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Varmus H. The Art and Politics of Science. New York: W.W. Norton & Company; 2009.

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The Art and Politics of Science.

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Chapter 11Priority Setting

One of the most difficult aspects of the job of running the NIH, or of directing any individual institute, is the designation of research priorities. This is an emotionally and politically sensitive part of the job because it is closely watched by some of NIH’s strongest supporters, who often advocate for the NIH because of a passionate interest in a small fraction of what the NIH does. That fraction is almost always a specific disease or even a subset or facet of that disease.1

Setting Priorities by Disease

Shifts in funds assigned to the mechanisms for supporting research, such as the intramural versus the external grant programs, or differential growth of budgets for individual institutes, are often easier to absorb than changes that affect the dollars devoted to specific diseases. Directives to alter allocations for disease-oriented programs are especially problematic if they occur abruptly or come at the expense of research on another disease. The situation may be further complicated if the directives are demands from powerful people rather than consensual decisions.

One of my first exposures to this problem occurred soon after I arrived at the NIH, when I received a call from my own former congresswoman, Nancy Pelosi, asking me to add $50 million to the budget for AIDS research. As the representative from one of the districts most heavily affected by the epidemic, her wishes were understandable. Since she was a member of the House Appropriations Subcommittee for the NIH, she was in a position to try to increase funds for AIDS research when the subcommittee was debating the size of the NIH budget, without taking the money from some other research program. But, in that period of spending caps, she had presumably been unsuccessful in negotiations with her fellow committee members and was now trying to fulfill a promise to her San Francisco constituents by asking me to shift funds from some other budget categories into the OAR account. I declined as politely as I could.

Sometimes it was not so easy to say no. Late one afternoon in May of 1996, as I was walking on the NIH campus, my driver pulled up with an urgent expression and asked me to take an emergency call on the car phone. A senior member of the administration—Jack Lew, then deputy director, later director, of the Office of Management and Budget—told me that the president had just met the recently paralyzed actor Christopher Reeve for the first time that afternoon and had promised in the presence of the press to increase spending on spinal cord research by $10 million. I started to explain the difficulties of doing this, when the phone was passed at the other end to a more junior person, who said, basically, just do it, don’t argue, or you won’t get the money. Of course, the White House was not in a position to send us any additional funds directly. But the president’s wishes are always obeyed. When the next accounting was made of disease-specific spending at the neurology institute (formally known as the National Institute for Neurological Diseases and Stroke, or NINDS), the funds for spinal cord research were accordingly higher, and funds for other purposes were proportionately lower.2

Advocacy narrowly focused on a single disease is often problematic for leaders of the NIH, because such advocacy is likely to be inconsistent with the ways science works best. Furthermore, the goals of such advocacy are often spending levels that are difficult to measure accurately. For example, research on a specific neurological disease, like ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease), should, in principle, include basic studies of nerve cells and mechanisms of cell death, in addition to clinical trials in ALS patients, which are readily classified. The basic work may be impossible to classify by disease category, since it could help to understand many neurological diseases or others. This is where the concept of scientific opportunity comes into play: spending funds to seize a chance to understand a fundamental principle in biology is often a more effective approach to disease than mandating funds for research on a specific disease. Furthermore, efforts to understand another disease, even one that does not affect neurons, might prove to be a more valuable means to understand ALS than work on ALS itself.

My favorite examples of such serendipity come from the world I know best, cancer research. In the 1980s, as I described in part 2, our studies of retrovirus-induced breast cancer in mice led to the discovery of a class of genes, the wnt genes, which work in concert with several other genes that make components of what is called the wnt signaling pathway. Although there is still little evidence that this pathway plays a major role in human breast cancer, virtually every case of colon cancer is now known to be attributable to a defect in some part of the wnt pathway. Conversely, studies of a rat neuroblastoma (a brain tumor) in Bob Weinberg’s laboratory revealed a new cancer gene (called neu, or HER2) that is often aberrant in human breast cancer. Today, an antibody (called Herceptin), formed against the protein made by the neu (HER2) gene, is used successfully in many thousands of women to prevent and treat metastatic breast cancer, as mentioned in chapter 7. So studies of breast cancer have helped with colon cancer, and studies of brain tumors have helped with breast cancer.

