ALZHEIMER'S DISEASE RESEARCH CENTERS

Release Date:  January 22, 1999

RFA:  AG-99-003

P.T.

National Institute on Aging

Letter of Intent Receipt Date:  March 1, 1999
Application Receipt Date:  May 19, 1999

PURPOSE

The National Institute on Aging (NIA) invites applications from qualified
institutions for support of Alzheimer's Disease Research Centers (ADRCs).  These
are designed to support and conduct research on Alzheimer's disease (AD), and to
serve as shared research resources that will facilitate research in AD and
related disorders and distinguish them from the process of normal brain aging. 
Alzheimer's disease may presently affect as many as 4 million older people in the
United States.  Although it is occasionally identified in patients in their
forties and fifties, it is most frequently associated with advancing age.  It
doubles in prevalence with every five years past the age of 65; thus, extending
life by ten years quadruples the probability of the disease.  Alzheimer's disease
is the most frequent cause of institutionalization for long-term care.  It
destroys the active, productive life of its victims and devastates their families
financially and emotionally.  In 1993, it was estimated that the United States
spent as much as 100 billion dollars/year for the direct and indirect costs of
care for patients with Alzheimer's disease.  With the rapidly increasing
percentage of the population over the age of 65, the number of persons with AD
will increase proportionately, as will the toll it takes.

Both the Executive and Legislative Branches of the Federal Government have
expressed concern about the enormity of the problem posed by this disease. 
Congressional concern about Alzheimer's disease has focused on funding for
research on the causes and treatment of the disease, and on the cost of care. 
In 1984, Congress directed the National Institutes of Health (NIH), and in
particular the National Institute on Aging (NIA), to foster further research
related to Alzheimer's disease.  The NIA Alzheimer's Disease Centers (ADCs)
program is authorized by the Public Health Service Act, Section 445, and includes
fourteen Alzheimer's Disease Research Centers (ADRCs) and thirteen Alzheimer's
Disease Core Centers (ADCCs).

Centers are expected to provide an environment and core resources which will
enhance ongoing research by bringing together biomedical, behavioral, and
clinical science investigators to study the etiology, pathogenesis, diagnosis,
treatment, and prevention of AD, and to improve health care delivery.  Centers
will also foster the development of new lines of research and provide a suitable
environment for fellows and junior faculty to acquire research skills and
experience in interdisciplinary AD research.  The Centers provide investigators
and research groups with well characterized patients and control subjects, family
information, and tissue and biological specimens for use in research projects.
Each Center should develop in accordance with local talents, interests, and
resources, but should also be responsive to national needs related to Alzheimer's
disease.  Centers should be willing to work together with other Alzheimer
research groups in collaborative research activities and cooperate with other 
Federal, State, and Local agency-supported Alzheimer's disease programs in
furthering mutual goals.  Potential applicants are encouraged to utilize the
strengths of their particular institutions in preparing an application that will
cover the spectrum of required activities.  While types of activities that should
be included are indicated in these guidelines, specific approaches to accomplish
them are left to the applicant.

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 priority areas. This Request for Applications (RFA),
Alzheimer's Disease Research Centers, is related to the priority area of Chronic
Disabling Conditions.  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 for-profit and non-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of State or Local governments, and eligible agencies of the
Federal government.  Applications from racial/ethnic minority individuals, women,
and persons with disabilities are encouraged.  At the time of award, the
applicant institution cannot have another Alzheimer's Disease Center funded by
the NIA.

Institutions eligible for Alzheimer's Disease Research Center Grants (P50s) are
those at which there are (1) at least five principal investigators with any PHS
agency research grant or comparable peer reviewed research project (including
those funded by State governments or private foundations) related to
neurodegenerative diseases or aging of the nervous system, each with at least two
years of committed support remaining at the time of application or (2) one or
more program project (P01) grant(s) related to neurodegenerative diseases or
aging of the nervous system, which also have at least two years of committed
support remaining.  If P01 grant(s) exist, the work supported by the existing P01
should be different from that proposed in the ADRC and any overlap of the P01
cores with the P50 cores will be examined and adjustments made before funding.

MECHANISM OF SUPPORT

The support mechanism for this program will be the NIH Center Grant (P50). 
Investigators should request five years of support.  The anticipated award date
is April 1, 2000.

FUNDS AVAILABLE

The NIA intends to commit approximately $9,000,000 to fund five new and/or
competing renewal ADRC grants in Fiscal Year 2000.  The specific number will
depend upon the merit of the applications received and the funds available.  The
award of grants pursuant to this RFA is contingent upon the availability of funds
for this purpose.  Only applications of sufficiently high merit will be funded.

