Full Text AG-96-001

TRIAL OF A COGNITIVE INTERVENTION FOR OLDER ADULTS

NIH GUIDE, Volume 24, Number 34, September 29, 1995

RFA:  AG-96-001

P.T. 34, CC

Keywords: 
  Aging/Gerontology 
  Cognitive Development/Process 
  Clinical Trial 


National Institute on Aging
National Institute of Nursing Research

Letter of Intent Receipt Date:  January 15, 1996
Application Receipt Date:  March 20, 1996

PURPOSE

This Request for Applications (RFA) seeks applications to pursue a
cooperative field trial of a cognitive or related perceptual
intervention to maintain and promote independent functioning among
older adults.  This RFA targets older adults who are at increased
risk for loss of independence through hospitalization, need for
formal care, or other major restrictions in quality of life.

A number of recent findings have indicated some promise of preventing
or postponing declines in critical activities of daily living through
intervention to improve cognitive or related perceptual abilities and
skills.  However, differences in the outcome measures examined, the
kind of intervention chosen, and the samples tested indicate that it
is not possible to generalize from individual findings to reach
consensus on the success or failure of these techniques.

The objective of this project is to stimulate researchers to develop
a cooperative trial investigating whether a common cognitive
intervention conducted by several sites simultaneously can improve
functioning or postpone decline in different samples of subjects,
varying in racial, ethnic, gender, socioeconomic, and cognitive
characteristics.  The common protocol will then allow a consensus
assessment of the success of this approach with respect to the
likelihood of preventing or postponing the loss of independence, need
for formal care, or other major restrictions in quality of life.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priorities. This RFA, Trial
of a cognitive Intervention for Older Adults, addresses several
priority areas including chronic disabling conditions, physical
activity and fitness, and unintentional injuries as they relate to
older people.  Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report:  Stock No. 017-001-00474-0 or Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of
Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202/512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, 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 support mechanism for these awards will be the cooperative
agreement (U01), an assistance mechanism in which substantial NIH
scientific involvement with the awardee is anticipated during
performance of the activity, as outlined in the award.  Under the
cooperative agreement, the NIH purpose is to support and/or stimulate
the recipient's activity by involvement in and otherwise working
jointly with the award recipients in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the
activity.  Details of the responsibilities, relationships, and
governance of the study to be funded under the cooperative agreements
are discussed later in this document under the section "Terms and
Conditions of Award."

Five years of support should be requested.  At that time, depending
on the results of the exploratory trial, a second RFA may be issued
to pursue a full-scale trial of the intervention.

FUNDS AVAILABLE

Field Sites

It is estimated that $1,380,000 in total costs will be available in
the first year for start-up costs associated with the field sites.
Funds available for the field sites in the second and subsequent
years are expected to increase to $2,700,000 in total costs.  These
funds are expected to support five to seven sites at an average cost
of $450,000 in total costs.

Site-specific protocols will be allowed, but will have a maximum of
$50,000 in total costs each per year.  The purpose of the maximum
amount is to protect the integrity of funding for the common
protocol.

Coordinating Center

In the first year, up to $80,000 will be available for start-up costs
associated with the coordinating center.  In the second year up to
$200,000 is expected to be available.  In the third year these funds
are expected to increase to $400,000 and in the fourth and fifth
years the available funds are expected to be $600,000. All estimates
are expressed as total costs.  These funds will support one
coordinating center.

This level of support is dependent on the receipt of a sufficient
number of applications of high scientific merit.  Although this
program is provided for in the financial plans of NIA and the NINR,
the award of cooperative agreements pursuant to this RFA is
contingent on the availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

The long-term goal of this initiative is to reduce the increasing
public health problems of need for formal care, hospitalization, and
substantial loss of independence in the Nation's growing number of
older persons.  Persons over the age of 65 account for almost half of
all days of care in short stay hospitals and constitute the majority
of residents of nursing homes.  Interventions that can postpone or
prevent hospitalization or formal care, therefore, have much to
contribute both to public health and to the quality of life among
older people.  The immediate goal of this initiative is to examine
the effects of perceptual and cognitive interventions on more
proximal outcome measures that are associated strongly with
hospitalization and need for formal care.

The impetus for this trial comes from (a) the recent success of a
number of different cognitive, or related perceptual, intervention
techniques at enhancing some aspects of ability or functioning; (b)
the increasing evidence that cognitive factors are associated with
key public health outcomes such as hospitalization and death; and (c)
the increasing need to find preventative techniques that successfully
maintain the quality of life of the older population.