Apart from the difficulties of predicting where and how discoveries will arise, the priority setting process can be ugly—for instance, when advocates refuse to recognize, or to care, that funds for their disease must come from funds being spent elsewhere, including funds used for a disease important to another group of advocates. To justify their desires for more targeted spending, advocates will often claim that support for their disease has been historically inadequate or will focus on selected features of a disease that make the distribution of funds seem inequitable. Of course, very different impressions can be produced by the use of different criteria—the number of people living with a condition, the number who die from it each year, the age-adjusted death rate, the number of healthy individuals at risk, the number diagnosed each year, the annual medical expenditures, the annual costs to society, or the degree of pain and suffering. These are all legitimate aspects of the nation’s burden of disease, but they are crude tools for deciding how to spend research dollars appropriately.

Nevertheless, such numbers are used, often to the discomfort of NIH and its institute directors. For much of my time at the NIH, I was castigated by advocates for research on heart disease because the NIH was spending about as much on AIDS research as on studies of heart disease, even though there were about twenty times more deaths from heart disease than from AIDS in the United States each year. The arguments tended to ignore other important facts: that AIDS was a new and expanding disease, that it is infectious, that it is devastating large parts of the world, or that age-adjusted death rates from heart disease have fallen by two-thirds in the past fifty years.

The passion behind such perceived injustices could produce some very unpleasant episodes, even when the NIH was making a genuine effort to expand research in disease areas where need and opportunity were clearly growing. For instance, I recall sitting through vituperative rants against the NIH by a Connecticut physician named Abraham Lieberman from the National Parkinson’s Foundation, with his patient, a silent Muhammad Ali, by his side, while I was waiting to testify at a hearing about priority setting held by the House Commerce Committee in March 1998.3

Dr. Lieberman had (perhaps understandably) misconstrued an authorized level of funding for NIH research on Parkinson’s disease, $100 million, to be a mandate to spend that much. Indeed, by our measure, the NIH was spending at least $100 million, but we judged that some was spent on studies that directly affected patients with Parkinson’s disease (such as clinical trials or diagnositic tests) and some on the underlying disease mechanisms (such as nerve cell death or dopamine metabolism) that might also apply to other neurological diseases. This did not make Dr. Lieberman happy:

What we’re telling you is set up specific goals, conquer Parkinson’s disease, and then you know you’ve spent the money well. To just give the National Institutes of Health additional moneys to do more and better science, you’re going to be in the situation of saying to yourself, how do I know that I really did something. . . . [T]he scientists at the NIH have different priorities than the advocates of patients.4

It was not easy to listen to this from the back of the room.

In the same year, some advocates for diabetes research, responding to perfectly legitimate concerns about rising rates of diabetes, especially type 2 diabetes, adopted an unusually militant approach, openly criticizing my management of the NIH and even picketing the Illinois home of John Porter, the chairman of our House Appropriations Subcommittee. (The attack on Porter was ill-conceived: his wife was a diabetic, his concerns about the disease were evident, and his support for the NIH was unsurpassed.)

Responding to attacks of this kind is never easy, especially when the rhetoric becomes personal, the demands are excessive, and the budget isn’t very flexible. In most instances, we designed a public hearing on the topic—often a workshop or (as for diabetes research) a larger symposium at the NIH, followed by a formal report from an outside advisory group—to review the current state of the disease and discuss new opportunities for studying it. Even when these conferences succeeded in defining areas that deserved a greater effort by the NIH and its grantees, it was often difficult to determine the numbers of dollars that should be shifted in the direction of the new efforts. After all, most of the extramural scientists who participated were already working in the contested area and had a vested interest in budget proposals that were as large as possible. At the same time, NIH staff felt an understandable obligation to moderate programmatic shifts and to protect current expenditures in other promising areas of work. These conflicting goals meant that plans could not easily satisfy all parties.

