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Biomedical research is ripe for a stimulus

What it'll take to reinvigorate the enterprise

By | February 9, 2009

As Congress debates a major economic stimulus package, investment in energy research is high on the agenda. While this promises benefit to our economy and security, it highlights the value of reinvigorating our investment in another area of science -- biomedical research. The wealth and health of the nation can be measured in breakthroughs in the treatment of heart disease, AIDS and cancer, high quality jobs, and profitable industries. A recent report from the UK suggested a return on investment in biomedical science of 40%. So far, the US has managed to sustain its pre-eminence in biomedical research. Research publications and patent filings suggest our continued (though narrowing) leadership in innovation, our research universities continue their dominance of the global rankings, and the US remains the leading site of research conducted by pharma and biotech. But both the academic and industry sectors of our biomedical research enterprise are highly vulnerable. The budget of the National Institutes of Health (NIH) has declined by more than 10% in real terms over the past 5 years. Most strikingly, initial success rates for grants that mark scientific independence have dropped into single figures and the average age of first recipients is now in the mid forties. Ironically, just as other countries invest in science and base their funding strategies on the NIH, our system is reverting to the model previously prevalent in Europe and Japan: aging leadership and indentured scientific servitude of the young. Given the increasing options elsewhere, our restrictive visa policy post 9/11 and the cultural legacy of the Bush years, our workforce is vulnerable. Just as China finances our economy, it also provides much of the human capital that sustains our biomedical research enterprise. Both forms of support are vital, yet mobile. Many large pharmaceutical companies are, for now, cash rich and casting around for acquisitions. However, just like the auto industry, their current business model is unsustainable. The number of new drugs approved by the FDA has fallen linearly from 53 in 1996 to 17 in 2007, the same number as in 1983. A slight bump upwards to 21 approvals in 2008 includes 3 drugs eventually approved on reconsideration and 3 radiocontrast agents. In other words, it doesn't buck the trend. This coincides with downward pressure on drug pricing. The growth in prescription drug sales -- 10% of the $286.5 billion US healthcare budget in 2007 -- had plummeted even before the present crisis: generics now account for roughly 60% of the market and are rapidly growing in market share. Pharma has reacted by shedding jobs in the US -- more than 100,000 over the past 5 years -- and moving research to join drug production in lower cost economies overseas. Anticipated future revenue for the industry has shifted dramatically towards Asia. The current crisis is likely to accelerate these trends. As pharma conserves its resources, it becomes less likely to extend credit to the academic sector -- a source of funds for biomedical research complementary to the NIH. Indeed, the same political factors that will depress drug prices are likely to drive down Medicare reimbursements to our major academic health centers. This will be compounded by the dramatically shrinking endowments, both of our universities and the charities that support biomedical research. Given these interacting pressures, how might a portion of the stimulus package be used to reinvigorate the enterprise? - Restore funding for the NIH. The new director must have resources to fuel innovation by individual investigators and invest in infrastructure -- including the national integration of healthcare information systems -- to allow universities translate the fruits of basic discovery into clinical benefit. Welcome as the stimulus money will be, it is a 2-year injection of resources. It can best support research programs and preserve jobs by providing bridge funding for those many grants now funded on the second round of review. Restoration of programmatic stability will require an increase in year - on year funding for the NIH. The touted funding of 1500 2 year R01 project grants by April would be a foolhardy Procrustean response to the constraints of stimulus funding. - Accelerate this translational process by integrating strategically the disparate missions of the NIH and the Department of Health and Human Services -- particularly its Agency for Healthcare Research and Quality and the Food and Drug Administration (FDA). - Introduce a more graded process of drug approval and withdrawal. Use this reform specifically to reward innovation and to foster the progressive personalization of medicine. Fund programs that foster interaction of the FDA with academia. This would afford FDA scientists access to critical mass in emerging sciences. It would also provide a neutral testing ground where unanticipated concerns or opportunities relating to drugs, before or after their approval, might be pursued -- something of a Jet Propulsion Lab for the FDA. - Incentivize both the academic and industrial sectors to reform outmoded restrictions on intellectual property. These are configured on unrealistic expectations and impede the evolution of a modular interaction between the sectors as a drug moves from discovery through development. - Finally, foster the re-engagement in science of American youth. Develop integrated programs from grade school to graduate school. Develop training programs that blend traditional disciplines both for "blue skies" research and for development of new therapies. Reinvest in the programs that had accelerated the time for visa approval for visiting scientists. Develop strategies, just like our competitors, to recruit and retain top talent from abroad. Garret FitzGerald directs the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania and serves on the Peer Review Advisory Committee of the NIH and the Science Board of the FDA.

