DIVERSITY IN MEDICATION USE AND OUTCOMES IN AGING POPULATIONS

Release Date:  May 7, 1999

PA NUMBER:  PA-99-097

P.T.

National Institute on Aging
National Center for Complementary and Alternative Medicine
Office of Research on Minority Health
Office of Research on Women"s Health

THIS PROGRAM ANNOUNCEMENT USES MODULAR GRANT PROCEDURES. IT INCLUDES DETAILED
MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN
PREPARING APPLICATIONS IN RESPONSE TO THIS PA. (SEE APPLICATION PROCEDURES. ALSO
SEE MODULAR GRANT APPLICATION AND AWARD NOTICE
http://www.nih.gov/grants/guide/notice-files/not98-178.html

PURPOSE

The National Institute on Aging (NIA) in collaboration with the National Center
for Complementary and Alternative Medicine, the Office of Research on Minority
Health and the Office of Research on Women"s Health invites qualified researchers
to submit applications to investigate issues relevant to medication use and
outcomes among older people.  This program announcement solicits both basic and
applied research proposals to investigate the multiple factors that influence
medication use by the elderly.  Goals of this announcement are to 1) identify the
epidemiological, psychosocial, health care and clinical factors associated with
medication use by older people, including the use of unconventional medical
products, 2) assess social, behavioral, psychological and cognitive factors that
play a role in older people"s understanding of and adherence to medication
regimens, 3) determine the role of medical and pharmaceutical professionals in
facilitating or hindering proper use of prescribed and over-the-counter
medications and unconventional medications including herbs and dietary
supplements, 4) refine methodologies to link these factors to medical or
psychosocial outcomes, 5) investigate interventions to improve medication
adherence and 6) increase our understanding of biological factors which
contribute to therapeutic outcomes in the use of medications by the elderly. 
This Program Announcement solicits research on people in a range of residential
or treatment settings (e.g., home, community, hospital, nursing home), with
interventions directed at older people themselves, their family caregivers, or
health care professionals.  There is primary interest in understanding the
influence that racial/ethnic, SES and gender play on the use of and outcomes of
different drug regimens or unconventional medical products, and the need to
develop and evaluate culturally sensitive interventions. Similarly, there is
interest in cross-cultural influences on medication behaviors and outcomes. While
the main focus is on human populations, studies utilizing animal models of human
aging and age-related diseases are also appropriate to this program announcement.

HEALTHY PEOPLE 2000

Each NIH PA addresses one or more of 22 Health Promotion and Disease Prevention
priority areas identified. These areas can be found via the WWW at
http://odphp.osophs.dhhs.gov/pubs/hp2000/hppub97.htm

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic for-profit and non-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of state and local governments, and eligible agencies of the
Federal government. Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

The mechanism of support will be the individual research project grant (R01). NIA
is also soliciting applications on this topic that have the potential for
commercial application (see SBIR and STIR solicitations, which are available on
the World Wide Web at: http://www.nih.gov/grants/funding/sbir.htm).
Responsibility for the planning, direction, and execution of the proposed project
will be solely that of the applicant.

RESEARCH OBJECTIVES

A recent report (Lazarou, Pomeranz, & Corey, 1998) found the incidence of serious
and fatal adverse drug reactions (any noxious, unintended, and undesired effect
of a drug which has been properly prescribed and administered, as defined by the
World Health Organization) to be extremely high among hospitalized patients. 
What is unknown is the extent of the broader problem of errors in drug
administration, or nonadherence, among the older population.  Failure to follow
medication instructions or to take medications as prescribed, whether intentional
or unintentional, is a significant problem in virtually all younger and older
patient populations.  However, adherence among older patients may be of greater
concern due to their heightened susceptibility to adverse drug reactions,
differential responsiveness to side effects, greater exposure to prescription and
over-the- counter drugs, physical and cognitive limitations, or a combination of
these and other risk factors (e.g., the higher prevalence of co-morbidities). 
Furthermore, adverse drug effects may manifest differently in older people
compared to younger age groups.  Because older people living in the community
consume one-third of all prescriptions, with most taking at least one medication
and typically as many as four, these problems represent a serious health concern
for the elderly.

