Statement before Subcommittee on Public Health and Safety

Four years ago, at my confirmation hearing before this Committee, I counted among my central goals as the Director of NIH a pledge to "encourage NIH investigators to extend their biological discoveries to clinical settings." I am pleased to be here today to help evaluate the status of clinical research: its importance, the unprecedented opportunities to change the practice of medicine, the obstacles facing clinical research, and the several efforts the NIH has undertaken to confront these issues.

The NIH serves the nation by conducting and supporting medical research, with the goal of improving human health. Medical research is a continuum that spans diverse realms of laboratory research and several kinds of clinical research. Any single weak link in this continuum reduces the likelihood that major research findings will benefit the public in the form of new treatment and prevention strategies. Clinical research is a crucial element in this endeavor.

What is clinical research?

Clinical research refers to research conducted with human beings, including studies of specimens collected from specific patients. It encompasses some laboratory research on the mechanisms of human disease, translational research (in which laboratory and clinical activities are closely aligned), clinical trials of preventive and therapeutic strategies, epidemiology, behavioral research, and health services and outcomes research.

Because it covers so many topics, clinical research is necessarily multidisciplinary. It requires the skills and expertise of many kinds of investigators, including individuals whose primary training is in medicine (so-called "physician scientists"), dentistry, public health, nursing, psychology, and various laboratory sciences. Other professionals such as dieticians, computer programmers, bioengineers, and technicians are also essential for clinical research. Clinical research is conducted at a variety of sites and by a variety of entities. Academic Health Centers (AHCs), government labs and clinics, community hospitals, State health organizations, and managed care and pharmaceutical industry sites are all active participants in the Nation's clinical research enterprise.

The success of clinical research depends on funding from both Federal and private sector sources. In FY l996, 27 percent of competing projects at the NIH and 38 percent of our competing research dollars were accounted for by clinical research. (Approximately one-third of these dollars and 20 percent of these grants were invested in clinical trials.) Data from the Pharmaceutical Research and Manufacturers Association reveal that in l995, the latest year for which figures are available, clinical trials accounted for an outlay of more than $4 billion by the pharmaceutical industry, equivalent to 35 percent of company-financed research and development.

Examples of the benefits of clinical research

Clinical research has changed the face of modern medicine. Fifty years ago, at the end of World War II, physicians had little ability to effectively treat or prevent any of the deadliest diseases. Most of the staples of modern medicine we enjoy today were still unknown: antibiotics, vaccines for polio and several other severe infections, most hormone replacements and steroid therapy, effective drug therapies for cancer and psychotic illnesses, testing for genetic disorders, coronary bypass surgery, transplanted organs, and artificial joints. These and other successes have encouraged public enthusiasm for research and belief in the potency of modern medicine.

It is useful to consider in more detail the scope of changes in medical approaches to some common diseases that have occurred in the past few decades as a consequence of clinical research sponsored by the NIH and others.

Atherosclerotic cardiovascular disease remains the leading cause of death in the United States and is increasing in incidence elsewhere in the world as the population ages. However, since the late 1960s, the age-adjusted mortality rates for this disease have declined greatly in all segments of the U.S. population. Epidemiological and biochemical studies have identified risk factors, including hypertension, obesity, lack of exercise, smoking, and high blood cholesterol; efforts to control these factors with behavioral change and drugs have helped to decrease the development and mortality of heart disease. percent Further decreases in mortality are due to more effective care of victims of coronary artery disease. Clinical research has yielded a wealth of diagnostic and treatment options, including cardiac catheterization, coronary artery bypass surgery, balloon angioplasty, thrombolytic ("clot busting") therapy, and a vast array of new drugs to help the heart patient control arrhythmias and improve the strength of the heart muscle.

Osteoporosis afflicts 25 million Americans, most of them older women, and the loss of bone mass due to osteoporosis contributes to 1.5 million fractures annually; such fractures are a major cause of admission to hospitals and nursing homes and a major financial burden. Over the last decade there has been a revolution in thinking about osteoporosis. A major insight comes from the recognition that osteoporosis and fractures are not a necessary consequence of aging. NIH support for clinical studies of nutrition and physical activity interventions have provided strong evidence that fractures can be prevented and bone loss reduced even in older individuals---for example, with calcium and vitamin D supplements. More recently, studies of postmenopausal women with osteoporosis have led to the identification of several classes of medications, including estrogen, that appear to slow the actions of bone-resorbing cells and thereby improve bone strength.

