ALZHEIMER'S DISEASE CORE CENTERS

Release Date:  May 16, 2000

RFA:  AG-00-002

National Institute on Aging (http://www.nih.gov/nia/)

Letter of Intent Receipt Date:  July 1, 2000
Application Receipt Date:       September 15, 2000 

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.  It is estimated that the United States spends as much as 100 
billion dollars/year for the direct and facilities and administrative (F&A) 
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 seventeen Alzheimer's Disease Research Centers (ADRCs) and eleven 
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 are expected 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 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas.  This Request for 
Applications (RFA), Alzheimer’s Disease Core Centers, is related to one or 
more of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/. 

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 Alzheimer’s disease, other 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 Alzheimer’s disease, other 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. Applications from 
institutions not previously funded as Alzheimer’s Centers will compete on an 
equal basis with competing continuation applications. The anticipated award 
date is July 1, 2001.

FUNDS AVAILABLE

The NIA intends to commit approximately $7,000,000 to fund seven new and/or 
competing renewal ADCC grants in Fiscal Year 2001.  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 primarily from persons with AD but also from persons 
with other neurodegenerative diseases 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, in 
addition to non-federal funding sources for the funding of investigator-
initiated applications.

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 are expected 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 National Alzheimer's Coordinating Center, which was 
established in 1999.  This ADC network will be used to standardize clinical 
and pathological diagnostic procedures, to pool patient information and to 
study unique aspects and subtypes of this very complex and heterogeneous 
disease process. Particular attention should be paid to the similarities and 
differences in the pathogenesis and clinical presentation among the 
neurodegenerative disorders that may be related to and confused with 
Alzheimer’s disease. The NIA expects the ADCCs to participate in cooperative 
studies involving many or all of the Centers as well as making Center data 
and specimens available for collaborative studies with qualified 
investigators not affiliated with an Alzheimer’s Disease Center.  The 
National Alzheimer’s Coordinating Center (NACC) will serve as a clearinghouse 
for requests to use data and specimens from the ADCs by outside investigators 
seeking to participate in collaborative projects.

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 an ADCC. For continuation as an Alzheimer’s center, there 
must be a clear emphasis on AD but involvement of research subjects with 
related dementias is encouraged.

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 
National Alzheimer's Coordinating Center (NACC) where data from all ADCs are 
centrally collected.  The Steering Committee of the NACC 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 NACC.

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 along different lines related to local 
interests and expertise and that one or more cores may have unique strengths 
while other cores within the Center may perform more routine functions.

Administrative Core (required):

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 NACC.

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, oversight of ethical concerns involving human subjects and 
animal research, 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 and recommendations of the advisory committee 
should be included in annual progress reports together with a short response 
to the recommendations.

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.

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 and involvement with other research programs of the University 
including the provision of core resources for development of related 
projects;

6) interaction with other Centers and the NACC to develop trans-ADC research 
projects;

7) timely and routine transmissions of the complete ADCC data set to the 
NACC;

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.

Pilot Studies (required):

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 Alzheimer’s disease research, and who wants to work in the 
Alzheimer research field; or study by an established investigator who wants 
to try a new hypothesis, method, or approach that is not an extension of 
ongoing research.

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

3) A study to determine the availability of sufficient subjects with specific 
characteristics, such as ethnic or minority status, 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.

Clinical Core (required):

The clinical core serves the functions of patient and control subject 
recruitment, patient registry, longitudinal follow-up of patients and control 
subjects, evaluation, acquisition of clinical and laboratory data including 
data pertaining to the last 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, other dementias and normal aging. The data must be shared with 
the National Alzheimer's Coordinating Center according to standardized 
protocols developed by the ADC Directors and the Steering Committee of the 
NACC.  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 and controls; 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 and to involve them in studies are strongly encouraged. 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 can then be 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 as well 
as facilitate studies that address issues specific to minority populations.  
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. These 
studies can be addressed by Centers individually and/or by cooperative 
studies involving multiple Centers and the NACC.

Neuropathology Core (required): 

This core will provide post mortem diagnosis on dementia cases, other 
cognitively impaired individuals 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, DNA, 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 NACC by mutually agreed upon protocols. To 
facilitate data sharing and cross Center comparisons of diagnosis, all 
Centers shall state clearly which neuropathological criteria they are using 
for routine diagnoses and are encouraged to use NIA-Reagan Institute 
Criteria.  (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 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 appropriate 
informed consent for present and future use of 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 immediately before 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. Monies should be 
budgeted to cover the costs of distributing tissue to scientists outside of 
the ADC. Information about testing for infectious diseases and safe handling 
of tissues and samples should be included. A mechanism to publicize 
availability of tissue, evaluate requests for samples and prioritize their 
use should be detailed. Cooperation with the NACC in cataloging the holdings 
of biological specimens from all Centers is required.

Education and Information Transfer Core (required): 

This core will support both the development of physicians and other 
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 about the disease and serve as a 
vehicle for recruitment of research subjects. 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 
physicians and other professionals including possible reciprocal exchange 
programs between Centers to provide access to different research environments 
and technologies; 2) descriptions of seminar or lecture series, workshops and 
continuing education programs; and 3) cooperation with other organizations 
such as state and local agencies and the Alzheimer's Association.  Attention 
should be directed to issues of cultural sensitivity and, where appropriate, 
the information should be structured so that it can effectively reach 
minority populations, including non-English-speaking people.  Clearly stated 
objectives and a systematic plan as to how these objectives will be met are 
required. Specific assessment methodology is also required to evaluate the 
effectiveness of outreach programs.  Consideration should be given to 
cooperation with other ADCs and the ADEAR Center at NIA when developing 
education programs for broader distribution.