Studies reporting success with laboratory-based interventions
include: Interventions to increase scores on intellectual abilities
(e.g., Baltes & Willis, 1982; Labouvie-Vief & Gonda, 1976; Hayslip,
1989; Hayslip, Maloy, & Kohl, 1995; Willis, 1987); techniques to
improve speed of reaction (Baron & Mattila, 1989); training to boost
functional perceptual abilities (Ball, Beard, Roenker, Miller, &
Griggs, 1988) and training on various aspects of memory (Greenberg &
Powers, 1987; Yesavage, 1985).

Several studies have also identified a relation between the abilities
and skills being intervened on and performance on everyday activities
of critical importance to independent functioning (Leirer, Morrow,
Pariante, & Sheikh, 1988; Owsley, Ball, Sloane, Roenker, & Bruni,
1991; Ball, Owsley, Sloane, Roenker, & Bruni, 1993).

Recent research has confirmed earlier findings of an association
between decline in cognitive functioning and measures of
hospitalization, need for formal care, and mortality.  Analyzing data
from the Longitudinal Study on Aging, Wolinsky and Johnson (1991)
found that a factor they call advanced activities of daily living
(advanced ADL) was uniquely associated with bed-disability days,
hospital contact and mortality.  The advanced ADL measure was
constructed to focus on cognitive capacity and included measures of
telephone communication and planning for the future.  Several studies
using a range of measures of cognitive impairment have established
associations with quality of life of family members and risk of
institutionalization (e.g., Branch & Jette, 1982).  More recently,
Kelman, Thomas, and Kennedy (1994) have identified an association
between both mild and severe cognitive impairment and mortality in
community-dwelling elderly.  Swan, Carmelli, and LaRue (1995)
reported that performance on the digit-symbol substitution test was
associated with five-year mortality in their sample of older men.
The association remained after adjustment for age, education,
baseline serum cholesterol, and blood pressure. The association was
of the same order as that of a subgroup of subjects with a history of
cancer.

The above promising findings demonstrate the success of cognitive
interventions at improving performance in activities of daily living,
and illustrate the now clear links between decline in cognitive
function and subsequent hospitalization, need for formal care, and
mortality.  Nevertheless, no clear consensus exists on the likelihood
of success of cognitive interventions at reducing the public health
problems of hospitalization and need for formal care in the older
population.  Differences in the outcome measures examined, the
interventions tested, and the samples recruited have made
generalizations across different findings impossible.  This trial
seeks to address these problems by testing a planned intervention on
defined samples using common outcome measures. Therefore, the trial
will explore whether site-specific variations or specific sample
characteristics limit the applicability of the findings.

Study Design

The scientific goal of the trial is to test the efficacy, using field
measures of functioning, of a cognitive or related perceptual,
motivational and attitudinal intervention that has previously been
found to be successful at improving functioning under laboratory or
small-scale field conditions.  The focus should be on older adults
who are identified to be at risk of loss of independence from causes
to which the variables under study contribute.  The particular
protocol to be developed must provide tests of theories linking
changes in degree of independence, to increases or decreases in
intellectual and perceptual strategies and processes.

Therefore, in order to retain the advantage of a multisite field
trial, yet capitalize on the interventions already found to be
successful in laboratory studies (see below), the trial should focus
on a class of outcome measures that are basic to living
independently, have a strong cognitive component, and whose decline
has been associated with loss of independence.  These significant
everyday tasks include, but are not limited to: communicating via the
telephone, remembering key events and activities (e.g., remembering
to eat, remembering to take medication), and financial planning and
management.  The intended subject populations must be living largely
independent of formal care at the point of entry into the study.
Improvement, or postponement of decline, in the activities of daily
living (telephone communication, financial management, etc.) should
be the primary outcome variable.  The final protocol will be designed
to allow maximum power on tests of the intervention on this class of
variables.  Investigators are also encouraged to develop tests for
secondary outcome variables, such as hospitalization, need for formal
or informal assistance, disability, morbidity, or mortality.
However, power calculations should be based on the primary indicator
(or indicators) of outcome.

