ALZHEIMER’S DISEASE RESEARCH CENTERS
 
RELEASE DATE:  January 30, 2004
 
RFA:  RFA-AG-04-011 (Reissued as RFA-AG-09-001)
 
Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute on Aging (NIA)
 (http://www.nih.gov/nia/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE: NUMBER: 93.866

LETTER OF INTENT RECEIPT DATE:  April 15, 2004
APPLICATION RECEIPT DATE:  May 18, 2004 
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The National Institute on Aging (NIA) invites applications from 
qualified institutions for support of Alzheimer's Disease Research 
Centers (ADRCs).  These are designed to support and conduct research on 
Alzheimer's disease (AD), and to serve as shared research resources 
that will facilitate research in AD and related disorders, distinguish 
them from the process of normal brain aging and mild cognitive 
impairment (MCI), and lead to better diagnostic and treatment 
strategies.  

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, treatment, and prevention 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 
twelve Alzheimer's Disease Core Centers (ADCCs).

The Alzheimer’s Centers provide a platform for training as well as the 
stimulation of research related to clinical-pathological correlations 
in normal aging and neurodegenerative diseases, studies of many basic 
research questions on AD and related dementias and strategies for 
prevention and treatment.  

RESEARCH OBJECTIVES

Alzheimer's disease is estimated to affect more than four 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 has been estimated that the United 
States spends 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.

The principal aim of the ADRCs should be to enhance the performance of 
innovative research on AD and related topics.  Centers are now also 
requested to concentrate their attention to better defining normal 
aging, the transition from normal aging to mild cognitive impairment 
(MCI) to the earliest stages of dementia, whether AD itself or other 
dementias associated with aging.  Clinical and pathological information 
about the earliest cognitive changes will make it possible to develop 
strategies to prevent the disease from developing or slow its 
progression.  Attention should also be paid to mixed dementias and 
overlapping neurodegenerative syndromes that sometimes occur with AD.

In order to foster the range of science necessary to advance AD 
research, Centers are being given the opportunity to diversify their 
clinical populations for specific scientific purposes.  Centers are 
expected to provide an environment and core resources which will 
enhance cutting-edge 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 should also foster the 
development of new lines of research and provide a rich training 
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 brain tissue and biological 
specimens and should incorporate contemporary biochemical/molecular 
techniques and pursue research, when feasible, in genomics and 
proteomics.  Centers are encouraged to develop in accordance with local 
talents, interests, and resources, but should also be responsive to 
national needs related to Alzheimer's disease. 

Centers should 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 as well 
as the Alzheimer’s Association in furthering mutual goals.  Centers 
should cooperate with other NIA Centers such as Pepper, Shock, and 
RCMAR Centers when possible, as well as with Udall Centers sponsored by 
National Institute of Neurological Diseases and Stroke (NINDS) as well 
as the National Alzheimer’s Coordinating Center (NACC).  Because of 
increased emphasis on collaborative research across multiple Centers, 
and additional required data reporting, Centers are now mandated to 
have a Data Management Core. 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 and the flexibility to accomplish them 
are left to the applicant.
 
The main function of the ADRCs is to support cutting-edge research 
either directly or indirectly by providing well-characterized patients, 
patient and family information, and tissue and other biological samples 
from persons with AD and from age-matched control subjects for research 
projects.  As research into the causes of AD has begun to address 
preclinical stages, Centers should now place more emphasis on the 
clinical and neuropathological changes that distinguish the initial 
stages of AD from normal aging and place less emphasis on late stage 
AD.  In addition, since several other of the neurodegenerative diseases 
(such as vascular dementia, Parkinson’s disease, Lewy body disease and 
frontotemporal dementia) have features that overlap or coexist with AD, 
ADRCs should organize the clinical cores to collect diagnostic 
information that allows differentiation among the various diseases 
while documenting features in common. To this end, applicants must 
agree to collect an expanded standard clinical data set that will be 
common to all Centers and be transmitted to the National Alzheimer’s 
Coordinating Center (NACC). Core resources from the centers should be 
used for research projects and pilot projects funded by the Center 
itself as well as for projects funded by NIH and other Federal agency 
grant mechanisms and by non-federal and private organizations.

ADRCs are required to include administrative, data management, 
clinical, and education cores. Another required function is 
neuropathological diagnosis that can be accomplished either by 
establishing a core or by subcontracting this function to other Centers 
or local organizations that have the capacity to carry out this 
function. This RFA reinstates the need to have an Education Core within 
each ADRC to underscore the importance given by NIA to education, 
information transfer, and subject recruitment. Other cores can be 
proposed if they contribute to the overall mission of the Center, are 
scientifically justified, support projects funded by the Center or by 
other mechanisms, and fit within the budget guidelines for the cores.  
ADRC applications will include, in addition, three research projects 
with a duration of up to five years (equivalent to small R01 grants) at 
least one of which should depend on clinical or neuropathology core 
resources at the home Center or another Center. The number of research 
projects funded and their duration will depend upon scientific quality. 
Funding for smaller ($35,000/year) one year pilot grants should also be 
requested.  

The ADRCs provide a mechanism for integrating, coordinating, fostering 
and developing the interdisciplinary cooperation of a group of 
established investigators conducting programs of research on 
Alzheimer's disease and related dementing disorders of older people.  
They provide financial, intellectual, patient, and biological specimen 
resources to support cooperative interactions among scientists in the 
local Center, other Alzheimer’s Centers and the research community at 
large.  A prime objective of the Center Grant is to provide an 
environment that will strengthen research on AD and related disorders 
at the institution, increase productivity, and generate new ideas 
through formal interdisciplinary collaborative efforts both locally and 
nationally.  The central focus may be clinical – pathological research, 
basic research or a combination. Applicants are strongly encouraged to 
include efforts to address the needs of, and research on, ethnically 
diverse populations. 

