COLLABORATIVE STUDIES ON ALZHEIMER AND RELATED DISEASES
 
RELEASE DATE:  September 2, 2004
 
RFA Number:  RFA-AG-05-006  

EXPIRATION DATE:  December 22, 2004

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATION: 
National Institutes of Health (NIH) 
 (http://www.nih.gov)
 
COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute on Aging (NIA) 
 (http://www.nih.gov/nia/)
National Institute of Neurological Diseases and Stroke (NINDS) 
 (http://www.ninds.nih.gov/)
 
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.866, 93.853
 
LETTER OF INTENT RECEIPT DATE:  November 21, 2004
APPLICATION RECEIPT DATE:  December 21, 2004  
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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 Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The NIA and NINDS encourage wider use of data and samples generated by 
grants supported by the institute(s) including the Alzheimer’s Disease 
Centers (ADCs). The purpose of this RFA is to accelerate collaborative 
cross-disciplinary and multi-institutional approaches that will 
contribute new and vital information about the clinical and 
pathological course of normal aging and the neurodegenerative diseases 
associated with aging.

This RFA requires the utilization of data and/or samples from at least 
three currently funded NIA ADCs with the possibility of using 
additional relevant data or samples from outside of the Centers. The 
project must use the National Alzheimer’s Coordinating Center (NACC) 
http://www.alz.washington.edu/ for expert advice on planning, study 
design, and also utilize NACC for statistical analyses and data 
management during conduct of the research projects. Applicants can be 
from the Alzheimer’s Disease Centers, the Morris K. Udall Centers, or 
the research community at large. There should be a plan to share data 
originating from these studies by archiving them at NACC or another 
appropriate National databank so that other investigators will be able 
to conduct additional analyses when appropriate. There must also be a 
plan to encourage sample utilization after the current study.

This is a research opportunity for scientists both within and outside 
the ADCs to gain access to unique resources related to Alzheimer’s 
Disease, other neurodegenerative diseases, and normal aging and to 
support collection of new data and samples. Applicants can also propose 
to utilize Center data and samples to investigate other age-related 
neurodegenerative diseases, such as Vascular dementia, Parkinson’s 
dementia, Lewy Body disease, Fronto-Temporal dementia, as well as study 
psychiatric symptoms associated with dementia, socio—behavioral aspects 
of dementia, and management and care of dementia patients.

The National Institute of Neurological Disorders and Stroke (NINDS) is 
interested in those specific applications which include the Morris K. 
Udall Centers of Excellence, or other Parkinson’s research centers, in 
the pursuit of those research objectives focused on Parkinson's Disease 
(PD) or related parkinsonisms.  The PD center need not be located with 
ADCs, but collaboration with those ADCs with existing samples and data 
sets focused on PD is required. Specific scientific projects of 
interest include the use of clinico-pathological correlations to study 
mechanisms of pathogenesis in PD or other parkinsonian conditions, 
characterization of the pathological features of these conditions, and 
the collection of patient data on their associated symptoms.

RESEARCH OBJECTIVES

Background
 
As research on Alzheimer’s disease (AD) has matured, new aspects of the 
disease are being addressed. More emphasis is being placed on the 
clinical and neuropathological changes that distinguish the initial 
stages of AD from normal aging as well as variations in the initial 
symptomatology (endophenotypes). At the same time it is becoming 
increasingly clear that AD shares features with neurodegenerative 
diseases that include Parkinson’s disease, Lewy Body disease, and 
Fronto-Temporal dementia.  Therefore, research is also encouraged that 
focuses on collecting diagnostic information, brain tissue and 
biological samples that allow further differentiation among these 
diseases and documentation of common features.  

Using the large subject pool enrolled at the Alzheimer’s Disease 
Centers, larger scale multi-site collaborative studies are feasible to 
study successful aging, normal aging, mild cognitive impairment (MCI) 
and mild AD. It is expected that access to larger data sets through 
data pooling will increase statistical power and permit 
characterization of the rarer and mixed phenotypes among the various 
diseases. Presently a minimum data set (MDS) including demographic and 
clinical and pathological diagnostic variables is available at the 
National Alzheimer’s Coordinating Center and plans are nearly complete 
to greatly expand data collection from all future enrollees in the ADCs 
that will provide uniform clinical and psychometric data for future 
studies, the Uniform Data Set (UDS). Applicants are urged to consult 
with NACC to determine the data elements available. Use of these 
elements may help in the detection of potential biomarkers or patterns 
that will help identify persons at risk for disease, characterize and 
diagnose the different disease entities, refine description of disease 
course, and monitor response to treatment in different subsets of AD 
and other patients e.g., genetic subsets, ethnic minorities, the oldest 
old, or those with less common neurodegenerative diseases. For 
information about the data elements included in the MDS and the UDS, 
contact NACC.