The common intervention should involve training of basic abilities or
skills, or training on factors expected to boost such basic abilities
or skills.  Thus, the study should not intervene directly on the
outcome variables.  The study should include intermediate
examinations of maintenance of training effects on the basic
abilities and skills.  Failure to show maintenance of these effects
may be considered a reason to stop the trial.  These tests do not
substitute for final analyses of the effects of the intervention on
the primary outcome variables.  Such a test should be planned to be
conducted at a time beyond the initial intervention determined by
power calculations on differences in the expected relative rate of
decline among experimental comparison groups.

Particular sites may also propose studies that are planned as site-
specific.  These studies should be planned to complement or extend
the multisite protocol.  For example, they may address issues of the
specificity of transfer.  They may compare the efficacy of training
versus cuing (or other environmental support) as a means of
maintaining or increasing competence in critical everyday tasks. They
may compare the efficacy of intervening on basic abilities alone
versus on outcome variables alone, or in combination with training on
basic abilities.  Such separate hypotheses must be integrated with
the planned cooperative project in such a way that their
investigation does not compromise the integrity of the cooperative
trial across sites.

Each application (except for the coordinating center) should propose
one intervention as its candidate for the cooperative trial as a
whole.  The intervention should be designed to improve performance on
outcomes that:  (a) rely on intact cognitive functioning; and (b) are
critical for maintaining independence. These outcomes include but are
not limited to: telephone communication, financial management and
planning, and remembering key events or instructions.  Subsequently,
a common protocol will be developed by the steering committee
combining the best features of the proposed protocols; this
intervention will be used by all field sites.

The outcome measures must be justified by:  (a) an analysis showing
the degree to which the intervened abilities or skills are related to
the outcome being measured; (b) their association with direct
measures of loss of independence or disability, morbidity or
mortality (e.g., hospitalization, need for formal care, bed-
disability days); and (c) their estimated sensitivity to tests of the
effect of the proposed intervention.

Applications must address the issue of the likelihood of transfer of
training from the cognitive abilities and skills examined to the
primary outcomes proposed.  Several recent studies have found that
although training is successful at boosting cognitive abilities,
transfer to other skills is limited (e.g., Dittman-Kohli, Lachman,
Kliegl, & Baltes, 1991, Neely & Backman, 1995).  Applications must
offer a theoretical rationale as to why transfer would be expected.

If the proposed outcome assessment is limited to self- or proxy-
report of functioning, the particular self-report or proxy-report
surveys used must previously have been validated against relevant
outcomes.  Simulations may be used as manipulation checks or to
provide additional measurement of the outcome.  However, the primary
outcome measures upon which the intervention is evaluated must be a
clearly delimited set, justified by the criteria described above.

The intervention that is adopted for this trial as a whole will be
conducted cooperatively by all field sites participating in the
trial.  Therefore, in order to ensure uniform administration across
sites, investigators must propose standardization criteria for
assessing baseline and follow-up performance on the outcome measures
as well as standardization criteria for implementing the
intervention.

The initiative will examine an intervention designed to prevent, or
reduce the risk of, future loss of independence rather than
rehabilitate older adults who are already dependent.  Therefore,
subject groups should be selected who are at recognizable risk of
loss of independence but who are living independently at the point of
entry into the study.  Relevant risk factors can include demographic
and social, as well as cognitive factors.  Applications may propose
screening and eligibility criteria to identify target subjects.  The
criteria should be expected to eliminate both those who are at little
risk of loss of independence over the term of the study and those
who, because of a prevailing disease or medical condition (e.g.,
Alzheimer's disease), would be poor candidates for intervention.
However, costs of screening must be carefully controlled to
accommodate the overall budget for the study.  Investigators may wish
to consider collaborating with sites in which there are studies
ongoing that use well described samples whose cognitive abilities are
already known.  Such collaboration may substantially reduce the costs
of screening.

This initiative is focused on an assessment of the intervention at a
substantial interval after treatment.  Therefore, proposed designs
must be able to accommodate attrition as well as test the efficacy of
the treatment on those subjects who adhere to instructions throughout
the testing period.  Potential applicants should be familiar with
appropriate methodological approaches to minimizing attrition, should
indicate the expected amount of attrition, and  should justify the
approach to minimizing attrition that they propose to adopt.  Because
this field trial is preliminary, power calculations on the primary
outcome measures should be based on the number of subjects expected
to complete the study, rather than the total number recruited into
the study.  However, attrition rates substantially higher than
expected will be considered a reason to stop the study.