The Center Grant may incorporate ancillary activities such as 
longitudinal studies and prolonged patient care necessary to support 
the primary research effort.  The spectrum of activities should 
comprise a multi-disciplinary approach to the problem of Alzheimer’s 
disease.  An important role of Centers is to perform collaborative 
studies on particular research topics and to serve as a regional or 
national resource for special purpose research. Currently many of the 
Centers are active participants in NIA multi-disciplinary/multi-Center 
studies such as the initiative on the genetics of late onset AD and are 
contributing subjects and blood samples for multiplex family projects.  
All Centers are required to be linked with the NACC and the network of 
Centers linked to NACC is being 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.  

MECHANISM OF SUPPORT

This RFA will use the NIH P50 award mechanism.  As an applicant you 
will be solely responsible for planning, directing, and executing the 
proposed project.  This RFA is a one-time solicitation. New proposals 
or competing-continuation applications for ADRCs will only be accepted 
by solicitation under future RFAs. The anticipated award date is April 
1, 2005. 

This RFA uses the non-modular budgeting format (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Follow the 
instructions for non-modular budget research grant applications.  This 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.  

FUNDS AVAILABLE

The NIA intends to commit approximately $16 million in fiscal year 2005 
to fund eight new and/or competing renewal ADRC grants in response to 
this RFA.  An applicant should request a project period of five years. 
The total costs (direct + F&A) requested for new applications may not 
exceed $1.4 million for the first year. Competing renewal applications 
have no overall limit but the combined budgets (direct + F&A) for all 
cores (both required and optional), the other listed required 
functions, satellites, and pilot grants may not exceed the combined 
cost of all presently funded core activities including satellites and 
pilot grants awarded during the final year of the present funding 
period plus a 3% increase. In addition all applications should request 
three research projects. Although the financial plan of the NIA 
provides support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications. Limited funds are 
available for competing supplement applications. Competing supplement 
applications for projects or optional cores will be limited to a 
maximum of two during a 5-year funding cycle. 

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the 
following characteristics:
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic institutions/organizations 
o Foreign institutions are not eligible to apply
 
Your institution should support an ongoing base of high-quality 
Alzheimer’s research or research in other neurodegenerative diseases, 
or in aging of the nervous system.  To be eligible your institution 
must support:

o at least five principal investigators with any PHS agency (or 
comparable peer-reviewed federal, state, or foundation) funded research 
grants related to neurodegenerative diseases or aging of the nervous 
system and each with at least two years of support remaining at the 
time of application.

or,

o one or more program project grants (P01s) related to 
neurodegenerative diseases or aging of the nervous system and with at 
least two years of support remaining at the time of application.

The work that you propose in the ADRC should be different from the 
ongoing supported research. NIA will review overlap of existing support 
through P01s or other mechanisms and adjust support of the center 
appropriately prior to any award.  Your institution can have only one 
active Alzheimer’s Center receiving NIA support.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

The P.I. should be a scientific leader experienced in the field of 
Alzheimer’s and/or other neurodegenerative 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 P.I. Individuals from underrepresented racial and ethnic groups as 
well as individuals with disabilities are always encouraged to apply 
for NIH programs.   

SPECIAL REQUIREMENTS 

An Alzheimer's Disease Research Center will be an identifiable 
organizational unit formed by a single institution or a consortium of 
cooperating institutions.  Therefore, lines of authority must be 
clearly specified.  Each applicant institution will name an ADRC 
Director (P.I.) who will be the key figure in the administration, 
management and coordination of the ADRC grant.  The Director will be 
responsible for the organization and operation of the ADRC.  The 
Director should be a scientific leader experienced in the field of 
Alzheimer’s disease research and must be able to coordinate, integrate, 
and provide guidance in the establishment of programs in Alzheimer's 
disease research and allied areas. 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 specimens with 
other research scientists both within and outside the Centers network 
as well as data concerning patients and control subjects with the NIA -
sponsored National Alzheimer’s Coordinating Center (NACC) where data 
from all AD Centers is centrally stored. Any genetic specimens 
collected by the Center should be made available to the National Cell 
Repository for Alzheimer’s Disease (NCRAD), if they meet the criteria 
for inclusion in the repository, in accordance with agreed upon 
protocols and policies.  Centers may also be requested to contribute 
other biological samples such as serum and cerebrospinal fluid, using 
agreed upon protocols, for trans-center studies examining biomarkers 
that might relate to risk, diagnosis or progression of AD.  The 
Steering Committee of the NACC in conjunction with the ADC Directors 
and the NIA sets policies that allow the individual Centers to conduct 
research on patients and control subjects collected by the individual 
Center while also sharing common data sets with NACC. Applicants should 
follow NIA policies on data and sample sharing.

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

The required elements for an ADRC include cores, research projects, and 
pilot research projects.  Additional cores may be proposed but only if 
they are needed to advance the local research effort and if they fit 
within the budget limits described elsewhere in this RFA.  Applications 
must include a data management core that also includes a capacity to 
provide biostatistical consulting to the scientific staff associated 
with the ADRC. Applicants must have the capacity to provide 
neuropathological confirmation of the diagnosis for all subjects who 
die while enrolled in the clinical core of the center and to store 
selected brain specimens for research. This may be accomplished by 
either having a Neuropathology core or by using the services of another 
Alzheimer’s Center Neuropathology Core or by a pathologist specializing 
in neurodegenerative diseases. 

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

A core is a shared central laboratory or clinical research facility, 
service, or resource whose function is essential to the scientific 
purpose of the ADRC.  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 stated goals.   Several important and 
related considerations are (1) the degree to which currently funded 
investigators within or outside the Center will use and will benefit 
from core resources, (2) the degree to which the cores coordinate with 
each other to further the overall Center mission and (3) the degree to 
which the resources will promote new and/or expanded AD research 
efforts locally, regionally or nationally.  Applicants should document 
and describe briefly the projects, both existing and planned, whether 
funded by the Center or not, that have, or will depend upon resources 
provided by the requested cores. At least one of the proposed ADRC 
projects must depend directly upon resources provided by the clinical 
core or the neuropathology component of the Center.