Other Cores (optional):

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.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

All investigators proposing research involving human subjects should read the 
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register of March 28, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, 
Volume23, Number 11, March 18, 1994, and is available on the web at 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted. Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows IC staff to 
estimate the potential review workload and avoid conflict of interest in the 
review. The letter of intent is to be sent to the program staff listed under 
INQUIRIES by the letter of intent receipt date listed in the heading of this 
RFA.

APPLICATION PROCEDURES

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, email: 
GrantsInfo@nih.gov. Applications are also available on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html 

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 RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note that this sample label is in pdf format.

Submit a signed original of the application, including the Checklist, and 
three signed photocopies of the application 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, send two additional copies of the application plus 
all appendices to:

Mary Nekola, Ph.D.
Chief, Scientific Review
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Room 2C212
Bethesda, MD  20892-9205

It is important to send these copies and the appendices at the same time as 
the original and three copies are sent to the Center for Scientific Review. 
These copies are used to identify conflicts and to help ensure the 
appropriate and timely review of the application.

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an introduction addressing the previous critique.

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 write-up. Applicants 
should include tables detailing 1) Publications and grants (source, amount 
and title) resulting from each component funded by the ADCC 2) Publications 
and grants (source amount and title) resulting from pilot projects, 3) 
minority enrollment into research projects or clinical trials and 
specifically, into any research projects addressing minority issues.

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 or annotated lists 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 Alzheimer’s Centers, the 
National Alzheimer’s Coordinating Center, the Alzheimer’s Disease Cooperative 
Study, 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. Detail separately NIH and 
Pharmaceutical Industry sponsored trials.

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 (in tabular form, 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.  Include the numbers and kinds of 
subjects recruited for each clinical trial and each clinical research 
project, 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, related 
neurodegenerative disorders, and control autopsies, gender and minority 
status, 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 (in tabular form, where appropriate).  
Any developmental work carried out by the core should be presented and 
resulting publications listed.

Education and Information Transfer Core Progress Report: Competing renewal 
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. Also include 
recruitment and outreach programs targeting ethnic and minority groups and 
the success of these 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 National Alzheimer’s 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 + F&A) 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, neuropathology core, and 
education core leaders, data managers, 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.  F&A 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 F&A 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 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.

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. NIH has recently 
revised its requirements for Institutional Review Board (IRB) approval. Now 
IRB approval is not required prior to the NIH peer review of an application. 
See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-031.html.  This 
change in policy is intended to provide flexibility at the institutional 
level.  The institution may still determine that certain lines of research 
(e.g., scientifically or ethically controversial research) or mechanisms of 
research (e.g., multicenter clinical trials) should receive IRB review prior 
to submission of the application. Policy on Institutional Animal Care and Use 
Committee (IACUC) approval has not changed. Therefore, it is strongly 
recommended that IACUC approval be secured before the application is 
submitted.  Otherwise, it is the applicant's responsibility to ensure that 
this certification is 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 all 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.


Review Criteria

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 NACC in collaborative research, and 
attract both senior and new investigators to AD research.

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 plans for future activities 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 including utilization of Center resources by non-Center funded 
scientific projects (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) Unique contributions of the Center, including significance, innovation, 
scientific productivity, and recognition, (publications, new research grants, 
honors and awards).

4) Extent of Center interactions with the Alzheimer community including 
cooperative interactions with local organizations and nationally with other 
ADCs and cooperative studies.
B.  Cores:

1) For competing continuation applications, progress in meeting stated aims 
of cores in previous application, publications, and securing of other funding 
listed 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, across Centers (including the 
NACC) 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? Specifically include discussion of minority related research 
in the Center.

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

C. Research:

1) For new applications, the existence of a base of ongoing high quality 
research in Alzheimer's disease, other related neurodegenerative disorders or 
normal aging at the applicant institution and, for competing renewal 
applications, evidence for progress in increasing research on Alzheimer’s 
disease and related dementias.

2) For competing continuation applications, progress in meeting stated aims 
of cores in previous application, including utilization of subjects/specimens 
in other grants, publications, and securing of new funding. (Refer to 
progress report sections for details)

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 
interrelations 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 and related dementias within the applicant 
institution and cooperative studies with other ADCs and the NACC.

D.  Data Management:

1) Are data management and support procedures developed sufficiently to a) 
allow ADCC investigators to access and utilize data, b) comply with data 
requests from the NACC, and c) participate in cooperative studies with other 
ADCs and the NACC. Does the Center provide statistical design and support to 
aid 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 
National Alzheimer's Coordinating Center and to share data and specimens and 
participate in collaborative projects with other ADCs and outside 
investigators according to guidelines being developed by the NACC and the 
NIA.

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 benefited from advisory board 
input?

o Evidence for full cooperation with the NACC.

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.

3) Involvement with studies using the NACC and /or the Alzheimer’s Disease 
Cooperative Study.

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.

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

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

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

Schedule:

Letter of Intent Receipt Date:  July 1, 2000
Application Receipt Date:       September 15, 2000
Date of Initial Review:         February, 2001
Review by Advisory Council:     May, 2001
Anticipated Award Date:         July, 2001

AWARD CRITERIA

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 Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review

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


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