Moreover, because the initiative focuses on a delayed assessment, the
design for the multisite trial should include intermediate tests of
maintenance of the intervention on the targeted basic abilities.  The
design may also include strategies to ensure maintenance of the
intervention's effects, including booster training sessions.

SPECIAL REQUIREMENTS

A coordinated multisite protocol is dictated by the need to have a
planned intervention examined on a defined sample using a common set
of outcome measures.  The terms and conditions section describes the
elements and organization required to assure that a common protocol
can be agreed upon, and that recruitment and operating procedures are
standardized across intervention sites.  Multiple intervention sites
will conduct the common protocol.  A coordinating center will
interact with the intervention sites to ensure the smooth conduct of
the trial and to organize data collection and analysis.  A steering
committee will be the main decision-making body for the trial.  An
advisory panel, chosen by the steering committee, will provide advice
to the committee on the performance of particular sites and on the
progress of the trial.

These intervention sites may also run site-specific studies designed
to complement the multisite protocol.  Such studies will not be part
of the multisite protocol.

The following terms and conditions will be incorporated into the
award notice.

Terms and Conditions of Award

The following special Terms of Award are in addition to, and not in
lieu of, otherwise applicable OMB administrative guidelines, HHS
Grant Administration Regulations at 45 CFR Parts 74 and 92 and other
HHS, PHS and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a
cooperative agreement (U01).  Consistent with this concept, the
dominant role and prime responsibility for the activity resides with
the awardees for the project as a whole, although specific tasks and
activities in carrying out the collaborative aspects will be shared
among the awardees and the NIA/NINR scientific coordinators.

1.  Organizational Components

Intervention Sites

An intervention site is one of several institutions that will receive
awards for conducting the multisite protocol under this RFA.  The
Principal Investigator at each applicant intervention site is
encouraged to form a multidisciplinary team, including a senior staff
member or consultant who has expertise in clinical trials.  Each
intervention site will be responsible for recruiting subjects,
collecting data using the common protocol, and submitting data to the
coordinating center.  Intervention site may conduct site specific
studies.

Coordinating Center

The coordinating center will interact with the intervention sites, an
advisory panel, and the NIA/NINR scientific coordinators on a variety
of topics ranging from seeking and compiling information, to
providing technical assistance, to conducting cross-site analyses.
In consultation with other organizational components, the
coordinating center will have the primary responsibility for
instrument development and testing activities (e.g., compiling the
listing of proposed common measures; reviewing the literature and
assessing the advantages and disadvantages of different measures for
common study variables; conducting psychometric analyses on the
common data set; and making recommendations at the end of the study
about the most parsimonious set of measures to be archived).

Moreover, the coordinating center will be responsible for tracking
recruitment and retention across the different sites, and advising
the sites on strategies for enhancing recruitment/retention,
especially in minority populations.  The coordinating center will
also ensure that data collection is standardized, and will manage and
analyze the common data set.  This work will also include setting up
data collection systems at the different intervention sites and
visiting the sites to set up these data systems.

The coordinating center will also provide certain support functions.
It will develop a cross-project manual of procedures, maintain a
directory of intervention sites' staff, arrange all conference calls
and meetings, and facilitate information exchange among the sites and
NIH, and with the general research community.

Steering Committee

A steering committee, composed of one principal investigators from
each field site, the principal investigator at the coordinating
center, and the NIA/NINR scientific coordinators, will be the main
governing body of the study.  The steering committee will elect a
chair from among the principal investigators.  The steering committee
may also establish subcommittees to oversee major operational
components of the study.  One vote will be given to each principal
investigator and to the NIH.  The steering committee will meet at
least every six months.  The steering committee will have overall
responsibility for the multisite intervention and will review, for
inclusion in the protocol, proposals from its members for any
modifications designed to facilitate any aspect of recruitment,
design, or analysis.  The steering committee will specify the common
data set to be collected, using the information in this RFA as a
guide.  With the advice of coordinating center staff, it will specify
procedures and frequency of data submission to the coordinating
center.  It will specify rules concerning access to data generated
from the multisite protocol.

The steering committee will establish a publications subcommittee to
advise on publication and presentation of data collected through the
multisite protocol.  The chair of the steering committee will also
serve as the chair of the publications subcommittee.  The
publications subcommittee will review all  proposed presentations and
publications using data from the common protocol.  The subcommittee
will be responsible for setting standards and guidelines for
presenting and publishing data from the common protocol.  The
subcommittee will also advise on public information dissemination
activities regarding the common data set. These requirements are not
intended to jeopardize individual investigators' rights to their own
data, but are intended to facilitate data sharing and collaborative
work.

