tom management being the prime goal. At this stage, chronic diseases remain chronic, and if as- sociated with ..... L., Reicher-Reiss,. H., Stern, S., and Behar, ...
LIFE
SCIENCES
FORUM
Monitoring Changes in the Health of the U.S. Elderly Population: Correlates with Biomedical Research and
Clinical
Innovations
KENNETH Center HEALTH
G. MANTON,
for Demographic
LARRY Studies,
S. CORDER,
Duke
AND
University,
Durham,
tional
CHANGES
Biomedical research has had tremendous positive effects on the health and day-to-day functioning of the
U.S. population; by stimulating the growth of biotechnology, it has greatly affected the U.S. economy as well, including exports. These effects on the health of the U.S. elderly population can be demonstrated
ERIC
STALLARD
North
Carolina
cause-specific
27708-0408,
mortality
rates
USA
(from
1950 to
1992, there was a 52% decline for heart disease mortality, 71% for stroke). Declines in diseases not typically recorded in mortality statistics, such as dementia and chronic joint disorders (4), could not so easily be anticipated at a national level, even though analyses of concurrent risk factor trends found in other data sources suggest the plausibility of a significant
in a number of ways. Using data in the National Long Term Care Surveys (NLTCS), Manton et al. (1) found that the prevalence rate of chronic disability and institutionalization declined significantly-by almost 15%-for the U.S. population aged 65 and older from 1982 to 1994. This confirmed the decline in chronic disability prevalence of about 8% observed from 1982 to 1989 (2), and suggested that the rate
recent decline in dementia prevalence rates: large declines in heart disease/stroke mortality and hypertension prevalence would reduce the risk of microinfarct
of decline in the prevalence of disability in U.S. elderly populations had actually increased (to 1.5% per annum) between 1989 and 1994.
estrogens
Not only did the prevalence of, and institutionalization rates for, chronic disability decline, but the
prevalence
of many
chronic
degenerative
diseases
measured in the NLTCS, and thought to generate chronic disability, manifested significant declines (3, 4). The declines in chronic morbidity suggest that chronic disability prevalence rates will continue to decline, at least over the period between the time of chronic disease onset and its eventual progression to a stage generating serious chronic disability. Longer term declines are implied by lower disability prevalence, and higher survival, rates at corresponding ages across three elderly cohorts defined by date at birth from the NLTCS sample population in 1982 and followed to 1991 (5). Some of the observed declines in morbidity could be anticipated-for example, drops in atherosclerosis and chronic circulatory diseases such as stroke and heart disease-based on long-term declines in na-
0892-6638/97/0011
-0923/$02.25
© FASEB
dementia (6). Other studies suggest that the prevalence of dementia among females might be reduced by as much as 50% by the increased use of exogenous estrogens (there was an increase from 3 to 10 million
postmenopausal between
women
in the U.S. using exogenous 1995; ref 7), increased (originally taken to treat joint disor1985 and
use of NSAIDS ders; ref 8), increasing
education in the elderly population (9, 10), and likely improved nutrition [e.g., consumption of antioxidants such as vitamin E (11) and possibly increased consumption of phytoestrogens (12)1. Likewise, there were numerous advances from 1965 to 1985 in disease management/modification and therapies for chronicjoint disorders (13), progress that continues to this day. The 15% decline in U.S. chronic disability prevalence rates translates into 1.2 million fewer elderly persons with chronic disability, or in institutions, in 1994 than would be expected based on the age-specific rates observed in 1982. The large declines in dis-
Correspondence: Center for Demographic Studies, Duke U., 2117 Campus Dr., Box 90408, Durham, NC 27708-0408, USA. Abbreviations: NLTCS, National Long Term Care Surveys; DALYs, disability-adjusted life years; QALYs, quality-adjusted life years.
