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THA ALZHEIMER'S TRIAL
Question. Starting several years ago the NIA funded a THA trial which was to determine the effects of the drug on enhancing memory. I understand the study has been completed. Have the data and the findings been released yet?
Answer. This study has been completed, and the full results are being prepared for publication which we expect to be in late spring to summer of 1991. A portion of the results has been analyzed independently by Warner-Lambert, the co-sponsors of the study, and results from that analysis were presented to the Food and Drug Administration (FDA) for regulatory purposes as part of the company's process for seeking approval to market THA.
CLAUDE PEPPER OLDER AMERICANS INDEPENDENCE CENTERS
Question. Last year the Committee asked that at least 5 Claude Pepper centers be established. How many do we now have in operation and what is the research focus of these centers?
Answer. A Request for Applications for these Centers was issued on February 15, 1991, and applications are due on May 17, 1991. Testing interventions to maintain or increase independence of older persons is a central, required component of these Centers. Other key aspects of the Centers include career development of new investigators to test further interventions to increase independence, and information dissemination to translate research results of the Centers into health care practice. We expect to make three or four awards at the end of FY 1991. Approximately twenty applications are anticipated.
Based on contacts between prospective applicants and NIA staff, we expect that several will propose testing of interventions to increase muscle strength, mobility, balance and/or endurance in frail older persons through exercise, administration of growth hormone or other trophic factors, or the combination of both. Prospective applicants have also proposed numerous other important interventions, including techniques to prevent disabling falls, preventing institutionalization by improved identification and treatment of health problems in frail older persons, reducing disability from cardiovascular disease through better drug treatment, preventing dehydration, malnutrition, and their debilitating consequences (common problems among frail older persons), and better treatments for urinary incontinence.
GERONTOLOGICAL RESEARCH AND LIFE EXPECTANCY
Question. According to research published in Science this past fall, University of Chicago scientists have determined that it is highly unlikely that Americans' life expectancy will exceed age 85, even if cancer and other life-threatening diseases are eradicated. Are you familiar with this research?
Answer. The research referred to concludes "that life expectancy should not exceed 85 years at birth or 35 years at age 50 unless major breakthroughs occur in controlling the fundamental
rate of aging." The authors however suggest that "major advances in genetic engineering and new life-extending technologies are forthcoming, and these will be followed by commensurate declines in mortality and extensions of longevity." Finally, the authors recommend that "the time has come for a shift toward ameliorating the non-fatal diseases of aging."
Question. What implications do these findings have for NIA's research agenda, specifically research that attempts to distinguish between aging and age-related diseases such as Alzheimer's disease?
Answer. At least one major breakthrough has already occurred in this research. This discovery is that when you restrict the intake of calories by rodents to 30-40 percent below what these animals would normally eat they live longer and are healthier. The importance of this provocative finding cannot be underestimated: decreasing the rate of aging delays the age at which debilitating illnesses strike. Experimental animals in which aging processes have been retarded are healthier, more active, and more often disease-free than animals half their age. These animals are not decrepit, diseased animals that simply live longer. Observations in mice suggest that as few as 3-7 genes can double the healthy lifespan. The methods that researchers have used to retard aging, such as very stringent diets and generations of selective breeding, cannot be directly applied to people. Therefore, basic gerontological research is essential if we are to understand how these methods work in animals, learning which genes, which hormones, which cell types make the difference between mice that live two years and those that live four years, and seeing whether the basic aging processes in humans can also be altered.
The realization that the normal aging process itself is linked to diseases of old age carries profound implications concerning the role of basic research in improving the quality of life for the elderly. The U.S. currently spends billions of dollars on caring for people who suffer from age-dependent diseases. Yet if we could produce even a small change in the rate of aging, we would postpone the age at which these illnesses strike. Interventions in basic aging processes would lengthen the healthy lifespan as effectively as "cures" for Alzheimer's dementia, heart diseases, osteoporosis and cancer. With very rare exceptions, thirty-year old people do not lose their memories to Alzheimer's, do not have heart attacks due to advanced atherosclerosis, do not fracture their hips if they fall, do not die when they catch the flu, are not confined to their homes by painful arthritis. Yet all thirty-year olds are experiencing the processes of aging as well as the cumulative effects, positive and negative, of life style and environmental exposures that will turn them into people who are vulnerable to all of the conventional diseases and more.
We can now set ourselves the realistic goal of learning how slowing the rate of aging by caloric restriction works in animals, and whether the processes involved can be safely altered in humans. Modern molecular techniques have suddenly allowed us to ask and solve problems that seemed hopelessly complicated even
five years ago. Like other kinds of basic science, basic aging research is likely to produce unanticipated benefits. But, in addition, fundamental progress in our understanding of aging is likely to lead to understanding of all the age-dependent diseases.
CLINICAL TRIALS ON ALZHEIMER'S DISEASE
Question. Dr. Williams, according to a recent report by the Battelle Research Center, if we are able to develop some promising new drugs for Alzheimer's we could reduce the number of severe cases of the disease by 395,000 over the next 25 years. At the same time, we would save about $68 billion in direct care costs.
Last year, this Subcommittee specifically earmarked funds for clinical trials to test some of the more promising drugs. We want to be certain that you move ahead as quickly as possible.
How soon can we expect actual drug testing to be underway?
Answer. The Request for Applications for the clinical
studies was issued on March 8, 1991, and the date for receipt of applications is May 21, Review will take place during the summer, and funding will be on or before September 30. Drug testing will begin soon after the award is made. We do not expect to have results to report until at least one year after testing begins.
Question. In your professional judgement, when might we expect some results from the trials?
