Comments for:

---

Climate changes in NIH funding

Submitter: Don C. Rockey | Don.Rockey@UTSouthwestern.edu

University of Texas at Southwestern

Published May 3, 2006

I read with interest earlier this month the comments by Dr. Marks about the NIH. Since I have never met “the Dude” in “The Big Lebowski”, nor Dr. Zerhouni, I would not consider commenting on any association between the two. However, I have very clearly seen the current “climate shift” in the biomedical research environment, which is largely driven by the NIH; it is obvious that the winds are rapidly shifting.
Having been involved at some level in biomedical research now for the last 17 or so years, first as a trainee who observed my mentors navigate funding issues, and now as someone dealing with funding myself, what strikes me as most unhealthy about this entire scene are the rapid climate swings, that seem to occur over a short time span. We seem to have very good times, and very bad times and these seem to cycle repeatedly. While it is clear that the best and brightest can and will weather all storms, the shifts are unhealthy. Humans, by their very nature, do poorly in unsettled environments that have unclear future expectations - and I think this is a much greater problem than the current acute decline in realized NIH funding. When someone (i.e., a mentor) is exposed to bad weather, the response is to find calmer weather (i.e. leave research) or complain about the weather (i.e., bad mouth the NIH). Neither of these responses is good for research, or more importantly trainees. Trainees see their mentors complain about the climate, and who could blame them abandoning research? An analogy comes from athletics. If you want to win, you need a great coach and good players; if you have a coach with a bad attitude, how can you expect to be successful? As the coach goes, so goes the team.
In any event, if people are happy with these incessant firestorms brought on by dramatic shifts in NIH funding, then biomedical research will continue as it has for the last several decades. However, if people are unhappy about this, then it is time for all of us to stop complaining about the NIH and help do something to help fix it. It is my belief that the biomedical research community and the NIH should consider fundamental changes in the way it funds biomedical research. Most importantly, it is essential that mechanisms be put in place that circumvent these rapid climate shifts. It’s time to step outside the box and get creative.
Some suggestions are as follows: (1) Change the way funding is allocated. Specifically, why not fund individual researcher’s programs as well as projects? NIH Institutes (and/or medical schools) could decide how many investigators they can (or should) reasonably fund, and investigators, so long as they remain productive would be assured of some level of uninterrupted funding. In addition, a proportion of funds could be allocated to allow funding of specific projects. There is no question that this would be challenging, but a carefully designed mix of program and project funding would alleviate the wide swings, (2) Consolidate research centers. Consider how much money could be saved and reallocated if research were performed primarily in a focused number of large, but highly adept research institutions? The NIH could even consider funding entire academic centers, which could then prioritize research locally based on local talent and programs. While this would also be a lot of work to implement, and may not be politically appealing, this would help reduce redundancy at many levels, (3) Combine funding sources. Imagine what could be done by combining resources from the NIH, industry, and philanthropy? This is a lot easier said than done of course, because this would require people to put aside their own agendas and egos for the sake of science and research.
These are only a few suggestions - there are undoubtedly many others that could and should be considered. Nonetheless, it seems to me that it’s time to get imaginative and inspired about biomedical research funding.

---

Divide and Conquer?