Collections of biological specimens including brain tissue (fixed and 
frozen), serum, plasma, CSF, DNA and cell lines are stored at the 
various Alzheimer’s Centers (contact NACC for locations) and DNA and 
cell lines for genetic studies are stored at the National Cell 
Repository for Alzheimer’s Disease (NCRAD), 
http://ncrad.iu.edu/forResearchers/samples.asp. Applicants are also 
encouraged to use samples from other specimen repositories supported by 
NIH, if appropriate. 

The NIA Alzheimer’s Disease Centers 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 have provided a platform for 
the growth of research and training of scientists for AD research and 
have been the leaders in research on clinico-pathological correlations 
to compare normal aging and AD as well as in answering many basic 
research questions on AD and related dementias. The main function of 
the ADCs is to support cutting-edge research either directly or 
indirectly by providing well-characterized patients and family 
information and tissue and other biological specimens from persons with 
AD and from age-matched control subjects for various projects.

The National Alzheimer’s Coordinating Center was established to collect 
a common data set from all NIA funded Alzheimer’s Disease Centers in 
order to facilitate collaboration among the Alzheimer’s Disease Centers 
on important unanswered questions pertaining to AD, related disorders, 
and normal aging. The database consists of several datasets including 
the MDS, data from previous collaborative projects, and soon will also 
contain the UDS mentioned above.
 
Objectives

This RFA invites studies that utilize existing samples and data 
gathered by the Centers and/or studies that collect additional data and 
samples within the Center network to target specific research questions 
best addressed by collaborative studies. In such projects, collection 
and utilization of data and/or samples need not be confined to the 
applicant Centers but also could involve other Centers and other data 
sources. Applicants will find on the NACC website the current directory 
of the ADCs as well as a description of the data collected at the 
Centers. To initiate the process, potential applicants may contact the 
NIA Program Officer listed below, or the Director of NACC to determine 
which Centers to contact to set up collaborations. Alternatively the 
applicant may contact Centers directly to discuss potential 
collaborations. Searches may be done on the entire database or on 
individual datasets after approval for access has been granted. NACC 
can use the MDS data to help applicants locate subjects with particular 
characteristics for whom tissues and biological specimens may be 
available at participating ADCs and will facilitate contact among 
applicants responding to this RFA with the ADCs to locate information 
and specimens for this project. Any questions regarding the UDS can be 
directed to NACC or the NIA program officer listed below. Additionally 
NACC provides statistical and epidemiological consulting concerning 
research questions, study design and analytic methods best suited to 
the overall NACC database or the individual Centers. Applicants should 
budget funds to subcontract to NACC for consulting and data management 
expenses for the tenure of the award. 

Possible examples of scientific problems that could be addressed by 
applications include but are not limited to collaborative projects 
that:

o Study expression of Alzheimer’s disease, other related dementias and 
normal brain aging in specific minority groups, in terms of 
clinicopathological correlations, diagnostic issues, biomarkers, co-
morbidities, particular risk factors, differential prevalence, clinical 
presentation or course of disease. 

o Determine the impact of co-morbid pathological conditions (such as 
diabetes; hypertension; heart disease; altered metabolic profiles) on 
normal and abnormal cognitive brain aging, especially in relation to 
vulnerable individuals, such as the oldest old.

