Robert M. Nerem, Ph.D. (Chair), Kenneth D. Taylor, Ph.D. (Vice-Chair), Frances Arnold, Ph.D., Shu Chien, M.D., Ph.D., Peter G. Katona, Sc.D., Candace Littell, William D. Young

NIH is the major federal sponsor of bioengineering research, with total expenditures of over $300 million in fiscal year 1993. Less than $80 million of this, however, is dedicated to basic research. Such research, which concentrates on concepts and technologies rather than on specific diseases, is an essential ingredient for advancing health care and bringing innovations and new medical technologies to market.

To ensure that limited governmental funds for basic bioengineering research are spent in an optimal manner, the following five recommendations are made.

Recommendation 1 : NIH should establish a central focus for basic bioengineering research. This central focus should be at the highest level and should include resources for the collaborative support of extramural research.

Recommendation 2: The NIH should significantly expand representation of the medical and biological engineering community on advisory groups and in the peer review process.

Recommendation 3: NIH should establish an intramural bio-engineering research program. This program would focus on cutting-edge research of national significance that complements ongoing intramural and extramural programs.

Recommendation 4: Communication and cooperation should be enhanced among governmental agencies with significant research activities in health-related bioengineering.

Recommendation 5: The public sector should increase efforts to foster greater private sector participation in determining basic research needs and in facilitating technology transfer.

With increased commitment and effective cooperation among governmental agencies and with industry, our country's investment in bioengineering will continue to yield important advances in health care through technology, while containing healthcare costs. The recommendations presented here are directed at not only maintaining our current edge over other countries, but widening that lead. The ultimate outcome will be improving the health and welfare of our fellow citizens and maintaining U.S. leadership in the worldwide marketplace.

1. Introduction

The External Consultants Committee met six times between November 1993 and May 1994, including two telephone conference calls. The committee also arranged two focus group meetings, one with representatives from industry and the other from academia. The process culminated with a workshop on April 21- 22, 1994, to which more than 100 individuals were invited. The workshop allowed time for three smaller breakout groups to meet and develop specific recommendations for the External Consultants Committee. This report is an outgrowth of this workshop and the deliberations of the Committee.

The next section of this report describes bioengineering and how research in this field is improving health care in the United States. Section 3 discusses the role of bioengineering research in helping the United States maintain its leadership in health care technology. Section 4 reviews an NIH inventory of the current investment in bioengineering research in the United States. Finally, Section 5 presents the recommendations of the External Consultants Committee.

2. Bioengineering and Its Benefits to Society

For the purposes of this report, bioengineering refers to a discipline that uses engineering principles and quantitative methods to improve human health. (The report does not deal with other areas of bioengineering, such as the development of high-yield agricultural processes, that do not address the prevention, diagnosis, or treatment of disease.) Bioengineering spans the spectrum from basic research to the development of processes and products.

Basic research in bioengineering advances knowledge at the genetic, molecular, cellular, tissue, organ and system levels through the use of engineering principles and methods. Such knowledge is a prerequisite for the prevention and conquering of disease. Basic bioengineering research also seeks methodologies that enable the development of novel biologicals, devices, materials, processes, and systems. It concentrates on concepts and technologies that are generic, rather than being oriented toward any specific disease, product, or device. It includes the advancement of knowledge in the basic engineering sciences, e.g. materials science and engineering, robotics, and information science, as they relate to basic health care technologies.

Once the basic methodologies are available, applied research adapts the technologies to solve specific health problems. Bioengineering research, basic and applied, thus includes such areas of activity as artificial organs, bioinst rumentation, biomechanics, biomaterials, bioprocess engineering, cellular bioprocessing, clinical engineering, medical informatics, rehabilitation engineering, tissue engineering. The fruits of bio-engineering research are improved heath care and restoration of function to those with physical impairments.

While technology has been primarily utilized for improving the quality of care, it is clear "that the appropriate use of technology can also contribute to the containment of health care costs. Replacing invasive procedures with noninvasive ones, delivering care at home rather than in the hospital, and allowing the disabled to lead a productive life are examples where technology is part of the solution to escalating health care costs.