Required Cores and Functions

ADMINISTRATIVE CORE: The administrative core should set the overall 
direction of the Center and ensure optimal utilization of Center 
resources. Effective development of Center programs requires 
interaction among the Director, the principal investigators of the 
cores, the principal investigators of research and pilot projects using 
the cores, other researchers at the applicant institution, appropriate 
institutional administrative personnel, the staff of the awarding 
agency, and the members of the community in which the Center is 
located.  The ADRC should recognize that it is part of a large network 
of ADCs and be prepared to work cooperatively with the other Centers 
and the National Alzheimer’s Coordinating Center.
 
The success of the ADRC is dependent upon involving scientific and 
professional personnel from a variety of disciplines and subspecialties 
who interrelate in order to facilitate the acquisition of new 
knowledge. In addition to coordination of the ADRC, the Director, with 
the advice of his or her executive committee, will be responsible for 
allocating and monitoring ADRC funds and identifying and selecting key 
personnel. An executive committee (composed of core and project leaders 
and the administrator) will be established to assist the Director in 
making the scientific and administrative decisions relating to the 
Center.  The executive committee should 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.

A committee to review pilot grant applications should be established 
and include scientists from outside the ADRC with expertise relevant to 
the types of pilot applications received by the Center. This committee 
will make funding recommendations to the Director. Alternatively, the 
external advisory committee could be responsible for pilot reviews. 

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

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

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

1) coordination and integration of ADRC components and activities; (for 
example, the clinical and data management cores with the neuropathology 
and education components)

2) direction for future planning and optimal utilization of resources

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

4) interaction with the scientific and lay communities to develop 
relevant goals for the ADRC

5) assurance of compliance with human subjects, animal welfare, 
scientific integrity, and financial policy requirements of NIH

6) interaction with other Centers, the Data Coordinating Center and 
other researchers to develop trans-ADC and outside research projects

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

8) timely and routine transmissions of appropriate ADRC data sets to 
the NACC
  
CLINICAL CORE: The Clinical core provides well-characterized patients 
and control subjects for cutting edge research projects involving e.g. 
clinicopathological correlations, comparison of disease states to 
normal aging, and drug/intervention studies.  The Clinical core in 
close collaboration with the Education core of the Center is the 
primary contact point with the community. The Core provides resources 
to patients, aging control subjects, and caregivers while charting the 
course of the disease in patients and age-related changes in the 
research population being followed by the Center.  Previously, clinical 
cores of ADCs have usually been based in university medical center 
neurology or psychiatry department memory disorders clinics and have 
concentrated mostly on middle to later stages of AD. With this RFA NIA 
is providing the opportunity to structure clinical cores to include 
special control or elderly populations that might be available to some 
applicants such as an ethnic or minority population, a religious 
community or a community population living in elderly housing where the 
likelihood of being able to study the full spectrum from normal aging 
to mild cognitive impairment to AD would be possible.

Recent improvements in evaluation for memory disorders in normal aging 
and MCI present new opportunities for research on early stages of 
disease and decrease the necessity to enroll middle and later stage 
patients. In addition, our increased understanding of the relationship 
of AD to, or coexistence with, other neurodegenerative diseases 
commonly seen in the elderly population provides the opportunity to 
broaden the mission of the ADRCs to include mixed dementias and 
diseases such as vascular dementia, Lewy body disease, frontotemporal 
dementia, and Parkinson’s dementia in order to better differentiate 
among them, to recognize commonalities and to study older demented 
individuals with mixed etiologies and medically co-morbid conditions. 
Therefore it is more appropriate that applicants concentrate on 
preclinical AD, normal aging, MCI and early AD as well as enhancing the 
recruitment of research subjects with other neurodegenerative diseases 
rather than concentrating only on full blown or pure AD. If applicants 
choose to diverge from the traditional structure (memory disorders 
clinic model) of the clinical core by including special populations, 
the responsibility is on the applicant to provide a complete 
description of the characteristics of the subject population and to 
justify the added value to research at the Center resulting from using 
a different subject population so peer reviewers can evaluate the 
comparative strengths and weaknesses of proposed clinical core subject 
populations. 

The clinical core, in addition to patient and control subject 
recruitment, provides evaluation, and diagnosis,  maintains a patient 
registry, conducts longitudinal follow up of patients and control 
subjects, and acquires clinical and laboratory data including agonal 
data pertaining to the last several weeks of life if post mortem 
material is to be used for molecular research.  Procedures and 
facilities should be described related to collection, storage, and 
distribution of biological samples, including, but not limited to, cell 
lines, cerebrospinal fluid (CSF) and plasma. Applicants should follow 
agreed upon protocols for multi-center projects involving specimen 
collection. Details for collecting specimens, recording information 
about clinical status of patients immediately preceding and at time of 
death, and procedures for storage and distribution of human biological 
samples to investigators both within and outside the Center should be 
provided. See the supplementary instructions section in this RFA for 
details regarding informed consent. 

Data on preclinical stages of AD (MCI), possible and probable AD, other 
neurodegenerative disorders and normal aging should be collected and 
transmitted to the Data Management core.  The data must be shared with 
the National Alzheimer’s Coordinating Center according to standardized 
protocols developed by the ADC Directors, the Clinical Core leaders and 
the Steering Committee of NACC.  A clinical task force is presently 
developing the criteria for collection of an expanded standard clinical 
data set from all Centers.  Applicants must state in this section of 
the application that they agree to provide this expanded data set to 
NACC where it will be combined with data from other Centers and made 
available to scientists for collaborative studies.

