Lawrence
Berkeley National Laboratory, and the University of Illinois at
Urbana-Champaign to study biofuels and the production of genetically
modified crops that might improve their energy efficiency. As of this
writing, the deal is still being negotiated. However, according to
Berkeley's official proposal, released in early March, the deal is
unusual in many respects. First, it is huge, spanning roughly 25 labs at
three campuses. Second, it permits 50 BP employees to lease commercial
research space on campus, side by side with Berkeley's traditional
academic labs. On the academic side, all research is publishable. On the
BP side, by contrast, the research is proprietary; there is no
obligation to publish.



Tadeusz Patzek, an engineering professor at Berkeley who formerly worked
as a scientist at Shell, believes the deal compromises the university's
ability to look objectively at long-term energy solutions to global
warming. He fears that professors, following the money, will steer their
research toward BP's specified area of commercial
interest-biofuels-without adequately exploring other energy options.
Patzek's concerns are supported by survey research in the medical field
conducted by David Blumenthal and Eric Campbell, policy analysts at
Harvard University. Their research finds that academic scientists who
receive industry funding are significantly more likely to select
research projects that have a higher potential for commercial
application. Industry ties, they report, are also associated with longer
delays on publication, confidentiality restrictions, and a greater
withholding of information from academic peers.



Richard Nelson, a professor emeritus of economics at Columbia
University, finds these commercial restraints on the free flow of
academic knowledge troubling from the standpoint of innovation. The
biggest change resulting from the Bayh-Dole Act, he says, is the way
that academic knowledge is transferred to industry. In the past,
university research was picked up by industry mostly through open means:
publications, conferences, consulting, et cetera. After the passage of
Bayh-Dole, patenting and licensing became more common-not because it was
always the only or best way to transfer knowledge to industry but
because it enabled universities and their professors to share in the
profits.



The rise in academic patenting and licensing also gives universities and
their professors growing financial ties to outside companies, not to
mention growing investments in their own research (including patent
rights, stockholdings, and royalty shares). "What academic institutions
always argue is that they have sufficient safeguards in place to protect
against any influences on the academic research," Bero says. "Here at
UCSF I sit on what's called a conflict of interest advisory committee,
and believe me, I'm familiar with our gazillion policies. Universities
do have a lot of policies, but I would argue that they're not
sufficient."



Bero points to a large body of research by herself and others that shows
industry-funded studies preferentially reach conclusions that favor
sponsors' products or interests. One meta-analysis published in BMJ
(British Medical Journal) found that pharmaceu-tical--industry-funded
research was four times more likely to reflect favorably on a drug than
research not financed by industry. Even when Bero controls for a variety
of other factors, she finds that the effect of industry funding on the
research outcome is huge. Research on secondhand smoke conducted by
researchers with industry ties is 88 times more likely to find no harm;
industry-funded studies comparing cholesterol drugs are 20 times more
likely to favor the sponsor's drug.



This happens, Bero contends, because private industry has become
increasingly sophisticated about how it uses "science" to achieve its
commercial objectives. "We've looked at the tobacco and pharmaceutical
industries, and now we're looking at legal documents pertaining to the
asbestos, vinyl chloride, and lead industries," she reports. The
techniques they use are remarkably similar: Positive research gets
published; negative research doesn't. The sponsor's drug is given at a
higher dosage than the competitor's drug. The sponsors control study
design, access to data, and statistical analysis. They ghostwrite
articles and pay prominent academics to sign on as "authors."



Bero observes that many professors are desperate to find funding for
their research, and a lot of them are naive about the potential for
industry influence. "You never think you're at risk for conflicts of
interest," she says. "You always think your coworker is."



University policies governing conflicts of interest and research
integrity vary widely from campus to campus-and most still have a lot of
holes, Bero contends. One 2005 study examining more than 100 academic
medical centers found that half would allow the corporate sponsor to
write manuscripts reporting on study results and only allow faculty to
"suggest revisions"-a policy basically authorizing commercial
ghostwriting of academic research. Thirty-five percent allowed the
sponsor to store clinical trial data and release only portions to the
investigator; 62 percent allowed the sponsor to alter the study design
after the researchers and the sponsor had signed an agreement.



+++



Scientific advisory panels are frequently filled with experts who have
close financial ties to the same industries that manufacture the
products they review.



"I think universities really need to think more carefully about
protecting their investigators from their sponsors," Bero says. "A lot
of these things are not illegal; there's no university policy against
them."



Most Americans rarely think of science as something crucial to the way
government operates. Yet, as Seth Shulman explains in his book
Undermining Science, "the U.S. government runs on information-vast
amounts of it." Scientists at the Department of Agriculture track
airborne bacteria resulting from farm wastes, experts at the Centers for
Disease Control examine samples to help guard against large-scale
disease outbreaks, and regulators at the EPA set standards for pesticide
use and exposure. By necessity, most of these federal agencies work
closely with industry, but more and more their internal functions are
also being privatized. Scientific advisory panels are frequently filled
with experts who have close financial and other ties to the same
industries that manufacture the products they are reviewing. Agencies
also outsource their regulatory functions to private-sector contractors
and forge new public-private research ventures.



Consider the Center for the Evaluation of Risks to Human Reproduction,
part of the National Institutes of Health (NIH). The center has only two
full-time employees and one part-time; until recently the rest of the
center's workforce was supplied by Sciences International (SI), a
private consulting firm that has been funded by more than 40 chemical
industry clients. For nearly a decade, the center had been outsourcing
much of its work to SI, which assessed health risks and drafted reviews
for 21 chemicals that the center was reviewing for their possible impact
on human reproductive health. This April, NIH terminated its contract
with SI after learning that the company or its employees had business
ties to the chemical industry.