These comments are not meant to imply that advocacy for research on specific diseases is necessarily wrong, or that NIH leaders can simply divide up the funds according to the quality of grant applications, regardless of the research objectives. NIH must be (and it is) attentive to subject matter, and it must ensure (and it does) that at least some work is going on in all important areas. It should (and does) stimulate work on relatively neglected problems, especially when new opportunities arise, by advertising that funds are available for such research. One of the potential strengths of the NIH is its ability to encourage scientists throughout the country to pay greater attention to underserved and deserving problems, even when the new opportunities may not be obvious. Simply by encouraging attention to such problems—autism, rare neurological diseases, imaging methods, emerging infections, or bioengineering, to mention a few areas promoted during my tenure—new ideas may emerge to create those opportunities. In this regard, the NIH must walk a narrow line: to respond responsibly to public health needs and yet to provide the freedom for investigators to exercise their imaginations as fully as possible.5

Whenever the NIH tries to assign funds to defined categories of research, it enters a land of uncertain criteria and subjective judgment, and it risks undercutting the use of its resources for the best kind of unfettered research. The failure of other national research systems—most flagrantly, the Soviet system—is often attributed to excessive direction from a scientific hierarchy.

One of the by-products of the repeated debates about priority setting at the NIH was a 1998 report by the Institute of Medicine (IOM), entitled Scientific Opportunities and Public Needs: Improving Priority Setting and Public Input at the NIH. While the study group recognized the inherent difficulties of allocating funds by disease category and acknowledged that the NIH generally made fair decisions, it was also critical of the limited avenues for redress that the NIH was said to provide.7 One solution offered by the IOM report was especially useful—one that I wished I had conceived myself: the creation of a Council of Public Representatives (COPR). We swiftly established a group composed of thoughtful, well-known advocates for specific diseases who would agree to relinquish their individual loyalties when they entered a meeting room in order to give the NIH balanced advice about how to spend its money. After a complex nominating and vetting process, my staff and I brought together a truly remarkable group of individuals to serve on the COPR.8 The council provided excellent advice on a wide variety of topics, not just on priority setting; as a result, we generally included some members in virtually all major relevant activities, such as the annual retreat of institute directors and various kinds of workshops. The COPR also offered safeguards against partisan attacks by disgruntled advocacy groups and showed that the NIH was open to public inspection and comment.

Balancing Growth of Institute Budgets

One of the strengths of the NIH is the fierce support it receives from members of the public, especially from those who are eagerly awaiting progress against disease. This kind of support is often focused on individual institutes and centers by patient advocacy groups and professional societies. These groups can limit the possibilities for adjusting the distribution of funds across the institutes, since annual changes in each institute’s budget are scrutinized carefully, to one hundredths of a percentage point, and any downward deviation from the NIH average is likely to result in appeals to influential congressional or administration advocates. This has the sometimes stultifying effect of keeping institute budgets in approximate lockstep, simply to avoid the inevitable outcry if one of them doesn’t do well.

For these reasons, intense favoritism for one institute, especially a large one, can be problematic. Still, steep changes in the fortunes of a couple of institutes and centers were not deeply controversial. In the latter half of my time at the NIH, I was able to accelerate the growth of budgets at the Fogarty International Center, where the total was so low that a high growth rate to boost investments in global health had no significant effect on others, and at the National Human Genome Research Institute, which was understood to be funding the Human Genome Project, an enterprise highly valued by the entire NIH and by the worldwide scientific community.

But Vice-President Al Gore posed a potentially serious dilemma for the NIH late in 1997 when he proposed that the National Cancer Institute (NCI) should receive a much larger share than the other institutes in the record-breaking $1 billion budget increase that the president was going to request for the NIH for fiscal year 1999. Possibly as a result of promises made to cancer research advocates, possibly because of his personal concerns about cancer (his sister had died of lung cancer at an early age), possibly because cancer research was popular politically, Gore asked that the cancer institute’s budget grow at twice the rate accorded the others.

I was very unhappy about this. The differential rates of growth were not in accord with clearly defined medical needs or with carefully considered scientific opportunities. No major changes in disease rates or outcomes and no sudden developments in cancer research made the needs for the NCI any greater than those for brain disorders, metabolic diseases, or infections. By any measure, the NCI was already the largest institute by a considerable margin, and Gore’s plan would further accentuate the differences. And, of course, there would be a strong negative reaction from the supporters of the other institutes when the plan was announced. But he was the vice-president, and conceivably the next president, so the idea of arguing with him about this issue on my own was not appealing.