923
ability prevalence
were partly due to declines
frailest portions of the chronically disabled tion, residents of chronic care institutions,
largest
relative
declines
observed
in the populawith the
in the oldest
age
group examined (persons 95 and older). The institutional group was 19.0% smaller in 1994 than would have been expected if 1982 institutionalization rates
had not changed. This difference reflects a third (400,000) of the total U.S. decline in the expected number of chronically disabled elderly persons from 1982 to 1994. Large declines in the rate of institutional use in the U.S. by persons aged 65 and over
were confirmed by comparing the 1995 National Nursing Home Survey with a similar survey conducted by the National Center for Health Statistics in 1985 (14). Disability declines in the U.S. community (vs. institutional) resident population in the 1980s were confirmed by extensive analyses of survey and other types of data, done by Waidmann et al. (15). Declines in chronic disability are consistent with national trends reflected in other health measures; declines
ing, found
in chronic
disease
hypercholesteremia, in four
risk
and
National
Health
factors
such
hypertension Examination
as smok-
were Surveys
conducted
factors attributable to recent biomedical research on both the fundamental biology of disease mechanisms and modifications of those disease mechanisms by a range of biomedical interventions, from preventive efforts such as immunizations against hepatitis B to reduce future liver cancer risks (20) to a series of improvements in the medical management of advanced cancers.
Some authors have suggested that from 1982 to 1994 may have occurred significantly
reflect
recent
major
the changes
too early to biomedical break-
throughs in the treatment of chronic diseases manifest at late ages. There is evidence to suggest that nutritional, ervation),
hygiene (e.g., and infectious
water quality, food disease treatments
preshad
been changing the health of the U.S. population since the beginning of the 20th century. Fogel (21) showed
that
the prevalence
of chronic
disease
had
declined 6% per decade from levelsfound in Civil War veterans age 65 (the cohorts born from 1825 to 1844) being examined for pensions in 1910 compared erans
to the prevalence examined during
found in World War II vetthe period from 1985 to
1988. Declines in stroke served since 1925 (22);
mortality have been obgastric cancer declined
between 1960 and 1990 (14). The decline in serum cholesterol levels is interesting in that National Cholesterol Education Program guidelines for
from being the leading cause of death by cancer in the 1930s to the sixth ranked cause of death by can-
the year
cer today
2000,
which
were
introduced
in 1988, were
achieved, in part, 10 years ahead of schedule, by 1991 (16, 17). More rapid dissemination of health information by the mass media to the U.S. population, an increasing popular awareness of health issues, and the emergence of new private markets for health services may mean that new biomedical research findings, especially with regard to nutritional (vitamin E) and behavioral (physical activity and stroke; ref 18)
risk factors, may be translated more rapidly into healthy patterns of behavior and a realization by the public of the actual benefits of health changes at late ages (age 80+), with consequent increases in the use of health services (see ref 19), thus producing greater and more rapidly emerging health changes in the U.S. elderly
population.
IMPACT OF BIOMEDICAL INNOVATIONS OBSERVED HEALTH CHANGES
ON
It is important to identifi and understand the mechanisms responsible for changes observed in the health and functioning of high-risk populations, such as those who are institutionalized derly. It is likely that major health
and the changes
very elbefore
1994 involved socioeconomic factors, affecting the receptivity of the elderly population to preventive services, changes in health behavior, and the motivation to seek health-modifying interventions at later ages. The changes in disability/disease ratesalso reflect 924
Vol.
11
October
1997
(23, 24).
there is also ample evidence of the contribution of specific biomedical innovations to the success of surgery performed, for example, on patients of extremely advanced age (90 to 103 years; ref 25) and in aortic valve replacements at ages 80+ (26) over the 1982 to 1994 period. A recent study of persons aged 75+ showed that innovations and improvements in the clinical management of myocardial infarction, such as reperfusion therapy, from 1981/ 83 to 1992/94 reduced the incidence of their 1-year However,
mortality
by 42%
(i.e.,
life was extended)
perfusiontherapybecame quitecommon during
this same
opments
period.
The
pace
(27).