The clinical core may perform a limited amount of developmental work, 
but should not directly support research per se. The developmental work 
allowable in a clinical core must be directly related to the function 
of the core.  It may be directed toward improving and expanding the 
core functions, e.g., improving existing diagnostic strategies, or 
developing additional methodologies, techniques or services.  Proposed 
developmental work should be described as completely as possible in the 
application.  Planning for patient and age-matched control subject 
recruitment should include sensitivity to research design and 
biostatistical analysis. Procedures for communicating recruitment needs 
to the Education Core and for evaluating success should be outlined. 
The application should include a description of the types (with 
specific examples) of research projects and clinical trials that use or 
will use the core and what benefits will obtain to other research 
activities from the existence of the clinical core. While conducting 
clinical drug trials is one function of a clinical core, it should not 
be the major effort of the core.  

Efforts to recruit diverse population subgroups including minorities 
and rural populations must be outlined.  One option is to set up 
Satellite Diagnostic and Treatment Clinics (SDTCs) designed to increase 
the heterogeneity of the research patient pool and to enhance the 
research capabilities of the ADC by extending the activities of the 
clinical core.  Existing Centers should retain any satellites already 
in existence unless there are compelling reasons to restructure these 
components.  New satellite clinics may be proposed as part of the 
clinical core.  The satellite clinics are not required to conduct 
research but should serve as vehicles for the recruitment, diagnosis 
and management of AD patients control subjects from rural and minority 
communities, who are then offered the opportunity to participate in 
research protocols, clinical drug trials and autopsy.  Effective 
satellites usually include multicultural staff members who have links 
to the community being involved.  In addition, the satellite should 
have clearly delineated interactions with the educational outreach 
activities of the Center.  Applicants should detail appropriate 
strategies for outreach to recruit and retain ethnically diverse 
subjects and describe the culturally sensitive materials that will be 
used.  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.

DATA MANAGEMENT and STATISTICS CORE: This core should provide data 
management and statistical consulting to the research projects and the 
cores of the ADRC.  Data cores are important to facilitate local 
analyses and collaborations between and among Centers and with NACC. 
The data core must be adequately funded and staffed to allow required 
tasks to be carried out. (New applicants may contact NACC to learn more 
about NACC procedures and the regular updates to the datasets required 
from all Centers; http://www.alz.washington.edu/ ) A model for the data 
core might consist of two arms:  1) computing and data base management 
and 2) statistical consultation and liaison with other cores and 
projects.  The core director must be keenly aware of and experienced 
with database management practices and computing but is not necessarily 
the architect and day to day manager of the database.  The core 
director must have the time and the authority to work administratively 
with other cores/projects.  The core should include a systems manager 
for computing and database management who will be the architect of the 
database structure and responsible for its maintenance.  This person 
will be an experienced database programmer and systems analyst with 
sufficient background to select and implement database management 
software, represent data structures, specify and organize data flow, 
construct detailed “error-check” programs, develop/implement data 
checking and cleaning procedures, and provide for data entry and 
access, as well as information distribution, through electronic means 
(e.g., the internet or intranet).  Communication and cooperation with 
all cores and projects where data are (or will be) generated, with 
NACC, and a close working relationship with the statistics arm of this 
core should be primary goals for this core.  The systems manager should 
be given the authority:

1. to establish data flow schemes, 
2. to construct data forms (electronic or hard copy; following 
core/project specified content), 
3. to implement a Center-wide system of subject ID numbers that meets 
privacy standards 
4. to require adequate filing systems for raw data within the 
cores/projects and within the data core itself, 
5. to establish a mechanism to track data edits,
6. to provide for longitudinal follow-up data storage/retrieval 
consistent with the protocols of the center.  

The staff of the data core must work with clinical and research 
personnel to interpret their data into computer usable form, and 
simultaneously work with statisticians to insure that the data are 
represented in a fashion that will allow the desired analysis files to 
be produced and analyses to be accomplished. Data core staff should 
have a working relationship with core/project data collectors and must 
have their cooperation to reconcile errors and missing or incomplete 
data elements as discovered through error check programs or through 
‘hands-on’ inspection procedures. In addition the core staff is 
required to work cooperatively with the NACC staff and respond 
appropriately to data calls issued by NACC.

A biostatistician(s) should be involved in the design and analysis of 
studies within the Cores and projects and will work closely with the 
data manager to insure analysis files are produced consistent with the 
needs of the question at hand.  It is expected that the Clinical and 
other cores and projects in the ADC, where data are collected, will 
fully cooperate and participate with the data core by providing data in 
the form specified and in a timely way. Cooperation, concurrence and 
collaboration should continue from the initial specification of data 
content through data collection to database management and analysis.

NEUROPATHOLOGY: Neuropathology operations are expected to provide state 
of the art diagnostic services and collection of well-prepared brain 
material appropriate for the research requirements of local research 
efforts as well as cooperative research across Centers and with other 
researchers outside of Centers.  Centers must be able to provide post 
mortem diagnosis on cases and normal control subjects enrolled in the 
clinical core and on other well documented AD cases and controls.  A 
significant value of having the Center infrastructure is the support of 
research studies that permit clinical-pathological correlations across 
Centers.  Therefore, Centers should agree to follow standardized 
procedures so that cross-Center correlations are possible. (New 
applicants may contact NACC to get the most recent pathology 
requirements). Centers can choose to establish a neuropathology core or 
can obtain services from outside the Center (usually another 
Alzheimer’s Center). 