An estimated 16 million people in the United States have one of the several forms of diabetes mellitus, a chronic disease that affects how our bodies use food for growth and energy. Following the discovery of insulin and its first use in the treatment of diabetes in the early 1920s, progress was slow, especially towards effective treatments for the many serious complications accompanying the disease. In recent years, advances in diabetes research have led to better ways to manage diabetes and treat its complications. It has been recognized that there are two major forms of diabetes: Type I, or insulin-dependent diabetes mellitus, that commonly begins in childhood, and the more common Type II, or non-insulin-dependent diabetes mellitus that appears during adult life. Examples of advances to control these forms of the disease include: new forms of purified insulin, such as human insulin produced through genetic engineering; better ways for doctors to monitor blood glucose levels and for people to test their own blood glucose levels at home; development of external and implantable insulin pumps that deliver insulin, replacing daily injections; better ways of managing diabetic pregnancies; new drugs to treat Type II diabetes and better ways to manage this form of diabetes through weight control; laser treatment for diabetic eye disease, reducing the risk of blindness; evidence that intensive management of blood glucose substantially reduces microvascular complications of diabetes such as eye, kidney, and nerve damage; and demonstration that antihypertensive drugs called ACE inhibitors prevent or delay kidney failure in people with diabetes. Still, diabetes is a leading cause of chronic ill-health and mortality in this country, and definitive therapies continue to elude us.

The partially successful efforts to control the AIDS pandemic, even in the absence of an effective vaccine, has depended heavily on epidemiological, behavioral, and pathophysiological, as well as basic viral and immunological research. Recent advances with anti-viral drugs and immune augmentation have been strongly influenced by methods to measure virus levels accurately in the blood of infected patients, showing that the treatments are capable of rapidly reducing virus levels and that virus levels are indicators of beneficial effects on well-being and longevity in clinical trials. Clinical research has also played important roles in the definition of the many manifestations of this new disease, development of improved therapies for its complications (including opportunistic infections and unusual cancers), and recent studies of genetic resistance to HIV infection and AIDS that results from mutations in newly-discovered genes encoding viral receptors.

What are the clinical research opportunities of the future?

Medical research has visibly transformed the practice of medicine over the past fifty years, but even greater benefits may be possible in the next fifty years, if we are positioned to capitalize on the many profound developments that have recently occurred in fundamental science---especially in genetics, structural biology, molecular and cell biology, computer science, and imaging technologies.

Studies of the human genome---and the genomes of many other organisms---hold great promise for approaches to medicine not even imagined a decade ago. The complete DNA sequence of human beings will make it possible to define a unique signature for every gene. This situation has already been achieved for several bacteria and yeast, providing new opportunities for combating infectious diseases and understanding fundamental cell processes. Rapidly evolving technologies, comparable to those used in the semi-conductor industry, will allow scientists to build detectors that trace hundreds or thousands of these gene signatures in a single experiment. Scientists will use the powerful new tools to reveal the secrets of disease susceptibility and the mechanisms by which diseases develop, create broad new opportunities for preventive medicine, and even provide unprecedented information about the origin and migration of human populations.

In the last two decades, we have learned that genetic changes lie at the root of all cancers. We are now working to identify all of the genes responsible for the establishment and growth of cancer. To be able to peer into a single cell and read its molecular signature will allow researchers to determine what is different between a normal cell and a cancer cell and will lead to the development of highly specific, sensitive molecular markers for cancer detection. These findings will provide the clinical tools for determining, at the earliest possible stage of cancer development, those tumors that will respond to therapy, which therapies they will respond to, whether a particular cancer will grow quickly or slowly, and whether or not it will metastasize.

Advances in high performance computing are revolutionizing the practice and teaching of medicine. Perhaps one of the most fascinating examples of this is the Visible Human Male and Female, the world's first "computerized cadavers." Detailed images of the bodies of a male and female who donated their bodies to science have been compiled into a computer database, providing complete, anatomically detailed, computer-generated 3-D representations of the human body. More than 850 licensed users have developed remarkable applications for the data, as well as technologies to create Visible Human-like representations of live patients. Doctors can now practice procedures on surgical simulators. Non-invasive cancer screening techniques, such as virtual colonoscopy, are being developed, which may eliminate the need for costly, uncomfortable invasive procedures.