Re-
in theU.S.
of recent
devel-
to have accelerated the per annum decline in chronic health problems from a persistent 0.6% per year from 1910 to 1988 to 1.5% per annum from 1989 to 1994. Although there is clear evidence of major advances in the prevention and treatment of chronic circulatory diseases, there is still considerable controversy over the magnitude of benefits gained from cancer research (see ref 28 for a criticism of the 1971 National Cancer Act). However, many problems cited with cancer research may result in part from incomplete population analyses. Cancer can be viewed as many different diseases, thus causing the “effective” level
appears
of funding
at that
time
(1971)
to be “diffuse”
and much smaller on a per disease basis. The overall level of research effort expended per person affected by specific
The FASEBJournal
cancer
types in the 1970s is small relative MANTON
ET AL.
to the per capita level of effort expended to 1997, for example, on AIDS research. Biomedical research now offers the
finding
more “rational”
and different
from
1987
prospect
of
organizational
bases for research on neoplastic diseases, which include the role of mutations in the p-53 growth control gene in roughly 50% of all cancers (see ref 29); the effects of the immune system on tumor growth;
(39). Ifsmoking cessation increased, larger declines
might be possible (40). In addition, many promising new therapeutic approaches are being pursued. Roughly 33 new anticancer drug compounds either are or will shortly be in clinicaltrials.These compounds represent 10 distinct biological modes of action against
declines
cancer
in cancer
(41).
This may further
accelerate
mortality.
and general
processes of tumor neovascularization ref 30) and metastatic spread. This approach
(e.g., may help focus cancer research number of more fundamental, sions. New advances in circulatory may emerge, some representing “spillover” effects from cancer
efforts on a smaller physiological dimendisease treatment major technological research: the role of
apoptosis in cardiomyocytes during ischemic reperfusion injury (31); the role of altered matrix metalloproteinases in aortic aneurysms (also involved in metatastic processes; refs 32, 33); and the uses of gene therapy in heart failure (34). Recent criticisms(35) of cancer research effortsdo recognize that many important technologies that ad-
vanced
clinical
science
progress
against
specific
1971 “war on cancer.”
in general, cancers,
and generated resulted
The 1971 National
from
the
Cancer Act of both CAT
was instrumental in the development and MRI scanning technologies.Cancer mortalityfor persons aged 55 or less declined by 30% between 1973 and 1994, although cancer mortality for those over age 55 increased by 15%. One problem in eval-
uating cancer disease
research
mortality
progress
showed
rapid
is that cardiovascular declines,
with which
the slower progress against cancer mortality is generally compared (36). The critiques also tend not to fully acknowledge that much of the recent increase in cancer mortality is due to a single type of cancer (lung cancer, especially for increases above age 55) and the effects of one major preventable risk factor, smoking. For all cancers except those of the lung, there was a 10% decline in mortality from 1970 to 1990 (37). Heart
disease
mortality
from
1970 to 1990 declined
40%.
Lung cancer mortality,in contrast to both trends,in-
creased 45.8%. Thus, criticism of the failure of the war on cancer to deal with solid-tumor mortality largely involves a single public health phenomenonlung cancer-and a failure in primary prevention (increased smoking): in other words, the lung cancer epidemic in middle-aged males due to cohort-related increases in smoking
(38).