There is a relative lack of valid and reliable data on medication use in older
age, especially among racial/ethnic minorities.  Estimates suggest that 90% of
all outpatients make mistakes in taking prescribed medicines, and that failure
to follow the proper regimen results in 30 þ 50% failure rate in achieving
clinical results (National Council on Patient Information and Education, 1995). 
Prescription drug-related illnesses cost over $1 billion a year, including costs
associated with 1.5 million extra hospital days, and over 100,000 deaths annually
from side effects of prescription medicine.  Nonadherence is potentially more
serious in older people and is associated with higher treatment costs.

Among the elderly, there is increasing availability and use of dietary
supplements, herbal products, vitamins, minerals and hormones taken for the
prevention and treatment of disease and in an attempt to improve well being.  The
reasons, motivations, and patterns of this use are not well understood nor is the
potential for adverse effects of such use along with conventional drugs. Failure
of many patients to discuss this use with their physicians makes the situation
more complex and risky (Eisenberg, 1993).

The current focus on medication use and outcomes among the elderly is
particularly timely, due to growing concerns about polypharmacy and associated
drug side effects, chronic drug use among older people, heightened industry
testing of medications for the elderly, women"s health and minority aging issues,
and changes in the health care system.  To get a clear picture it is important
to examine health system and provider prescribing patterns as well as patient
drug taking behaviors.  It is becoming increasingly clear that medication
adherence is a complex behavior and that effective interventions to improve
adherence can be developed only when mechanisms underlying the behavior are
better understood (Park & Jones, 1997).  The behavioral and social sciences have
contributed to knowledge in this area through research on comprehension of drug
labeling and information, behavioral and social factors influencing compliance
in older people, influence of changing health care system on drug management
issues, and interventions to enhance adherence and appropriate prescription
behaviors.  Research has identified some effective strategies for improving
adherence, including patient information strategies, patient-centered counseling,
behavioral reinforcement and patient support strategies, strategies related to
the regimen, strategies aimed at health professionals, and organizational-level
strategies.

Cultural and gender diversity among the elderly may be another barrier to
medication adherence.  Issues in dealing with special populations include
provider misconceptions about cultural or gender beliefs or practices and the
impact of these misconceptions on provider patterns, culturally-based beliefs
about medications, illness, and aging among patients and their families, and
language and other barriers to effective communication with health-care
providers.  Furthermore, there may be differences in the prevalence of conditions
among minority populations, as well as variation in the pathophysiology of
disease processes.  Attention to issues of medication adherence unique to special
and minority populations, along with current research on diseases and conditions
that disproportionately affect minority elders, may further help to alleviate the
disease burden faced by these populations (Institute of Medicine, 1997).  The
Food and Drug Administration Office of Women"s Health has initiated a targeted
public information campaign to raise awareness about safe use of medicines and
ways in which women as principle users of medications and family health
counselors can use medicines more wisely (1999).

Further research is needed to understand which elderly subgroups are at greater
risk for various types of nonadherence, the specific barriers encountered by
aging individuals, and ways to address these problems.  Topics needing research
attention include: the extent and costs of inappropriate drug use, the cognitive,
behavioral, and social factors influencing medication use, strategies for
reducing medication errors and increasing compliance, development of drugs for
specific conditions (dementia, sleep, cancer) and drugs that reduce side effects
that limit compliance, and minority/ethnic and gender considerations in
pharmacokinetics and drug taking behaviors.

Institute of Medicine.  1997.  Pharmacokinetics and drug interactions in the
elderly and special issues in elderly African-American populations.  Workshop
summary.  Committee on Pharmacokinetics and Drug Interactions in the Elderly. 
National Academy Press, Washington, D.C.