RESEARCH OBJECTIVES

ADCs are required to include administrative, clinical, neuropathological, and
information transfer cores.  Other cores can be proposed.  ADRC applications will
include, in addition, at least 3 full research projects (equivalent to small R01
grants).  The number of research projects funded and their duration will depend
upon scientific quality and availability of funds.  At least two pilot research
projects will be funded per year.  The ADCs will provide well-characterized
patients, patient and family information, and tissue and other biological samples
from persons with AD and from age-matched control subjects for research projects. 
As research into the causes of AD begins to address preclinical stages, Centers
should begin to address the clinical and neuropathological changes that
distinguish the initial stages of AD from normal aging.  Research activities that
use core resources can be supported by both the ADRC itself and by NIH and other
Federal agency mechanisms for the funding of investigator-initiated applications
in addition to non-federal funding sources.

The ADRCs provide a mechanism for integrating, coordinating, fostering and
developing the interdisciplinary cooperation of a group of established
investigators conducting programs of research on Alzheimer's disease and related
dementing disorders of older people.  They provide financial, intellectual,
patient and tissue resources to support cooperative interactions between a group
of projects that have been reviewed and supported on an individual basis, as well
as for the development of new research projects.  A prime objective of the Center
Grant is to provide an environment that will strengthen research, increase
productivity, and generate new ideas through formal interdisciplinary
collaborative efforts.  The central focus may be clinical research, basic
research or a combination.

The Center Grant may involve ancillary supportive activities such as longitudinal
studies and prolonged patient care necessary to support the primary research
effort.  The spectrum of activities should comprise a multi-disciplinary approach
to the problem of Alzheimer's disease.  The ADCs have played and will continue
to play a major role in Alzheimer's disease research by providing an
infrastructure and core resources around which institutions can build innovative
research programs. Centers may be asked to perform collaborative studies on
particular research topics or to serve as a regional or national resource for
special purpose research.  The ADCs provide a unique opportunity for multi
disciplinary/multi Center studies.  These will be facilitated by linkage to the
new Alzheimer's Disease Data Coordinating Center to be funded in 1999.  This ADC
network could be used, for example, to standardize clinical and pathological
diagnostic procedures, to pool patient information more effectively and to study
unique aspects and subtypes of this very complex and heterogeneous disease
process.  The NIA encourages ADCs to participate in cooperative studies involving
many or all of the Centers, as well as studies with other separately funded
longitudinal research projects.

SPECIAL REQUIREMENTS

An Alzheimer's Disease Research Center will be an identifiable organizational
unit formed by a single institution or a consortium of cooperating institutions. 
Therefore, lines of authority must be clearly specified.  The existence of a base
of ongoing high quality research in Alzheimer's disease, other related
neurodegenerative disorders or aging of the nervous system is a prerequisite for
establishing or continuing to fund an ADRC.

Each applicant institution will name an ADRC Director (P.I.) who will be the key
figure in the administration, management and coordination of the ADRC grant.  The
Director will be responsible for the organization and operation of the ADRC.  The
Director should be a scientific leader experienced in the field of Alzheimer's
disease research and must be able to coordinate, integrate, and provide guidance
in the establishment of programs in Alzheimer's disease research and allied
areas.  A significant time commitment (at least 10%) must be made by the
Director.  An Associate Director may be named who will be involved in the
administrative and scientific efforts of the Center.

Applicants must commit to cooperate fully and to share data concerning patients,
control subjects and specimen resources with the NIA -sponsored Alzheimer's
Disease Data Coordinating Center (ADDCC) where data from all AD Centers will be
centrally collected. The Steering Committee of the ADDCC in conjunction with the
ADC Directors will set policies that allow the individual Centers to conduct
research on patients, control subjects and specimen resources collected by that
Center while also sharing common data sets with the ADDCC.

The required elements for an ADRC include cores, research projects and pilot
research projects.  The required cores are administrative, clinical,
neuropathological, and education and information transfer cores.  Additional
cores may be proposed and justified as required to advance the local research
effort.  Applicants must demonstrate a data management capacity either by
creating a data core or by having a clearly defined data management section in
the administrative or clinical core.  In either case, data management should also
include biostatistical consulting to the scientific staff associated with the
ADC.

Specific instructions for preparing overall progress reports (competing renewal
applications), progress reports and plans for individual cores and research
projects, and a list of review criteria are detailed later in this RFA.

CORES

A core is a shared central laboratory or clinical research facility, service, or
resource.  Each core is directed by a faculty investigator with substantial
expertise related to the core. Facilities may be proposed that will enhance
productivity or in other ways benefit a group of investigators to accomplish the
stated goals.  Two important and related considerations are (1) the degree to
which currently funded investigators within or outside the Center will use and
will benefit from core resources and (2) the degree to which the resources will
promote new and/or expanded AD research efforts locally, regionally or
nationally.  Applicants should document and describe briefly the projects, both
existing and planned, whether funded by the Center or not, that will depend upon
resources provided by the cores (clinical and neuropathology cores, in
particular).