The situation for cancer now appears to be changing rapidly. Overall cancer mortality declined 3.9% from 1990 to 1995 (37), the first sustained decline ever observed for overall cancer mortality (39). Much of this is due to the structure of male cohort smoking patterns. If the current pattern of nonsmoking among men continues, this by itselfcould cause a 25% decline in cancer mortality in the next 20 years LIFE SCIENCES FORUM
ASSESSING
RESEARCH CHANGES: Although
OF INDUCING RECENT HEALTH ISSUES AND DIFFICULTIES THE
ECONOMIC
the degree
of success
EFFECTS
of U.S. biomedical
research to cure or prevent specificdiseases varies
considerably,
the general
level of success has been both at disease-specific and global health levels by improvements in survival and function. The U.S. has the lowest mortality rate dramatic. This is shown
among developed countries for persons above age 80 (42).Ifnot for increasesin lifeexpectancy and in the
average age at onset of disease and disability, it might not be feasible to increase the normal retirement age for Social Security from the current age of 65 to age 67 by 2027 (i.e., for the birth cohort of 1960), as legislated in 1983. Significant health improvements at later ages likelyare also necessary to justifyrecent proposals to increase the Medicare eligibility age from 65 to 67 by 2027. Increases of a year in the age of retirement in order to collect Social Security or in the age of eligibility for Medicare made feasibleby significant improvements in health at late ages have
“dual” benefits: not only is the period of public support reduced by a year, but the period over which taxes are paid by the individual also increases by a year. If health at later ages continues to improve, there ispotential for further amendments of age at eligibility, as suggested by the recent Kerry-Danforth Commission (43).
Assessments of the economic benefits of biomedical research, although identifiable in specific areas, are difficult to quantif’ for the entire U.S. population. Some types of biomedical research may be translated into improved population health without significant costs. For example, a recently discovered risk factor for atherosclerosis is the presence of an elevated levelof homocysteine (an amino acid) re-
sulting from inadequate folic acid intake. Recent research suggests that the systematic supplementation of food with folicacid might prevent 51,000 coronary arterydisease deaths per year. Folic acid supplemen-
tation
may also reduce
the risk of cerebrovascular
and peripheral arterialdiseases (44). However, the supplementation of foodstuffs mandated by the FDA (45) isnot chargeable to Medicare and, arguably, is
privately financed to compete as a value-added product in the marketplace. For example, McCully (46) 925
presented such an argument to explain large increases in the production and consumption of B vitamins in the 1950-1980 period. Programs to prevent circulatory disease that rely on behavior modification, costing $4.95 per person per year to lower cholesterol by 2%, would save 624,000 person-years of life at a discounted cost of $3200 per life year saved. If serum cholesterol levels are reduced by 3%, money would be saved for all of the risk reduction scenarios reviewed in the calculations done by Tosteson et al. (see table 1 in ref 47). One can also identif’directeffectson econonc productivity(e.g., the growth of the dollar volume of biotechnology contributions to the gross domestic product can be measured; each dollar spent on NIH research has been estimated to translate into $2.50 spent by private drug companies on research). However, even though there is almost daily news of biomedical research advances and new medical treatments, there remains uncertainty about the cumulative national economic effectsof these events. Even though new scientific insights are being gained into the molecular and genetic bases of disease, the same degree of effort and scientific precision have not been demanded by the scientific community as it (and others) attempts to assess the general societal and economic consequences of major scientific advances. Although such an appraisal is an unfamiliar activity for most scientific investigators, it is nonetheless an important area of research for biomedical science that requires the same methodological and conceptual care used in other areas of scientific endeavor: it requires that appropriate population health data be collected, over time, to monitor specific health changes in individuals. If biomedical researchers do not make, or at least significantly contribute to, these economic and public health assessments with their usual analytic rigor and concern about data quality, nonscientists will necessarily make them, possibly without either the necessary scientific rigor, appropriately and specially collected data, or with a clear understanding of the fullrange of potentialpopulation benefits,short and long term, of scientific advances. This is why the Vannevar Bush “paradigm,” presented in 1945, which suggests that 1) scientists should “work independently in choosing what to examine and to strive only for scientific excellence,” and 2) federal funding of research should respect this paradigm, has been criticized (e.g., ref 48). These criticisms may be inappropriate since the full benefits of a specific scientific discovery may affect multiple health outcomes and require considerable time before becoming fully apparent. This is not because the rate of scientific discovery has been slow, but because it takes time to translate basic scientific discoveries into clinical and public health applications at the national level. For example, vitamin E was
