GUEST EDITORIAL FROM THE CLINICAL CENTER DIRECTOR

A SPACE ODYSSEY: REGARDING THE NEED TO UTILIZE UNUSED CAPACITY AT THE CLINICAL CENTER

John Gallin

If you’d appreciate a lively discussion with colleagues, ask how the NIH Clinical Center can best be used. That’s a topic that has generated interesting and thoughtful discussions since the original hospital opened in 1953. And now, with the opening of the new Mark O. Hatfield Clinical Research Center just over two years ago, these discussions are as energetic as ever.

Indeed, on July 12, 2007, the NIH institute directors held a mini-retreat to contemplate a new direction for the Clinical Center. During that meeting, I presented a vision to initiate cross-institute intramural activities as well as new partnerships with the extramural academic community and industry, ideas aimed at infusing new intellectual vigor while capitalizing on unused resources at the Clinical Center. The ideas I presented need and are getting further discussion and vetting, including a joint meeting of the scientific directors and clinical directors in early September at which exciting long- and short-range topics were endorsed for continued development.

Who and How Many Are the Clinical PIs ?

There has always been unused capacity at the Clinical Center. Historically, the situation was related to limited resource availability in the intramural programs. More recently, however, the reasons have become more complicated and driven by a convergence of factors, including declines in funding availability and in the number of senior investigators writing research protocols.

The number of talented principal investigators (PIs) writing clinical protocols is perhaps the most important driver of patient activity and the quality of clinical investigations.

Although the absolute number of PIs writing clinical research protocols has increased—from 461 in 2001 to 547 today—both the absolute numbers and the percentages of clinical protocol writers among the total tenured and tenure-track investigator pools have declined.

In 2001, the 192 tenured senior investigators writing clinical protocols represented 21 percent of the total pool of senior investigators at NIH. Today, 156 tenured investigators, representing 16 percent of the pool, are writing such protocols. The decline in clinical PIs among tenure-track investigators is even more dramatic: from 48, or 19 percent, in 2001 to 18, or 7 percent, today. The PIs at NIH to whom credit can go for the absolute increase in clinical research protocols are NIH’s staff clinicians.

The decline in the number of tenured and tenure-track scientists writing clinical protocols is worrisome and indicates we have a problem recruiting and nourishing the career paths of young clinical investigators. The Careers in Clinical Research Working Group of the Advisory Board for Clinical Research, chaired by Lynette Nieman, is working actively to provide new opportunities for clinical investigators at NIH.

Difficulties in recruiting and retaining clinical investigators are not unique to the NIH Clinical Center (1). It is a national problem. NIH Director Elias Zerhouni has championed the need to revitalize clinical research in the United States (2). The new Clinical and Translational Science Awards led by the National Center for Research Resources were designed to invigorate the national clinical research effort by providing a network of academic homes for clinical research around the nation.

As we contemplate the future of the Clinical Center intramurally, we also need to consider its role in rebuilding the nation’s clinical research enterprise. A strong Clinical Center that serves the needs of the intramural program while serving as a resource for the country is an ideal goal.

MEC Suggestions To Pool Resources
In Recruiting Clinical Investigators . . .

A top priority of the Medical Executive Committee (MEC) is reversing the falling numbers of tenured and tenure-track clinical investigators who are patient-oriented. Creating improved career paths for clinical investigators is one approach. The MEC has also suggested central recruitment and trans-institute pooling of resources to create exceptional recruitment packages to attract the most promising tenure-track investigators. Our salaries are competitive for young investigators, and recent increases allow for reasonable pay in the subspecialties, but it is this unique ability to draw resources from multiple institutes that can offer an unrivaled opportunity for clinical investigators—and that is what we need to provide.

The expectation is that young tenure-track clinical investigators will develop strong scientific programs with clinically based components. After central recruitment, each investigator would be assigned to the appropriate institute among those that had agreed in advance to participate in the recruitment process.

