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Astatus report on neuroscience research without grade inflation.

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A Status Report on Neuroscience Research,
without Grade Inflation
The fact is that most of us (then) doing research on poliomyelitis
were motivated mainly by curiosity, and for the challenges of the
many unsolved problems concerning the interaction of virus and
host, rather than by the hope of a practical solution in our lifetime. —David Bodian discussing the reaction of the academic
community after an outline for conquest of polio set forth by
Thomas Rivers in 1938 had failed to inspire scientists to work
collaboratively on a practical, pragmatic approach to a pressing
health problem.
From Oshinsky, DM. Polio: an American story. New York: Oxford University Press, 2005
The efficiency and productivity of medical research
and all its formidable institutions are being questioned
now more than ever. The doubling of the NIH budget
in the late 1990s did not lead to any appreciable increase in approved medical therapies, and this has been
taken as evidence that the NIH must change, both
within its own structure and in its association with the
pharmaceutical, biotechnology, and device industries,
who many see as key partners in translating discoveries
to interventions.
Research in neurosciences has fared no better, as revealed in an analysis by Dorsey and colleagues in this
issue of the Annals.1 While public funding for neuroscience research increased 2.6-fold in the last decade,
private funding also increased by 3.3-fold. Nonetheless,
the number of approved therapies in the neurosciences
has stayed flat, so efficiency, measured loosely as new
interventions per dollar invested in research, has decreased. In an accompanying article, Moses and Martin2 discuss potential explanations, including inadequate access to materials, instruments, and compounds,
and barriers to collaboration. They identify barriers between public and private institutions as an important
drag on productivity.
Of course, the goals of industry, disease foundations,
and academia are distinct. Industry is looking for the
optimum ratio of risk-to-return on its research investment; it reports to its investors. Disease foundations
are generally focused on finding treatments; they report
to donors. Academics have fewer responsibilities and
less focus; since most funding decisions are based on
peer review of investigator-initiated research, academics
essentially report to their peers. Academia often produces research at the cutting edge (taken up by other
institutions) and fills in gaps based on public health
need. Inefficiencies are inherent in barriers between institutions thus aligned. How can such distinct institutions work together to combat disease?
Ultimately, improving health is in the best interest
of all three groups. For industry, drugs that improve
health are likely to make money: the larger the public
health need (at least in developed countries), the larger
the market, and greater drug benefit can garner a
higher price premium. For academia, most support
comes from the NIH, and its funding is dependent in
part on whether congress and the executive branch see
its value, particularly with respect to its role in improving health. Finally, donors to disease foundations, who
often have personal experience with a disease, often expect to see progress in developing treatments. Thus,
the ties to improving health are common to academia,
foundations, and industry, and become the major motivation for collaboration.
Proposed solutions to the inefficiency of biomedical
research can be divided into two major strategies. The
first involves changing industry, academia, and foundations separately to better align them with the goal
of finding therapies. For example, industry is currently rewarded for developing copycat drugs: these
are the drugs with lowest risk of development and
with the highest potential rewards.3 However, their
contribution to public health is limited. A shorter
patent life for copycat drugs has been proposed as a
way to encourage development of novel therapeutics,
thereby aligning the pharmaceutical industry’s profit
motive with public good.4 Similarly, to realign academic priorities, several of the Roadmap Initiatives,
including the Clinical and Translational Science
Awards, are designed to increase funding and attention to finding treatments. Such proposals may represent the easiest first steps and may have a real impact, although there are plenty of skeptics.
The second major strategy has been to reduce the
barriers that separate academia, foundations, and industry. These are difficult programs because they require a meeting of distinct cultures, with suspicion and
confusion about motives. Although no approach has
been proved, there are many models of public–private
partnership currently being tested, and we have selected a few innovative ones to highlight.
• The Alzheimer’s Disease Neuroimaging Initiative
is the largest NIH-private partnership in brain research.5 It is a $60 million 5-year study sponsored by the NIH, the FDA, and several foundations and pharmaceutical companies. The
multicenter center study aims to identify MRI
and PET correlates of cognitive decline. Industry
© 2006 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
partners were motivated by the potential to define disease surrogates, and thus accelerate clinical
development of future drugs.
