ALZHEIMER'S DISEASE CORE CENTERS

Release Date:  January 27, 1999

RFA:  AG-99-002

P.T.

National Institute on Aging

Letter of Intent Receipt Date:  March 1, 1999
Application Receipt Date:  May 14, 1999

PURPOSE

The National Institute on Aging (NIA) invites applications from qualified
institutions for support of Alzheimer's Disease Core Centers (ADCCs).  These
are designed to serve as shared research resources to facilitate research in
Alzheimer's disease (AD) and related disorders and distinguish them from
normal 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 Core 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.  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 Core Center Grants (P30s) 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
P01 should be different from that proposed in the ADCC and any overlap of the
P01 cores with the P30 cores will be examined and adjustments made before
funding.

MECHANISM OF SUPPORT

The support mechanism for this program will be the NIH Center Core Grant
(P30).  Investigators should request five years of support. The anticipated
award date is May 1, 2000.

FUNDS AVAILABLE

This NIA intends to commit approximately $5,000,000 to fund five new and/or
competing renewal ADCC grants in Fiscal Year 2000.  The specific number will
depend upon the merit of the applications received and the funds available. 
Only applications of sufficiently high merit will be funded.  The award of
grants pursuant to this RFA is contingent upon the availability of funds for
this purpose.

RESEARCH OBJECTIVES

ADCCs are required to include administrative, clinical, neuropathological, and
information transfer cores.  Other cores can be proposed and at least two
pilot research projects per year should be requested.  The ADCCs 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 ADCC core
resources can be supported by the NIH and other federal agency granting
mechanisms for the funding of investigator-initiated applications in addition
to non-federal funding sources.

The ADCCs 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 financial, intellectual, patient and
tissue resources to support research projects that have been reviewed and
supported on an individual basis.  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 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 ADCCs 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 ADCCs 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 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 ADCCs to participate in cooperative studies involving many or all
of the Centers as well as studies with separately funded longitudinal research
projects.

SPECIAL REQUIREMENTS

An Alzheimer's Disease Core 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 by the appropriate institutional officials 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 ADCC.

Each applicant institution will name an ADCC Director (P.I.) who will be the
key figure in the administration, management and coordination of the ADCC
grant.  The Director will be responsible for the organization and operation of
the Center.  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 ADCs
are 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 ADCC include administrative, clinical,
neuropathological, and education and information transfer cores, and a pilot
projects program.  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
administrative or clinical core which also includes the capacity for
biostatistical consulting to the scientific staff associated with the ADCC.

Specific instructions for preparing overall progress reports (competing renewal
applications), progress reports and plans for individual cores, 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 an 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 locally, regionally or nationally.  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 ADCC 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; a 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, appropriate institutional
administrative personnel, the staff of the awarding agency, and the members of
the community in which the Center is located.  The ADCC 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 ADCC is dependent upon the involvement of scientific and
professional personnel from 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 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 ADCC, the Director, with the advice of his or her
executive committee, will be responsible for allocation and monitoring of ADCC
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 ADCC Director.  The committee should
be composed of scientists from outside the ADCC with expertise relevant to the
programs and interest of the Center. The responsibility of this group will be
to review the applications for pilot studies and to make recommendations to
the ADCC Director.

An external advisory committee to the ADCC, consisting of scientists from
outside of the institution will also be established.  Unless already
appointed, external advisory committee members should not be recruited until
the NIH review is complete.  This committee will be used to evaluate the
programs of the ADCC, research progress, the effectiveness of communications
within the ADCC, 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 ADCC.  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 ADCC 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 ADCC 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 ADCC administrative structure will facilitate the
following:

1) coordination and integration of Center components and activities;

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

3) support and advice for the ADCC 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 ADCC 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 ADCC data set to the
ADDCC.

In order to assure active collaboration with other ADCs, the ADCC 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 ADCC 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 investigators associated with the Center 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, longitudinal followup of patients and control
subjects, evaluation, acquisition of clinical and laboratory data including
data pertaining to the last several weeks of life, 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 ADCC.  This will include data necessary
for evaluation of differences among preclinical stages of AD, possible or
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 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. 
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 do not 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 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 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.  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. 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 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 ADCC 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 ADCC, 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.

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 nonrenewable single 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 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 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 ADCC 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 major publications.  If an optional core has
terminated, include a final report with a summary of activities and
publications.  If an optional core is continuing, include the progress report
in the component writeup.  Applicants should include tables detailing 1)
Publications and grants (source, amount and title) resulting from each
component funded by the ADCC 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 ADCC has brought new investigators into the field and has stimulated
funded research in the last funding period. In addition to text summaries,
applicants should also include summary tables detailing:

1) Funded grants and projects that use or have used major resources supplied
by the ADCC, 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 public and private 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 to 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?  What key findings and
publications have resulted 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 inside and outside the Center 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 clinicians 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 ADCC proposals should request and provide justification for five years of
support.

The total costs (direct + indirect) requested for new applications may not
exceed $900,000 for the first year. Competing renewal applications may request
an increase up to 10% over final year total costs or $900,000, 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                        10%
Pilot Studies                              10%
Clinical Core                              50%
Neuropathology Core                        20%
Education and Information Transfer Core    10%

Where expensive 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
ADCC may be funded through the ADCC, provided there is no overlap of funding. 
Only those research patient costs directly related to Center activities may be
charged to the ADCC.

Domestic and foreign travel of project personnel directly related to the core
and scientific activities of the ADCC 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 and 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 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 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 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
(P30 Centers version) available from the program staff listed in the Inquiries
section.  Page Limitation: Applications may not exceed a total of 25 pages
each for the overall introduction/progress report and parts a-d of the
research plan for each core.

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,
MSC 7910 Bethesda, MD 20892-7910, telephone (301) 435-0714, E-mail:
grantsinfo@nih.gov or from the internet website 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 CORE 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 Disease Core Centers)

Complete applications must be received by May 14, 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 and/or non-
responsive applications will be returned to the applicant 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 undergo 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 ADCC will
contribute to the growth of local research programs, support on-going
projects, cooperate with 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 ADCC
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. 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 Overall Progress Report section); 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 ADCC
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 Center 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 ADCC activities? 
If Center 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) The existence of a base of ongoing high quality research in Alzheimer's
disease and other related neurodegenerative disorders or normal aging.

2) For competing continuation applications, progress in meeting stated aims of
cores in previous application, publications, and securing of other funding.
(Refer to progress report sections)

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 subsequent success in publications
and obtaining further funding.

4) The experience and commitment of the investigators responsible for the
individual research projects which will be associated with the ADCC and their
ability to interrelate with the other elements of the ADCC and with other
scientists at their institution and elsewhere.

5)  The expected role of the ADCC 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
ADCC investigators to access and utilize data.  Does the Center provide
statistical design and support to ADCC investigators?

2) Is there a thoughtful 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 ADCC Director
and his/her staff, and their commitment to devote adequate time to the
management of the ADCC program.

2) The proposed administrative organization including:

o  Coordination of the ADCC resources including procedures for allocating
Center resources in response to requests made by investigators and
documentation of resources used and resulting publications.

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

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?

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 ADCC?

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

G.  Facilities:

1) Facilities should be 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, 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 May 1, 2000. Funding criteria will be
scientific merit (based on the review criteria listed above), availability of
funds, and programmatic priorities.

INQUIRIES

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

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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