Submitter: Gary R Cutter | cutterg@prodigy.net

UAB School of Public Health

Published May 3, 2006

Dr. Marks makes his impassioned plea on the state of NIH citing Dr. Zerhouni’s lack of being a scientist and large studies as the root of all evil. Thus, responsible for the plight of NIH. Frankly, I felt like this editorial was putting blame for all the sins of the nation on Dr. Zerhouni and that, to me, was obviously not done scientifically.
I should state that I have no conflict of interest in that I do not personally know Dr. Zerhouni. Hmmm, I do receive funding from the NIH! I, on occasion, consult for NIH on Study Sections; advisory committees and DSMBs; and despite my lack of direct contact with Dr. Zerhouni, this could be seen as a potential conflict of interest, so in light of the current rules, I guess I must declare a potential conflict. In addition, I pay my taxes to the IRS and as such, I could be seen as having a vested interest in the expenditure of public funds. I am certified to do research having passed my annual update for certification of human subjects, but I’m not sure I can use names or birthdates in this editorial.
So, what is my point? Much of what has been happening and is happening is in part a problem of the scientific community. Dr. Zerhouni didn’t start the Woman’s Health Initiative Trial – hard work, a lot of scrutiny, good politics (scientific and otherwise) built this study in the early 1990s. Was it a good investment? The IOM Committee that reviewed it was lukewarm to the idea (1). The Committee was lukewarm, in part because it was going to become unethical to complete the study. Why? Because it was clear that HRT protected against heart disease. So, was this investment a good one? Personally, I’m not sure, my wife was more comfortable when she was taking HRT, my electric bills were lower and I wore fewer sweaters around the house during the summer. Rarely has a trial impacted so rapidly the prescribing habits of physicians. Oh yeah, the roadmap focuses on translational research because so much is ignored, maybe this study is demonstrating it. I don’t know what was the cost of the “n” articles in the current issue of this journal, but on a per capita basis, supporting 400 scientists to do these experiments for 5 years may not be the correct currency to bolster one’s arguments about the importance of RO1s.
Pitting confirmatory research, phase III trials and the like against basic science is exactly what bureaucrats would like to see happen. We’ll get them to fight about whose ego is more important for the next few years, while they ignore the many real problems in the research arena. We can pacify them later. Dr. Marks plays this card right into the hands of those who would like us to fight internally over our value rather than take a hard look at what the system is doing.
The argument that pharmaceutical companies should do the big trials is like arguing for prayer in the schools. As long as you are pushing for my prayers, I’ll support you. We need both kinds of research and the pharmaceutical companies are funding these trials - except that more and more are being done outside the research community of the US. We need to ask why and how much is because of our increasing cumbersome research management systems and restrictions.
Many trials need to be done that will not be conducted by Pharmaceutical Companies. I frankly have one. There is no company that wants to know whether thymectomy plus prednisone is better than prednisone alone in treating Myasthenia Gravis – the drug is cheap, but the question has remained unanswered for 50 years. This trial is quite far from hundreds of millions, but I’m sure someone can examine quite a lot of cytokines for the money spent on this trial. But both kinds of research are needed: Research on diseases that impact the masses and research on diseases that impact a few, whether profitable or not. Relegating one form or another more desirable doesn’t recognize the interdependence all science has on one another. An argument could be made that NIH should do the mega-trials and all these basic science studies should be done by pharma so that we would get more targeted and relevant drugs. My view is that argument is just as silly, but it has as much truth or deep thought as saying all big ticket studies should be done by pharma.
Such a narrow view of research is taking away from the scientific needs of the community and the public. The scientific community has to ask what it is doing with all the money it receives. How much productivity has been lost to certification procedures, documentation that we are free from conflicts of interest, that our HIPAA and human use training are up to date, that our subjects are assured that we are ethical by signing various forms? How many of our dollars earmarked for research go for infrastructure ratios (indirect costs) that reward bureaucracy and take more of the resources than the large scale trials?
Certainly, we need infrastructure, but where is the cry from the researchers that this should be curtailed to enhance the pool of RO1s? Procedures that train, evaluate the ethics of studies, etc. are all good things, but where is the cry to have these procedures evaluated, like ideas for RO1s or calls to do so on the Roadmap? Just how much of our research is wasted on these endeavors to which there is little or no evaluation? The (self) protectionism of the Universities isn't looking for changing this part of the equation.
The first call to arms in Dr. Marks’ editorial is a major source of the problems we face – get your congressman involved. How many earmarked (direct or indirect) initiatives have been created by this kneejerk reaction? How much money has been wasted on pet grants and initiatives? Each of us must defend the use of women, minorities and children on every NIH grant because of these “champions” who stepped forward to fix a problem. Our lobbying is egocentric and often short sighted, which is appalling for a group that is focused on the future value of our efforts. Maybe all those researchers who have been excited about receiving bioterrorism money will turn it back in. Maybe researchers will have to have an hypothesis about the value of all the SNP data from the Affimetrix chips they are collecting? None of us are free of waste, poor direction and self focused or self serving perspectives, but pitting one side against the other – has been well known since Caesar’s time.
The process of funding might better be streamlined for new investigators and maybe made more difficult for established investigators. It is not the number of publications that matter, but rather the quality and contribution. Of course we owe the public something for taking their money and usually this is returned in the form of scientific publication.
Quite possibly one of the major problems we face is that nearly every research institution in the US developed a plan to grow during the doubling period of NIH. Where was the wisdom that this cash cow would end? Where was the realization that maybe competition produces quality and during the doubling period, maybe quality was sacrificed for quantity? Why did everyone think they could or should grow? Universities expect external funding of high proportions of salaries of the very people they employ? Where is their commitment to science? Shouldn’t Institutions decide what they need and what they want to be good at? They dodge the issue by allowing success to be defined by the money one brings to the table. There are well heeled criteria for academic success, but this is often bastardized by funding. Maybe we should all be on salary by the University with no indirects and no salary recovery and let the purity of science drive the investments. Then let's see the University keep who they will and that they accept the risk if they invest poorly. Maybe we wouldn’t add so many unfunded mandates to the plates of the researchers if Universities had to spend their own money for them? These issues are not mega trials versus basic science, these are issues of how we spend what is allocated.
NIH is in trouble, it has a demoralized staff; restrictions of all sorts and having difficulty attracting the caliber it once did. Some of it is expense of Washington without the possibility of offsetting the costs with some consulting – but some of it are policies that should be criticized and while maybe not the direct work of Dr. Zerhouni, the buck stops with the Director. How much research is targeted by RFPs and not RO1s; How much is directed into RFAs or UO1s that supplant the ideas of RO1s, but infuse NIH Staff dominance in the process. Those are legitimate issues and the scientific community has done little to fix or help the NIH even with public criticism.
There are many problems in science, some real, some perceived, but using the approach that waste is always on the outside and not in my house – well, it is probably as effective as all of us taking our shoes off when we get screened at the airports.