Advisory Panel

An advisory panel will be selected by the steering committee to serve
in an advisory capacity to the study and all its organizational
components.  The functions of this panel include reviewing the
multisite intervention protocol and making suggestions to the
awardees and the NIA/NINR scientific coordinators; monitoring
individual site performance, using material provided by the
coordinating center and through site inspections;  advising the
steering committee on design and protocol changes requested by
individual investigators; reviewing site-specific protocols and
advising on disagreements regarding site-specific studies; and
advising the awardees and NIA/NINR scientific coordinators regarding
analyses and publications arising from the multisite protocol.  The
panel will also serve as a data and safety monitoring board for the
multisite protocol.  In that capacity panel members will monitor the
protocol at individual sites for possible adverse effects associated
with the design and for variations from prevailing NIH policy on
treatment of human subjects.

The panel will consist of at least six experts in relevant
behavioral, clinical, statistical, and bioethical fields and will
convene at least once a year.  The experts must be independent of all
components of all sites participating in the multisite protocol and
be free from conflicts of interest with awardees.  A chair will be
elected by members of the advisory panel with input from the NIA/NINR
scientific coordinators.  The chair of the steering committee, the
principal investigator of the coordinating center, and the NIA/NINR
scientific coordinators will all participate as non-voting members
during each panel meeting.  Interim conference calls and other
correspondence may be necessary between meetings.  Two panel members
will visit each of the field sites and the coordinating center twice
during the course of the multisite protocol.  The members will report
back to the full advisory panel on the site's compliance with data
collection and record keeping procedures and with safety and ethical
issues concerning human subjects.

2.  Responsibilities

Awardee Rights and Responsibilities

Awardees individually propose a research design for the common
protocol and collectively decide on the design for the common
protocol.  They are responsible for data analysis.  Through the
steering committee, they are responsible for changes in the direction
of the project and the scope of activities at particular sites.
Through a publications committee, they are responsible for preparing
publications from the multisite protocol.  The individual awardees
are responsible for recruitment and retention at their own sites.
The coordinating center awardee is responsible for developing and
updating a manual of operations and for quality control at the
different field sites.

Awardees will retain custody of and have primary rights to the data
developed under these awards, subject to Government rights of access
consistent with current HHS, PHS, and NIH policies.

NIH Staff Responsibilities

The NIH scientific coordinators will have substantial
scientific/programmatic involvement during conduct of the activity,
through technical assistance, advice, and coordination above and
beyond normal program stewardship for grants.  Such assistance is
intended to facilitate, not to direct, the design, implementation and
analysis of the trial.  Awardees agree to accept assistance from the
NIA/NINR scientific coordinators in:

o  providing technical assistance for developing the common protocol
for the multisite intervention, and for formulation or consideration
of refinements and adjustments to the study objectives, design and
protocol;

o  monitoring of performance issues involved in recruitment, follow-
up, quality control, adherence to protocol, and attainment of study
objectives;

o  assistance in analysis and reporting of the multisite intervention
study results;

o  assistance in identifying subject-matter and financial experts to
help the steering committee;

o  assistance in locating potential replacements for key personnel
involved in the project.

The NIA/NINR scientific coordinators may also provide advice on
statistical requirements.  In instances where the NIA/NINR scientific
coordinators has had significant input into study design and
analysis, and in accordance with publication guidelines developed by
the publications committee,  and with NIH policies regarding staff
co-authorship of publications resulting from extramural awards,
he/she may cooperate with awardees as a co- author in preparing
manuscripts that report results from these studies.

As part of these duties, the NIA/NINR scientific coordinators will
meet at least three times with other steering committee members in
the first year of the award, and at least twice a year in subsequent
years.  The scientific coordinator will also meet at least once a
year with advisory panel members.

Collaborative Responsibilities

Development and monitoring of common protocol.  The awardees, with
the assistance of such other experts as are deemed necessary by the
steering committee, shall develop, within six months of the official
start date of the awards, a single common protocol for multisite
testing of the intervention, drawing upon the best aspects of the
applicants' proposals.  The protocol will be reviewed by an advisory
panel that is chosen by the steering committee.  The advisory panel
will recommend changes to the steering committee not later than three
months after receiving it.  The steering committee will then decide
on the final form of the protocol.  Awardees will be required to
accept and implement the common protocol and procedures approved by
the steering committee.

