ALZHEIMER'S DISEASE RESEARCH CENTERS

NIH Guide, Volume 26, Number 39, December 5, 1997

RFA:  AG-98-003

P.T.

National Institute on Aging

Letter of Intent Receipt Date:  March 1, 1998
Application Receipt Date:  May 14, 1998

PURPOSE

The National Institute on Aging (NIA) invites applications from qualified
institutions for support of Alzheimer's Disease Research Centers (ADRCs), which
are designed to serve as shared research resources to facilitate research in
Alzheimer's disease (AD).  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).  ADCs expand the capacity of the applicant institution to
conduct basic and clinical research in AD by increasing the available research
resources.  ADCs are expected to provide core resources which will enhance
ongoing research by bringing together biomedical, behavioral, and clinical
science investigators in a manner that will enrich the effectiveness of research
on the etiology, pathogenesis, diagnosis, treatment, and prevention of AD, and
ultimately improve health care delivery.  The ADCs 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.  ADCs, in general, are required to include
administrative, clinical, neuropathological, and information transfer cores. 
Other cores can be proposed.  ADRCs will fund, in addition, at least three full
research projects (equivalent to small R01 grants) and at least two pilot
research projects 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. 
Research activities that use 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, and fostering 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 support for cooperative interactions between a group
of related projects that have been reviewed and supported on an individual basis,
as well as for the development of new research projects.  The 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 protracted
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.  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 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. 
However, it is now just as important to extend studies to include groups of
Centers.  The ADCs provide a unique opportunity for multidisciplinary/multi-
Center studies especially through linkage to the new Alzheimer's Disease Data
Coordinating Center presently being established.  This ADC network could be used
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 is encouraging ADCs to
participate in cooperative studies involving many or all of the Centers as well
as studies with separately funded longitudinal research projects.

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 Center Grants, 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.  No foreign or international components will be considered
in this RFA. 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, each with at least two years of committed support
remaining at the time of application or (2) one or more program project (P01)
grants related to neurodegenerative diseases, 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 need to 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, 1999.

FUNDS AVAILABLE

The award of grants pursuant to this RFA is contingent upon the availability of
funds for this purpose.  The intent is to fund nine new and/or competing renewal
ADRC grants in Fiscal Year 1999.  The specific number will depend upon the merit
of the applications received and the funds available.  These applications do not
compete for funding within the general pool of dollars available for
investigator-initiated research proposals.  Only applications of sufficiently
high merit will be funded.

RESEARCH OBJECTIVES

Background

Alzheimer's disease (AD) 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.
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 long-range development plans for AD research have included several
strategies.  One of the most prominent was the development of a cadre of
Alzheimer's Disease Research Centers (ADRCs) in major university medical centers. 
The ADRC program was designed to support a multi-faceted approach to AD including
clinical and other core services, basic and clinical research, professional and
public information and education activities.

The ADRCs provide university investigators and research groups with well
characterized patients and control subjects, family information, and tissue and
biological specimens for use in research projects. Each ADRC will develop in
accordance with local talents, interests, and resources, but should also be
responsive to national needs related to Alzheimer's disease.  ADRCs should be
willing to work with other ADCs 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.

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. 
Such a Center will involve the interaction of broad and diverse elements. 
Therefore, lines of authority and sanction by the appropriate institutional
officials must be clearly specified.

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 creative 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 new 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 share data concerning patients,
control subjects and specimen resources with the NIA -sponsored Alzheimer's
Disease Data Coordinating Center (ADDCC) where data from all ADCs is 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 recruited by that Center while also sharing common data sets with the
ADDCC.

The required elements for an ADRC include administrative, clinical,
neuropathological, and education and information transfer cores, along with
research and pilot projects.  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 with biostatistical
expertise or having a clearly defined data management section in the clinical
core which also includes the capacity for biostatistical consulting to the
scientific staff associated with the ADC.

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 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.  Applicants should document and describe briefly
the projects, both existing and planned, that will depend upon resources provided
by the cores (clinical and neuropathology cores, in particular).

The ADRC cores support resources that allow or provide for the following: the
acquisition of subjects for research; the evaluation, 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; a well-planned 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.

REQUIRED CORES

Administrative Core

While the final administrative structure of the ADRC will, for the most part, be
left to the discretion of the applicant institution, NIA's experience has
demonstrated that the 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, 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 representing a variety of disciplines and subspecialties
who must be willing to relate to each other in order to facilitate the
acquisition of new knowledge.  An executive committee (composed of core and
project leaders) 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 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 be
composed of scientists from outside the ADRC with expertise relevant to the
programs and interest of the ADRC. The responsibility of this group will be to
review the applications for pilot studies.

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 grant application review 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 in which problems arise
for which outside expertise is required or desirable.  The committee should
usually meet annually and prepare a report including recommendations to assist
the ADRC to correct any deficiencies.  However, the nature of its
responsibilities may require occasional ad hoc meetings or teleconferences.  A
member of the NIA extramural program staff should be invited to attend each
meeting as an observer and should receive a copy of the advisory committee
report.

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 Administrator's meeting.

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

1) coordination and integration of ADRC components and activities;

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

3) support and advice for the ADRC Director in his/her efforts to oversee 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 transmission of the complete ADC data set to the ADDCC.