---

I Feel Your Pain,

Submitter: Stephen M Schwartz | steves@U.washington.edu

University of Washington

Published May 3, 2006

I am not sure that Dr. Marks is right to focus only on the politicians. WE are a big part of the problem. Science needs leadership willing to be more honest with the public and more aggressive with the politicians:
Let me offer three major examples where the "community" has made bad decisions.
1. Fiscal Responsibility. During the doubling years, we acted like the famous rabbit of the rabbit and the hare fable. Funding 5 yr grants on a year to year basis with doubling funds was irresponsible.
2. NIH Initiatives. These are usually the result of community lobbying. Clinical studies are not the only abuse. Without stronger scientific leadership and under the shadow of the politicians, the system will misfunction. Examples:
a. Public lobbying clearly distorts funding priorities toward "popular" diseases. Does anyone have the courage to speak out against research on AIDS?
b. Do study sections represent a misplaced effort at affirmative action to assure "equal" treatment of clinical specialties?
c. Given the wonderful outcome of the genome project, the term "omics" has become as pervasive in pursuit of new dollars as "new, improved" is in selling soap. is ready for a global, methodological breakthrough. I shudder to read the translationomics initiative. d. Opposition to the restrictions on stem cells should not lead to irrational commitments of funds. The example of premature expenditures in gene therapy needs to be taken a lot more seriously.
3. The Intramural Program. Not only does the intramural program use large resources it provides a highly visible "face" for science in Washington. Some aspects are wonderful but does anyone feel we are well represented by the overall program? Would it survive if it had to compete for grant funds?
All of this begs for leadership. Ideally this could come from the NIH itself. Dr. Zerhouni's background as an administrator may not be the entire issue. Generals in the Army are not permitted public dissent over Iraq. Similarly, under the rules of his job, Dr. Zerhouni is not able to speak out about his opinions. So where can the leadership come from?
First, as Dr. Marks shows, we have a powerful podium in our journals.
If the editors of Science, Nature, Cell, JCI, NEJM, and so on were to join together they would comprise a very powerful lobbying group.
Second, we need to lobby to create an NIH directorship that is as apolitical as possible. One approach to this may be the privatization of intramural program. The head of such an institute might have the prestige and independence to speak out in away prohibited for current directors.

---

NIH Funding

Submitter: Richard O. McCann | rmcca1@uky.edu

University of Kentucky College of Medicine

Published May 3, 2006

The comments of Editor-in-Chief Andrew R. Marks in the April 2006 issue are welcome. As a some-time golfer, I agree wholeheartedly with his simile: Attempting to get "into the RO1 system" is indeed like hitting a bowling ball with a golf club. The ball is ridiculously easy to hit. However, making it go anywhere is also ridiculously improbable, with award levels at 10-15% in both the NIH and NSF. At these levels, who gets funded is either largely predetermined or stochastic. Either way, many newer investigators will be pushed out of science.
Not only that, but graduate students and postdocs see what is happening and start looking for the exits. And who can blame them? Having one's work evaluated variously as "outstanding-excellent-very good-strongly recommended" and still not getting a grant is more than deflating. Even the very best students (maybe because they are the best) will pause before climbing onto this treadmill. They recognize that the difference between "outstanding" and "excellent" is too fine a line to be meaningful, and that "incremental" is usually in the eye of the beholder. Notwithstanding the fate of any particular scientist, this exodus will severely damage American biomedical research. The future looks bleak indeed.