The required ADRC cores support resources that allow or provide for the
following: the acquisition of subjects for research; the evaluation, monitoring
of clinical course, and treatment of patients; the design and support of research
protocols; the neuropathological diagnosis of the disease; documentation of the
cognitive, behavioral and social aspects of Alzheimer's disease; data collection,
storage and biostatistical analysis capacity; and training and outreach programs
related to Alzheimer's disease.  Consequently, each application should
demonstrate the presence of, or propose, methods to accomplish the above tasks. 
Within these parameters, it is expected that individual Centers may develop one
or more cores with unique strengths while other cores within the Center may
perform more routine functions.

REQUIRED CORES

Administrative Core

Effective development of Center programs requires interaction among the Director,
the principal investigators of the cores, the principal investigators of research
projects using the cores, other researchers at the applicant institution,
appropriate institutional administrative personnel, the staff of the awarding
agency, and the members of the community in which the Center is located.  The
ADRC should recognize that it is part of a large network of ADCs and be prepared
to work cooperatively with the other Centers and the Alzheimer's Disease Data
Coordinating Center.

The success of the ADRC is dependent upon the involvement of scientific and
professional personnel from a variety of disciplines and subspecialties who
interrelate in order to facilitate the acquisition of new knowledge.  An
executive committee (composed of core and project leaders and the administrator)
will be established to assist the Director in making the scientific and
administrative decisions relating to the Center.  In addition to coordination of
the ADRC, the Director, with the advice of his or her executive committee, will
be responsible for allocation and monitoring of ADRC funds and the identification
and selection of key personnel.  The executive committee should be encouraged to
seek outside advice and consultation, both from within the institution and from
other institutions, in its monitoring and development of the scientific content
and direction of the program.

In addition to the executive committee, it will be necessary to establish an ad
hoc review committee advisory to the ADRC Director.  The committee should include
scientists from both within and outside the ADRC with expertise relevant to the
programs and scientific interests of the ADRC. The responsibility of this group
will be to review the applications for pilot studies and to make recommendations
to the ADRC Director.

An external advisory committee to the ADRC, consisting of scientists from outside
of the institution or consortium, will also be established.  Unless already
appointed, external advisory committee members should not be recruited until the
NIH review process is complete.  This committee will be used to evaluate the
programs of the ADRC, research progress, the effectiveness of communications
within the ADRC, and any other activities for which outside expertise is required
or desirable.  The committee should meet annually and prepare a report including
recommendations to assist the ADRC.  A member of the NIA extramural program staff
should be invited to attend each meeting as an observer. A copy of the advisory
committee report should be routinely sent to the extramural program staff member.

The administrative requirements of the ADRC will necessitate the assistance of
an administrator with business management expertise.  It is important that such
an individual be identified and directly involved with the fiscal and
administrative aspects of the ADRC application and grant.  The administrator
should be a member of the executive committee.  While budget formulation and
planning will undoubtedly begin with the Director in collaboration with the
scientific staff, the administrator must be involved in the process and provide
consultation in matters of fiscal administration. The administrator should attend
the annual ADC Administrators' meeting.

It is expected that the ADRC administrative structure will facilitate the
following:

1) coordination and integration of ADRC components and activities;

2) Planning and review of utilization of funds, including funds for pilot
studies;

3) support and advice for the ADRC Director in his/her oversight of the
activities of the Center;

4) interaction with the scientific and lay communities to develop relevant goals
for the ADRC within the immediate environment of the Center;

5) interaction with other Centers and the Data Coordinating Center to develop
trans-ADC research projects

6) timely and routine transmissions of the complete ADRC data set to the ADDCC.

In order to assure active collaboration with other Centers, the ADRC Director and
other staff should attend semi-annual meetings of the ADC Directors and other ad
hoc meetings arranged by the ADCs or the NIA to share research findings and plan
for cooperative research or to refine and standardize operating procedures among
the Centers. The ADRC application should include funds for travel of the Director
and other key personnel 1) to the semiannual meetings of the Center Directors,
2) for at least 2 ad hoc meetings on special topics, 3) for visits of Center
investigators to other ADCs for the exchange of scientific ideas, planning of
multi Center research projects and to receive training in specialized techniques,
4) for the Administrator to attend the Administrators' meeting and 5) for core
leaders to attend meetings with core leaders from other ADCs.