Fortunately, Donna Shalala strongly supported my position, and she insisted that we take up the matter directly with Gore. To his credit, he agreed to see us late one afternoon in early January of 1998, then listened stonily to our point of view. It was apparent that he felt committed to the goal of favoring cancer research in some fashion and that he needed a way to show that he had done so. To try to convince us that his formula would benefit the entire NIH, he speculated that rapid growth of the NCI would “act like an engine” to pull the other institutes up the budgetary hill. This idea was not persuasive. But we were able to reach a rapprochement when I pointed out that many institutes did cancer research, not simply the NCI, and he was surprised and pleased to learn this. That gave us an opening for a compromise: we would ensure a relatively large increase for cancer research, but it would be spread among all the institutes that could legitimately be said to work on cancer. Cancer research would have a short-term boost in funding, but discrepancies in the sizes of institute budgets would not increase in the long run. The percentage increase in funding for the NCI during the eventual doubling of the NIH budget would not—and ultimately did not—exceed the increases at other institutes. Of course, this was true, in part, because the pace of the doubling set by Congress exceeded the administration’s plan. In those five years of bounty, no one needed to be pulled along by anyone else.

Enlarging the Director’s Powers

One of the limiting factors in my own efforts to respond to complaints about how the NIH spent its money was the lack of significant fiscal authority in the Director’s Office. Of course, I had a role in determining the annual increase in budgets for individual institutes, and I tried to exercise this role by asking the institute directors to provide me with lists of new and expanded initiatives for the coming year. This allowed me to describe our budget request in a coordinated and appealing fashion by grouping the initiatives into Areas of Research Emphasis, which spanned the institutes, and it helped me to justify increases with substance, not simply with a vague or self-serving need to maintain budgetary growth. I also had, in most years, a very modest discretionary fund (usually no more than about $10 million, not enough to do much more with than fund a few grants that were scored just below the funding level) and the authority to transfer a limited amount of funds, usually up to 1 percent of the total, between institutes. Still, the Director’s Office lacked the personnel required to plan and oversee research programs, so (without funds to build such staff ) it was unrealistic to think about issuing contracts or grants from the central office, even if that was a desirable option.

The transfer authority, however, offered an opportunity for me to get more involved in the substantive work of the NIH, the awarding of grants. But the transfer of funds between institutes was also a mechanism that made institute directors anxious. Understandably, they did not welcome the thought of losing control over any of their appropriated dollars. Nonetheless, they recognized that the transfer authority could be useful to the agency, as a mark of its flexibility, and that it was better to use it, even if sparingly, than to lose it. So, in most years, we would identify some projects that interested several institutes. Then, usually with the advice of some senior extramural investigators, we would move money from one or a few institutes into the pockets of another to allow such projects to be adequately supported.

The use of the transfer authority allowed me to see how the institutes could sometimes work more effectively together to achieve things that even the larger institutes could not easily do on their own. (Remember that the budgets of the institutes and centers ranged from under $50 million to more than $2 billion.) As I became more comfortable with my role as director—and sometimes frustrated by my limited options for involvement in scientific program development—I began to propose “trans-NIH” research initiatives that would benefit all parties without creating new institutes or centers.

For example, in the mid-1990s I learned that rapid progress was being made through studies of zebra fish, a versatile animal model that was a vertebrate (unlike fruit flies and roundworms) with relative rapid embryonic development and a short generation time, compared with mice and rats. I invited Leonard Zon, an especially articulate leader of zebra fish research at Harvard Medical School, to speak to a meeting of the institute directors. With Zon’s help, I was able to persuade them to contribute to a fund, administered by one institute, that would accelerate the analysis of the zebra fish genome, isolate and characterize mutants, and study development and disease with this model organism.

Subsequently, similar successful initiatives were launched to study the genome of the laboratory mouse and the expressed genes of the laboratory rat. But, with time, the institute directors, even those with whom I was particularly friendly, became resistant to these efforts, seeing them as incursions on their turf and claiming that the initiatives complicated their budgets and oversight mechanisms. The message I took away from these discussions was that the NIH needed some reorganization to allow the director to have a stronger hand in program development. I will say more about this possibility later.