Lazarou, J., Pomeranz, B.H., & Corey, P.N.  (1998).  Incidence of adverse drug
reactions in hospitalized patients:  A meta-analysis of prospective studies. 
JAMA, 279(15), 1200-1205.

National Council on Patient Information and Education.  1995.  Prescription
medicine compliance:  A review of the baseline of knowledge.  Washington, D.C.

Eisenberg, D.M., Kessler, R.C., Foster, C., Norlock, F.E>, Calkins, D.R., and
Delbanco, T.L. (1993) Unconventional medicine in the United States þ prevalence,
costs, and patterns of use. N. Engl. J. Med., 328:246-252.

Park, D.C. & Jones, T.R.  1997.  Medication adherence and aging.  Handbook of
Human Factors and the Older Adult.  Academic Press, pp. 257-2871.

The following are offered as illustrations of appropriate topics for research. 
Applications need not, however, be limited to these specific issues.

Medication use among older people.  While there are some widely quoted statistics
about drug prescribing and taking behaviors, more research is needed in pharmaco-
epidemiology to provide better data on who is being prescribed and who is taking
specific types of medications.  Further research is needed to determine the
magnitude of the problem of medication misuse and adverse side effects among
older adults.  Suggested topics for research:

o Racial, cultural and gender differences in medication prescription and use
patterns, adverse side effects, and consequences of noncompliance in old age

o The magnitude of and costs due to inappropriate prescribing or medication
misuse in the elderly, including additional physician, clinic, or emergency room
visits, hospitalization, and care of uncontrolled chronic disease.

o The extent of over-the-counter medication and alternative therapy use by the
elderly, the impact of alternative medicine on the use of conventional
medications, the level of awareness among alternative medicine users of possible
adverse interactions between alternative and conventional medications, and
differences by ethnicity, income and education.

Individual, social and cultural factors that may predispose elderly to
nonadherence.  Studies are inconsistent in their findings regarding age as a risk
factor for non-compliance (in many cases studies did not include large numbers
of old people, and rarely are the oldest old included).  Factors associated with
age, rather than age per se, appear to explain the higher non-adherence rates
sometimes found in older populations.  Additional research is needed on the
individual and contextual factors that may predispose people to nonadherence as
they age.  Possibilities include number of medications prescribed or taken over-
the-counter,  complexity of prescribing schedules, physical or cognitive
limitations, lack of information regarding appropriate use, or failure to
comprehend medication instructions.  Additional research suggestions include:

o Influence of minority or ethnic status, socioeconomic status, illiteracy, and
education on medication prescribing practices and adherence behaviors among the
elderly.

o The impact of gender expectations, multiple family/work roles, and women"s
health concerns on prescription patterns and compliance behaviors.

o The role of caregivers in facilitating or hindering adherence to prescribed
regimens.

o The extent to which older peoples" noncompliance is related to erroneous health
beliefs, denial of illness or disease, or erroneous expectations from treatment.

o The extent to which age-related  cognitive changes limit compliance to
medication regimens.

Health care factors.  Some data suggest that as many as 20% of prescriptions
remain unfilled by patients.  These and other nonadherence issues may suggest a
lack of communication between medical providers/health care systems and patients
that may be exaggerated among racial/ethnic minorities, low income populations
or older women.  Areas to investigate include:

o How the content and format of delivery of prescription information to older
patients as well as mode of drug delivery (e.g., pill, patch, inhalants) may
influence adherence.

o How changes in the health care system, different health care settings, and
multiple providers may increase or decrease the vulnerability of older people to
medication errors.

o The role of physicians and pharmacists in medication prescription and
dispensing, including factors associated with initiating discussions about
adverse drug reactions.

o The role of aspects of the patient/health care provider relationship, 
including treatment satisfaction, inadequate communication, poor rapport, and
physician failure to elicit patient feedback.

o The economic aspects of medication behaviors, including both reimbursed and
out-of-pocket costs, and implications for prescription and use patterns.