926
Vol.11
October1997
The
identified in 1922 at the University of California, Berkeley. However, its multiple positive effectson health have only recently been researched extensively and demonstrated: the effects of vitamin E on heart disease, stroke, and atherosclerosis (as an antioxidant) were identified in population studies by Stampfer et al. (49) and Rimm et al. (50); the effects of vitamin E on glucose metabolism in diabetes were identified by Paolisso et al. (51); the role of vitamin E in cancer prevention and cellularredifferentiation was reviewed by Prasad and Prasad-Edwards (52); and the effects of vitamin E in slowing the formation of cataracts were reviewed by Taylor (53). It may also be necessary to use vitamin E to counterbalance the effects of some asthma treatments (use of inhaled steroids) on cataract formation (54). Most recently, vitamin E’s role in slowing the progression of Alzheimer’s disease was demonstrated (11), as was its potential for enhancing certain immune responses in healthy elderly persons (55). Vitamin E research is of particular interest because the cost of the compound and its use to intervene for a wide range of health outcomes are intrinsically low. Consequently, research identifying new areas of application of existing therapies can be highly cost-effective. There are other similar recent discoveries: aspirin used in heart attack and stroke recurrence prevention (56); effects of nonsteroidal anti-inflammatory drugs on dementia (8) are inexpensive in that the treatment was often started for another purpose; antibiotic therapies for curing gastric ulcers by eradicating Helicobacterpylo’ri, the infectious agent responsible, are much less expensive than previous palliative therapy
of ulcers
with
H2 blockers.
Many
other
such
possibilities for finding new uses for existing, relatively inexpensive drugs remain to be explored: hepatitis B immunization in children to prevent chronic liverdiseaseand livercancer (20, 57); the interaction of nutritional deficiency with selection for virulent viral phenotypes (e.g., group A and B Coxsackie virus causing
cardiomyopathy
in a selenium-deficient
en-
vironment; ref 58); and the role of chlamydia pneumonia in circulatory diseases (59), which might lead to eradication of a large portion of circulatory disease by acute infectious disease interventions (e.g., antibiotics or immunotherapy; ref 60).
MODELS FOR ASSESSING THE ECONOMIC AND SOCIAL IMPACT OF BIOMEDICAL RESEARCH
In biomedical research, measurement isadapted to the phenomena studied. When assessing the broader social and economic consequences of scientificadvances, there is often no universal yardstick with which to quantifi health effects. The most broadly accepted measure is life expectancy, the average
FASEB Journal
MANTON
ET AL.
number of years a person can expect to live past birth, or a select age. However, even the use of life expectancy as a population health measure has been questioned: is it equally applicable to biomedical advances made for diseases early and late in life? It has been proposed that person-years of life should be weighted by the social value of the quality of life and health experienced at each age (e.g., quality- [QALYs] or disability-adjusted life years [DALYs]). Using QALYs or DALYs to assess the societal impact of medical interventions is potentially hazardous morally because social and economic factors, as well as a vague notion of patient morale, may significantly affect the estimated value of an additional year of life for a given individual (61). A person in excellent physical health may be depressed with a poor quality of life (recognizing that the depression may itself be a manifestation of complex and subtle biochemical dysfunctions in the brain or, more speculatively, the results of a virus; refs 62, 63) whereas severely physically disabled persons may maintain full social and economic independence. Thus, it is probably best to measure health changes in terms of objective population measures such as life expectancy or the numbers and degree of physical and psychological impairments in a population. These have relatively objective interpretations and cost implications. Therefore, because it can be interpreted as an objective, readily measured phenomenon, the national decline in physical disability prevalence at late ages observed from 1982 to 1994 has been recognized as important evidence of recent U.S. population health changes (1). It is also difficult to assign an economic value to a given health benefit when measured at the population