Universities started to establish bioengineering departments in the 1960s; since then the field has undergone enormous growth. Twenty-one universities now have accredited undergraduate bioengineering programs; a number of other institutions offer courses at the undergraduate level. More than 40 universities offer formal graduate programs; another 40 conduct research or teach graduate courses in bioengineering. In 1993, 147 Ph.D. in bioengineering were awarded. lt is estimated that at least an equal number of doctorates were granted through more traditional engineering departments based on bioengineering doctoral research. There are more than 20,000 bioengineers working in universities, hospitals, and industry in the United States. There are at least 30 professional bioengineering societies and an equivalent number of journals in the field.

3.Maintaining the Nation's Leadership in Health Care Technology

Generally, the academic community devotes significant resources to basic research, thereby adding to the body of scientific knowledge and discovering novel scientific knowledge and discovering novel techniques and approaches. These discoveries are typically refined and transformed into nascent products by small start-up companies, which eventually pique the interest of larger companies. Larger firms in general then devote the necessary resources to navigate the regulatory maze, complete product development, and manufacture and distribute the product.

The funding of research and development differs significantly between the various entities. Basic bioengineering research, primarily performed by the academic community, is funded largely by the government. Applied research and development are performed primarily by the private sector. Small start-up companies typically raise funding from nontraditional sources such as venture capital investors, while larger companies typically obtain funding through more traditional investment channels such as their own ongoing product sales, the stock market, and commercial banks.

The U.S. healthcare technology industries have built a leadership position in the worldwide healthcare technology products market, with 49 percent of the global production in 1993. Growing industry exports have led to a $4.6 billion trade surplus. Commitment to basic bioengineering research, coupled with an environment that is supportive of technology transfer and commercialization, was instrumental to achieving this success.

The ability of U.S. industry to maintain its preeminence in the global market will be a function of dealing with many difficult issues. One essential ingredient is steadfast support for basic bioengineering research, which is critical for the spawning of new technologies. Industry looks to the federal government to support basic research, not only as a source of new ideas, but as part of training the workforce required by the commercial sector. Active government support of basic bioengineering research, and enhancing research and technology partnerships, are imperative for bringing innovations and new medical technologies to market.

The increasingly stringent U.S. regulatory environment can adversely affect the private sector's ability to commercialize basic research results. The regulatory climate and uncertainty about healthcare reform have resulted in the tightening of criteria by venture capital investors, affecting mainly small start-up companies. The litigious legal environment provides a disincentive to invest in new technologies and has led to an alarming recent shortage of materials used in implantable medical devices. A U.S. tax law that provides financial incentives for manufacturing in foreign countries promotes the relocation of research and product development as well.

In response to these environmental forces, companies are increasingly forming alliances with foreign institutions. In a recent survey of medical technology companies, one third of those responding indicated that they were moving manufacturing facilities to other countries. Close monitoring of these developments will be necessary to determine the extent to which they will affect future innovations and ultimately the U.S. leadership in world markets.

4.Current Funding of Basic Bioengineering Research

It has not been possible for the Committee to verify the reported figures. Agencies may interpret definitions differently and it is unclear whether the responses have been prepared using a uniform interpretation. lt is recommended that future inventories ask that bioengineering research be classified into different categorical areas. This would provide a more comprehensive view of the different agencies, help in the identification of voids in research funding, and also would allow at least partial verification of the reported figures.

The government-wide total support for bioengineering has been reported to be just under $500 million. Less than one third of this is for basic bioengineering research. The three lead organizations in the support of basic bioengineering research are the NIH, NSF, and The Whitaker Foundation, a private foundation. NIH by far provides the most support for bioengineering research: more than $300 million in FY 1993. Yet less than $80 million of the total, or 25 percent, was directed towards basic research. This is out of line with NIH as a whole. Across the board, NIH devotes 60 percent of their funding to basic research.

NSF provided $15 million in FY 1993, $10 million of which was for basic research. Within the non-profit private sector, the Whitaker Foundation stands out in its commitment to biomedical engineering. In 1993, its total support of bioengineering research was $23 million, including $14 million for basic research.