o Study biological samples (brain tissue, blood, CSF, and other body 
fluids) collected by standardized methods and currently stored at 
selected Alzheimer’s Disease Centers to get sufficient numbers of 
samples to reach statistical significance; set up biochemical screens 
to identify molecules indicative of disease state (messenger RNAs, 
proteins, carbohydrates, and lipids) and their relative concentration 
in brain, serum, CSF, and other body fluids in various subject 
populations. For example, protein identity, concentration, and 
localization could be analyzed by proteomics methodologies, such as 
MALDI-TOF spectroscopy, protein arrays, antibody arrays or tissue 
microarrays using biological samples from persons with 1) successful 
aging, 2) normal aging, 3) mild cognitive impairment, 4) early stages 
of AD, 5) late stages of AD, 6) AD with Lewy bodies, 7) AD with 
cerebrovascular disease, 8) Parkinson’s dementia, etc., at various ages 
and degrees of disease progression. It may then be possible to identify 
patterns or profiles of molecules that could be used to distinguish 
among the various conditions, serve as biomarkers for preclinical 
disease, diagnosis or disease progression, or offer clues to molecular 
changes causing initiation and progression of disease processes in 
vulnerable cell types in specific brain regions.

o Conduct microarray studies in specific brain regions and studies of 
gene expression in single identified cells to illuminate the local and 
widespread changes in gene expression that accompany successful aging, 
normal aging, MCI, the different stages of AD and related 
neurodegenerative diseases. Appropriately characterized brains from 
persons who died with minimal agonal stress, with relatively short 
postmortem intervals, and from whom brain RNA can be analyzed 
quantitatively could be identified from Center resources for such 
studies.  Microarray or cellular data generated by different 
investigators and compiled into a reference dataset would be one step 
towards identifying genomic expression changes in brain regions and 
particular cell populations that consistently parallel age or disease 
phenotypes and endophenotypes. 

o Characterize the pathological features (such as plaques, tangles, 
Lewy bodies, selective cell vulnerability, synapse loss, atrophy, white 
matter lesions, and micro infarcts), in different brain regions of 
selected individuals to elucidate the temporal and spatial development 
of pathologies in successful aging, normal aging, MCI, and early stages 
of AD.

o Identify the pathology or combination of pathologies that best 
explains the neuropsychological deficits, if any, in individual 
subjects. 

o Determine whether any of the possible precursors of overt pathology 
distinguish brains of persons with “normal” aging from brains of 
persons who show subtle age-related cognitive changes often preceding 
AD, from brains of persons with early AD. These changes could include 
but are not limited to regional alterations in levels or processing of 
tau or APP, changes in energy metabolism, oxidative markers, calcium-
regulatory mechanisms, inflammatory processes, inappropriate neuronal 
entry into the cell cycle, altered folding, metabolism or degradation 
of proteins, changes in axonal transport, or synaptic function. 

o Investigate relationships between exposure to certain agents (such as 
ACHE inhibitors, statins, antihypertensives, anti-inflammatories, 
antioxidants, hormones, or vitamins) and onset or progression of the 
disease.

o Study the incremental value of imaging on the clinical diagnosis of 
AD and non-AD dementias.

o Investigate common mechanisms of disease pathogenesis in Alzheimer’s 
disease, Parkinson’s disease, and Lewy Body disease, through molecular 
studies and/or clinico-pathological correlations.

o Characterize the role and impact of different socio-cultural 
environments in terms of risk of or protection from dementia.

o Evaluate caregiver characteristics and the dynamics underlying care 
management across socio-economic groups, ethnicity, demographic 
variables, and along the continuum of disease development and 
progression.

o Define the disease-related and/or socio-cultural factors impacting on 
consent to participate in clinical research, and testing of the 
validity of various approaches to determine consent to clinical 
research in different subgroups of patients in the Alzheimer’s Disease 
Centers.

o Utilize and/or collect data on behavioral components and psychiatric 
symptoms associated with the development and progression of Alzheimer’s 
disease and other dementias such as vascular dementia, Parkinson’s 
dementia, Lewy body disease, and mixed dementia.

Applicants are encouraged to contact the Program Officers listed below 
to clarify requirements and to discuss potential projects. 

MECHANISM OF SUPPORT
 
This RFA will use the NIH R01 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.  Future 
unsolicited, competing-continuation applications based on this project 
will compete with all investigator-initiated applications and will be 
reviewed according to the customary peer review procedures. The 
anticipated award date is July 2005. Applications that are not funded 
in the competition described in this RFA may be resubmitted as NEW 
investigator-initiated applications using the standard receipt dates 
for NEW applications described in the instructions to the PHS 398 
application.  

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting as well as the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular budget format.  
Otherwise 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_2003/NIHGPS_Part2.htm.