Imaging technologies also promise to change the way we diagnose disease and follow responses to innovative therapies, replacing more costly and invasive approaches. For example, because atherosclerosis and congestive heart failure (CHF) develop over decades without symptoms, their true prevalence is unknown, and identification of those at greatest risk of myocardial infarction, stroke, or overt CHF has yet to be achieved. We also do not yet know the events leading to atherosclerotic plaque rupture and loss of cardiac muscle function in CHF. Noninvasive cardiac MRI techniques can already image coronary arteries, map blood flow through the peripheral vascular system, and measure cardiac wall strain with accuracy approaching, or equal to, now standard methods, echocardiography and coronary angiography. Use of MRI imaging in large population studies may reveal pathways of progression from presymptomatic to overt disease, gender and racial differences in disease progression, and biological markers of imminent risk. Equally dramatic changes are occurring through the use of new imaging devices in the study of diseases of the brain, including the neurodegenerative disorders of aging, multiple sclerosis, psychiatric illnesses, drug abuse, and trauma.

Accelerated methods for studying the three-dimensional structure of proteins, including those proteins that serve as targets for drugs against disease, are likely to have profound effects on approaches to drug development in the public and private sectors. Rational drug design has already influenced the production of the protease-inhibitors used in the treatment of HIV infection. A firm understanding of disease mechanisms and well-designed clinical trials will be required to reap the benefits of these coming changes in therapeutics.

Advances in biomaterials and bioengineering also offer new health improvements in the near future in the form of artificial tissue and organs, devices for monitoring disease, and new methods for delivering therapies. For example, scientists are developing a promising new drug delivery system---tiny, drug-filled beads that, when administered orally, stick to cells in the digestive tract and slowly degrade to release the drugs into the bloodstream. The beads may one day be used for the oral administration of drugs that are currently given only by injection and could be used to deliver a wide variety of substances, including DNA-based vaccines, cancer chemotherapy, hormones, and gene therapy.

The take-home message is simple: every one of these advances and opportunities they engender are dependent on a sustained and heightened clinical research effort.

What are the barriers to effective clinical research?

Despite these extraordinary past successes and remarkable future opportunities, clinical research in this country appears to be threatened by several factors, some relatively new and some recognized for more than a decade.

The recruitment, training and sustenance of clinical investigators, especially of physician-scientists, are prominent among the long-term problems. Medical students and young physicians in training continue to show a high interest in research careers, with 26.6 percent of respondents to a 1996 Association of American Medical Colleges-sponsored survey of medical students indicating their intended first career choice was a full-time academic appointment with research involvement. Despite this abiding interest, the recruitment of young investigators is hampered by the large debt burden borne by recent graduates, by the difference between incomes of clinical investigators and those of colleagues who have chosen to enter private practice, and by the perception that there is a high rate of failure in clinical research careers, due in part to the difficulty of obtaining financial support for research proposals. Clinical investigators also report a discrepancy in academic advancement between those who enter clinical research and those entering basic research, where accomplishments in the laboratory tend to come sooner and are often held in higher regard by academic promotion committees. Clinical research suffers from an insufficient number of clinical research-specific training programs nationwide, particularly those that incorporate formal, didactic course work in areas such as protocol design, statistics, medical ethics, and regulatory issues. Finally, there is also a need for more successful clinical researchers who can serve as role models for their successors.

Clinical research has also been made more difficult by the advent of managed care. Because of the costs of conducting research and the need to serve indigent patients, academic health centers (AHCs) typically charge higher fees than their non-academic counterparts. In an effort to reduce costs, managed care organizations are thus generally reluctant to refer patients to AHCs, and when they do, they typically pay only a limited portion of the costs of providing care. The resultant reductions in clinical income has led to increased pressures on research faculty to turn their attention away from research and to bring in clinical revenues. The end result of this spiral of change is a decrease in the infrastructure and personnel to conduct clinical research, a consequence little recognized by the American public. This trend has recently been documented by a study showing that AHCs, in areas with the greatest growth of managed care, have been adversely affected in the competition for NIH research grants.

Finally, further medical progress requires a sound and modernized physical infrastructure. Accordingly, continuing investment and support in such infrastructure elements as new buildings and refurbished facilities, and state-of-the-art instrumentation and information technology must be a key component of the Nation's overall strategy for sustaining its capacity for world class health research. There is substantial evidence that the research infrastructure is eroding in many research arenas, including clinical research.