Comments

Avatar of: anonymous poster

anonymous poster

Posts: 5

February 9, 2009

Although you may criticize the idea of a splurge of funds for 2 years mini-R01, the fact is the CSR review system at NIH is woefully broken. CSR thinks by changing the grading format, by killing A2 grants and cutting grants from 25 to 12 pages will fix the problem, but it will not. \n\nThe external review system is broken because only 10% of the grants are getting funded. it is impossible to discriminate between the top 10 to 20 to 30% of grants being reviewed: they are all outstanding. The NIH is putting its money in increasing percentages to intramural not extramural projects. \n\nTo revitalize basic biomedical research in the US the funding percentiles for 5 year RO1 grants must climb back to 20% for all applicants (not just new investigators). And this % must never fall below 20% in the future. \n\nHow do you do this? More new monies and save old money. First of all, restrict the number of grants any one PI can control. Every R01 funded should require 25% effort of the PI. And the salary of the PI should be paid by their employer not the NIH. The indirect costs should be 50% for every institution. Intramural programs should be cut back to the core of unique clinical trials and a small cadre of superb scientists.
Avatar of: ERIC J MURPHY

ERIC J MURPHY

Posts: 18

February 9, 2009

Professor Fitzgerald brings into question multiple different facets of U.S. science policy. Certainly the NIH funding rates must improve if we are truly going to maintain our status as the leader in biomedical science. The fact that drug approvals are down is of interest, I am not sure there is a strong correlation with NIH funding in that there is undoubtedly a serious lag between NIH funded research leading to a potential drug versus the pharmceutical industry's own research efforts leading to a usable drug candidate. Most noted and problematic is the inability of scientist to replace themselves. The reliance on other nations to provide graduate students and post-doctoral fellows is an increasingly dangerous position from a practicle and policy point of view. We must provide the necessary stimulation to invigorate our nations children to pursue careers in science using a bottom up approach. Our own gloom and doom attitudes don't help matters on that front as many youngsters wonder why should they put up with all the problems when I can go to Wall Street and make lots of money. \n\nIn addressing the NIH funding, I propose the following radical idea. What if the NIH looked at a funding model using endowments. How much does the average scientist need to run a very good laboratory? Maybe $500,000 - $750,000 per year. Would we have not been better off awarding $10 or $20 M endowments that would last a scientist forever and then be passed onto another scientist as the other leaves the business? Then we would not be continually writing grants and looking for money, but rather working on science and doing what scientists should do best, follow our nose. This type of model would engage us in the art of science rather than the art of grantsmanship.\n\nJust some food for thought and discussion.\n\n\n\n\n
Avatar of: anonymous poster

anonymous poster

Posts: 2

February 9, 2009

I wonder if Dr. FitzGerald could be more specific about his comment below. Are the unrealistic expectations from industry, academia or both? What is his suggestion? \n\n- Incentivize both the academic and industrial sectors to reform outmoded restrictions on intellectual property. These are configured on unrealistic expectations and impede the evolution of a modular interaction between the sectors as a drug moves from discovery through development. \n
Avatar of: anonymous poster

anonymous poster

Posts: 125

February 9, 2009

Before scientists complain or whine about the underfunding in science, let's fix our own house, first, by reducing the petty politics, cronism, racism, and sexism that exist in science (particularly in academia), and by increasing more tangible results and accountability, shall we? Just arguing that investing in science will bring handsome returns somewhere down the road won't be enough, I'm afraid. If the federal or state government underfunded basic science research before, then what makes people think they will be any more generous or understanding at the current financial crisis? Especially the Republicans who already dismissed the spending on school construction and Head Start program as nonstimulative "porks"?
Avatar of: anonymous poster

anonymous poster

Posts: 1

February 9, 2009

"A recent report from the UK suggested a return on investment in biomedical science of 40%." \n\nWhere does this figure come from?