Another variant of privatization can be seen at the FDA, which currently
draws more than 50 percent of its total drug review budget from user
fees paid by the pharmaceutical industry. David Kessler, a former head
of the FDA, recently told The Wall Street Journal, "There is no doubt
that user fees give the industry leverage on setting the agency's
priorities. There are significant risks." Marcia Angell, the former
editor of The New England Journal of Medicine, puts it more bluntly:
"The FDA has been captured by the industry it is supposed to regulate."



What's troubling about these trends is that most federal agencies are
poorly equipped to protect themselves from undue corporate influence,
says David Michaels, an epidemiologist at George Washington University
and former assistant secretary for environment, safety, and health at
the Department of Energy. Regulatory agencies must rely on large
quantities of scientific evidence submitted to them by private industry.
This evidence is needed to determine the hazards and characteristics of
industrial chemicals, products, and wastes. But according to Michaels,
most of these federal agencies lack even the most rudimentary tools that
a medical journal editor would use to assess the quality and scientific
integrity of industry-funded research.



At the EPA and the Occupational Safety and Health Administration,
regulators do not have the authority to inquire as to who paid for the
studies they receive. The Mine Safety and Health Administration, the
Consumer Product Safety Commission, and the National Highway Traffic
Safety Administration also lack any formal mechanisms for identifying
potential conflicts of interest or for assessing the level of industry
influence over the research.



In general, industry-funded studies are also subject to far less
oversight than comparable federally funded studies. The data underlying
private research do not have to be made public, unlike the data from
federally sponsored research. A privately funded study can also avoid
external scrutiny simply by being labeled "confidential business
information." One study by the Government Accountability Office found
that a majority of the applications submitted to the EPA to market new
chemicals contained science-based information that industry had labeled
confidential.



As a result of these trends, Lisa Bero says, science has become one of
the most powerful tools that private companies can use to fight
regulation. The strategy they most often deploy was pioneered by the
tobacco industry, which learned to foment scientific uncertainty as a
means of staving off regulation. A famous tobacco industry document from
1969 spells out the strategy succinctly: "Doubt is our product, since it
is the best means of competing with the 'body of fact' that exists in
the mind of the general public. It is also the means of establishing
controversy."



In 2003, Frank Luntz, a political consultant to the Republican Party,
recommended using the same strategy to combat public environmental
concerns. "Voters believe that there is no consensus about global
warming within the scientific community," he wrote. "Should the public
come to believe the scientific issues are settled, their views about
global warming will change accordingly. Therefore, you need to make the
lack of scientific certainty a primary issue in the debate."



"Some policymakers fail to recognize that all studies are not created
equal," says Michaels, the author of a forthcoming book, Doubt Is Their
Product: How Industry's Assault on Science Threatens Your Health. "This
results in the existence of what appear to be equal and opposite
studies, encouraging policymakers to do nothing in the face of what
appear to be contradictory findings."



Virtually everyone interviewed for this ar-ticle agrees about one thing:
The U.S. government must strengthen its investment in science. The
members of Norman Augustine's 2005 National Academies panel continue to
call for an immediate doubling of federal investment in basic science,
arguing that basic science is a quintessential public good that only the
federal government can properly fund. The rewards of basic research are
risky and diffuse, making it difficult for individual companies to
invest in.



The question of whether privatization has tipped the balance too far
from noncommercial, public-interest science is more contested. "I'm more
worried about the converse: Not that industry is dominating science but
rather that government is abdicating what I think should be its role,"
panel member Richard Zare says. Augustine agrees, but he acknowledges
that commercialization of the public sphere does present challenges.
"The environment we've seen does apply pressure in the direction of more
applied work at our universities and our government labs. It just
requires balance and that's what makes it difficult," he says. "If the
end product of basic research is articles published in scientific
journals, that's very commendable, but it doesn't likely impact on the
economy short-term. On the other hand, if scientific research is
neglected to focus on near-term, quick payoff pursuits, then very
quickly the supply of knowledge will be exhausted."



Some critics of privatization say that more public funding is pivotal
not just for basic science but for public health and regulatory science
as well. Their argument is much the same: Who else, other than the
federal government, can ensure that this science for the public good is
reliably carried out? They also say stronger "public interest"
protections are urgently needed: stricter conflict of interest rules in
both academia and the government, and prohibitions against commercial
ghostwriting and corporate control of statistical analysis and raw data.



Once the genie is out of the bottle, it isn't easy to get it back in.
The more that public---sector scientists become invested in the status
quo-through industry grants, patents, and the like-the less likely they
are to support reforms. Not so long ago, academics and government
scientists insured that the basic building blocks of science were freely
available to everyone. Today, the Columbia economist Richard Nelson
points out, a sizable portion of this public knowledge is private
property. Is this something that should-or even could-be reversed?



The dilemma, says Eric Campbell of Harvard, is that industry
partnerships yield many positive benefits: funding opportunities, the
conversion of knowledge into products that benefit the public, rewards
for inventors, jobs, economic growth. On the other hand, "the
fundamental reason the public invests in science is out of the belief
that it represents truth, untainted by commercial interests," he says.
"So to call that into question, I think, is really one of the great
risks."