T H E   N I H    C A T A L Y S T      J A N U A R Y  –  F E B R U A R Y   2004

Scratching a Niche

BLUE RIBBON PANEL POINTS INTRAMURAL PROGRAM TOWARD CLINICAL RESEARCH UNIQUENESS

by Celia Hooper
Edward Benz

Once upon a time, NIH was just about the only game in town, at least according to the NIH Director’s Blue Ribbon Panel on the Future of Intramural Clinical Research. When the Clinical Center opened in 1953, it was one of the few—if not the only—place that had the staff, infrastructure, and resources to conduct cutting-edge clinical trials.

Introducing the report and the panel’s chair, Edward Benz, at his Advisory Council (ACD) meeting on January 12, 2004, Elias Zerhouni said today’s landscape is radically different. Outstanding scientists interested in training for or conducting clinical trials can now find such opportunities at dozens of academic health centers. Benz related the report’s grounding in the fact that NIH’s intramural clinical research program "is no longer unique or the only place for talented clinical investigators."

Benz described the report’s recommendations as an effort to help the intramural program "find a niche that complements and is distinct from extramural clinical research centers." The panel tried not to be "too prescriptive," Benz said. (For example, he cited NIH’s 14 Institutional Review Boards as being "too many" and likely contributing to duplication and unnecessary complexity—and thereby impeding research. One IRB probably wouldn’t be enough, but the current number "sounds like too many," he said.)

The group also recognized that its report would be considered along with recent recommendations from the Institute of Medicine and ideas emerging from NIH’s road map initiatives for reengineering clinical research. NIH Director Elias Zerhouni acknowledged that reconciling all the various inputs would be hard, and said he would begin sorting them out at a staff retreat later this winter and with the help of his intramural research working group.

Key recommendations from the report include establishing new pathways for clinical training and career development, emphasizing research on rare diseases, establishing partnerships with extramural investigators to advance translational research, and streamlining both the high-level oversight of clinical research and ground-level, administrative complexities that create unnecessary hurdles for clinical investigators.

Discussing clinical career issues, Benz decried what he perceived as a tendency to categorize people as "staff clinicians" who are actually conducting clinical research and thus more appropriately deemed "clinical investigators."

When Zerhouni asked about this perceived reluctance to count clinical research as "real" research, Benz said that the nuances contributing to the phenomenon are quite similar to what he’s witnessed at academic health centers: Bench research proceeds faster, generates more publications more quickly, and is somehow easier to judge on its merits soon after it is published. Clinical research often involves complex teams, with each individual’s contribution somewhat fuzzy and with its quality embedded in the overall quality of the hospital’s services.

"And it’s hard to tell good from excellent from outstanding clinical investigation," until it is manifest in clinical practice long afterwards, Benz said, jokingly suggesting it was only possible posthumously. "How do we evaluate excellence in clinical research?" he asked rhetorically. "What we saw here was very familiar."

The panel did suggest a couple of ways that NIH could improve training and thereby help stem the national depletion in numbers of clinical investigators. It suggested establishing a postdoctoral fellowship in translational research for recent PhDs and an advanced visitors’ training program, similar to the Fogarty Scholars program, which would bring in senior scientists for 12 to 18 months to learn clinical research skills, including access to the latest therapeutic approaches and gadgets.

Discussing the report’s recommendations for the type of clinical research the intramural program should pursue, Benz said "excellence and distinctiveness" were the key. One recommended route to this distinctiveness is emphasizing research on diseases that are so rare that patients must be collected from all over the country—or the world—to reach informative numbers. Benz suggested that NIH could serve as the hub of a network of health centers studying rare diseases. NIH could conduct lengthy initial work-ups, maintain tissue banks, train research nurses, develop biomarkers of the disease processes, and coordinate follow-up, treatment, and data collection by this network of partners.

This model also demonstrates another recommended path for intramural clinical research: collaboration with extramural partners. Benz said the committee had seen some nice examples of such partnerships already in place, but that there should be a systematic pursuit of such relationships, not a series of one-of-a-kinds.

Benz said that before NIH can reclaim and retain its legacy of attracting the world’s most elite clinical investigators, "you first need to improve governance." To this end, the panel recommended establishing a single clinical research oversight committee as well as an external advisory pane of scientists for whom clinical research is "a front-burner issue." These committees and a proposed "deputy director for clinical research" in the Office of Intramural Research would set priorities and cut away unnecessary administrative hurdles and duplication of efforts across IC clinical programs. Where duplication and complexity exists, there should be a rational reason for it, Benz said.