Following implementation of the protocol, the steering committee will
meet at least twice a year, once may be by teleconference, to
consider progress at individual sites, progress in the multisite
protocol as a whole, and any modifications to the protocol either at
individual sites or across all sites.  The steering committee will
consider advice from the advisory panel as well as input from
steering committee members in making decisions regarding the common
protocol.

Site-specific studies.  Individual awardee investigators who conduct
site-specific studies in conjunction with the overall trial must
submit any proposed study, or modification to a study, to the
steering committee regardless of whether the study or modification is
considered to affect the management or implementation of the common
intervention protocol.  Before approving a single-site protocol, the
steering committee will determine whether the proposal complements or
extends the overall project, and whether it interferes with the
common protocol.  The $50,000 maximum funds for a site-specific study
may be reduced by the steering committee.

Arbitration Process

Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the NIH
may be brought to arbitration.  An arbitration panel will be composed
of three members - one selected by the steering committee (the NIH
representative will not vote) or by the individual awardee in the
event of an individual disagreement, a second member selected by the
NIH, and the third member selected by the prior two selected members.
This special arbitration procedure in no way affects the awardee's
right to appeal an adverse action in accordance with PHS regulations
at 42 CFR 50, Subpart D, and HHS regulations at 45 CFR Part 16.

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 subpopulations 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 new policy results
from the NIH Revitalization Act of 1993 (section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.

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

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by January 15, 1996, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of the key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.  Although a letter of intent
is not required, is not binding, and does not enter into the review
of a subsequent application, the information that it contains allows
NIH staff to estimate the potential review workload and avoid
conflict of interest in the review.

The letter of intent is to be sent to:

Dr. Jared B. Jobe
Behavioral and Social Research
National Institute on Aging
Gateway Building, Room 533
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-3137
FAX:  (301) 402-0051

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 6701 Rockledge Drive, Room 3034, Bethesda, MD 20892-7762,
telephone 301/435-0714, girg@drgpo.drg.nih.gov; and from the program
administrator listed under INQUIRIES.

The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title and number must be typed on
line 2a of the face page of the application form and the YES box must
be marked.

With the exception of coordinating center applications (see below),
instructions in the PHS-398 form should be followed as if the
application were a regular (R01) research grant request.

Additional Information

The information below is requested in addition to the requirements in
the PHS 398 package.  With the exception of the budget information,
all additional information described below should be presented as
part of the research plan, which is limited to no more than 25 pages.

1.  Choice of Outcome Variables

As part of the proposed common intervention each application must
propose primary outcome variables that are:  (a) measures of
activities of daily living; and (b) have a strong cognitive or
perceptual component.  In particular, applications must offer
empirically supported models of the relation between the outcome
variables and the cognitive or perceptual abilities and skills being
trained.  Estimates of the effects of the intervention on these
outcome variables must yield sufficient power so that a multisite
trial with the budget structure and amount shown under FUNDS
AVAILABLE can provide an adequate test of the hypotheses on these
outcome variables.

2.  Multisite and Single-site Interventions

Any intervention proposed by  an applicant as the common protocol
must be justified by prior published work.  These studies must be
directly related to the proposed intervention and allow estimates of
the likely size of effect of the intervention on samples to be
recruited through this trial.  Such prior publications are not
necessary for interventions proposed as single-site studies.  As with
a conventional grant, however, theoretical rationale, supporting
literature, and some supporting pilot data are an advantage.

3.  Sample Population

The application must specify the desired sample characteristics
(e.g., age, sex, ethnic status, health-status) and size of the
multisite sample required to test the proposed multisite
intervention.  The application must also specify characteristics of
the sample to be recruited at the local site.  The application must
specify the particular recruiting strategies to be used to attract
target subjects and any special outreach procedures that will be used
to ensure retention of diverse subject groups in the common protocol.
If the applicant is proposing collaboration with other investigators
who have already recruited well-defined samples to ongoing studies,
the letter of collaboration from the principal investigator of such
studies must specify the numbers of subjects available for the study
and their demographic profile.

4.  Screening Instruments

Any screening instruments that are proposed for the cooperative trial
must be justified both in terms of reliability of measurement and
validity in relation to the target subject populations. Estimates of
the proportion of subjects who would be excluded through these
instruments, and the costs of recruiting replacement subjects should
be clearly indicated.