February 10, 2009

Here is the reference for ROI\nMedical research yields big returns\nBy Clive Cookson \n\nPublished: November 21 2008 02:00 | Last updated: November 21 2008 02:00\n\nMedical research yields an annual return of almost 40 per cent in economic benefits and health gains, according to a study published yesterday by UK funding and scientific institutions. The study analysed research in mental health and cardiovascular medicine carried out between 1975 and 1992 - long enough ago for the effects to feed through. It showed the average time lag between research spending and health benefits was 17 years.\n\nEvery £1 spent by a public body or charity on cardiovascular research "produced a stream of benefits equivalent to earning 39p per year in perpetuity". The total return is made up of 30 per cent in direct returns to the UK economy (for example through the pharmaceutical industry) and 9 per cent in health gains through new treatments. The combined return for mental health research was 37 per cent.\n\nThe study was commissioned by the Wellcome Trust, Medical Research Council and Academy of Medical Sciences, and carried out by Brunel University, the Office of Health Economics and Rand Europe.\nCopyright The Financial Times Limited 2009\n\nAs for reform of intellectual property, I believe that this is an issue for both academia and industry. Together, they need to drastically expand the precompetitive space and also develop novel approaches to foster interaction.
Avatar of: anonymous poster

anonymous poster

Posts: 5

February 10, 2009

This stimulus package will depress R01 percentile scores.\n\nThe stimulus package must be spent in two years for R21's or the like. Also part of that money goes to maintain/expand intramural programs/buildings such that they will require more intramural funding in the future, taking money away from the extramural pot.\n\nWhen the NIH goes to congress and asks for expanded funding for extramural R01's the congress claims they got 10 billion extra in the stimulus package and that will have to do for the next two years. So the funding percentile for R01's will continue to languish.
Avatar of: PAUL STEIN

PAUL STEIN

Posts: 23

February 10, 2009

Eric J. Murphy is really on to something. I would, however, propose something similar and probably more outlandish; fund the universities directly. Think about it. Just like universities already need to put together packages for program grants discussing their past successes, let them compete the same way, but for the whole pot!\n\nIn the end, universities would each then get a huge sum of money based on their scientific productivity. Then the university administrations would dole out the money as they see fit. Think of it... Individual investigators would no longer need to spend half their time, or any time, writing grants that never get funded anyway. Universities would hire professors based on brains and brilliant ideas rather than simply if they can pay for their own salaries. Younger scientists would start the research where they will make their names known ten to fifteen years earlier.\n\nIndentured servitude would disappear as young scientists would have real jobs when there is a flowing tap of hard money. The term research assistant professor would become a thing of the past.\n\nFuture generations of scientists would see a future in science! Few Americans are going into science now because they rightly recognize that there are no real job opportunities.\n\nTenure would be based on output, not monetary input. It would still be sink or swim, but it would be based solely on scientific productivity.\n\nAlthough some might think that certain universities would garner the bulk of the money, duh, it's already happening, but it probably would not be any worse than now as there is just so much physical space to do work. Maybe there could be a slight disproportionate preference to funding levels at smaller universities.\n\nMany talk about how the highly centralized NIH funding system is broken. Remember the recent Saturday Night Live skit where the balding economics correspondant's solution for the recession was "Fix it!!"? Regarding the entire scientific biomedical research doldrum spiral of the last thirty years, I believe I just did.
Avatar of: Michele Kadnar

Michele Kadnar

Posts: 1

February 12, 2009

To find out where your Congressional representative stands on the issues of science innovation and education, visit Scientists and Engineers for America and click on People.
Avatar of: anonymous poster

anonymous poster

Posts: 2

February 13, 2009

"As for reform of intellectual property, I believe that this is an issue for both academia and industry. Together, they need to drastically expand the precompetitive space and also develop novel approaches to foster interaction."\n\nIt sound to me you have no proposal. I suspect that you'd like Universities to give it all away -which is what indutry wants. If I misinterpreted you, why don't you state at least one cogent idea of what it is you are suggesting so that all can understand what the nebulous statement above means. Thanks
Avatar of: Tom Gillette

Tom Gillette

Posts: 1

February 13, 2009

It seems clear that the business of science in the US is in disarray, not only from lack of funding, but from a system that results in the loss of highly trained individuals due to the lack of opportunities.\nI was intrigued by your comment to\n"Fund programs that foster interaction of the FDA with academia. This would afford FDA scientists access to critical mass in emerging sciences."\nI was wondering if you could expand on that a little. For example,\nWhat do you perceive to be lacking at the FDA, and how do you envision this type of program filling that void?