. . . and in Responding to Public Health Crises

Another way for central planning to attract clinical investigators, the MEC has suggested, is for NIH to identify trans-institute "Manhattan Projects" to address top public health priorities. NIH has gathered such forces in response to such public health crises as the AIDS epidemic in the 1980s and the current obesity epidemic.

But we need additional compelling projects that enlist diverse groups of basic and clinical investigators to find solutions to serious public health problems. The recently established trans-NIH effort in inflammation, autoimmunity, and immunology, led by Neal Young (3), is one example of a large group effort to pool the talents of investigators to address an area of emphasis from which will evolve projects related to specific diseases.

In addition to large trans-NIH efforts, the MEC recommended that each institute identify at least three areas of emphasis for its intramural programs that articulate the strengths and directions of that institute. The MEC has also called upon NIH to establish a trans-NIH strategic plan for clinical research, something we have never had in the past.

More Suggestions: Reopen Clinics
For Undiagnosed Patients with Rare Diseases . . .

Sustaining the intellectual vitality of our clinical programs is essential. One important contributor to the vitality of programs is a diverse population of patients with challenging clinical problems. Such a population of patients helps strengthen the clinical skills of the practicing physicians and provides an environment for generating hypotheses for clinical research. Before the mid-1990s, the Clinical Center operated clinics for patients who presented difficult clinical challenges, or "fascinoma clinics."

These clinics served two major purposes: They offered a beacon of hope for many patients who obtained access to the special clinical expertise at NIH, and they generated intellectual excitement and support for hypothesis generation at the Clinical Center. I recall well the fever-of-unknown-origin clinic created by the late Sheldon Wolff in the 1970s. It benefited patients with previously undiagnosed clinical problems and helped to spawn the field of clinical immunology. There are many other past examples of such rewarding developments throughout the NIH institutes. But this innovative clinic activity was curtailed dramatically in 1994 by an inspector general who believed the clinics were catering to the rich and the famous. We need to reopen these clinics with clearly defined trans-NIH planning, coordination, and strong oversight.

. . . and Open Clinical Center Doors
To the Extramural Community

The Clinical Center has special resources that in some cases are unique. Despite the reduction in rare-disease clinics, the cohorts of patients with rare diseases are still substantial. A recent review of our patient population indicated that about 44 percent of our 2006 admissions were patients with a rare disease, and we estimate that we are now actively following 37,500 such patients. Years of studies of patients with rare diseases has led to unequaled phenotyping capability at the Clinical Center. Special resources also include our new metabolic patient unit designed to study obesity, extraordinary imaging capacity, the biomechanics laboratory in our Rehabilitation Medicine Department, and training in clinical research extended to trainees ranging from medical students through senior investigators (4). These resources can be utilized to a greater extent.

Making these resources available to extramural colleagues in academia and industry will generate new partnerships, collaborations that enrich both the intramural and extramural communities. Strong relationships with the extramural community will also serve the intramural program well politically—we will be viewed not only as a beacon of hope for patients whose therapeutic options have been exhausted but also as a valued resource accessible by and contributing to the nation’s clinical research enterprise.

What’s Required?

To succeed in meeting the vision for a strong Clinical Center in the future that continues to make new discoveries about human disease leading to new therapies, we need active leadership of a strategic plan that encompasses NIH intramural clinical research programs. This form of coordination and priority-setting, which in my opinion is long overdue, will result in recruitment of more and better tenure-track clinical investigators and bring new extramural partners to our community while contributing to the needs of colleagues in academia and industry.

—John Gallin
Director, NIH Clinical Center

1. N.S. Sung, W.F. Crowley, M. Genel, M., et al. "Central challenges facing the national clinical research enterprise," JAMA. 289, 1278 (2003).

2. E. Zerhouni, "Translational and clinical science—time for a new vision," NEJM ; 353, 1621 (2005)

3. J. Rivera and M. Gottesman, "Trans-NIH intramural scientific initiatives," The NIH Catalyst, 14 (5), 2 (2006).

4. M. Gottesman, "Turning medical students into physician-scientists," The NIH Catalyst, 15 (2), 2 (2007).

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