The NIH comprise of more than twenty disease-related, and patient-need focused institutes. There is one further institute of General Medical Sciences (NIGMS). NIGMS supports basic biomedical research that is not targeted at specific diseases, but aims to increase the understanding of life processes. This lays the foundations for advances in disease diagnosis, treatment, and prevention. They dispose of a budget of $13.6 x10⁹ (FY 1998) of which over 80% goes to extramural contracts; most of the rest is spent on their own research laboratories.

There was a poor success rate for proposals involving the engineering community which had no natural route to NIH funding. As a result of this difficulty, a bioengineering consortium (BECON) was established to define, and lay down guidelines for NIH funded bioengineering projects. This has provided the central focus for bioengineering issues at NIH. The membership comprises a senior level representative from each of the interested institutes, centres and divisions.

"Bioengineering integrates physical, chemical, or mathematical sciences and engineering principles for the study of biology, medicine, behaviour, or health. It advances fundamental concepts, creates knowledge from the molecular to the organ systems level, and develops innovative biologics, materials, processes, implants, devices, and informatics approaches for the prevention, diagnosis, and treatment of disease, for patient rehabilitation, and for improving health."

The funding of extramural bioengineering research created some difficulties, together with a low success rate of grant proposals. The main reason identified was that funders and referees required an understanding of the design-driven, technology development approach to research which is significantly different to the hypothesis-driven approach normally adopted in fundamental biological research. This was in addition to the complexity of the field. As each application will have three reviewers, many taken from the Institutes’ own staff, a group of potential reviewers needed to be educated in the validity of the design-based approach. The differences between the two approaches are even greater in the general medical area.

It was important for the NIH to make a response to the 32,000 bioengineers in the American Society of Bioengineering. The problems with peer review outlined above, lead to a difficulty in constituting proper committees. As a result, design-based proposals suffered at the hands of standard biology reviewers. In the programme for tissue engineering, a special review group was constituted, which consisted both design-based and hypothesis-based reviewers.

A further question is how can truly innovative work be funded, and how do funders avoid missing out on the truly novel, whilst reviewers tend to be over protective of their own areas? It was decided to put aside some funds for ‘paradigm-shifting’ ideas, and for this to be administered from the Directors’ office.

Of the 16 existing panels, not one is concerned directly with bioprocessing. However, there are common themes which include bioprocessing, and it was expected that NIH funding would overlap with the NSF eventually. The NIH felt the need to encourage collaboration, and ensure that research was related to patient needs. Therefore, the existing strengths in science needed to be applied to engineering. The desired approach was to boost areas, rather than to cut, but they did not feel that a bioengineering institute was a good idea. It is not anticipated that the number of institutes should grow, despite of some community pressure. It was in this light that BECON was founded, and this may be the right model to be used for other cross-cutting research themes. Such themes are difficult to manage, and NIH currently does not have a good feel for them.

The immediate solution was to find $12m for the financial year 2000 from all of the participating institutes and centres of the NIH, and all groups would conform to a common policy for the evaluation of the proposals. This was in the context of some $420m (1996 figure) used to fund bioengineering research across all institutes. There were 123 proposals, with 33 receiving funding. Both successful and unsuccessful applicants were invited to discuss their work at the launch and will be brought back together after a year or so; this, it is hoped, will help build the community.

Bioengineering areas of particular relevance to the mission of the NIH are identified below; this list is not intended to be exhaustive. It is noteworthy that many of these, but not all are of direct relevance to biochemical and biomedical engineers. Particularly relevant are 2, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 17, which account for over 60% of the areas. Joint programmes exist with other agencies, and bring institutes together in order to acquire a critical funding level (e.g. NSF, DoE, ONR). Shared interests exist (e.g. implant infections) and can lead to a joint call.

Of these, computational science and bioinformatics, imaging and tissue engineering, have been consistently named as significant to the biochemical engineering community.

Two main methods of funding were envisaged for the main call: grants and partnerships. Bioengineering Research Grants (BRG), are typically awarded for three to five years, and are usually awarded to a single group in a single institution. Bioengineering Research Partnerships (BRP) are for multidisciplinary research teams, and are usually for five to ten years. The BRPs must apply an integrative, systems approach to developing knowledge and/or methods to prevent, detect, diagnose, and treat disease and understand health and behaviour. In addition, must include bioengineering expertise in combination with basic and/or clinical investigators. A BRP may propose to undertake design-directed or hypotheses-driven research in universities, national laboratories, medical schools, private industry and other public and private entities.

Rules for the funding of both grants and partnerships are broadly similar, and have specific criteria for evaluation.

A BRP should focus in a significant area of bioengineering research, and develop a long term research plan, to justify a BRP organisation. There are eight main elements which a BRP proposal must demonstrate:

• The plan must be adaptable enough to permit change as the research proceeds.
• Clearly indicate: current activities, why a BRP is necessary, and what unique opportunities will be provided by the proposed BRP.
• Explain the integrative-engineering approach, and why such an approach is essential to the proposed research.
• Provide a tentative timetable for the project.
• Include how the data will be collected, analysed, and interpreted.
• Describe how the data and technological advances will be disseminated to other investigators.
• Describe the rôle of each partner, and how they will be integrated and organised to accomplish the specific aims of the project.
• If relevant, how the technology or information (intellectual property) will be transferred to the commercial sector for product development.

If the proposed BRP research is closely related to on-going research, or an existing centre, the plan must explain how the research activities of the BRP will complement, but not overlap, with existing research.

The NIH review criteria were adapted to ensure that a BRG application was evaluated appropriately. The evaluation should reflect the overall impact that the BRG award could have on the selected area of bioengineering research. This was based on consideration of five criteria, with the emphasis on each criterion varying from one application to another, depending on the nature of the application and its relative strengths. It is important to note that an application need not be strong in all categories to be judged likely to have major scientific impact, and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. The review criteria are:

(1) Significance. If the Specific Aims of the BRG are achieved, will they provide significant advances in the selected area of bioengineering research? Is the research likely to have a significant impact on other areas of research?

(2) Approach. Are the BRG approaches and methods adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

(3) Innovation. Does the BRG propose new approaches or explore new research paradigms or new concepts which will affect bioengineering, basic, or clinical sciences? Are extant approaches or concepts applied to new scientific problems in novel ways?

(4) Investigators. Are the Principle Investigator and key personnel appropriately trained in their disciplines and capable of conducting the proposed research? For partnerships, there are also issues of management and complementarity. Especially important is justifying the cost effectiveness of incorporating distant sites.

(5) Environment. Does the scientific and technological environment in which the work will be done contribute to the probability of success? Does the proposed research take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of other support which will contribute to the success of the research?

In addition to these five review criteria, applicants must demonstrate adequate provisions for the protection of human and animal subjects, the safety of the research environment, and conformance with the NIH "Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research," and the "Policy And Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects."

Dr. Wendy Baldwin, and Dr. John Watson.