In order to assure active collaboration with other ADCs, the ADRC Director and
other staff should attend 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 two 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, patient registry, patient coordination and follow up, evaluation,
acquisition of clinical and laboratory data, data coordination and biostatistical
analysis (if a separate data core does not exist).  A research database that
maintains confidentiality of all patient and control subject records should be
established at the ADRC.  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.  This will include data
necessary for evaluation of differences between AD and normal aging.  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 of existing, or
developing of 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.  While
facilitating the conduct of 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
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 of 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 and clinical drug trials. The inclusion of
patients with different characteristics will assist investigators in providing
answers to questions about AD diagnosis, treatment and management strategies that
are more likely to be applicable to the broader 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 aged control
subjects enrolled in the clinical core and from 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, CSF and plasma.  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. 
The Neuropathology Core may also perform 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 as completely as possible 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. Particular attention should be paid to obtaining
autopsy permission from patients and families and informed consent from patients
for biological samples.  Provisions for 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 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.  Data gathering
and storage activities should be coordinated with those of the Clinical Core.
Pathology data and a catalog of all samples should be included in the data set
transmitted to the ADDCC by mutually agreed upon protocols.

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 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 is
not allowed 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 projects that will use core
resources.

RESEARCH PROJECTS

New applications shall include a minimum of three and a maximum of five research
projects.  Competing renewal applications shall include a minimum of four 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 R01 grants and
subprojects of program grants. 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.

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 a
maximum of one year of support.  In very special circumstances, that must be
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 clinical research, and who wants to work in the Alzheimer's disease
research field; or study by an established clinical 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 study to determine the availability of sufficient subjects with specific
characteristics, needed for a study be sought if the study is deemed to be
feasible.

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.

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 $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, 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 competing 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 indirect 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 1, 1998, a letter of intent
that includes a descriptive title 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 should be prepared using instructions in this RFA and those in
supplementary instructions for preparation of multi component applications
(Centers version) available from the program staff listed in the Inquiries
section.  Page Limitation:  Applications may not exceed a total of 23 pages for
parts 1-4 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. 5/95) 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) 710-0267, Email: [email protected].

The RFA label available in the PHS #98 application kit 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 (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (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 14, 1998.  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 fail to include all required
components, 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 enough to stand on its own and
should be prepared as if no site visit will occur.  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 this merit review, a process may be used in which
applications will be determined to be competitive or non-competitive based on
their scientific merit relative to other applications received in response to the
RFA.  Applications judged to be competitive will be reviewed in detail by an
initial peer review group and also receive a second level of review by the
National Advisory Council on Aging.  Applications determined to be "non-
competitive for funding" will be so designated, and an abbreviated summary report
noting the major weaknesses will be sent to the principal investigator and the
application withdrawn.  The factors to be considered in the evaluation of the
merit of each application will be those used in the review of the cores and
projects in standard multi - project research grant applications and, in
addition, how well the applicants have outlined collaborations and coordination
within the Center.  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 work and
plans for implementation of the new program.

The following review considerations will apply:

A.  Research:

1.  The scientific relevance, significance, approach, innovation, quality of the
investigators, and research environment for each of the projects will be
considered.  The likelihood for meaningful collaborations and the relationship
to the central theme of the ADRC will also be assessed. The existence of a base
of ongoing high quality research in Alzheimer's disease and other related
neurodegenerative disorders is a prerequisite for establishing and continuing an
ADRC.

2.  The experience and commitment of the investigators responsible for the
individual research projects and their ability to interrelate with the other
elements of the ADRC and with other scientists at their institution.

3.  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.

4.  For competing continuation applications, progress in meeting stated aims of
cores and projects in previous application and securing of other extramural
funding.

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

B.  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.

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

o  Procedures for allocating the resources of the ADRCs in response to requests
made by internal and external investigators and documentation of resources used
and resulting publications.

o  Mechanisms for selecting or replacing professional or technical personnel
within 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.

C. Institutional Commitment:

1. Evidence for institutional commitment to the program, including provision of
funding, space, faculty positions, 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.

3. The institutional commitment to helping recruit individuals responsible for
conducting essential ADRC functions and research on AD.

D. Investigators:

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

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

3. Does the group have stability? Plans for recruitment of new personnel should
be addressed.

E.  Facilities:

1.  Facilities should be adequate.  Are they reasonably contiguous or physically
separated?

2.  If funds for renovation are requested, do these seem appropriate in terms of
available resources, including space and its utilization?

3. Will requested changes in facilities fit in satisfactorily with available
ones?

F.  Cores:

1.  The fit of each proposed core into the overall research program.  Will it
enhance collaborative and/or interdisciplinary research? In competing
continuation applications, how have the cores supported research and educational
activities of the ADRC?

2.  How many of the ADRC funded research projects or other NIH-funded
investigators have used or will be using each core, for what purpose, and to what
extent?  What is the anticipated future use?

3.  Would the proposed core(s) duplicate existing resources or services?  If so,
are the requested new resources justified?  Do other grant funds already provide
any of the requested capabilities?

4.  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?

5.  History, or planning, of cooperative ventures of  the ADRC with state and
local agencies such as the Alzheimer's Association in coordinating training and
education programs.

6.  Evidence for professional education activities that effectively impart
research knowledge to clinicians with the possibility of leading to improved
health care for patients.

G.  Data Management:

1.  A thoughtful plan to manage clinical and neuropathological data.  Are
adequate safeguards to protect patient confidentiality addressed?  Are staffing,
hardware and software adequate?

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

AWARD CRITERIA

The anticipated date of award will be April 1, 1999.  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:  [email protected]

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:  [email protected]

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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