level.There are practical reasons for this difficulty. The first is that prices are determined by market forces. Should the cost efficacy of a drug change dramatically when generic versions, at 10 to 20% of the initial price, become available? Neither production costs nor the health consequences of the drug are altered,yet such price changes may significantly affect the cost efficacy calculated for the treatment (64). Another difficulty is that the economic consequences of a particular intervention treatment cannot be unambiguously delimited. For example, inhaled steroids may be beneficial in reducing asthma risks. The use of inhaled steroids presumably increases with the severity of asthma. However, there is a dose-response relationship between the amount of steroids used and the risk of cataracts (65). Thus, the side effects of steroid therapy create a new health problem, which in turn may be reduced by the use of vitamin E (and other antioxidants). How does one cost account the benefit of the vitamin E intervention if it used to treat a problem generated by another necessary treatment? This may reflectthe fact that the therapy for either asthma or cataracts has not pro-
LIFE
SCIENCES
FORUM
gressed sufficiently for “normal” physiological control mechanisms to have been identified. Likewise, the use of exogenous estrogens has reduced heart disease risks, which are the most prevalent morbidity problems at lateages.However, usage for more than 10 years may significantly raise the risk for breast cancer (66). Thus, the duration and age associated with exogenous estrogen use affect its cost:benefit ratio as well as which disease risks are lowered and which are increased. Applications of new health care technologies generated by research to the U.S. population have occurred slowly and often are incomplete. Flowers and Melmon (67) examined the process whereby a lead scientific observation is translated into a clinically approved drug, a process now requiring roughly 12 years and costing $231 million (in 1987 dollars). In 1950, George Hitchings (68) of Burroughs-Wellcome stated that his lab had conducted studies since 1942 of the chemical relation of pyrimidine and purine bases in cell growth and how those processes were influenced by folicacid, and found that “bacterial, viral, rickettsial, and neoplasticdiseases” were differentiated from normal tissue function by rapid rates of cell replication and growth. Therefore, intervening in these processes of rapid cell growth might offer major new opportunities for treating disease. That basic research (1942-1950) eventually produced a number of new drugs for many diseases (6-mercaptopurine, an anti-leukemic; FDA-approved in 1953), azathioprine (an immunosuppressant; FDAapproved in 1968), allopurinol (an anti-gout agent, 1965), acyclovir (an antiviral, 1982), and ganciclovir (an antiviral, 1989); however, tip to 40 years elapsed before some of the drugs emerged as clinically effective agents. Returning to the \Tannevar Bush paradigm of research, another possible concern is its apparent reliance on chance or serendipity in the scientific endeavor. However, science iscumulative and its very progress depends on previous findings and the emergence of new technologies (e.g., polymerase chain reaction, liposomal delivery of drugs, gene therapies, monoclonal antibodies, PET scanning, automated drug screening). Thus, a reliance on “chance” at one leveldoes not mean that the overall rate of scientific breakthroughs will not accelerate due to rapidly improving research technologies. The accumulation of improved laboratory and scientific procedures means that progress and breakthroughs will be made at increasing rates for a given levelof scientific investment. To illustrate, the war on cancer may have had little early success in developing treatments for solid tumors, because until 1985 drug screening was often done with the P388 leukemia and other murine cell lines. Progress in treating leukemia and lymphoma was relativelyrapid in the early period
927
of the war against cancer. However, rapidly growing murine cell lines were not good models for screening for drugs with which to treat solid tumors in humans. In 1985, the drug screening program was changed to better represent nine human cancer types and 60 cell lines, including some expressing intrinsic drug resistance. Accelerated by AIDS funding in 1987, adoption of the new screening program was almost complete by 1990. Advances in screening for drugs to treat solid tumors were also improved by computerization of the crystallographic structure of proteins (e.g., the Brookhaven database) for use in rational drug design, along with the expanding use of supercomputers. These factors combined to produce relatively rapid progress in the treatment of AIDS, along with modifications of the design of clinical testing programs to more rapidly evaluate the potential efficacy of specific drugs and therapies (69). It appears that similar advances, due to such advances as rational cancer therapy (70, 71), may be forthcoming in the treatment of solid tumors. In discussing the technologies used