Clinical Core

The clinical core serves the functions of patient and control subject
recruitment, evaluation, and diagnosis; patient registry; longitudinal follow up
of patients and control subjects; acquisition of clinical and laboratory data
including clinical data pertaining to the last several weeks of life; and data
coordination and biostatistical analysis (if not included as a function of the
administrative core or a separate data core).  A research database that maintains
confidentiality of all patient and control subject records should be established
at the ADRC.  This will include data necessary for evaluation of differences
among preclinical stages of AD, possible and probable AD, and normal aging.  The
data must be shared with the Alzheimer's Disease Data Coordinating Center
according to standardized protocols developed by the ADC Directors and the
Steering Committee of the ADDCC.  A clinical core may perform a limited amount
of developmental work, but should not directly fund research per se. The
developmental work allowable in a clinical core must be directly related to the
function of the core.  It may be directed toward improving and expanding the core
functions, e.g., improving existing diagnostic strategies, or developing
additional methodologies, techniques or services.  Proposed developmental work
should be described as completely as possible in the application.  Planning for
patient and age-matched control subject recruitment should include sensitivity
to research design and biostatistical analysis.  Describe the procedures for
obtaining informed consent for research on cognitively impaired human subjects;
attach samples of information given to patients and families and copies of all
consent forms.  Particular attention should be paid to obtaining autopsy
permission from patients and families and informed consent for current and future
use of biological samples from patients. While conducting clinical drug trials
is one function of a clinical core, it should not be the major effort of the
core.  The application should include a description of the types (with specific
examples) of research projects and clinical trials that will use the core and
what benefits will obtain to other research activities from the existence of the
clinical core.

Efforts to recruit diverse population subgroups including minorities and women
must be outlined.  One option is to set up Satellite Diagnostic and Treatment
Clinics (SDTCs) designed to increase the heterogeneity of the research patient
pool and to enhance the research capabilities of the ADC by extending the
activities of the clinical core.  Existing Centers should retain any satellites
already in existence unless there are compelling reasons to restructure these
components.  New satellite clinics may be proposed as part of the clinical core.
The satellite clinics are not required to conduct research but serve as vehicles
for the recruitment, diagnosis and management of AD patients and their families
from rural and minority communities, who are then offered the opportunity to
participate in research protocols, clinical drug trials and autopsy. The
inclusion of patients with different characteristics will assist investigators
in providing answers to questions about AD diagnosis, treatment, and management
strategies that are likely to be applicable to the broad U.S. population.
Additionally, a more diverse patient pool will facilitate investigations of the
neuropathology and genetics of AD in minority groups as well as studies of care
giving and family burden in rural and minority group cohorts.

Neuropathology Core

This core will provide post mortem diagnosis on cases and normal control subjects
enrolled in the clinical core and on other well documented AD cases and controls. 
Procedures and facilities should be described related to criteria for diagnosis,
and the collection, storage, and distribution of brain tissue and other
biological samples, including, but not limited to, cerebrospinal fluid (CSF) and
plasma.  Data gathering and storage activities should be coordinated with those
of the Clinical Core.  To facilitate data sharing and cross Center comparisons
of diagnosis, all Centers shall use the new neuropathological criteria recently
developed by the NIA-Reagan Institute Working Group (Neurobiology of Aging, vol.
18, suppl 4, pp S1-S2 ,1997).  More detailed criteria for research purposes
should also be described.  Pathology data and a catalog of all samples should be
included in the data set transmitted to the ADDCC by mutually agreed upon
protocols. The Neuropathology Core may propose a limited amount of developmental
work, but should not directly fund research per se. The developmental work
allowable must be directly related to the function of the core.  It may be
directed toward improving and expanding the core functions, e.g., improving
existing, or developing additional methodologies, techniques or services. 
Proposed developmental work should be described in the application. 
Neuropathology core leaders from all of the ADCs should plan to meet yearly to
share ideas and discuss technical aspects of tissue sampling, development of
standardized tissue processing for diverse research protocols, cataloging and
data management, and banking and distribution of tissues and biological samples.

The procedure for prioritizing the use of tissues and other biological samples
should be discussed along with a description of the research projects that will
use material from this core.  Provisions for obtaining informed consent and
protecting the privacy of research subjects must be detailed. A procedure to
provide blinded samples to investigators should be described.  Details for
collecting specimens, recording information about clinical status of patients
just preceding and at time of death, and procedures for storage and distribution
of all human biological samples to investigators both within and outside the
Center should be provided.  A mechanism to evaluate requests for samples and
prioritize their use should be detailed.

Education and Information Transfer Core

This core will support both the development of professional staff to improve
clinical and research skills related to Alzheimer's disease and outreach programs
that will publicize the ADRC and educate families and other care givers.  The
methods and techniques to be employed to disseminate information and the audience
targeted to receive information should be defined including 1) approaches to
training of professionals including possible reciprocal exchange programs between
Centers to provide access to different research environments and technologies ;
2) descriptions of seminar or lecture series, workshops and continuing education
programs; and 3) cooperation with other organizations such as state and local
agencies and the Alzheimer's Association.  Attention should be directed to issues
of cultural sensitivity and, where appropriate, the information should be
structured so that it can effectively reach minority populations, including non-
English-speaking people.  Clearly stated objectives and a systematic plan as to
how these objectives will be met are required. Specific assessment methodology
is also required to evaluate the effectiveness of outreach programs. 
Consideration should be given to cooperation with other ADCs and the NIA ADEAR
Center when developing education programs that could be shared among the Centers.