5.  Data Analysis

The data analysis section should describe both the specific analyses
to be performed on site-specific studies, and the analytic plan that
yields the power estimates on which the proposed multisite
intervention is based.  A limited set of primary outcome variables
must be identified in the analysis plan.

6.  Cooperation

The applicant must indicate a willingness to work cooperatively with
the NIA/NINR scientific coordinators, the data coordinating center,
fellow principal investigators, and the advisory panel in pursuing
the research project.

7.  Organizational Structure

An organizational structure for the intervention site should be
described in the application, designating lines of responsibility and
authority.

8.  Budgeting

The applicants should prepare a detailed budget for the first twelve
months of the project at the applicant's institution (including sub-
contracts).  The applicants should assume that data collection does
not begin until the tenth month of the project.  During the first
nine months, funds should be budgeted for the principal investigator,
and two other investigators to travel to three steering committee
meetings in Bethesda.  Funds should also be budgeted for one meeting
a year subsequent to that in Bethesda.  Applicants should also
prepare a budget for the investigator's site-specific costs in all
years of the cooperative agreement.  Finally, the applicant should
prepare a budget for all years of the proposed cooperative
intervention across all sites.

The budget should reflect all costs of the multisite trial across all
sites.  Investigators are not required to identify all sites in their
application.  Costs should be projected using direct costs at the
applicant site as the base.  Applicants should use a 50 percent
indirect cost rate to estimate total costs at sites other than those
identified in the application.  Acceptance of funding under this RFA
implies agreeing to be a participant site for the multisite field
trial.

9.  Advisory Panel

Candidates should not be contacted or recruited to serve on the
advisory panel or be named prior to the onset of the project.
However, applicants are encouraged to specify areas of expertise
appropriate for representation on the panel.

Advisory panel members will be reimbursed for necessary travel and
attendance at advisory board meetings, but will not receive
consultant fees for input to individual projects.  Travel funds for
members of the panel are to be included as a line item in the
coordinating center budget.

Special Instructions for Coordinating Center Applications

Two completely different applications, with different principal
investigators, must be submitted if an institution seeks selection
both as an intervention site and as the coordinating center.

The coordinating center will provide expertise in multisite field
trial design, in the data management and communication associated
with such trials, and with multivariate statistical techniques
required for analysis and reporting of the results.  It is essential
that applicants show such expertise among the personnel selected for
the coordinating center.

Completion of PHS 398

The data coordinating center applications should use the form PHS 398
(rev.5/95).  However, the following procedures should be applied in
completing it.

1.  Human Subjects

The data coordinating center is not responsible for Institutional
Review Board review of human subject protocols. That is the duty of
the individual sites.

2.  Budget

Both the detailed budget for the first year and the full budget for
all years should reflect only costs specific to the data coordinating
center.  The first year budget should assume that data collection
begins in the tenth month of the award.  The budget should include
projected costs of travel by the advisory panel to the individual
field sites and to Bethesda.  The budget should include funds for one
annual visit to Bethesda by the advisory panel (assume six members of
the committee), and funds for two site-visits to each of the field
sites by two panel members across the five years of the trial.

3.  Research Plan

This section should reflect plans for data management (including
entering, editing, and storing of data); plans for data archiving;
plans for establishing an effective communication network among the
different project sites; plans for producing forms, protocols, and a
manual of operations for the multisite trial; plans for receiving
information from the sites on a regular basis; and plans for
integrating that information and providing summaries to the sites,
the NIA/NINR scientific coordinators, and the advisory panel.  The
section should also discuss strategies for enhancing recruitment and
retention of subjects at intervention sites, especially among
minority populations.  This section should also discuss succinctly
the alternative benefits of different approaches to data analysis.
(The data coordinating center will provide a key role in the design
of the multi-phase trial at the start of the project.  The center
will provide key expertise on how best to integrate the data from the
different sites, on the costs to data quality of individual site
variation in project design, and on the advantages and disadvantages
of different methods of pooling data.  These and other relevant
issues must be discussed in the application.)