The NIH’s Organizational Dilemma

Anyone who looks at an organizational chart of the NIH will be immediately struck by its complexity, especially by the multitude of institutes and centers, now twenty-seven, then twenty-four, each with its own authorities, leaders, and (nearly always) appropriated funds.

This, of course, is not the way the agency was initially designed. The individual components have been created over the past seventy years, in a fashion that reflects one of the most appealing things about the NIH—its supporters’ passionate loyalty to the idea of using science to control disease. Each of the centers and institutes was legislated into being by members of Congress, commonly working together with citizen advocates, who believe that some aspect of biomedical research—a specific disease (like cancer or arthritis), a specific organ (like the heart or lung), a time of life (like aging or childhood), or a discipline (like nursing or bioengineering)—can benefit from the creation of a unit of the NIH devoted to it.

But the resulting proliferation of institutes and centers has not been healthy in every way. It has doubtless helped to drive budgetary growth for the NIH as a whole, but it has also created administrative redundancies. (Some of these were partly reversed during my time at the agency by the creation of inter-institute administrative centers.) The multitude of institutes has helped to focus attention on many important diseases and conditions and to sustain public advocacy for the NIH. At the same time, it has placed some topics at a disadvantage, because they are overseen by relatively small institutes that may lack the capacity to conduct large-scale efforts, like major clinical trials. Most plainly, the diversity of institutes complicates the central management of the NIH by the Director.

Despite my efforts to restrain further proliferation, three new centers and institutes were created during my tenure as director or shortly thereafter: the National Center for Complementary and Alternative Medicine (NCCAM), the National Institute of Biological Imaging and Bioengineering (NIBIB), and the National Center on Minority Health and Health Disparities (NCMHD). Each of these three new entities illustrates the same problem: their activities are pertinent to the studies of virtually all diseases, organs, and stages of life. For that reason, in my view, the research activities overseen by the new organizations would have been more properly assigned to the many preexisting institutes and centers, then monitored and coordinated by offices under the NIH director or by coalitions of representatives of the relevant institutes. Indeed, such coordinating bodies—the Office of Alternative Medicine, the Office of Minority Health Research, and the Bioengineering Consortium—preceded and gave birth to the new centers and institute. But passionate advocacy for the creation of these new organizations, by congressional leaders (such as Senator Tom Harkin for NCCAM), by congressional groups (such as the Congressional Black Caucus for NCMHD), and by leading academics (bioengineers and radiologists for NIBIB), proved too difficult to resist.

Resistance to these developments is especially difficult because the advocates are among the agency’s best friends, so the legislation that creates a new unit is unlikely to be something over which an NIH director wants to take an unalterable stand. I well remember receiving a phone call from Tom Harkin, one of the NIH’s strongest supporters, during the period when Congress was considering his proposal to convert the OAM into the NCCAM. We discussed my concerns about concentrating research on alternative medical practices in a new and separate center and my efforts to create a coordinating body that included representation from the CDC and FDA, as well as from most of the existing NIH institutes. But Harkin was not convinced. Then he said that if I didn’t agree with his position and he got his way in Congress, I could simply resign. I was surprised by this proposal, since I was quite sure that he didn’t really want me to leave, and I didn’t perceive the issue as one that would compel me to fall on my sword. I told him that I was unlikely to change my views if he prevailed, but that I’d do my best to comply with the law by finding an outstanding leader for the NCCAM and helping the new center prosper. Needless to say, he did prevail, and I did not quit. Instead, I was able to recruit an extraordinary scientist, Steve Straus, to run the center,9 and the center has done well. But the episode reveals how deep these passion may run.

During my final year at the NIH, I expressed my anxieties about the continuing proliferation of autonomous units at the NIH in public talks and extended the discussion in an essay published in Science magazine shortly after I left the agency.10 In these presentations, I argued that, unless proliferation was stopped, the NIH would become an unmanageable collection of over fifty units within a decade or two at its current rate of growth. I then took the argument a step further, and proposed that the current organization of the NIH be reconsidered and redesigned, creating six centers of approximately equal size, including one for the director, giving him or her increased authority over coordinated programs, new initiatives, and budgets. Although this might have been the right way to build an NIH if it had been newly created, I did not expect my proposal to be adopted, given the strength of the advocacy for many of the existing components of the NIH. But I did hope to stimulate debate and find some measures adopted.

