examining the proposed budgets. Cost changes for the future noncompeting years of a grant proposal are carefully examined to ensure that these changes reflect scientific need; requirements may differ from year to year depending upon the particular nature of the research.

Mr. Early: What impact will limiting the average increase in the cost per award have for your institute, particularly with respect to clinical research and clinical trials?

Dr. Williams: If individual grant budgets were to be unduly restricted, the cost of the research would have to be spread over a longer time, which would then slow the rate at which research results are obtained and also increase the duration of the studies. Limiting the increase would thus result in extended durations of studies and the potential of incurring extra costs because of limitations of economies of scale.

BIOMEDICAL RESEARCH AND DEVELOPMENT PRICE INDEX

Mr. Early: In general, Doctor, what do you see as the "down side" of using the BRDPI? What is your professional judgment on this?

Dr. Williams: The Biomedical Research and Development Price Index (BRDPI) is calculated to estimate the specific effect economic pressures have had or will have upon the theoretical, typical "market basket" that a biomedical researcher must fill in order to conduct research. Whereas the consumer price index is calculated to reflect aggregate price changes for gasoline, food, clothing, automobiles etc., the BRDPI reflects changes for items such as research chemicals, glassware, investigator salary levels, laboratory animals, etc. The BRDPI has risen faster than other measures of inflation, including the consumer price index.

While I believe that this index should be used as a guide for gauging cost increases associated with biomedical research, use of it should be individually tempered with considerations such as the specific research requirements for the outyears of a particular grant. For example, it is often the case that for applied clinical studies, significant cost increases will occur in the second year of the award because of transition into the patient accrual stage. Other grants may require the purchase of equipment in one year, and not in the other. Thus, while the use of the index is beneficial as a guide, in my professional judgement its use should not overshadow research needs and scientific judgement.

OUT OF ORDER FUNDING

Mr. Early: What is your professional judgment on out of order funding?

Dr. Williams: In my professional opinion, one has to take a balanced view of research need, opportunity, and available resources when making those difficult decisions as to which grants will receive funding, and which ones will not. Certainly, if several grants are judged to be of nearly equal scientific value in light of the NIA mission, and some of these are more costly

than others, I would make funding decisions to harvest the most scientific knowledge possible for the resources invested. Given these circumstances, it is likely that some grants will be funded out of order.

AVERAGE LENGTH OF A GRANT

Mr. Early: What is your professional judgment on shortening the average length of a grant?

Dr. Williams: Again, I believe that a balance must be maintained, weighing the need to provide stable, predictable support for our established investigators with exemplary track records against the need to provide an adequate pool of funds to support investigators, including emergent scientists, who have applied for new or renewal grant support. Specifically in reference to the four year average length of award in the report language, the NIA in 1990 reflected an average length of award of 3.95 years; we plan to maintain this approximate average in both 1991 and in 1992.

PROFESSIONAL JUDGMENT BUDGET

Mr. Early: What was the NIA professional judgment budget and how does it differ from the request before us?

Dr. Williams: In my professional judgment, a budget level of $593.2 million for FY 1992 or $243 million above the President's Request, would allow the NIA to fully capitalize upon recent advances brought forth by our extramural and intramural scientists. This budget was carefully constructed to reflect the real opportunities for aging-related research that should be pursued to accelerate progress in containing the rapidly escalating human and economic costs of mental and physical frailty, disability and long-term care. While our preliminary FY 1992 budget request to NIH was $512.5 million, scientific opportunity, particularly for Alzheimer's diesase research, has significantly grown in a year's time since the developemnt of this preliminary figure. A $593.2 million budget for NIA is consistent with a budget of $1 billion for aging research throughout the Federal government recommended by the Alliance for Aging Research.

These resources would allow the NIA to develop fully our research and research training programs, whose goals are to prevent or cure those disorders such as Alzheimer's disease and physical frailty that produce the greatest need for long-term

care.

For example, if we could simply delay the onset of the cognitive dysfunction from Alzheimer's disease by five years, then we could reduce by half the approximately $90 billion annual cost of the disease. Similar savings would be realized through minimizing or reversing physical frailty; these impairments cost the nation at least $54 billion annually. Amelioration of these conditions is critical if society is to prevent health and economic adversity for a significant portion of its rapidly growing older population.

Of the additional funds above the President's budget, $142 million for research project grants would support a 50 percent success rate for competing applications and funding close to study

section recommended levels. Many high quality research applications which would otherwise go unfunded could now be supported; the pace of all aging related research programs would quicken.

My professional judgement budget for the centers program would add $20 million to support an additional six Geriatric Training and Research Centers, five Claude D. Pepper Independence Centers, two rural health centers, four centers to specialize in aging demographic studies, and two centers to serve as resources for animal model development. Also, the satellite program for the Alzheimer's Disease Research Center would be expanded to extend this outreach program into more underserved rural and minority populations. Our centers programs coalesce scientific and professional expertise and serve as models in the fields of aging research and geriatric medicine.

Support for research training and career development programs is critical to the continuation of advances in aging-related research. In this professional judgement budget, an additional $8 million over what NIA has budgeted within the President's Request would be provided for these programs. A total of 535 NRSA trainees and 142 investigators funded by career awards would be supported by this budget, compared to funding for 395 trainees and 109 investigators in the career program, as provided in the President's budget.

Minority initiatives would receive special emphasis in the professional judgement budget: support over requested levels would more than double for minority supplements to research project grants, minority biomedical research support grants, dissertation awards, and other small grants for minority investigators.