What methods are being used by the NIH to evaluate the status of clinical research?

Over the past four years, the NIH has been attempting to define the problems that afflict clinical research and to develop a program for alleviating them. We have also benefited from the views of other organizations and individuals. (For example, long-standing concerns about the number of individuals pursuing careers in clinical investigation prompted the Institute of Medicine (IOM) to initiate a study in 1991 to address career paths for clinical investigators, leading to their important and useful report, "Careers in Clinical Research: Obstacles and Opportunities" in 1994.) One of my first actions as NIH Director was to appoint Dr. Lawrence Shulman, a former NIH Institute Director, to serve as my emissary for clinical research and to seek the opinions and suggestions of those investigators who are actively engaged in clinical research. A panel headed by Dr. Gordon Williams from Harvard Medical School was convened to examine the review of applications for clinical research grants as performed by the NIH Division of Research Grants (DRG). In l995, I established The NIH Director's Clinical Research Panel, which includes representatives from major U.S. medical centers and private industry and is chaired by Dr. David Nathan, President of the Dana Farber Cancer Center. The Panel was charged with broad responsibilities to review the status of clinical research in the United States and to make recommendations to improve its effectiveness. I asked the Panel to examine many specific aspects of clinical research, including its financing and the roles of the General Clinical Research Centers (GCRCs) and the Warren Grant Magnuson Clinical Center (CC) at the NIH, as well as the recruitment and training of clinical researchers and peer review of clinical research. (The Panel has made a number of recommendations, and we are already implementing many of them.) To define the needs of clinical research in the context of specific diseases, I have stimulated the development of workshops, conferences, and panels centered on certain clinical problems. Prominent among these meetings have been workshops on Parkinson's disease, autism, diabetes mellitus, and spinal cord injury.

Clinical research and training in the NIH intramural program

A crucial component of our campaign to enhance the Nation's clinical research enterprise is focused specifically on the NIH intramural activities, as carried out principally within the Clinical Center (CC). For 40 years, the CC has been the embodiment of the NIH mission to improve the Nation's health through medical research. It provides a critical venue for the translation of basic research into clinical practice and vice versa. It has traditionally drawn patients and clinical trainees from all over the world who come for the study and treatment of myriad diseases and disorders, ranging from chronic infection, metabolic diseases, and cancers to rare hereditary diseases. Unlike most of the AHCs at which most extramural clinical studies are conducted, the NIH intramural program is not directly threatened by recent changes in provision of health care that limit recruitment of research subjects and make clinical research programs unaffordable. As a result, clinical research within the NIH intramural program will likely become even more important to the Nation than it has been in the past.

The most visible evidence of our efforts to renew the intramural clinical research effort is the recently initiated construction of a new facility, the Mark O. Hatfield Clinical Research Center (CRC), to replace many components of the existing CC, whose physical deterioration has been well documented. Support from the Administration and Congress has provided the funds that allow us to proceed with the detailed planning and construction of the CRC. The CRC will encompass a state-of-the-art research hospital with 250 beds, 100 day hospital stations, allied clinical facilities, and adjacent research laboratories for work that is closely intertwined with clinical activities, a traditional strength of the existing CC.

The prospect of a new CRC has re-energized clinical investigation at the NIH. Governance of the existing CC is benefiting from a thorough evaluation of its administrative practices, carried out in 1996 by a team of intramural and extramural experts, led by Dr. Helen Smits, then Deputy Administrator of the Health Care Financing Administration. I have also initiated efforts to ensure that the intramural program continues to recruit, retain and train the best clinical researchers. I appointed an NIH Committee on the Recruitment and Career Development of Clinical Investigators in order to review the current status of intramural clinical research activities on the NIH campus. That committee's recommendations indicated that increased resources should be made available for clinical research, and suggested that improvements in tenure and promotion procedures be instituted to support clinical investigators. It was also recommended that more clinical researchers serve on the Boards of Scientific Counselors and on ICD Promotion and Tenure Committees. These recommendations are being implemented by a Clinical Research Revitalization Committee, composed of Scientific and Clinical Directors and clinical investigators.