to treat disease, Weisbrod (72) referred to three levels (73). The first (when knowledge of chronic disease mechanisms is primitive) is palliative, with symptom management being the prime goal. At this stage, chronic diseases remain chronic, and if associated with serious disability, due often to a lengthy disease duration, expensive. “Halfway” technologies are those where the science has advanced to the point where some disease modification is possible; examples are the use of methotrexate and cyclosporine in rheumatoid arthritis, the use of steroids in managing systemic lupus erythematosus (see ref 13), or the use of cyclosporine in ulcerative colitis refractory to steroids; ref 74). Here, the course of the disease may be lengthened, and costs therefore may increase. In the “high-technology” level, the disease mechanisms are fully understood and cure or eradication is possible. In this case, chronic diseases are cured and hence transformed into acute diseases. Hightechnology, by shortening the period of treatment, has the greatest potential for cost efficacy. A number of dimensions actually underlie this technology continuum. For example, invasive surgery will tend to be replaced by less invasive surgery. Surgery itself may be replaced by the use of drugs. Diseases, once defined at the level of organs, may be redefined on a molecular or genetic leveland clinically regrouped; fully systemic therapies may develop, such as treating solid tumors by cytotoxic, anti-angiogenesis, and antimetastatic therapies and with the use of granulocytecolony-stimulating factor and biphosphonate therapy for bone marrow support and antiosteolytic lesion therapy.
928
Vol.11
October1997
THE NEED TO MONITOR AND FORECAST “REAL TIME” CHANGES IN POPULATION HEALTH Not only has the current system of scientific research and funding produced many important public health advances to date, but-assuming adequate and stable levels of financial support for biomedical researchwe may expect it to generate major health advances in the near future at an increasing rate. This could have important consequences for controlling the federal and private costs of health services, especially if a large proportion of innovations result in what is referred to as high-technology, leading to true disease cures, or even eradication. Clinical trials effectively demonstrate the efficacy of specificinterventions,developed from more basic biomedical research, precisely targeted to specific diseases and conditions. What has been lacking until recently is a systematic empirical base from which to monitor the long-term benefits for the entire U.S. population of clinical interventions generated from biomedical research.This situationhas changed due to the recent availability of a system of coordinated longitudinal surveys (the 1982, 1984, 1989, 1994, and planned 1999 NLTCS) linked to a national poulation register(i.e., Medicare program data) for allpersons aged 65 and over. This longitudinal,nationallyrepresentative database can be used to assess, in a temporally consistent fashion, long-term changes in health, disability prevalence, and survival in the U.S. elderlypopulation (1).Such a national longtitudinal database is necessary in order to isolate effects introduced at a specific time from changes in health and survival for cohorts or individuals. With such a database, it will be possible to examine changes in population health due to biomedical research and clinicaladvances as they emerge over time and are diffused through the health servicesystem to the national population. The need to monitor the overall benefitsof biomedical research investment on health is likely to only increase in the future as greater oversight of the investment in biomedical research is demanded in a period of tight federal budgets. In addition, such monitoring may help identif’ the areas of greatest need for future research and determine the appropriate levels of investment in research in those areas. Appropriate longitudinal data are necessary, but not sufficient, to satisfactorily achieve these goals. Appropriate analytic models are needed to complement the longtitudinaldata. Such models willhave to be increasingly biologically detailed in order to evaluate how specificinterventions willaffectspecifichealth benefits achieved over time-and in what specific population groups. Thus, to forecastfuture needs for investments in research, one needs the combination of longitidinaldata and biologicallyrealistic models
The FASEBJournal
MANTON
ET AL.
to enhance the detail and precision of forecasts that can guide the settingof research priorities. Although a rational basis for such forecasts can help greatlyin planning the broad outline of future research needs, there are limits to the predictability of when certain research goals might be ahieved and how they will be achieved. There is simply no way to exactly predict the outcome of individual creative processes;nevertheless,confidence can be increased about the aggregate health impact of many investigator-initiated projects and activities.
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