OTHER CORES

The NIA, through the ADRC, will support additional cores that provide
opportunities for scientific accomplishments beyond those attainable solely
through support of the mandatory cores.  It is important to note that support
should not be requested for cores that only replace or centralize resources
supported on individual project grants. In a Center grant application, it is not
sufficient for the principal investigator merely to identify such centralized
resources.  Rather, it must be demonstrated exactly how each core would augment
or enhance the present capabilities of the investigators and make possible new
activities.  There should be a thorough discussion of the project(s) that will
use resources of additional cores.

RESEARCH PROJECTS

Applications will include a minimum of three and a maximum of six research
projects.  The research projects should be requested for five years of funding
and incorporate the latest techniques and propose studies that will advance our
understanding of the basic and clinical underpinnings of Alzheimer's disease in
areas such as etiology, genetics, pathogenesis, epidemiology, diagnosis,
therapeutic interventions, patient management, and care giver issues.  The
projects should be similar in quality to small R01 grants and subprojects of
program project grants.  It would be desirable to propose at least one project
that utilizes patients or patient material from the Center cores.  The ADRC
should not be the primary source of research funding for the investigators
associated with the Center.  ADRC - supported research should complement other
funded research related to Alzheimer's disease taking place at the applicant
institution.

PILOT STUDIES

A plan to support pilot studies for basic and clinical, biomedical,
epidemiological, or behavioral research should be included and budgeted in the
application.  The description of a plan to solicit, review and administer pilot
grants should be included with the Administrative Core and a separate budget
including the total request for pilots should be submitted.  Criteria for review
of pilot studies should be developed and included in the application.  These
funds may be used for new investigators, investigators from other fields willing
to bring their research expertise to Alzheimer's disease, and investigators whose
proposed research would constitute feasibility testing.  This funding mechanism
is intended to provide modest support that will allow an investigator the
opportunity to develop preliminary data sufficient to provide the basis for an
application for independent research support through conventional granting
mechanisms.

Pilot studies are typically limited to a one-time nonrenewable award for one year
of support.  If described and well justified, two years of support may be
requested.  Any one investigator is eligible only once for pilot support, unless
the additional proposed pilot study constitutes a real departure from his or her
ongoing research.  Pilot study support is not intended for large undertakings of
established investigators for which it would be appropriate to submit separate
research grant applications.  Pilot funds are not intended to support or
supplement ongoing-supported research of an investigator.  Since eligibility for
pilot studies is difficult to define, some examples may be helpful:

1) A study proposed by an established investigator who has experience in areas
other than AD research, and who wants to work in the Alzheimer's disease research
field; or a study by an established investigator who wants to try a new
hypothesis, method, or approach that is not an extension of ongoing research.

2) A study proposed by a new investigator, with an interest in research in
Alzheimer's disease, before the study has developed to the point of being
suitable to apply for individual grant support.

3) A preliminary study to determine the availability of sufficient subjects with
specific characteristics, before undertaking a larger study.

Each pilot project is limited to no more than $30,000 direct costs each year. 
If the pilot project is requested and justified for two years, the direct costs
are limited to $30,000 per year.

No pilot applications should be submitted with the ADRC application but, instead,
the number requested for each year (2 minimum, 4 maximum) and the plans for
soliciting pilot proposals should be described.  A plan must also be presented
within the administrative core for peer review of the pilot studies including the
structure and composition of the review panel.  Pilot proposals should be
reviewed locally and those chosen for funding should be submitted to the NIA for
approval in the annual noncompeting renewal application.

PROGRESS REPORTS

Overall Progress Report

For competing renewal applications, the overall progress report should include
summaries of progress in achieving the major aims of the Center during the last
funding period, including each core and funded research project and major
publications.  If a project or optional core has terminated, include a final
report with a summary of results and publications.  If a project or optional core
is continuing, include a progress report in that component writeup. Applicants
should include tables detailing 1) Publications and grants (source, amount and
title) resulting from each component funded by the ADRC and 2) Publications and
grants (source amount and title) resulting from pilot projects.

The overall progress report should also include details of how the presence of
the ADRC has brought new investigators into the field and has stimulated non-ADRC
funded research in the last funding period.  It should describe how the presence
of the Center has facilitated and improved Alzheimer research at the Institution
and beyond.  In addition to text summaries, applicants should also include
summary tables detailing:

1) ADRC and Non-ADRC funded grants and projects that use or have used major
resources supplied by the ADRC, including principal investigator, source and time
of funding, types and amount of resources (e.g., clinical or neuropathological
diagnoses, numbers of patients, specimens etc) and any resulting publications.