Recalling a highly territorial environment in the intramural program before he left to become an executive vice-president at Lilly Research Laboratories in Indianapolis, ACD member Steve Paul applauded the report—and observed that the great challenge would be in its implementation.

NIH leaders who will implement the report are optimistic. "With the opening of the new Clinical Research Center next year," says Michael Gottesman, deputy director for intramural research, "we will take into our hands the most powerful tools and the best-designed environment ever created for clinical research. This report will assure that the human components—the management, training, career development, organization, and, most importantly, the definition of our clinical research niche—are as excellent as our state-of-the-art facilities."

 

BLUE RIBBON PANEL RECOMMENDATIONS

1. Revise the NIH intramural clinical research oversight structure.

Create a single high-level oversight committee to replace all existing governing bodies that have oversight responsibilities for intramural clinical research.

– The new committee should report to the NIH director.

– The committee should include representatives of institute and center (IC) directors, scientific directors, clinical directors, the Clinical Research Center (CRC) director, and outside representatives.

– The committee should be staffed by the Office of the Director.

– The committee should be responsible for governance, strategic planning, priority setting, and budget development. Importantly, this committee would make recommendations about transdisciplinary clinical initiatives and resource allocation.

Create an external advisory committee to the NIH director to periodically and systematically consider the overall quality and vitality of the NIH intramural clinical research program (ICRP).

– This committee would function in an analogous fashion to the IC Boards of Scientific Counselors (BSCs), but would evaluate clinical research across the entire NIH, reporting to the NIH director at least biennially.

– Although the committee would be advisory only, it should be composed of visible and influential leaders.

Strengthen the roles of the Office of the Director and IC leadership in clinical research.

– Revise the internal structure for coordinating and managing clinical research at NIH, including the creation of a new position of Deputy Director of Clinical Research in the Office of Intramural Research, who also would assume an influential role in the Office of Extramural Research.

– Maintain the role of the CRC Director as an influential senior leader. It is essential that the position of CRC Director remain an attractive and prominent position within NIH. By recommending the creation of a Deputy for Clinical Research, reporting to the NIH Deputy Director for Intramural Research, it is not the Panel’s intent to demote the position of Director of the CRC. The NIH Director should determine what reporting relationships best meet the needs of the NIH.

– Strengthen the role of the IC clinical directors. The Panel respects the need of each IC to craft its own organizational structure. However, the position and role of the clinical director in each unit was regarded by the Panel as too variable and, in some cases, weak. The clinical directors should be highly placed, with a direct reporting relationship to the institute director.

2. Develop new training and career pathways in patient-oriented research.

Strengthen career pathways and mentoring in the ICRP for patient-oriented research that culminate in tenure.

– Individuals in these pathways should be provided with the necessary infrastructure to achieve success as defined by clearly defined benchmarks. Clear distinctions should be made between the clinical service role and that of investigators with independent research resources.

Establish a premier, highly visible postdoctoral fellowship program in translational research, administered by the CRC director, for individuals who have finished clinical residency training.

Create an advanced research training program for extramural faculty members in academic health centers who wish to take a sabbatical at the CRC as a means of obtaining "on-the-job" experience in clinical research.

Foster the recruitment and retention of innovative patient-oriented investigators in the ICRP by assuring salaries and benefits that are competitive with those at academic health centers.

Foster an interactive and creative clinical research environment that will attract outstanding postdoctoral fellows. Postdoctoral fellows will want to participate in those programs that are carrying out disease-oriented research or investigating timely clinical problems that cannot be easily studied in the extramural academic health centers.

3. Continue to emphasize the study of rare diseases at the CRC, and promote a strong emphasis on pathophysiology and novel therapeutics in the ICRP.

Initiate trans-NIH programs of patient-oriented research that combine the expertise of several ICs.

Make the best use of the unique features of NIH’s intramural research program and its ability to undertake bold and innovative research.

4. Create translational, multidisciplinary intramural and extramural partnerships involving the General Clinical Research Centers (GCRCs), the Children’s Clinical Research Centers (CCRCs), NIH-funded extramural networks, the CRC, and the ICRP.

5. Intramural clinical research, including new programs in patient-oriented investigation, should be excellent and distinctive, as well as distinguishable from research conducted at academic health centers.

This mandate for change should be the responsibility of the NIH director, IC leaders, the advisory committees, and the BSCs.

6. Regulatory barriers and impediments to clinical research should be reduced. This would include streamlining the regulatory process and providing adequate, effective infrastructure for supporting clinical research.

 

 

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