Answer. It is doubtful that reliable results will be available prior to one year after testing begins, but a realistic timetable is within one to two years.
Question. On March 15, the FDA is scheduled to make an announcement concerning THA, a drug that your Institute helped test. Can you give us some indication of what will be said? we hold out some hope?
Answer. The results from the FDA hearing have been widely disseminated in the news media. The committee did not recommend approval of Warner-Lambert's request for a New Drug Application (NDA) for THA. To approve an NDA, the FDA requires two studies with findings supporting the efficacy of the drug. Two studies supporting the efficacy of THA (the NIA supported clinical trial and an English clinical study supported by Warner-Lambert) were submitted to the committee, however, the committee did not accept the English study as scientifically and methodologically adequate. The committee did accept the NIA supported clinical trial of THA as methodologically sound and supporting the efficacy and safety of the drug. While during the course of the hearing the committee congratulated NIA on its leadership and efforts, the committee did not recommend approval of THA because it lacked a second positive clinical trial. It is expected that upon further testing, the company will have another opportunity to request approval. The NIA stands ready to cooperate with FDA, Warner-Lambert, the scientific community, and the families to expedite the process of determining whether the drug is safe and effective.
Research efforts stimulated by the NIA are proving to be the basis for the development of new treatments for AD. Currently, more than 40 existing drugs, compounds, and biologicals have been proposed or suggested as treatments for AD. At this time, however, there are no drugs or compounds available that offer the hope of curing or of permanently altering the course of this disease. On the other hand, drugs that can ameliorate the symptoms of the disease, even for a short time, will still be worthwhile since such agents may provide a welcomed relief psychologically and financially to the victims and their families. The current generation of potential treatments focus upon the replacement of transmitter deficits found in AD. New generations of treatments will focus upon nerve growth factors, calcium channel blockers, metabolic enhancers, transport mechanisms for the efficient delivery of drugs, regulators of gene expression, and more. While effective treatments for some groups of patients may be developed within the next five to ten years, at the present stage of knowledge, long-lasting cures for large groups of patients will require more time and more research.
Question. The oldest old (those age 85 and older) is the fastest growing age segment of the population, and you have reported that this group may grow more rapidly than official estimates. What is the latest information on these projections?
Answer. The 85 and older population continues to be the fastest growing age group in the United States. Population projections anticipating the size of the oldest old are dependent upon assumptions about the changing force of mortality at advanced old age. Projections continue to vary widely depending on the assumptions employed. The projections developed by the Bureau of the Census have underestimated the size of the oldest old population, due in part to the unexpected decrease in mortality among persons age 65 and older over the past 30 years. A number of researchers have developed forecasts that far exceed the Census Bureau's high range projections for the middle of the next century. One of these projections, using a modelling or simulation method, has forecast that healthier life styles, such as greatly reduced smoking, hypertension, cholesterol, etc., could plausibly result in some 40-60 million people over age 85 in year 2050 or 2060. It is important to remember that this is an extreme, and not necessarily the most likely, projection.
Researchers have not yet been able to fully explain the reasons for the recent improvements in life expectancy at age 65 and older. Further, we do not know if the same rate of decline in mortality rates will continue among America's elderly. Therefore, population projections of the size of the 85 plus population vary widely. As important as it is to accurately project the number of oldest old over the next decades, we desperately need information about the likely health status and functional status of the oldest old. Will increases in life expectation translate into more years of healthy, active life or more years of life in a disabled state? NIA supports research in projecting active life expectancy to assist program planners and policy makers in anticipating the future need for social services, hospital and nursing home beds,
community housing options, and income security programs for the oldest old. Continued research in this important area should unlock the mystery of recent improvements in life expectancy among the elderly and should improve the accuracy of population projections for the oldest old.
Question. The Committee strongly encouraged the NIA to undertake a demographic research program on the oldest old with special emphasis on a study that focuses on those who are relatively robust or capable of regaining function. What progress have you made on this study? Will any additional resources be needed? Will the study include adequate numbers of the black oldest old?
Answer. A study on the robust population age 85 and older, those capable of regaining physical functioning, may lead to insights into ways to modify the course of disability. As part of the enhancement of the demographic research program such a study is under discussion, although the age limit may be dropped from age 85 to age 75 to include a comparison group for the 85 plus group and also to follow these people through subsequent interviews, if possible.
During the planning stages for this study, a number of opportunities have surfaced which would allow NIA to take advantage of other planned research activities to minimize the cost of this study while enhancing data collection procedures. For example, the National Institute on Aging/Health and Retirement Survey Monitoring Committee Meeting of March 5, 1991 included a discussion of the opportunity to save a substantial amount of money by taking advantage of the Health and Retirement Study (HRS) sampling frame. In order to locate the 8,000 households
containing a person between the ages of 51-61 for the HRS, many households will be screened containing persons age 75 and older. The persons age 75 and older will be inappropriate for the HRS but appropriate for a study of the robust oldest old.
The National Center for Health Statistics (NCHS) is currently planning a second cohort of the Longitudinal Survey on Aging (LSOA), and it may be possible to have the data collection for both the study of the robust oldest old and the new LSOA cohort conducted by the same organization. Discussions along these lines will continue between NIA and NCHS.
NIA has allocated funds to begin designing the survey; plans are to ensure inclusion of adequate numbers of underrepresented groups. The cost of the study is dependent upon the actual design of the survey. It is certain that we will need to "over-sample" households to ensure inclusion of sufficient numbers of underrepresented groups, such as oldest old Black males.
QUESTIONS SUBMITTTED BY SENATOR DALE BUMPERS
Question. As you are well aware, the family is the major source of support for older Americans. However, current trends in fertility, divorce and women working outside the home are