2) Collaborations with other AD researchers, other Centers, cooperative studies,
and with biotechnology and pharmaceutical companies.

3) Clinical trial participation by patients enrolled in the Center including
trial name, sponsor, number of patients, and dates.

4) Institutional, state and other private and public resources committed to the
Center and its investigators.

Clinical Core Progress Report

For competing continuations the Clinical Core Progress report should include
Clinical Core objectives and progress in meeting them, including information
about satellites (if applicable).  Basic functions of the core should be
summarized (using tables where appropriate) including numbers, race, gender, age
of patients and controls recruited, diagnosis, percentage follow up and drop out
rate, autopsy consent and rate, diagnostic confirmation by autopsy, and
clinicopathological correlations.  Functions of Clinical Core in providing
services (a) for ADC-funded and (b) non-ADC funded investigators should be
clearly summarized.  These would include numbers and kinds of subjects recruited
and participation in clinical trials and other ongoing clinical research
projects, both local and national.  How has the clinical core contributed to AD
research?  Describe key findings and list publications resulting from use of core
patients.  Any developmental work carried out by the core should be presented and
resulting publications listed.

Neuropathology Core Progress Report

For the neuropathology core, competing renewal applications should outline core
objectives and progress in meeting them. Basic functions of the core such as
number of AD and control autopsies, post mortem intervals, tissue dissection and
storage, diagnoses, and type and quantity of tissue provided to investigators
both funded by the Center and by other means should be clearly summarized (using
tables where appropriate).  Any developmental work carried out by the core should
be presented and resulting publications listed.

Education and Information Transfer Core Progress Report

Applications should include evidence for training activities that effectively
impart knowledge to professionals and the lay public with the possibility of
leading to improved health care for patients.  Include a table presenting the
nature of training activities and the types of professionals trained - physicians
(including medical students, residents, fellows), nurses, social workers etc. 
Detail the history of cooperative ventures of the Center with state and local
agencies such as the Alzheimer's Association and community groups in coordinating
training and education programs.

Data Management and Statistics

Summarize progress and activities related to data collection, data management and
statistical consulting activities at the appropriate place in the core(s) where
these services are located.  Include progress and interactions with the Data
Coordinating Center.  List projects and publications in which data management and
statistical consulting played a role.

BUDGET CONSIDERATIONS

All ADRC proposals should request and provide justification for five years of
support.

The total costs (direct + indirect) requested for new applications may not exceed
$1.4 million for the first year. Competing renewal applications, whose final
budget year in the current funding period exceeds $2.0 million in total costs,
may request a 3% increase.  Other competing renewal applications, whose final
budget year in the current funding period is less than $2 million, may request
an increase up to 10% over final year total costs, or 10% over an average of the
final 3 years total costs, or $1.4 million, which ever is higher.  Direct cost
requests for subsequent years may increase above the prior year direct cost award
no more than 3%.

The direct costs are to be distributed approximately as follows: (This proposed
distribution is intended only as a general guideline and proportions may vary if
needed and justified.  If additional cores are proposed based on local needs, the
distribution may be adjusted accordingly.)

Administrative Core                      7.5%
Pilot Studies                            7.5%
Clinical Core                           35%
Neuropathology Core                     10%
Education and Information Transfer Core  5%
Research Projects                       35%

Where large items of equipment are requested, the application must document what
is already available and provide clear justification in terms of use by core
staff and how it relates to research projects dependent on the core.  General
purpose equipment needs should be included and justified only after surveying the
availability of such items within the institution.

Research patient care costs (both inpatient and outpatient expenses) will be
considered in the context of other existing institutional clinical resources. 
Attempts should be made by the applicant institution to utilize existing clinical
facilities, such as General Clinical Research Centers and individually supported
beds.  Costs relating to the clinical efforts of the ADRC may be funded through
the ADRC, provided there is no overlap of funding. Only those research patient
costs directly related to ADRC activities may be charged to the ADRC.

Domestic and foreign travel of project personnel directly related to the core and
scientific activities of the ADRC is allowable.  Budgeting should include travel
and lodging for 1) the semi-annual meetings of the Center Directors, 2) annual
meetings of administrators, clinical core leaders, education core leaders, data
managers, and neuropathology core leaders and, 3) representatives of the Center
to attend ad hoc meetings called by the ADCs or the NIA to discuss research
findings and plan cooperative projects, to promulgate data sharing, and to
discuss standardization of procedures among the ADCs.