All applicants, including coordinating center applicants, must submit
a signed, typewritten original of the application, including the
Checklist, and three signed photocopies, in one package to:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application
must be sent to:

Dr. Michael Oxman
Scientific Review Office
National Institute on Aging
Gateway Building, Room 2C212
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD  20892-9205

Applications must be received by March 15, 1996.  If an application
is received after that date it will be returned to the applicant
without review.  The Division of Research Grants (DRG) will not
accept any application in response to this RFA that is essentially
the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The DRG will not accept
any application that is essentially the same as one already reviewed.
This does not preclude the submission of substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by NIA/NINR.  Incomplete applications will be
returned to the applicant without further consideration.
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIA in accordance with the review
criteria stated below.  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 national advisory councils of NIA and NINR.

Review Criteria:  Field Sites

Both the proposed multisite intervention and single-site studies will
be evaluated for:

o  scientific significance and originality of the proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to conduct the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in
perceptual and cognitive functioning and aging;

o  availability of the resources necessary to conduct the proposed
research;

o  appropriateness of the proposed budget;

o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will be
evaluated.

The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.

The proposed multisite intervention will be evaluated for the
following additional criteria:

o  a demonstrated need for the intervention in the proposed target
population;

o  evidence that the intervention has worked in prior small-scale or
laboratory studies;

o  a theoretical rationale that links the targeted basic abilities to
the primary outcome measures proposed;

o  a recruitment strategy that shows how appropriate numbers of
suitable subjects can be recruited for the intervention and retained
in the study.  The recruitment strategy must include a description of
procedures to ensure adequate recruitment and retention of women and
minority subjects;

o  evidence of prior experience with multisite clinical or field
trial studies;

o  the time commitment of the principal investigator should be
sufficient both to ensure personal supervision of the day-to-day
running of that field site and to ensure time to work cooperatively
with the coordinating center, principal investigators of other field
sites, the advisory panel, and the NIA/NINR program administrators;

o  demonstrated willingness of the principal investigator and staff
to work collaboratively with the coordinating center, the other
principal investigators, the advisory panel and the NIA program
administrator.

Review Criteria:  Coordinating Center:

o  adequacy of the proposed operating procedures for the management
of the multisite intervention;

o  adequacy of the proposed plans for data management and archiving,
and for communication among field sites and the coordinating center;

o  appropriate discussion of alternative procedures for data
analysis;

o  leadership ability, relevant experience in appropriate areas, and
scientific stature of the principal investigator.  The time
commitment of the principal investigator must be sufficient both to
supervise the coordinating center staff and to liaise with principal
investigators of field sites, the advisory panel, and the NIA/NINR
program administrators;

o  qualifications and experience of other staff of the coordinating
center, and their investment of time in the project.  It is important
that some coordinating staff show prior experience in data analytic
and project-coordinating aspects of the management of a multisite
field trial;

o  Commitment from the host institution to the coordinating center's
activity and availability of appropriate facilities for the
activities proposed;

o  The appropriateness of the budget.

AWARD CRITERIA

Awards will be made on the basis of the availability of funds with
consideration being given to the compatibility of the different
projects funded and the overall representation of women  and
minorities across the sites selected.  Primary weight will be given
to results obtained through the NIH peer review mechanism.

Schedule

Letter of Intent Receipt Date:  January 15, 1996
Application Receipt Date:       March 15, 1996
Review by Advisory Councils:    September, 1996
Anticipated Award Date:         September 30, 1996

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Jared B. Jobe
Behavioral and Social Research
National Institute on Aging
Gateway Building, Room 533
7201 Wisconsin Avenue, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-3137
FAX:  (301) 402-0051
Email:  Jared_Jobe@nih.gov

Dr. J. Taylor Harden
Extramural Programs
National Institute of Nursing Research
Natcher Building 45, Room 3AN-12
45 Center Drive, MSC 6300
Bethesda, MD  20892-6300
Telephone:  (301) 594-6906
FAX:  (301) 480-8260
Email:  THarden@ep.ninr.nih.gov

Direct inquiries regarding fiscal matters to:

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

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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 Section 301 (42 USC 241)
and administered under PHS grant policies and Federal Regulations,
most specifically at 42 CFR Part 52 and 45 CFR Parts 74 and 92.
Special Terms of Awards applying to projects funded in response to
this RFA are in addition to, and not in lieu of, otherwise applicable
OMB administrative guidelines, HHS grant administrative regulations
at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH grant
administration policies.  Awardees will maintain custody of, and
primary rights to, their data developed under their awards, subject
to Government rights of access, consistent with current HHS, PHS, and
NIH policies.  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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