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, 
cell lines, cerebrospinal fluid (CSF) and plasma.  While Centers are 
encouraged to have brain banks, less emphasis should be placed on the 
routine collection and storage of late stage Alzheimer’s brains (unless 
specific research questions call for these) and more emphasis placed on 
collection of brain material in a fashion  that will support the 
specific research efforts of investigators affiliated with the local 
Center and other scientists. If collection of special material is 
proposed (e.g. tissues from Parkinson’s disease, oldest old controls, 
frontotemporal dementia, prion diseases, mixed dementias, or 
stereologically prepared specimens) justification should be included. 
Data gathering and storage activities should be coordinated with those 
of the Clinical Core and the Data Management Core. 

To facilitate data sharing and cross-Center comparisons of diagnosis, 
all Centers should use the neuropathological criteria for Alzheimer’s 
disease developed by the NIA-Reagan Institute Working Group 
(Neurobiology of Aging, vol. 18, suppl 4, pp S1-S2, 1997). If tissue 
from other diseases is collected, list the clinical diagnostic criteria 
used. More detailed criteria for research purposes should also be 
described.  Pathology data should be included in the data set 
transmitted to NACC as recently redefined by Center neuropathologists 
and approved by the Center Directors group.  (New applicants may get 
information from NACC about the pathology data set).  If the applicant 
chooses to include a neuropathology core in the application, the core 
may propose a limited amount of developmental work, but should not 
emphasize research per se. The developmental work allowable must be 
directly related to the function of the core.  It may be directed 
toward improving and expanding the core functions, e.g., improving 
existing, or developing additional methodologies, techniques or 
services.  Proposed developmental work should be described in the 
application.  Neuropathologists from 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.  All Centers are expected to send a 
representative to this meeting.

The procedure for prioritizing the use of tissues and other biological 
samples stored at the Center should be discussed along with a brief 
description of potential research projects that will use the samples.  
Provisions for obtaining informed consent and protecting the privacy of 
research subjects must be detailed.  Procedures to provide coded 
samples to investigators that protect the identity of the patients 
should be described. 

EDUCATION and INFORMATION CORE: The three major activities of the 
Education Core are to 1) help recruit and retain subjects for 
particular research protocols and clinical trials, with a special 
emphasis on minorities and other underserved populations; 2) spearhead 
effective outreach programs that will publicize the ADRC and educate 
families and caregivers; 3) support innovative development of 
professional staff on clinical and research skills related to 
Alzheimer’s disease and other dementias.  These efforts afford an 
important liaison and outreach from the ADRC to patients, their 
caregivers and the professional community. Collaboration with the 
Alzheimer’s Association local chapters and other groups is expected for 
dissemination and transfer of information to the lay community and 
other educational activities and assistance with subject recruitment. 
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; 
3) outreach to specific communities to publicize research; 4) 
collaboration with other organizations such as state and local agencies 
and the Alzheimer’s Association and 5) descriptions of materials (e.g. 
videos and printed matter) developed by the Center.

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.  Procedures by which the education and outreach activities are 
closely coordinated with the clinical core and satellite(s) (if 
appropriate) should be described, especially in recruitment of 
minorities and ethnically diverse populations. The education and 
outreach activities should also be prepared to support activities of 
the Centers group as a whole as well as recruitment for special NIA 
initiatives, such as subjects for genetic studies. 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.  Collaboration with 
other ADCs and the NIA Alzheimer’s Disease Education and Referral 
Center (ADEAR) in subject recruitment, education and coordinated 
dissemination of educational materials is expected.

Optional Cores

The NIA, through the ADRC, will support additional cores that provide 
opportunities for scientific research beyond those attainable solely 
through support of the mandatory cores and other functions. However, 
any optional cores must support one or more Center research projects 
and fit within the budget restrictions outlined in the budget 
guidelines for the application. 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 investigators using 
center resources to make possible new activities at the home Center as 
well as other Centers.  There should be a detailed discussion of the 
project(s) that will use resources of additional cores. Some examples 
of research support that core components could provide are: (1) 
imaging; (2) tissue and/or cell culture facilities; (3) complex 
instrumentation, e.g., electron microscopy, mass spectrometry, 
electrophysiology; (4) sequencing or microarray facilities (5) 
transgenic animal or cell preparation; (6) genetics; and (7) 
caregiving. 
 
Research Projects

Applications should request funding for three research projects 
(similar to small R01s).  The research projects should request up to 
five years of funding and propose studies that will advance our 
understanding of the basic and clinical underpinnings of Alzheimer’s 
disease and related disorders in areas such as preclinical etiology, 
genetics, pathogenesis, epidemiology, diagnosis, therapeutic 
interventions including small scale clinical trials, patient 
management, and care giver issues.  The projects should be similar in 
quality to small R01 grants and subprojects of program project grants. 
It is required that at least one of the projects predominantly utilize 
patients or patient samples from the clinical core or neuropathology 
resources.  The ADRC should not be the primary source of research 
funding for the project leaders funded by the Center.   

Pilot Studies

A plan to support pilot studies for basic or clinical biomedical, 
epidemiological, caregiving, educational 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 in 
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.  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 other 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.  Some examples are:

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 a study by an established 
investigator who wants to try a new hypothesis, method, or approach 
that is not an extension of ongoing research.

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

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

4) A study based on data in the NACC data set to determine the 
feasibility of conducting larger new studies.

Each pilot project is limited to no more than $35,000 direct costs each 
year.  If the pilot project is requested and justified for two years, 
the direct costs are limited to $35,000 per year.