Outcomes and Intervention Research.  Multiple outcomes should be assessed to
determine short- and long-term effects of medication nonadherence on the physical
health and functioning of older people.  Outcomes include recall and
comprehension of medical information, compliance with medication regimen,
functional and health status outcomes, as well as cost effectiveness. 
Intervention studies can be targeted to improving health behaviors as well as
health status outcomes.  Areas needing further study include:

o Development of new tools or refinement of existing tools for examining the
nature and extent of over-the-counter and prescription nonadherence.

o Cost-effectiveness analyses on the outcomes of interventions to enhance
adherence.

o Intervention research on theory-based strategies for improving adherence with
medication regimens.  Research directed at patients, family members, or providers
(or any combination of the above), is encouraged.

o Techniques to improve physician prescribing behaviors and pharmaceutical
practices, including improving skills in listening for and eliciting information
about potential side effects with patients.

o The design of medication instructions and other tools to facilitate
understanding of and adherence to medication instructions.

o Development of more reliable means of detecting noncompliance.

o Interventions to reduce the number of drugs community-dwelling and nursing home
residents consume

o  Strategies to eliminate inappropriate sharing of medications within family and
friend networks.

Biological issues affecting medication use in the elderly.  One of the most
crucial areas of needed research is the prevention of negative outcomes due to
drug-related problems in the elderly.  Causes of therapeutic failure can be
attributed to a variety of biological and clinical mechanisms.  Further research
is needed to inform clinical decision-making in the use of medications in older
persons.  Animal studies directed at basic mechanisms of drug action and
interactions among drugs can contribute to research in this area. Suggested
topics for research on pharmacokinetics and drug interactions in aging
populations include:

o Age-related changes in cellular transport mechanisms and extrahepatic
metabolism and transport including the activity of different enzyme isoforms.

o Mechanisms that cause variable responses to medications in aging racial and
ethnic populations (e.g., race, ethnicity or gender).

o Age-related hormonal changes affecting drug metabolism or drug sensitivity.

o In vitro models for multiple drug regimens and multiple drug interactions that
may be predictive of and correlated with in vivo research.

o Models for drug interaction related to altered reflex activity and changing
homeostatic mechanisms.

o Changes with age in the effects of medications on sensory and motor systems and
the implications for drug use or misuse.

o Investigation of sensory and motor systems side effects in limiting compliance
to medications.

o Effects of medications on neural transmission and signal transduction in
sensory  and motor systems of aging organisms.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification is provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them.  This
policy applies to all initial (Type 1) applications submitted for receipt dates
after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and is available at the following URL address:
http://www.nih.gov/grants/guide/notice-files/not98-024.html

NOTE FOR APPLICATIONS FOCUSED ON AGING RESEARCH

Applications received in response to this program announcement are expected to
focus on scientific issues related to aging and to aging-related aspects of
disease. In describing the plan to recruit human subjects, investigators may cite
a focus on aging or on aging-related aspects of disease as the justification for
why children will be excluded. In this regard, applicants may use Justification
1, the research topic to be studied is irrelevant to children, from the policy
announcement.

APPLICATION PROCEDURES

Beginning with the June 1, 1999 receipt date, modular application, review, and
award procedures will apply to all competing individual research project grants
(R01), small grants (R03), and exploratory/developmental grants (R21) whose total
direct costs do not exceed $250,000 in any year.  Instructions for preparing
applications in the modular format may be found at:
http://www.nih.gov/grants/guide/notice-files/not98-178.html

Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines as indicated in
the application kit.  Application kits are available at most institutional
offices of sponsored research, or may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-435-0714, email:
GrantsInfo@nih.gov. Applications are also available on the World Wide Web at
http://www.nih.gov/grants/funding/phs398/phs398.html

The program announcement title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked.

Submit the signed, original, single-sided application, along with five exact,
single-sided copies and five collated sets of appendix materials to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040-MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public Health Service
referral guidelines.  Applications that are complete will be evaluated for
scientific and technical merit by an appropriate peer review group convened in
accordance with NIH peer review procedures. As part of the initial merit review,
all applications will receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit, generally
the top half of applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national advisory
council or board.