February 14, 2009

Regarding possibilities for interactions between FDA and academic scientists see \nhttp://energycommerce.house.gov/Press_110/022508.ScienceBoardReport.EstimatedResources.pdf\nIdeas there for a JPL type of joint interaction\n\nAs for reforming IP, let's read the English and not get silly, "anonymous"..\nBoth sides need to stop protecting things that yield no value but retard opportinity. A couple of examples in systems biology and medicinal chemistry, but there are plenty more. See http://www.sciencemag.org/cgi/content/full/320/5883/1563
Avatar of: anonymous poster

anonymous poster

Posts: 27

February 18, 2009

PAUL STEIN said..."Then the university administrations would dole out the money as they see fit."\n\nDo we really want school administrators doling out money as they see fit? Tick off your Dean and you might not lose tenure but you will certainly never get any more grant money. Where is the evidence that University administrators would do a better job than NIH study sections.
Avatar of: Kenneth Strauss

Kenneth Strauss

Posts: 1

February 19, 2009

I agree that Eric Murphy may be onto something. And I agree that handing over funds dispersion to the "administration" would be a mistake. However, a viable alternative would be to give medical college faculty senates some teeth by enabling governance of funds allotment at the college level through a democratic process. An executive board with representation from each department and/or research division would be presided over by the college dean. There will be motivation to continue funding the best science because the size of the pot depends directly on this. Moreover, there will be continuing value of young investigators, scientists experiencing a "dry spell" or reduced productivity due to other factors. Voting could be conducted by secret ballot, or done openly depending on the politics at each institution. Keeping the best and the brightest at the bench will become a corporate matter; teaching and service activities would be assigned by the chairs and deans accordingly.\n\nWhy is this sort of change important? As a biomedical research professor in a clinical department, I can tell you first hand our profession is highly undervalued. Our "services" directly reduce the physicians' bottom line and do not directly provide much income, we are considered to be "luxury items" and often funded less than the office administration, in terms of salary and materiel support. There is precious little opportunity to teach or even to mentor residents. \n\nSo, when spending 50-80% of our time in grant writing to support 75-100% of our operating expenses results in failure (partly due to the near lack of lab time to perform the studies that yield preliminary data that get grants funded, no technical support, and partly due to the challenge of extraordinarily low payline at NIH) our clinical colleagues judge us to be worth less and we are forced out of bench science and into other medical research jobs, or out of the field entirely. I came within 40 days of losing my academic appointment in 2007, before my R01-A2 submission was funded (the A1 was in the 9th percentile but not funded). The dean's bridge funding that I was provided came only AFTER my notice of attaining 6th percentile on the A2 was received, I spent less than 40% of these funds before my R01 kicked in (an excellent way to spread the wealth, kudos to the Administration for such a clever cost-cutting measure).\n\nPublic universities have an especially onerous burden, inasmuch as there are fewer benefactors, and "the people" expect a first class institution for a minimum investment. Research is costly and in many ways, a "Catch-22." Breaking into the cycle of money begets money, greatness begets greatness, requires a quantum leap not only of money, but of greatness. What makes us great? Our work ethic, our creative energies, our tolerance of others, even the ability to incorporate the successes of others into our own repertoire. All of this adds up to great university research (improved numbers of funded grants, numbers of peer-reviewed publications, number of graduate students enrolled, number of patents issued). Yet much of this is not reflected at the national level by the grant applications submitted or the information reviewed by study sections and scientific councils.\n\nThe "ivory tower" has long stood for unfettered inquiry, a privilege made possible by and for tenured faculty. Thinking is an art form, and as with most true art, there is a risk of nothing attractive being produced. Research at the university level must provide both unfettered environments for intellectual creativity, as well as hold its corpus accountable for a net gain. Often this gain is in the form of producing graduates who go on to distinguish themselves, bringing real value (economic growth, improved quality of life) and/or the improved perception of the outside world. This prestige also attracts better students and faculty, more donations, and yields a sense of public pride that supports the University at many levels. Lest we become vocational institutions designed solely to provide bodies for the future workforce, we must continue to improve and change the way we support scientific investigations.

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