The CC is pioneering the use of information and telemedicine technologies to increase the pool of care providers available to participate in clinical research, especially clinical research protocols. Two telemedicine suites are currently under development at the CC with the potential to create a "virtual clinical research center" at the NIH. This would link rural communities to the CC and major academic centers throughout the country. Thus, with over 900 active clinical research protocols sponsored by the various ICDs, and an additional 250 collaborative research protocols, the CC is using telemedicine for patient recruitment, for patient follow-up, and for new collaborations with primary-care investigators in remote locations. Finally, in order to enhance intellectual exchange among medical centers, selected CC Grand Rounds are now televised live to more than 50 medical centers nationwide, and remote participants may phone in during the question-and-answer sessions.

Historically, the CC has also been profoundly important to the continued supply of new clinical investigators, especially physician-scientists. In fact, many--perhaps most--of today's stars in extramural clinical research trained at some point in their careers in the NIH intramural program. The CC, with its large number of studies and physicians from specialty areas, is also in a strong position to supplement ongoing efforts at some AHCs to recruit and train clinical investigators. To that end, two years ago the CC initiated a new curriculum in clinical research for physicians, physician assistants, nurses, and Ph.D. scientists, open to both intramural and extramural investigators. The syllabus for the course will be placed on the World Wide Web soon and a textbook is under development. Finally, in response to an innovative recommendation by the Clinical Research Panel, the NIH has initiated a new program to bring medical students to the NIH CC for one or two years of intensive training in clinical research. Over eighty students responded to the initial advertisement, and the ten students selected are already at work on the NIH campus. We hope to expand this program if it continues to prove successful, and we anticipate that it may serve as a model for use at several AHCs around the country.

Training of clinical investigators at extramural sites

The changing frontiers of medical science require a continuing supply of personnel from many disciplines, prepared to understand the implications of current discoveries and to apply them to future clinical research opportunities. Some of our efforts to accomplish these goals in the NIH intramural program are described in the preceding section. A wide variety of programs designed to develop the careers of clinical investigators through our extramural activities have also long been part of the NIH fabric.

Today, we must train more clinical investigators, but, more importantly, we must train them better. We must attract talented people to the challenges of clinical research and then provide them with the critical skills that will enable them to perform first-class clinical research. Unfortunately, it is not always easy to know which programs work well. Training programs, by definition, take many years to bear fruit and thus, years to gather the critical mass of data that permits adequate assessment. Nevertheless, NIH is committed to steps that we believe are likely to strengthen research training and career development and to ensure the recruitment of investigators from many disciplines, as well as under-represented groups, into clinical research. To these ends, NIH is mounting a multifaceted approach, one that involves the re-emphasis, modification, and expansion of existing programs as well as the design of new programs to meet specific needs.

This effort must span a variety of fields of research and encompass a broad range of clinical scientists, including Ph.D. students and recipients who are primarily laboratory-oriented, but also interested in the mechanisms of human diseases, and M.D.-Ph.D graduates of our highly successful Medical Scientist Training Program. Several training programs focused specifically on young clinicians will be expanded. We will encourage AHCs to organize existing resources into high quality training experiences in clinical research in order to attract an increased number of highly motivated candidates. Institutions will need to build strong clinical research programs by attracting faculty who have the didactic and research talents necessary for training clinical researchers. It is expected that such programs would recruit clinicians into a patient-oriented research fellowship either at the end of their general medical or surgical training or during the research fellowship portion of their subspecialty training. Individual training positions will also be expanded to provide three to five years of support for physicians and dentists who wish to engage in a period of closely supervised clinical research career development. Candidates for these programs generally will have completed their general residency and be ready for a research training experience.

A key feature to these training initiatives is the emphasis on a didactic portion that will ensure that the clinical investigator is well grounded in research design, data management and analysis along with issues of protection of human subjects and confidentiality of records. We must prepare this coming generation of clinical researchers to be competitive in seeking research grant support and be fully aware of the complexity of conducting sound clinical research.

The NIH's distributed network of 74 General Clinical Research Centers (GCRCs), usually located at academic medical centers across the country, play a key role in clinical research by providing both the infrastructure for the support of inpatient and outpatient research and effective sites for training and junior career development in clinical research. The purpose of the GCRCs is to support the clinical research infrastructure for investigators who receive their primary research support from the other components of the NIH, other Federal and State agencies, and the private sector. In FY 1995, the research support provided by various NIH components to nearly 8,000 GCRC-based investigators exceeded $1 billion.

