Clinical Research at NIH

If there is a unique feature of research at NIH, it is the Clinical Center. Conceived as a meeting place of bench and bedside biology, it has spawned innovative new disease therapies for more than 40 years. At a time of limited availability of funds for extramural clinical studies, the role of the Clinical Center in translational research is more important than ever for NIH Intramural Research Program (IRP) and for biomedical research in the country as a whole. Yet clinical researchers at NIH feel they are underappreciated and under siege. What does the future hold for clinical research at NIH?

In the recent External Advisors' Report on the Intramural Program, the physical infirmities of the Clinical Center were judged to be of sufficient severity to recommend strongly the reconstruction of a new hospital with associated laboratories. Although the report raised concerns about whether all Clinical Center protocols were truly innovative and suggested that the current hospital facility was almost twice as large as needed to support our essential research activities, the report did contain a ringing endorsement of the importance of the Clinical Center.

Acting on the recommendations of the External Advisory Committee, the Department of Health and Human Services has funded a concept competition as the first step toward construction of a new 250-bed hospital with laboratories, and has given tacit approval for future funding of such a facility. Although not the total replacement facility dreamed of by NIH planners, when completed around the year 2000, this new hospital attached to the Ambulatory Care Research Facility, will be the most modern, forward-thinking facility of its kind in the world, and it will be an attractive venue for the conduct of translational research in the 21st century. Beginning next year, the extant Building 10 will undergo essential maintenance and repair to central plumbing, electrical, and air-handling systems. This plan assures that clinical research will have a comfortable home at NIH for the foreseeable future.

What about the funding of clinical research? Because of the rising costs of clinical care, the assessment from each institute, center, and division (ICD) for clinical research activities has been increasing. Approximately 30% of the $1.1 billion NIH IRP budget now supports clinical research: $220 million dollars comes through the management-fund tap and the rest, approximately $100 million, is an estimate of the other costs paid by the ICDs to maintain clinical branches. One of the consequences of these rising costs is that some ICDs have begun to decrease their clinical research activities. It should be possible to stop this trend by increasing the efficiency of patient-care delivery by consolidating and closing patient-care units, managing Clinical Center services more carefully, and honing our protocols to eliminate expensive research and routine clinical care that are unlikely to yield important new findings. These goals will be accomplished at the ICD level through more rigorous scientific review of protocols and centrally, through improved management. In addition, the new hospital itself will be more efficient, saving as much as 10 - 15% in operating costs. Our hope is to keep the cost of clinical research from rising much above the current 30% of our total intramural budget.

Another concern has been the increasing administrative complexity of conducting clinical research. Public attention has been drawn to clinical research by recent media coverage of the use of radiation in medical research and of the recent deaths during NIH trials of the antiviral agent FIAU. Some researchers may feel there is an endless and needless proliferation of rules and regulations governing research on human subjects. Clearly, we do human subjects research at NIH under an explicit written assurance to the public that we will observe all relevant guidelines and regulations. Many of these regulations derive from a history of actual or perceived abuse of human subjects at other institutions, and they have evolved into explicit and verifiable ethical standards to which all bona fide clinical researchers subscribe. It is imperative that we adhere to these regulations for three reasons: 1) they represent high standards of ethical care for our patients, 2) strict adherence to the regulations protects both our patients and our researchers from the inherent risks involved in clinical research. We must remember that clinical research involves unknown risks to patients who have the courage and altruism to volunteer for these studies, and we must do everything possible to protect their interests and inform them about the research in which they are willing participants, and 3) violation of these guidelines and regulations will result in penalties to individual investigations and to NIH as a whole.

Recently, new Federal regulations have been developed that require that clinical research include women and minorities -- groups that have been excluded from certain studies in the past. A set of guidelines has been drawn up to allow our Institutional Review Boards (IRBs) to evaluate the proposed subject population for specific clinical studies. The IRBs will monitor the recruitment of women and minorities into these protocols. The point of this effort is not just to adhere to legal requirements; it is good science to determine whether there are human subpopulations with distinct physiologies or pharmakokinetics.

We are seeing significant progress in making the salary scale for our senior clinical researchers more competitive with salaries offered to physicians with patient-care responsibilities at other institutions. The Veterans Administration currently hires physicians under a legislative authority known as Title 38. For several years, NIH has attempted to use this authority, and recent discussions at the Department of Health and Human Services suggest that Title 38 salary supplements for physicians directly involved in patient care may be forthcoming.

I would also like to comment on changes in our clinical research training programs that should make the Clinical Center a more attractive environment for trainees. Currently, 20 different fellowship programs have been accredited by the Accreditation Council for Graduate Medical Education or boards in their respective disciplines. John Gallin, the new Associate Director for Clinical Research at NIH, has been working with a committee to construct a new training program in clinical research to attract young investigators to NIH. We have just launched a loan-repayment program for the educational debts of women, minority-group members, disabled people, and other disadvantaged physicians . This program will serve several functions: 1) it will allow us to recruit physicians to clinical research who would normally be constrained to the private practice of medicine because of personal financial limitations, 2) the quality and quantity of clinical researchers will increase, and 3) more minority clinical researchers will help us recruit more minority patients to our clinical research protocols.

I believe the future of clinical research at NIH is bright. The current NIH leadership strongly supports the high-quality, innovative clinical research for which the Clinical Center has become known. With John Gallin now poised to bring many initiatives to fruition -- with the building of a new hospital, the development of strong clinical research training programs, the redefinition of clinical protocols to minimize routine care and maximize innovative research, and the development of a personnel system to optimize salaries of our clinical researchers -- we can look forward to substantial improvements in the environment for clinical research at NIH. John Gallin will discuss details about these improvements in future issues of The NIH Catalyst.