GlaxoSmithKline (GSK) has made its large library of potential drug compounds available to a
research group at University College London to
screen for potential treatments for Creutzfeldt–
Jacob disease.6 The research is funded by the UK
Medical Research Council, though GSK is incurring the cost of retrieving the compounds. The
company will retain its patent rights, but representatives say it will likely accept a nonprofit deal
if a drug is found. In another initiative, GSK has
formed a partnership with Imperial College and
Hammersmith Hospital to develop a campus focused on translational clinical research. As part of
an ambitious 10-year agreement, GSK is placing
a large MRI and PET research facility in the
heart of the clinical research campus of Hammersmith Hospital; the parties have agreed to work
together on a wide range of brain disorders, inflammatory diseases, and cancer.
Foundations have funded research and development in the private sector by supporting companies targeting neglected diseases.7 The financial rewards for developing treatments for rare
diseases or those predominantly in the developing world are low while the risk is just as high.
By targeting funding to small companies devoted to finding treatments for these diseases,
foundations (most prominently, the Gates
Foundation) are dictating the disease targets for
drug development while capitalizing on the efficiencies of industry.
The Myelin Repair Foundation has developed a
blended academic–foundation–corporate structure that is narrowly focused on development of
new treatments for multiple sclerosis. Critical elements of this model are the top-down creation
of a highly interactive consortium between investigators at different institutions, targeted research
goals, shared intellectual property, close management of technology transfer, and clearly articulated expectations including a specific timetable
for drug development.
The University of California (UC) has created a
granting mechanism to fund research collaborations between university researchers and California businesses.8 Over the last decade, the program has funded 777 projects, about half in the
health sciences, with grants up to $2 million derived from state funds matched with equal support from a variety of collaborating companies.
Boundaries between industry and academia are
blurred because the two groups must cooperate
Annals of Neurology
Vol 60
No 6
December 2006
to get the funds, but the benefits to each exceed
the monetary award. The State foots the bill because it sees a return on an investment to these
companies, with a quarter of US biotechnology
companies situated near a UC campus and a
third of them led by UC scientists.
All sides might also benefit from a period of soulsearching. For the academic community, structural issues
that represent real barriers to productivity and discovery
have been previously discussed in these pages and elsewhere. Foremost is an urgent need to increase the pipeline of young investigators by identifying and correcting
barriers to the efficient training of physician–scientists.9
Second, we need to recognize that the scope of activities
within medical specialties—and clinical departments—
represent “accidents of history”10 created prior to the
modern technological revolution in medicine. In the
worst-case scenario, these silos can inhibit interdisciplinary interactions that are essential to biomedical discovery; they can also lead to specialty-centric, rather than
patient-centric, clinical care. A final issue might question
whether the tenure system, sacrosanct at most academic
medical centers, and which by its nature rewards past
performance more than future promise, also reduces
flexibility and the overall effectiveness of the research
mission. The tenure system, centered on the traditional
academic model of a creative principal investigator
rather than an interactive research team, may also constrain the seeding of interdisciplinary “roadmap” science
in academic institutions.
There is no obvious fix for declining efficiency in
developing new drugs for neurological diseases. Creative reexamination of established institutions, a willingness to test new forms of collaboration, and an attentive eye to results of experiments testing new models
of development are all required. What is clear is that
the biomedical research engine is a diesel not a hybrid,
and that transformative research and thinking will be
required to improve efficiency and get us to our destination more rapidly.
S. Claiborne Johnston, MD, PhD
Stephen L. Hauser, MD
1. Dorsey ER, Vitticore P, de Roulet J, et al. Financial anatomy of
neuroscience research. Ann Neurol 2006;60:652– 659.
2. Moses H 3rd, Martin JB. What should be done to improve the
productivity of neurological research? Ann Neurol 2006;60:
647– 651.
3. Johnston SC, Hauser SL. Can industry rescue the NIH? Ann
Neurol 2006;60:A11–A14.
4. Wood AJ. A proposal for radical changes in the drug-approval
process. N Engl J Med 2006;355:618 – 623.
5. Alzheimer’s Disease Neuroimaging Study Launched Nationwide by the National Institutes of Health. Vol. 2006. Bethesda,
MD: National Institute on Aging, 2006.
6. Marshall E. U.K. science. Industry-academic drug screening
plan targets CJD. Science 2005;308:477.
7. Louet S. Public-private partnerships boost research on neglected
diseases. Nat Biotechnol 2003;21:1254 –1255.
8. The UC Discovery Program. Vol. 2006. Berkeley, CA: The
Industry-University Cooperative Research Program (IUCRP),
Accessed Oct 31, 2006.
9. Hauser SL, McArthur JC. Saving the clinician-scientist: report
of the ANA long range planning committee. Ann Neurol 2006;
60:278 –285.
10. Adapted from comments by Haile Debas, MD.
DOI: 10.1002/ana.21054
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