Requests and commitments for pilots in competing applications (new and renewal)
will be budgeted as a separate line in the "composite" budget at $30,000 per
pilot per year (without escalation).  They should not be included in the
Administrative Core or elsewhere in the application.  A brief description of the
first year pilot research and detailed pilot budgets for the first year of Center
funding will be due shortly before the award of successful applications and
future year pilots should be submitted with the annual noncompeting renewal
applications.  Indirect costs will be provided in accordance with these budgets.

Pilot grants are allowed for consortium arrangements but direct cost should not
exceed $30,000 with total consortium cost budgeted not to exceed $35,000 for each
pilot including the facilities and administrative costs of the consortium
institution.  No indirect costs will be provided to the grantee for pilot
projects conducted by consortia.  If consortium arrangements are contemplated,
the following information should be provided in the application:

1) A list of all proposed performance sites both at the applicant institution and
at the collaborating institutions

2) A separate, detailed budget for the initial and future years for each
institution and, where appropriate, for each unit of activity at each
institution.

3) A composite budget for all units of activity at each institution for each
year, as well as a composite budget for the total proposed budget for each year.

4) An explanation of the programmatic, fiscal, and administrative arrangements
made between the grantee institution and the collaborating institutions.

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
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 14508-145131), and in the NIH GUIDE FOR GRANTS and CONTRACTS, Volume 23,
No. 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.  However, the scientific goals of this RFA are focused on
aging.  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.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 1, 1999, a letter of intent
that includes a brief description of the proposed Center, the name, address, and
phone number of the Principal Investigator, the identities of other key personnel
including leadership of the cores and research projects, and the number and title
of this RFA. A letter of intent is not an absolute requirement, is not binding,
and does not enter into the review of subsequent applications. The information
that it contains is helpful in planning for the review of the applications. It
allows NIA staff to estimate the potential review workload and to avoid conflicts
of interest in the selection of reviewers. The letter of intent is to be sent to
Dr. Creighton Phelps at the address listed under INQUIRIES.

APPLICATION PROCEDURES

The application must be prepared using instructions in this RFA and those in
supplementary instructions for preparation of multi component applications (P50
Centers version), which may be obtained from the program staff listed under
INQUIRIES.  Page Limitation: Applications may not exceed a total of 25 pages each
for the overall progress report and parts a-d of each core and research project.

Prior to submission of the formal application, consultation with NIA program
staff concerning the technical aspects of preparing the application is strongly
encouraged.

The research grant application form PHS 398 (rev. 4/98) is to be used in applying
for these grants.  These forms are available at most institutional offices of
sponsored research and from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD
20892-7910, telephone (301) 435-0714, Email: grantsinfo@nih.gov and on the
internet at http://grants.nih.gov/grants/forms.htm

The RFA label available in the PHS 398 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, enter the title: "ALZHEIMER'S DISEASE RESEARCH
CENTER" and the RFA number on line 2 of the face page of the application form and
check the YES box.

Submit a signed original of the application, including the Checklist, and three
signed, exact photocopies, in one package 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)

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

Dr. Mary Nekola
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Room 2C212, MSC 9205
Bethesda, MD  20892-9205
(ATTN: Alzheimer's Centers)

Complete applications must be received by May 19, 1999.  If an application is
received after that date, it will be returned to the applicant without review.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the Center for
Scientific Review (CSR) and responsiveness by NIA.  Incomplete applications will
be returned to the applicant without further consideration.  If NIA staff find
that the application is not responsive (those that request amounts that exceed
allowable limits or are not directed to the goals of this RFA) it will be
returned without further consideration.

Each application must be thorough and complete.  Additional materials or
revisions will not be accepted after the receipt date.  It is strongly
recommended that Institutional Review Board (IRB) and, if appropriate,
Institutional Animal Care and Use Committee (IACUC) approval be secured before
the application is submitted.  Otherwise, it is the applicant's responsibility
to ensure that these certifications are sent to the Scientific Review Office,
NIA, within 60 days of the receipt date.  Applications failing to comply with
this requirement will be returned without review. There will be no further
notifications on this issue.

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.  As part of the initial merit review, a process may be used in which
applications receive a written critique and under a process in which only those
applications deemed to have the highest scientific merit, generally the top half
of the applications under review, will be discussed, assigned a priority score,
and receive a second level review by the National Advisory Council on Aging. 

Applicants should clearly demonstrate the ways in which the ADRC will contribute
to the growth of local research programs, support on-going projects, cooperate
with other ADCs and the ADDCC in collaborative research, and attract both senior
and new investigators to AD research.

Review Criteria

Listed below are the review criteria to be used in the evaluation of the ADRC
applications; these criteria will be applied to competing continuations by
evaluating progress and to new applications by evaluating preliminary
organizational work, history of Alzheimer's disease research and plans for
implementation of the new program.

The following review considerations will apply:

A. Center as a Whole:

1) For competitive renewal applications, impact of the Center on furthering
Alzheimer's disease research locally and nationally during the last funding
period (see details under Progress Report sections); for new applications, the
potential for such impact.