Comparable to increases envisioned for extramural support, NIA's intramural research program would also be bolstered by nearly $11 million and 78 positions to advance more rapidly the pace of research now supported in our own laboratories. For example, we would emphasize research into the relationships between cardiovascular disease and aging, and molecular neurobiological studies of Alzheimer's disease. These and other areas supported by intramural funds pursue research on the cutting edge of the field and yield new insights into both normal aging and disease processes. Increased resources are also provided for the research management and support function to meet the increased demands placed upon the scientific management and administrative function of the Institute.

Pending enabling construction authorization, a $45 million construction program would provide matching funds for the renovation or new construction of research facilities, particularly for basic and clinical research on Alzheimer's disease, at qualified institutions.

In brief, the professional judgement is, in effect, an increased investment to find and develop interventions for the prevention and control of disease and disability in later life, leading to a reduction in the need and cost for long-term care.

Mr. Early: Will any significant new research initiatives or opportunities be lost or delayed by lack of funds in the FY 92 budget request?

Dr. Williams:

The rate of new findings in Alzheimer's disease research is expanding, and new and exciting research areas are being opened up. NIA has recently undertaken a number of new initiatives and would like to stimulate other areas where there are exciting scientific opportunities. The NIA is ready to expand its research on long-term care, including care for Alzheimer's patients. Planned new initiatives extend research to assisted living, formal health care services, comprehensive assessment of health and functional status, minority issues, and forecasting the need and the cost of long-term care.

Similarly, the NIA is poised to undertake a significant research initiative on elder abuse. Although this is not a new phenomenon, its recognition as a growing social problem is recent. Research is needed on the epidemiology and cause of domestic elder abuse, interventions for prevention of abuse by household members, the identification of institutional settings with high rates of abuse incidents, and interventions to prevent abuse in

institutions.

Last year the Committee encouraged NIA "to undertake a demographic research program on the oldest old with special emphasis on a study that focusses on those who are relatively robust or capable of regaining function." Planning has begun for a national study on this unique population and an opportunity will exist in 1992 for "piggybacking" the study on other surveys at a greatly reduced cost. Additional opportunities exist to enhance the Health and Retirement Survey in this regard.

A major expansion of research on the aging of racial and ethnic minorities is needed in order to address better their special problems and needs and their rapid increase in the U.S. population. This encompasses studies of ethnic and cultural variation in attitudes, health-related behaviors, and family life, with a special emphasis on long-term care.

In addition to the above areas of research, several basic research initiatives aimed at understanding fundamental cellular, biochemical and molecular changes which underlie normal aging processes could be more rapidly advanced with additional funding. An important example includes NIA initiatives on the molecular basis of aging, where dietary intervention and genetic manipulation have been shown to significantly extend the healthy life span (health span) of experimental animals, and prevent or delay the onset of age-related cancers and other diseases. Another critical area is identification of longevity assurance genes which is an area of great promise for identifying specific genes which determine longevity (longevity assurance genes) in animals or humans.

The establishment of new Nathan T. Shock Centers of Excellence in Basic Biology of Aging would provide focal points for basic research development, research resources, and program enrichment for basic research studies on aging. Control of cell

proliferation is a critical area of basic research with important implications for unraveling the molecular bases of senescence (cellular aging) and cancer. Studies funded through these new center grants would encompass such lines of research.

With respect to the NIA intramural program, research that cannot be supported at a level comparable to the scientific opportunity and new research initiatives which will be delayed include: planned clinical trials of interventions directed towards Alzheimer's disease, frailty, and osteoporosis; molecular approaches to Alzheimer's disease including efforts to develop an animal transgenic mode of inherited AD; an integrated basic and clinical initiative on cardiovascular disease emphasizing microvascular changes in older persons; expanded studies of postmenopausal hormone replacement therapy; continuing efforts to increase the number of women in the Baltimore Longitudinal Study on Aging; investigation of how hormone, growth factors, and other therapies may promote bone formation and reverse osteoporosis; research on age-associated metabolic defects, particularly type II diabetes; and a new program on cancer and aging.

Mr. Early: What priorities would the institute pursue if additional resources were available? If an increase over the FY 92 request is provided, how would you use these additional funds?

Dr. Williams: If additional resources were available, I would utilize them in a balanced manner in support of the research areas I have just described. It is important to recognize that aging research encompasses many different disciplines and disease areas, and utilizes a number of different award mechanisms. The goal of aging research is to develop the means to reduce disease and disability in older adults, thus minimizing the key risk factors for long-term care and promoting health and independence. By supporting basic as well as applied research, we will generate knowledge of the basic biological processes that will provide a rationale for developing treatments and preventive interventions.

With specific reference to Alzheimer's disease, new initiatives begun in FY 1991 in the areas of development and testing of new drugs for Alzheimer's have generated more excellent applications than we will be able to fund. Recent basic science findings in the etiology of Alzheimer's disease have opened up the potential of developing new compounds to stop or slow the neuronal degeneration of Alzheimer's disease. Also, at the present time testing needs to be done for a number of compounds which have been proposed as potential treatments such as deprenyl (a drug which has been shown to be effective in the treatment of Parkinson's disease and may work by increasing the response of cells to neurotransmitters), nimodipine (a drug which allows reestablishment of proper levels of calcium within cells), and MK801 (a compound which blocks the death of cells which control memory). Additional funds would support more research permitting the discovery and development of new compounds to slow or stop the progression of the disease. Additional funds would also increase the number of clinical sites involved in the testing of drugs for efficacy in the treatment of Alzheimer's disease. This would