In 2001, at least in part in response to my published comments, the Institute of Medicine brought together a distinguished group to reexamine the structure of the NIH. While not subscribing to my more radical proposals, the IOM report did suggest an experiment with coalitions of institutes with related purposes (e.g., those devoted to studies of the brain and other parts of the nervous system), and it endorsed means for providing greater powers to the NIH director.11 When the NIH was reauthorized in 2006, for the first time since 1993, barriers were installed against the creation of additional institutes and centers, and the NIH director was awarded new means for assessing the research portfolio and for initiating new programs.12 The long-term effects of these changes on the NIH will be interesting to watch.

Footnotes

1

Any past director of the National Institute of General Medical Sciences, a major source for support of basic biological research, will say, “There aren’t many patient groups advocating for general medical sciences.” So support for the NIGMS depends on an enlightened understanding of the benefits of basic research; on the other hand, this institute is spared the internecine battles among disease groups that plague some of the other institutes.

2

Soon after the phone call, I was asked by the president’s advisers to go to Bedford, New York, to help Chris Reeve prepare for his appearance at the 1996 Democratic National Convention. Chris and I had a long and wonderful day together, talking about science, literature, movies, NIH, and other things. He subsequently visited the NIH and became, as is well known, a passionate and effective advocate for medical research generally and for stem cell research in particular. In his convention speech, he quoted the passage from FDR’s dedication of the NIH campus in 1940 that opens chapter 10, always remembering how much FDR accomplished despite his paralysis.

3

The fact that I was waiting suggested that the committee chairman, Mr. Bilirakis, had been persuaded to allow other witnesses to precede the government witnesses, who are usually heard first. But the transcript reveals that I had won Mr. Bilirakis’s favor by listening to the multiple panels that preceded mine.

4

Hearing before the Subcommittee on Health and the Environment of the Committee on Commerce, House of Representatives. New Developments in Medical Research: NIH and Patient Groups. Marc 26, 1998.

5

Some of these principles are set forth in a pamphlet on priority setting that the NIH published in 1997.6

6

National Institutes of Health. Setting Research Priorities at the National Institutes of Health. Sept., 1997. http://www​.nih.gov/about​/researchplanning.htm.

7

Committee on the NIH Research Priority-Setting Process, Institute of Medicine. Scientific Opportunities and Public Needs: Improving Priority Setting and Public Input at the National Institutes of Health. Washington, D.C.: National Academy Press; 1998. http://www​.nap.edu/openbook​.php?isbn=030906130X. [PubMed: 20845560]

8

Among the original members were David Frohnmayer, the president of the University of Oregon, who had three daughters with Fanconi’s anemia; Robin Chin, a pharmacist, breast cancer survivor, and advocate for people with diabetes and HIV/AIDS; Lydia Lewis, the Executive Director of the National Depressive and Manic-Depressive Association; Pam Fernandes, a diabetic who lost her vision at age twenty-one, then became a championship bicyclist following a renal transplant; Roland McFarland, a broadcast executive with strong interests in diseases that disproportionately affect African-Americans; Rosemary Quigley (now deceased), a University of Michigan–trained lawyer and expert in health policy, with cystic fibrosis diagnosed at the age of six months; Debra Lappin, a public advocate on health and science policy and the former chair of the Arthritis Foundation; Barbara Lackritz (also now deceased), a speech pathologist who had battled chronic lymphocytic leukemia for a decade, cared for a husband with Parkinson’s disease, wrote a book about adult leukemias, and established online services for leukemia patients; and several other extraordinary people.

9

Steve was a remarkable virologist, teacher, and leader, who unfortunately succumbed to a brain tumor in 2007.

10

Varmus H. Proliferation of National Institutes of Health. Science. 2001 March 9;291:1903–5. [PubMed: 11245194]

11

Committee on the Organizational Structure of the NIH, National Research Council. Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges. Washington, D.C.: National Academy Press; 2003. [PubMed: 20669477]

12
Copyright © 2009 by Harold Varmus.
Bookshelf ID: NBK190605

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