The total support for basic bioengineering research provided by federal agencies and The Whitaker Foundation should be considered in the context of an estimated $3-5 billion in support from the commercial private sector for applied research and development. The leverage of research is extraordinary since the gross revenue of the bioengineering industry, i.e. the private sector involved with manufacturing health care products, already exceeds $40 billion

.

The funds devoted to basic bioengineering research are relatively small, and the Committee is further concerned that these limited funds may not be spent in an optimum manner. There seems to be little coordination among the federal agencies, and even within the NIH, there is no coordination of the bioengineering activities scattered among its Institutes. For these reasons, the following recommendations focus on organizational issues.

5. Recommendations

Recommendation 1: NIH should establish a central focus for basic bioengineering research. This central focus should be at the highest level and should include resources for the collaborative support of extramural research.

Justification: Basic bioengineering aims to develop concepts and technologies common to a wide variety of diseases and devices. Consequently, the current disease-oriented NIH structure is not conducive to the support of basic bioengineering research. A central focus for bioengineering at NIH will foster basic bioengineering research that, while not directed to a specific disease, is critical to the translation of advances in basic biology into clinical application and commercializable technology. A central focus will facilitate coordination and cooperation within NIH, as well as with other federal agencies and industry.

The Committee believes that there is great need for a central focus, or a "champion" for bioengineering within NIH. The current fragmentation of bioengineering at NIH is evidenced by considerable difficulty that was encountered in conducting the research inventory. Of particular concern is the lack of mechanisms within NIH to identify and support important bioengineering research needs, particularly those leading to new generic technologies.

As NIH has evolved, a wide variety of organizational forms have been used to provide focus on specific areas of emerging interest. These have included new administrative positions, offices, centers, and institutes. While the Committee makes no recommendation for a specific structure, it believes that the central focus needs to be established at the highest NIH level. lt must be trans-NlH in nature, and it must have resources to provide coordination, facilitation and collaborative support of extramural bioengineering research within the Institutes and Centers. That this can be accomplished is illustrated by the recently established Office of Research on Women's Health.

Recommendation 2: The NIH should significantly expand representation of the medical and biological engineering community on advisory groups and in the peer review process.

Justification: Only 36 study section members out of a total of 1,650 are bioengineering researchers. Twenty-two percent of bioengineering proposals require ad hoc or special review, compared to less than 5 percent NIH-wide. Substantially increased representation of bio-engineering researchers on study sections wilt improve the quality of the review process for bioengineering and other technologically related proposals. This in turn will improve the quality of funded research, while reducing the burden of special study sections. lf there were to be a restructuring of study sections at NIH, this could provide the opportunity for implementing a more appropriate framework for the review of bioengineering research proposals.

In 1993, 320 individuals served on NIH senior advisory councils, participating in the formulation of research policies. Only two of these individuals could be identified as bioengineering researchers. The number of bioengineers on advisory councils should be expanded, and should include engineers and researchers from both academia and industry.

Recommendation 3: NIH should establish an intramural bioengineering research program. This program would focus on cutting-edge research of national significance that complements ongoing intramural and extramural programs.

Justification: While the extramural research community is developing programs in bioengineering, at the NIH there is no intramural program in bioengineering that would complement its intramural research in the life and clinical sciences. Not only does science drive technology, but technology also drives science. Thus, improvements in materials, measurement techniques, and information technology are often the key elements that result in revolutionary advances in the biological sciences.

Currently there is a lack of any commitment by NIH to an intramural bioengineering research program. The only identifiable intramural biomedical engineering activity is the Biomedical Engineering and Instrumentation Program (BEIP) of the National Center for Research Resources. This program, organized along traditional engineering disciplines, is the Outgrowth of what has been primarily a service activity, and it is funded by a tax" on the other institutes and centers. In its present form BEIP does not represent the type of intramural research program envisioned by the Committee; however, BEIP does contain several outstanding researchers who could form the core of such a program.