No pilot applications should be submitted with the Center application 
but, instead, the number requested for each year (2 minimum, 3 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.  The panel should include scientists from outside the 
Center.  One option is for the External Advisory committee to serve as 
the review panel for the pilot applications.  Following review, those 
pilots chosen for funding should be submitted to the NIA for approval 
in the annual non-competing renewal application. Successful Center 
applicants should conduct a competition and submit the successful 
applications to NIA for the first year of pilot funding after receiving 
notice of grant award; in subsequent years competition for pilot awards 
should be timed so successful applications can be submitted with the 
non-competing renewal application for NIA review

Progress Reports (for competing renewal applications)

Overall Progress Report: Address the major scientific achievements in 
research on AD and related topics carried out by Center personnel and 
by projects utilizing Center resources in the last funding period. 
Identify significant findings in research on aging, AD and other 
neurodegenerative diseases that were facilitated or supported directly 
through Center resources. Include summaries of progress in achieving 
the major aims of the Center and its projects and highlight major 
publications. Include details of how the presence of the ADRC has 
brought new investigators into the field and has stimulated non-ADRC 
funded research in the last funding period. Explain the Center’s role 
in generating new funding from grants as well as leveraging funds from 
donors and other private sources. Describe how the presence of the 
Center has facilitated and improved Alzheimer research at the 
Institution and beyond.  When a project or optional core has 
terminated, include a final report with a summary of results and 
publications.  If an optional core is continuing, include a progress 
report in that component write-up. Applicants should include tables 
detailing 1) Publications and grants (source, amount and title) 
resulting from each component funded by the ADRC, 2) Publications and 
grants (source amount and title) resulting from pilot projects, 3) 
Involvement in collaborative projects with other Centers including 
those funded by NACC, and 4) minority enrollment into research projects 
or clinical trials and specifically, into any research projects 
addressing minority issues.  

In addition to text summaries, applicants should also include summary 
tables detailing:  

1) ADRC and Non-ADRC funded grants and projects that use or have used 
major resources supplied by the ADRC, including principal investigator, 
source and period of funding, types and amount of resources 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. Detail 
separately NIH and pharmaceutical industry sponsored trials.

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

Clinical Core Progress Report: Describe the most important clinical 
core contributions to research on AD, related dementias and aging.  
Detail key findings and list publications resulting from use of core 
patients.  Any developmental work carried out by the core should be 
presented and resulting publications listed.  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, 
use of autopsy data in support of clinical correlations in research 
projects, and diagnostic confirmation by autopsy.  Functions of 
Clinical Core in providing services (a) for ADC-funded and (b) non-ADC 
funded investigators should be clearly summarized.  These would include 
numbers and kinds of subjects recruited and participation in clinical 
trials and other ongoing clinical research projects, both local and 
national. Applicants are required to ensure that patients’ privacy is 
protected as discussed elsewhere in this RFA.

Neuropathology Core Progress Report: Describe the most important 
neuropathology core contributions to research on AD, related dementias 
and aging. Competing renewal applications should outline previously 
stated core objectives and progress in meeting them. Any developmental 
work carried out by the core should be presented and resulting 
publications listed. The most important consideration in reporting 
progress should be reports of tissue use in research projects and the 
new insights obtained from these studies. Basic functions of the core 
such as number of AD and control autopsies, post mortem intervals 
(where this is important for specific research purposes), tissue 
dissection and storage, diagnoses, and type and quantity of tissue 
provided to investigators both funded by the Center and by other means 
should be clearly summarized (using tables where appropriate).  

Education and Information Transfer Core Progress Report: Applications 
should include information about training activities that effectively 
impart knowledge to professionals and the lay public with the 
possibility of leading to improved health care for patients.  Include 
efforts to assist the clinical core and NIA special initiatives, such 
as the genetics initiative, in subject recruitment, especially any 
efforts directed to recruitment of minority and ethnically diverse 
subjects. Using tables when appropriate, report 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. List 
educational materials developed by the core and any that may have been 
provided to ADEAR for national distribution.

Data Management and Statistics: Summarize progress and activities 
related to data collection, data management and statistical consulting 
activities at the appropriate place in the application detailing where 
in the core(s) these activities were located.  Include progress and 
interactions with NACC. Present evidence for meeting timetables for 
data transfer in the proper format to NACC.  List projects and 
publications in which data management and statistical consulting played 
a role.

Budget Considerations

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

The total costs (direct + F&A) requested for new applications may not 
exceed $1.4 million for the first year. Competing renewal applications 
have no overall limit but the combined budgets (direct + F&A) for all 
cores (both required and optional), the other listed required 
activities, satellites, and pilot grants may not exceed the combined 
cost of all presently funded core activities (required and optional) 
including satellites and pilot grants awarded in the final year of the 
present funding period plus a 3% increase.  Applicants should request 
three research projects each limited to $125,000 direct costs/ year for 
up to five years. Direct cost requests for subsequent years may 
increase above the prior year direct cost award by 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 depending on whether this is  a new application  
or a competing renewal, on the overall budget of existing Centers, and 
local needs.  If additional cores are proposed, the distribution should 
be adjusted accordingly.)

Administrative Core                       5%
Pilot Studies                             5%
Clinical Core                            35%
Data Management Core                     10%
Neuropathology                           10%
Education and Information Transfer Core   5%
Research Projects                       25-35%

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

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

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

Requests and commitments for pilots in competing applications (new and 
renewal) will be budgeted as a separate line in the "composite" budget 
at $35,000 per pilot per year (without escalation).  They should not be 
included in the Administrative Core budget 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 non-competing renewal 
applications.  Facilities & Administrative costs will be provided in 
accordance with these budgets.

