ALZHEIMER’s DISEASE CORE CENTERS
RELEASE DATE: January 30, 2004
RFA: RFA-AG-04-012 (This RFA has been reissued, see RFA-AG-05-010)
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 Core Centers
(ADCCs). These Centers are designed to serve as shared research
resources that will facilitate research on Alzheimer’s disease (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 ADCCs 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 support 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 ADCCs is to support cutting-edge research 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, ADCCs 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 pilot projects
funded by the Center itself as well as for research projects funded by
NIH and other Federal agency grant mechanisms and by non-federal and
private organizations.
ADCCs 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 restates the need to have an Education Core within
each ADCC 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 other grants, and
fit within the budget guidelines for the cores. Funding for smaller
($35,000/year) one year pilot grants should also be requested.
ADCCs 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 P30 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 ADCCs will only be accepted
by solicitation under future RFAs. The anticipated award date is April
1, 2005.
This RFA uses just 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/grants/policy/nihgps_2001/part_i_1.htm.
FUNDS AVAILABLE
The NIA intends to commit approximately $5 million in fiscal year 2005
to fund four new and/or competing renewal ADCC 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 $1.0 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. 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 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 ADCC 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 Core 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 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 ADCC. 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 ADCC
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 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
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 ADCC include four cores and two or three
pilot 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
ADCC. 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 ADCC. 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, that will
depend upon resources provided by the requested cores.
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 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 National Alzheimer’s Coordinating Center.
The success of the ADCC 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 ADCC, the Director, with
the advice of his or her executive committee, will be responsible for
allocating and monitoring ADCC funds and identifying and selecting key
personnel. 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. 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 ADCC 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 ADCC, 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
ADCC, research progress, the effectiveness of communications within the
ADCC, 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 ADCC 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 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 and be
familiar with NIH grant-related compliance policies. The administrator
should attend the annual ADC Administrators meeting.
It is expected that the ADCC 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 ADCC 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 ADCC
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 ADCC 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 ADCCs 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. 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.
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 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 other cores
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 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 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 in
the ADC, where the 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 ADCC 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 ADCC 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 ADCC, 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 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.
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 by using Center
resources. Include summaries of progress in achieving the major aims of
the Center and highlight major publications. Include details of how the
presence of the ADCC has brought new investigators into the field and
has stimulated non-ADCC 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 an optional core has
terminated, include a final report with a summary of activities 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 ADCC, 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) Funded grants and projects that use or have used major resources
supplied by the ADCC, 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 to funded investigators should be
clearly summarized. These would include numbers and kinds of subjects
recruited and participation in clinical trials and other ongoing
clinical research projects, both local and national. Applicants are
required to insure 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 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 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 $1.0 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. Direct cost requests for
subsequent years may increase above the prior year direct cost 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 10%
Pilot Studies 5%
Clinical Core 50%
Data Management Core 15%
Neuropathology 10%
Education and Information Transfer Core 10%
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 ADCC may be funded through the
ADCC, provided there is no overlap of funding. Only those research
patient costs directly related to ADCC 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 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 NIA 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) 710-0267, 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 core. Appendix
materials should be kept to a minimum and 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 sent 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 and any optional cores. 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 cores here; instead, place them with the corresponding core.
Justify all items carefully according to the PHS 398 form instructions.
A complete budget for a consortium agreement 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.
Each component core should be presented according to the Table of
Contents. Identify 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. Titles may not exceed 56 spaces.
Prepare each core 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; listing and evaluating
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 for 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
o Progress (competing renewal applications) and potential for
contributions 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 using the support provided by core resources both
locally and nationally
These criteria will be applied to competing continuations 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 in the application 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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