Within the academic institutions, the GCRC staff--through their professional activities in clinical research, experimental design, nutritional and nursing support, biostatistics, ethics, computer systems management--provide a focal point for training medical students and fellows, as well as updating experienced faculty in new developments in clinical research. Spread across 30 states, the GCRCs provide support for individuals through general and minority clinical associate programs. These programs provide a way for junior faculty to pursue a mentored research training experience. In some institutions, formalized GCRC lectures have attracted large audiences of medical professionals, while in others, more detailed curricula have been provided for preselected students for intense immersion in subjects related to patient-oriented research and clinical research trial design. In some institutions, such career development opportunities lead to advanced degrees in areas of specialization.

Finally, training in the ethics of clinical research deserves special attention. NIH is working with other agencies to issue an announcement for applications for individual post-doctoral support and a short-term institution-based program for scientists who want to specialize in bioethics. Training programs may address community involvement in research protocols, informed consent, privacy of records, and other topics, including issues related to minority patient populations and minority researchers.

Loan repayment

Most medical and dental students have accumulated considerable debt by the time they have finished their training. This debt burden poses a real barrier to young physicians and dentists interested in pursuing research careers. This is particularly true for under-represented minorities. Currently, NIH has authorization for loan repayment programs in the intramural research program, and we operate three such programs. These include the AIDS Loan Repayment Program, which supports medical professionals carrying out AIDS research and patient care at NIH; the Clinical Research Loan Repayment Program, which supports financially disadvantaged and under-represented minorities at NIH; and the General Research Loan Repayment Program, which largely supports senior post-doctoral fellows and individuals recently recruited to tenure-track positions. In general, these programs pay up to $20,000/year of educational debt and taxes. Programs last for two to three years and are renewable in some cases.

In conjunction with entry level research training programs, the NIH loan repayment programs have served as important tools for recruiting high quality candidates for careers in clinical investigation. Expansion of the loan repayment programs to extramural institutions, as recommended by many observers including my Clinical Research Panel, would require a legislative change.

Review of Clinical Research Applications

The clinical research enterprise, like all research areas, is dependent on the fair and equitable review of applications submitted to the NIH. The majority of the clinical trials and much of the other clinical research is reviewed within the Institutes and Centers. This ensures that these applications are reviewed by groups specifically constituted for a single review task and all members are likely to be skilled at reviewing clinical projects. The remainder of the reviewing responsibilities for clinical research applications resides in the Center for Scientific Review (formerly the Division of Research Grants), which provides reviews for most unsolicited research projects of all types at the NIH.

In its analysis of DRG's efforts to review applications for clinical research grants, the Williams Committee noted that the success rates for such applications were likely to be lower than expected when considered by a review group that does not see a high volume of clinical applications. To address this concern, Dr. Elvera Ehrenfeld, the newly appointed Director of CSR, has made the issue of the review of clinical research a major focus. She has met with representatives of numerous clinical professional societies, the Association of American Medical Colleges, and medical school deans and clinical department chairs. She has recruited Dr. Michael Simmons, a distinguished clinical investigator, to serve as a liaison with the extramural clinical research community. Drs. Ehrenfeld and Simmons have also met with directors and staff of each involved Institute to discuss this issue and potential solutions.

CSR will soon experiment with some new special emphasis panels--one, with a core of members expert in clinical trial design, execution, and evaluation, for review of applications to conduct clinical trials, and others to review clinical applications that are currently reviewed in study sections with a low density of clinical applications. To further ensure equitable review for investigators applying for clinical research grants, an experienced reviewer of clinical research will be available to provide guidance to study sections with a low proportion of clinical applications.

The impact of managed care

AHCs remain responsible for the lion's share of our national biomedical research effort and stand uniquely poised to transfer basic research knowledge into improved medical therapies. With changes in health care delivery, collaborations between managed care and AHCs have become increasingly important. For such collaborations to succeed, the leaders of the managed care industry and the companies that purchase such care for their employees must be persuaded of the importance of medical research to clinical practice. Experience shows that high quality health care and research go hand-in-hand, and organizations that conduct research are generally viewed as providing the best care. As collaborative ventures between managed care companies and academia proliferate, both partners stand to benefit, with a health dividend for all Americans.