Pilot grants are allowed for consortium arrangements but direct cost 
should not exceed $35,000 with total consortium cost budgeted not to 
exceed $40,000 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 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.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

o Direct your questions about scientific/research issues to:

Creighton H. Phelps, Ph.D.
Program Director, Alzheimer’s Disease Centers
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue 
Suite 350
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email: phelpsc@nia.nih.gov

o Direct your questions about peer review issues to: 

Mary Nekola, Ph.D., Chief
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue 
Suite 2C212
Bethesda, MD  20892-9205
Telephone:  (301) 496-9666
FAX: (301)402-0066 
Email: nekolam@nia.nih.gov

o Direct your questions about financial or grants management matters 
to:

Deborah Stauffer
Grants and Contracts Management Office 
National Institute on Aging 
7201 Wisconsin Avenue
Suite 2N212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email: stauffed@nia.nih.gov 

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

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 plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document. The letter of intent should be sent to:

Creighton H. Phelps, Ph.D.
Program Director, Alzheimer’s Disease Centers
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging 
7201 Wisconsin Avenue
Suite 350
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email: phelpsc@nia.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY INSTRUCTIONS: 

The page limit of 25 pages for Items a-d of the Research Plan, as 
stated in the PHS Form 398 instructions, applies to each research 
project and core. Appendix materials should follow the instructions in 
the 398 form with the following exception: The complete Appendix 
materials should be submitted on a Compact Disc (CD) that is identified 
with the name of the principal investigator and the name of this RFA. 
All appendix materials for the complete application should be on a 
single CD. Appendix materials should be submitted to the Chief, 
Scientific Review Office, NIA (see address below).

Information that is not included with the original application may not 
be submitted after the receipt date except with prior approval from the 
responsible Scientific Review Administrator. This will usually only 
include major corrections or changes in personnel.  

Table of Contents

Do not use Form Page 3, “TABLE OF CONTENTS” of Form 398 since it 
applies to applications for single projects.  In its place, use the 
sample format provided in the following link 
http://www.nia.nih.gov/NR/rdonlyres/BE40D316-62CE-4075-B2DC-DC577E283A65/
3114/P01GuideAttach.pdf.  Number all pages consecutively.  Since the 
first page of the application is the “Title Page,” begin the next page with 
the numeral “2”.  Do not use lettered numbers (e.g., 2A, 2B, etc.). 
Budgets. Insert a table describing the CONSOLIDATED DIRECT COSTS FOR 
FIRST YEAR OF REQUESTED SUPPORT, as shown in Attachment 3 in the above 
link for the three required cores, any optional cores and the three 
projects.  Next, insert budgets for the first twelve months and for the 
entire proposed period for the overall program.  Do not include 
detailed budgets for individual research projects and cores here; 
instead, place them with the corresponding project or core.  Justify 
all items carefully according to the PHS 398 form instructions. A 
complete budget for a consortium project is to be developed and 
identified as such. The period of support may not exceed five years of 
support. Any questions about budget development may be directed to the 
Grants and Contracts Management Office at the address above.
Biographical Sketches. Follow the PHS 398 instructions.  Include 
sketches for all key personnel and place them in alphabetical order; 
however, place the principal investigator’s/program director’s 
biographical sketch first. 

Distribution of professional effort (%) on this application. To aid in 
the review of the application, insert completed Table II from 
http://www.nia.nih.gov/NR/rdonlyres/BE40D316-62CE-4075-B2DC-DC577E283A65/
3114/P01GuideAttach.pdf after the biographical sketches. Follow the 
format delineated in Attachment 4 on this link.

Sharing of Data and Biological Resources
 
Restricted availability of unique research resources, upon which 
further studies are dependent, can impede the advancement of research. 
The NIH is interested in ensuring that particular research resources 
developed through grants become readily available to the broader 
research community in a timely manner for further research, 
development, and application, in the expectation that this will lead to 
products and knowledge of benefit to the public health.  Resources to 
be shared will include appropriate data, brain tissue and other 
biological samples collected.  Data sharing will be accomplished 
through NACC.
 
To address this interest in assuring research resources are accessible, 
NIH requires applicants who respond to this RFA to submit a plan for 
exercising intellectual property rights, should any be generated 
through this grant, while making such research resources available to 
the broader scientific community.
 
The sharing of research resources plan and intellectual property plan 
must make unique research resources readily available for research 
purposes to qualified individuals within the scientific community in 
accordance with the NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps/) and the Principles and 
Guidelines for Recipients of NIH Research Grants and Contracts on 
Obtaining and Disseminating Biomedical Research Resources: Final 
Notice, December 1999 
(http://www.ott.nih.gov/policy/rt_guide_final.html) and 
(http://ott.od.nih.gov/NewPages/64FR72090.pdf).  These documents 
also define terms, parties, responsibilities, prescribe the order of 
disposition of rights, prescribe a chronology of reporting 
requirements, and delineate the basis for and extent of government 
actions to retain rights.  Patent rights clauses may be found at 37 CFR 
Part 401.14 and are accessible from the Interagency Edison web page, 
http://www.iedison.gov.
 
NIA program staff will consider the adequacy of the plan and its 
consistency with NIH and NIA policies on data sharing and intellectual 
property when determining whether to recommend an application for 
award.  The approved plan will become a condition of the grant award 
and Progress Reports must contain information on activities for the 
sharing of research resources and intellectual property.
 
At least one of the three projects should use patients or research 
samples from the clinical core or from neuropathology resources.

Each component core and project should be presented according to the 
Table of Contents.  The cores should appear first, identifying required 
cores by letters as follows, (Core A = Administrative Core, Core B = 
Clinical Core, Core C =Data Management core); if the application 
includes a Neuropathology Core, it should be Core D; the Education Core 
should be Core E even if there is no Neuropathology Core. Optional 
Cores should be identified with subsequent consecutive letters. 
Individual research projects should appear in the application after the 
cores and identified with consecutive Arabic numbers (Project 1, 
Project 2, Project 3).  Titles may not exceed 56 spaces.

Prepare each core or project as a separate section that begins on a new 
page of the application.  Begin each with a title page (use the format 
of sample Attachment 2 in the link mentioned above; Do not use the face 
page of form 398) and include a detailed first year and summary budget 
for all years with each core and project.  Continue to number the pages 
consecutively.