Review Criteria

o  Significance:  Does this study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this
field?

o  Approach:  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

o  Innovation:  Does the project employ novel concepts, approaches or method? Are
the aims original and innovative?  Does the project challenge existing paradigms
or develop new methodologies or technologies?

o  Investigator:  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

o  Environment:  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?

The initial review group will also examine: the appropriateness of proposed
project budget and duration, the adequacy of plans to include both genders,
children and minorities and their subgroups as appropriate for the scientific
goals of the research, or the justification for their exclusion, plans for the
recruitment and retention of subjects, the provisions for the protection of human
and animal subjects, and the safety of the research environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding decisions:

o  Quality of the proposed project as determined by peer review
o  Availability of funds
o  Program priority

INQUIRIES

Inquiries are encouraged. The opportunity to clarify any issues or questions from
potential applicants is welcome (E-mail correspondence is preferred). Please note
that this is an ongoing solicitation and that standard application deadlines
apply.  Further information about NIA priorities and procedures can be found on
the NIA Home Page at: http://www.nih.gov/nia.

Direct inquiries regarding specific programmatic issues to the staff of the
appropriate Institute/Center:

Marcia G. Ory, Ph.D., M.P.H.
Behavioral and Social Research Program
National Institute on Aging
7201 Wisconsin Avenue, Room 533 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 402-4156
FAX:  (301) 402-0051
Email:  Marcia_Ory@nih.gov

Judith Finkelstein, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Room 3C07, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  Judith_Finkelstein@nih.gov

Stanley Slater, M.D.
Geriatrics Program
National Institute on Aging
7201 Wisconsin Avenue, Room 3E327, MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-6761
FAX:  301-496-1494
Email: Stanley_Slater@nih.gov

Frank Bellino, Ph.D.
Endocrinology Program Administrator
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Room 2C231, MSC 9205
Bethesda, MD  20892-9205
Telephone: 301 496-6402
Fax: 301 402-0010
Email:  Frank_Bellino@nih.gov

Division of Extramural Research, Training and Review
National Center for Complementary and Alternative Medicine
31 Center Drive, Room 5B-36
Bethesda, MD  20892-2182
Telephone:  (301) 402-2466
FAX:  (301) 402-4741

Direct inquiries regarding fiscal matters at NIA to:

Mr. David Reiter
Grants Management Office
National Institute on Aging
7201 Wisconsin Avenue, Room 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  David_Reiter@nih.gov

OTHER INTERESTS IN THIS RESEARCH AREA

Although not a formal sponsor of this program announcement, the National
Institute of Mental Health is interested in receiving applications on medication
use in older people as it relates to mental disorders or associated disability. 
Studies are particularly encouraged in the area of adherence and compliance to
medication regimens prescribed for the treatment of mental disorders. Proposals
to investigate factors associated with medication use and its outcomes, to study
influences on older persons" understanding of and adherence to psychotropic
medication regimens, to assess the roles professionals play in medication use
patterns, or to develop and refine new interventions or linking methodologies in
this area will be assigned to the Division of Mental Disorders, Behavioral
Research, and AIDS.  For such studies, please contact Peter Muehrer, Ph.D.,
Health and Behavioral Sciences Research Branch, NIMH at (301) 443-4708, Email: 
pmuehrer@nih.gov.  Proposals to investigate epidemiological patterns of
psychopharmacological medication use in the elderly population or to test
interventions designed to improve medication adherence will be assigned to the
Division of Interventions and Services Research.  For such studies, please
contact George Niederehe, Ph.D., Adult and Geriatric Treatment and Preventive
Intervention Research Branch, NIMH at (301)443-9123, Email:
gniedere@mail.nih.gov.

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.866.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410), as amended by Public Law 99-158, 42 USC 241
and 285) and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.



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