The Committee recognizes that there is considerable pressure to reduce and reorganize existing NIH intramural programs. A reorganization may provide an unusual opportunity to establish an intramural research program in bioengineering, where world-class researchers would focus on problems of special interest to the life science and medical community. The result could be a unique research environment available nowhere but the NIH.

Recommendation 4: Communication and cooperation should be enhanced between governmental agencies with significant research activities in health related bioengineering.

Justification; The inventory of health-related bioengineering research shows broad participation of various governmental agencies. lt is highly desirable for these agencies to form information linkages to exchange data on programs and their progress, as well as to identify unmet needs. Furthermore, a standing committee of agency representatives should be formed to further enhance cooperation between their agencies, and to provide a means of establishing personal contacts that could lead to further interagency collaboration. Such a committee could be a subcommittee of one of the existing National Science and Technology Council (NSTC) Committees (e.g. the Committee on Health, Safety and Food). This would give such a committee the stature needed to be effective.

Possible benefits of interagency coordination and cooperation include optimizing the use of resources, identifying important areas not being funded or which are underfunded, and developing joint new initiatives. Currently, there are isolated examples of the potential effectiveness of such interagency interactions. These include a joint program of the National Heart, Lung, and Blood Institute (NHLBI), and the National Science Foundation (NSF) on "Cardiovascular Device-Centered Infections." Additional joint programs are being discussed, NIH and NSF also have held a joint Workshop on Tissue Engineering, and have co-sponsored conferences on this topic. However, there are many other areas into which cooperation could be expanded.

Recommendation 5: The public sector should increase efforts to foster greater private sector participation in determining basic research needs and in facilitating technology transfer. Justification: The private sector commercializes new product innovations made possible by basic and applied bioengineering research. This sector thus has a unique perspective on the direction of basic bioengineering research. Health care technology firms can provide valuable advice that will both improve health care and provide for continued leadership in global markets.

The level of industry input and participation in public sector research efforts is variable. For example, some segments of industry are closely involved in the Advanced Technology Program of the National Institute of Standards and Technology, and industry representatives also participate in groups advising the National Science Foundation. NIH as well as other agencies could benefit significantly from industry input.

Private sector input could be increased through a variety of mechanisms. These include but are not limited to the following: participation on policy-making bodies such as the NIH Advisory Councils; identification of topics for SBIR program research solicitations; and implementation of a public sector outreach program with activities such as periodic mailings to health care technology companies. Such mailings may describe research activities, government participation in health care technology meetings, and collaboration with various groups associated with health care technology companies.

Conclusion: With increased commitment and effective cooperation among governmental agencies and with industry, our country's investment in bioengineering will continue to yield important advances in health care through technology, while containing health care costs. The recommendations presented here are directed at not only maintaining our current edge over other countries, but widening that lead. The ultimate outcome will be improving the health and welfare of our fellow citizens and maintaining U.S. leadership in the worldwide marketplace.

Frances Arnold, Ph.D.
Associate Professor Chemical Engineering
California Institute of Technology
Mail Code 210-41
Pasadena, CA 91125

Peter Katona, Sc.D.
Vice President
Biomedical Engineering Programs
The Whitaker Foundation
901 15th Street, NW, Suite 1000
Washington, D.C. 20005

William D. Young
Senior Vice President
Manufacturing and Process Sciences
Genentech, Inc.
460 Point San Bruno Boulevard
South San Francisco, CA 94080

Kenneth D. Taylor, Ph. D. (Vice-Chair)
Vice President
Research and Development
Valleylab, Inc.
5920 Longbow Drive
Boulder, CO 80301

Shu Chien, M.D., Ph.D.
Director
Institute for Biomedical Engineering
University of California, San Diego
La Jolla, CA 92093-0412

Candace Littell
Executive Director
Health Care Technology Institute
225 Reinekers Lane, Suite 220
Alexandria, VA 22314

Liaison Member

Fred G. Heineken, Ph.D.
Program Director
Biotechnology, Bioengineering, and Environmental Systems
National Science Foundation
Arlington, VA 2223