Informed Consent

Describe the procedures for 1) obtaining informed consent for research 
on cognitively impaired human subjects who may not have the capacity to 
consent, 2) obtaining consent for future participation in research 
studies if the patient becomes unable to consent (advanced directive 
for research) 3) obtaining consent to place data in the National 
Alzheimer’s Coordinating Center’s minimum data set and to share data 
and specimens with other qualified scientists, and 4) obtaining proxy 
or surrogate consent in the context of local and state law.  Attach 
samples of information given to patients and families and copies of all 
consent forms.  Attention should be paid to obtaining advanced 
directives for research, and obtaining autopsy permission from patients 
and families and informed consent for current and future use of 
biological samples by qualified investigators. Permission should be 
obtained for sharing of cells, DNA and phenotypic information and for 
storage in repositories.   

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) 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 RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
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)
 
Do not submit any appendix material to the Center for Scientific 
Review.

At the time of submission, two additional copies of the application and 
one CD of any appendix material must be sent to:

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

APPLICATION PROCESSING: 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.
 
Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
institute assignment within 8 weeks.

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.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIA. Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIA in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

o 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 and assigned a priority score 
o Receive a written critique
o Receive a second level review by the National Advisory Council on 
Aging

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. 
In the written comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals. The scientific review group will address and 
consider each of the following criteria in assigning the application’s 
overall score, weighting them as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

Your application does not need to be strong in all categories to be 
judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, you may propose to carry out important 
work that by its nature is not innovative but is essential to move a 
field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  What will be the effect of these studies on the concepts or 
methods that drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project 
challenge existing paradigms or develop new methodologies or 
technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to your 
experience level as the principal investigator and to that of other 
researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH: The adequacy of plans to 
include subjects from both genders and all racial and ethnic groups 
(and subgroups) as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will 
also be evaluated. (See Inclusion Criteria in the sections on Federal 
Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  

Sharing Research Data: 

Applicants requesting more than $500,000 in direct costs in any year of 
the proposed research must include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the 
reviewers. However, reviewers will not factor the proposed data sharing 
plan into the determination of scientific merit or priority score. (See 
sharing policy in the sections on Federal Citations, below).

BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

Other Review Criteria:

In addition to the above criteria, applications will specifically be 
reviewed with respect to the following: 

Progress in Achieving Stated goals (competing renewal applications)

o Adequacy of progress in stated goals from last application, most 
importantly, productivity as demonstrated by quality of scientific 
findings and their impact on AD research; include publications, honors 
and awards, grant funding, pilot grant success and research projects 
supported by core resources including collaborative research.

Scientific Potential of the Center (competing renewal and new 
applications)

o Potential to develop critical new knowledge and unique and innovative 
contributions to AD research locally and nationally
o Scientific/technical merit and innovation in the proposed Center 
goals
o Expertise and productivity of Center investigators
o Ability of Center to participate in coordinated national efforts for 
collaborative research and data sharing with other scientists and 
research Centers

Organization of the Center (competing renewal and new applications)

o Adequacy of organizational plan and management structure to meet 
Center goals and the requirements spelled out in this RFA
o Merit and appropriateness of institutional resources including other 
funding and dedicated resources 
o Appropriateness of functions described for External Advisory 
Committee
o Appropriateness of plans for review and award of pilot projects 

Core Facilities (competing renewal and new applications)

o Appropriateness of proposed core resources to facilitate research 
goals of the Center and a plan for prioritizing their use
o Adequacy of utilization of core support in research (competitive 
renewals)
o Adequacy of plans to facilitate subject recruitment and follow-up to 
meet the stated research goals of the Center
o Appropriateness of community and professional education programs to 
facilitate goals of the Center
o Merit of data management and statistical consulting plans to meet the 
needs of the Center investigators and the required reporting standards
o Appropriateness of plans for diagnostic pathology and biological 
specimen collection, storage and distribution
o Appropriateness of core resources to support research projects 
locally as well as nationally for individual and collaborative projects

Research Projects (competing renewal and new applications)

o Potential for contribution to the field and expansion of knowledge 
concerning mechanisms of normal aging, MCI, AD and other 
neurodegenerative disease of the aging as well as the  translation of 
research findings to diagnosis and care 
o Appropriateness and quality of research proposed in each project 
along with the experience, competence, and commitment of the 
investigators.
o Availability of Center resources to support the stated aims of the 
project

These criteria will be applied to competing renewal applications by 
evaluating progress and future plans, and to new applications, by 
evaluating preliminary organizational work, experience with Alzheimer's 
and other neurodegenerative disease research, potential for developing 
new and exciting research, and specific plans for implementation of the 
new program.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: April 15, 2004
Application Receipt Date: May 18, 2004
Peer Review Date: Fall 2004
Council Review: January, 2005
Earliest Anticipated Start Date: April, 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing  Investigators should 
seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule. Reviewers 
will consider the data sharing plan but will not factor the plan into 
the determination of the scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research 
projects unless a clear and compelling justification is provided 
indicating 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 clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  
NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at http://stemcells.nih.gov/index.asp  
and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the 
NIH Human Embryonic Stem Cell Registry will be eligible for Federal 
funding (see http://stemcells.nih.gov/registry/).   It is the 
responsibility of the applicant to provide, in the project description 
and elsewhere as appropriate, the official NIH identifier(s) for the 
hESC line(s) to be used in the proposed research.  Applications that do 
not provide this information will be returned without review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants are required to place data collected under this RFA in the 
National Alzheimer’s Disease Coordinating Center, which can provide 
protections for the data and manage the distribution for an indefinite 
period of time.  The application should include a description of the 
archiving plan in the study design and include information about this 
in the budget justification section of the application. In addition, 
applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for 
wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  
The Department of Health and Human Services (DHHS) issued final 
modification to the “Standards for Privacy of Individually Identifiable 
Health Information”, the “Privacy Rule,” on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as “covered entities”) must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on “Am 
I a covered entity?”  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.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.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 
site.

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 RFA 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/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284 and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92. All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and to discourage the 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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NIH Funding Opportunities and Notices


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