A number of activities under way at the NIH are focused on strengthening ties between managed care and academia, and fostering a better understanding between these communities. Over the course of this past year, I have established a productive dialogue about clinical research with a number of potential partners, including representatives of managed care organizations (MCOs) and member groups of the American Association of Health Plans (AAHP). To act as a liaison among NIH Institutes, AHCs, and MCOs, I initiated an NIH Fellowship in Managed Care, currently filled by Dr. Edward Wagner, a physician-scientist from the Puget Sound Health Plan. I have also established an NIH Managed Care Workgroup, comprised of representatives from each Institute and Center, which will serve as a central resource for coordinating collaborative efforts with the managed care community. The Workgroup will share strategies employed by various ICDs, develop proposals for grass-roots experiments in clinical research, and design innovative approaches for linking AHCs with managed care partnerships. One model of a successful partnership, announced this past year, was developed between the National Cancer Institute (NCI) and the Department of Defense (DoD), permitting beneficiaries of DoD's health benefits program access to NCI-sponsored clinical trials. This agreement should have the dual advantage of increasing the quality of health care for DoD employees, by providing them with promising cancer therapies, and helping to secure an adequate supply of patients for NCI's clinical trials. Similar partnerships have been negotiated between the NCI and the Department of Veterans Affairs and between the NHLBI and the Health Care Financing Administration.

This past July, the Board of Directors of the AAHP, with over 1000 member organizations, adopted a new policy intended to encourage health plans to permit their beneficiaries access to NIH-sponsored clinical trials. The Board indicated that plans participating in clinical trials should consider covering the routine patient care costs incurred during the course of those studies. A joint NIH-AAHP negotiating team will convene next month to develop a consensus regarding the central working principles underlying this arrangement. We look forward to achieving the benefits to clinical research that these developments promise. Earlier this summer, I also held an introductory meeting with purchasers of health care--the representatives of those large companies that employ significant numbers of Americans and pay for the health care benefits their employees receive--to discuss the value of research in the continuum of first-rate medical care. >

Partnerships with industry

Clinical research activities sponsored by the NIH have traditionally required close relationships with the pharmaceutical and biotechnology industries. NIH trains many of the people who work in those industries, NIH-supported basic research commonly serves as the point of departure for the development of new products by industry, discoveries in the public and private sectors are frequently exchanged through technology transfer agreements, and financial support of research flows in both directions (with NIH providing funds to industry through Small Business Innovation Research and Small Business Technology Transfer grants and industry providing resources to intramural NIH investigators through Cooperative Research and Development Agreements and to our extramural investigators through sponsored research agreements).

The relationship between NIH and the pharmaceutical industry is of particular importance for clinical research because of shared interests in the training of pharmacologists and chemists, in the design and conduct of clinical trials, and in the discovery of new therapeutic agents. This summer I met with representatives of several large pharmaceutical companies to discuss some of these issues and to explore ways in which NIH and the industry can work more effectively together. To this end, NIH will soon convene a series of collaborative forums, with representatives from government, industry, managed care organizations, and academia, to discuss the training of clinical pharmacologists, new methods for drug evaluation and drug development, and the conduct of clinical trials.

Outreach

NIH is also expanding its efforts to educate the public about the crucial importance of clinical research for the future health of the Nation. It is clear that both the public and policymakers, as well as State and local governments, need to be kept aware of the health and economic benefits of research as a public good. I have sought means to enhance communication of NIH activities more broadly to patients and their families, to traditional providers, and to the health care plans where more than half of all Americans now receive their health care. The NIH World Wide Web site, which includes sites for each Institute, Center and Division, contains a wealth of information about various activities, including interim reports from the Panel on Clinical Research. Efforts are under way to establish a web site that will provide public access to a more extensive database of NIH-supported clinical research protocols staged at all extramural sites. I anticipate that these web sites will enhance public knowledge about advances in research, stimulate participation in NIH-supported clinical trials, and accelerate the translation of research findings into widespread medical practice.

Conclusion

In this testimony, I have attempted to describe some of the many new initiatives that the NIH has launched in the past few years to sustain and re-invigorate the Nation's clinical research efforts. It is essential that today's remarkable laboratory findings--findings that reflect decades of Federal research investment--be translated into improved diagnosis, treatment, and prevention of disease. Through activities of our intramural and extramural programs and through exercise of our leadership in the medical research community, we intend to expand our partnerships with AHCs, universities, pharmaceutical and biotechnology industries, and health care providers. We pledge to use these partnerships to ensure that the infrastructure to support clinical research and its training programs will provide the American people with those extensions of "biological discoveries to clinical settings" that are required to achieve our traditional goal: improved health through science.

I would be pleased to answer any questions you may have.