2) Extent of "Centerness", i.e., does the Center as a whole serve a purpose
greater than the sum of the individual components?

3) Extent of Center interactions with the Alzheimer community including
cooperative interactions with local organizations and nationally with other ADCs
and cooperative studies.

4) Unique contributions of the Center, including significance, innovation,
scientific productivity, and recognition, (publications, new research grants,
honors and awards).

5) For competitive renewal applications, quality of progress reports according
to criteria specified in this RFA.

B.  Cores:

1) For competing continuation applications, progress in meeting stated aims of
cores in previous application, publications, and securing of other funding
detailed separately for each core.  (Refer back to overall and core progress
report sections)

2) How will the cores support research and educational activities of the ADRC and
what is the future anticipated use? The fit of each proposed core into the
overall research program.  Will it enhance collaborative and/or interdisciplinary
research within the ADRC and the wider research community?

3) Plan for recruitment of women and minority patients and control subjects to
the clinical core.  In competing continuation applications, has progress been
made in increasing participation of diverse populations in ADRC activities?  If
ADRC had funds for satellite clinics, how effectively have they been used?

4) Would any proposed optional cores duplicate existing resources or services? 
If so, are the requested new resources justified?  Do other grant funds already
provide any of the requested capabilities?

C. Research:

1) For competing continuation applications, progress in meeting stated aims of
projects in previous application, publications, and securing of other funding
detailed separately for research and pilot projects.

2) The scientific relevance, significance, approach, innovation, quality of the
investigators, and research environment for the Center as a whole and for each
of the projects

3) The feasibility of the pilot grant program proposed in new applications and
the success of pilots funded in the previous award period for competing
continuations as judged by documentation of publications and further independent
funding.

4) The experience and commitment of the investigators responsible for the
individual research projects, their interrelationship with the other elements of
the ADRC, and with other scientists at their own institution and elsewhere.

5) The expected role of the ADRC in increasing the quantity and quality of
research in Alzheimer's disease within the applicant institution and with other
ADCs and the Data Coordinating Center.

D.  Data Management:

1) Are data management and support procedures developed sufficiently to allow
ADRC investigators to access and utilize data.  Does the Center provide
statistical design and support to ADRC investigators?

2) Is there a sound plan to manage and utilize clinical and neuropathological
data.  Are adequate safeguards to protect patient confidentiality addressed?  Are
staffing, hardware and software adequate?

3) Statement of agreement to cooperate fully and share all core data with the
Alzheimer's Disease Data Coordinating Center.

E.  Program Administration:

1) The creative scientific and administrative leadership of the ADRC Director and
his/her staff, and their commitment to devote adequate time to the management of
the ADRC program.

2) The proposed administrative organization including:

o  Coordination of ongoing research and its use of the ADRC including procedures
for allocating the resources of the ADRC in response to requests made by internal
and external investigators and documentation of resources used and resulting
publications.

o  Procedures for internal communication and cooperation among the investigators
involved in the ADRC.

o  Mechanisms for reviewing the use of, and administering, funds for pilot
projects.

o  Management capabilities that include fiscal administration, procurement,
property and personnel management, planning, budgeting, etc.

o  For competing continuation applications, composition of the advisory board.
Is it appropriate?  Has it had regularly scheduled meetings?  Are its
responsibilities defined?  How has the ADC benefitted from advisory board input?

3) The appropriateness of the ADRC budgets for the core resources and research
projects.

F. Investigators:

1) The qualifications of the participants. What are their academic credentials
and their research records?  What is the current funding of investigators
associated with the ADRC? 

2) Evidence of collaboration and interdisciplinary research among the
investigators who will be associated with the ADRC.

G. Facilities:

1) Are facilities adequate?  Are they reasonably contiguous or physically
separated?

H. Institutional Commitment:

1) Evidence for institutional commitment to the program, including provision of
funding, space, faculty positions for AD research and other essential ADRC
functions, or commitments for construction or renovation.

2) The academic environment and resources, including equipment and facilities,
and the potential for interaction with scientists from other departments and
components.

AWARD CRITERIA

The anticipated date of award will be April 1, 2000.  Funding criteria will be
scientific merit (based on the review criteria listed above), availability of
funds, and programmatic priorities.

INQUIRIES

Requests for supplementary guidelines, letters of intent and inquiries regarding
programmatic issues may be directed to:

Dr. Creighton H. Phelps
Alzheimer's Disease Centers Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  phelpsc@exmur.nia.nih.gov

Direct inquiries regarding fiscal matters to:

Linda Whipp
Grants Management Office
National Institute on Aging
Gateway Building, Room 2N-212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  whippl@exmur.nia.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 Public Health Service (PHS) strongly encourages all grant 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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