FUNDS AVAILABLE 
 
The NIA intends to commit approximately $2 million in FY 2005 to fund 3 
to 5 new grants in response to this RFA. An applicant may request a 
project period of up to 5 years and a budget for direct costs of up to 
$350,000 per year.  (NIH no longer counts consortium F&A costs as a 
direct cost when determining if an applicant is in compliance with a 
direct cost limitation on a solicited application. See 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html 
for further details.)  NINDS is setting aside funds to make one award 
if the focus is on Parkinson’s Disease and related disorders and 
applicants utilize the resources of the Udall Centers. Because the 
nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award 
could also vary. Although the financial plans of NIA and NINDS provide 
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.
 
ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) 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 or foreign institutions/organizations
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS The Principal 
Investigator (PI) may be an ADC or Udall Center - based senior 
investigator or a scientist outside the Center network with 
demonstrated capability to organize and direct collaborative, 
interdisciplinary research activities. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs. 

SPECIAL REQUIREMENTS 

At least three Alzheimer’s Disease Centers have to be involved in the 
collaborative projects funded by NIA. Other Centers as well as 
different data and specimen sources also may be utilized for data or 
tissue collection. There must be a comprehensive collaborative 
agreement among all participating entities that defines the 
relationships among the PI, the participating Centers, other data 
sources, and NACC. The PI must have a documented agreement and a plan 
to subcontract with NACC and use NACC to manage data related to the 
project. The participating Centers and other data sources must agree to 
provide the data and/or samples necessary to complete the project 
including the minimum data set for patients not enrolled in an ADC 
Clinical Core. There should be clear agreement from all parties 
regarding relationships, plans for interaction, details of data sharing 
and mechanisms for transferring data to NACC. The letters of agreement 
should be signed by an authorized individual at each participating site 
and should accompany the application. Applications that at the time of 
submission do not include within the application documentation of 
collaboration with at least three ADC sites, other Center sites, if 
appropriate, and NACC, will be returned without review.

There must also be a plan for sample utilization beyond that of the 
initial application, including future access to data and samples. NIA 
will evaluate the adequacy of the sharing plan before making funding 
decisions. The PI should commit at least 10 percent effort to the 
project, whereas participating investigators at the Centers should 
commit at least 5 percent effort to this project. The application 
should provide detailed information regarding procedures for obtaining 
informed consent and adherence to local and state laws for surrogate 
consent. Applicants should provide insurance of compliance with 
relevant state and Federal regulations regarding confidentiality, 
consent and sharing of human data and biological samples. 

In order to assure active collaborations with the Alzheimer’s Disease 
Centers, Udall Centers and NACC, all senior members of the 
collaborative team in NIA-sponsored projects are expected to attend at 
least one of the semi-annual meetings of the Alzheimer’s Center 
Directors or in the case of NINDS-sponsored projects, the annual Udall 
Centers meeting. The cost of data transfer to NACC, data management and 
statistical consulting by NACC, and travel for senior investigators to 
the Centers meeting should be included in the proposed budget.

Sharing of Data and Biological Resources 
 
Sharing of Unique Research Resources and Data: 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. 
 
Data sharing promotes many goals of the NIH research endeavor.  It is 
particularly important for unique data that cannot be readily 
replicated. Data sharing allows scientists to expedite the translation 
of research results into knowledge, products, and procedures to improve 
human health.  The NIH endorses the sharing of final research data to 
serve these and other important scientific goals, and expects and 
supports the timely release and sharing of final research data from 
NIH–supported studies for use by other researchers. Data should be made 
as widely and freely available as possible while safeguarding the 
privacy of participants, and protecting confidential and proprietary 
data.  
 
To address this interest in assuring that research data and resources  
are accessible NIH normally requires that applicants seeking $500,000  
or more in direct costs in any single year submit a plan for data  
sharing.  However, this RFA requires a data sharing plan for all  
applications.  NIA requires applicants who respond to this RFA to 
submit a plan (1) for sharing final research data generated through the 
grant or state why data sharing is not possible, (2) for sharing 
research resources generated through the grant, and (3) for exercising 
intellectual property rights, should any be generated through this 
grant, while making such research resources available to the broader 
scientific community. 
 
The data sharing plan should conform to NIH Data Sharing Policy in  
accordance with the Final NIH Statement on Sharing Research Data  
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).   
Guidance on NIH data sharing policy and implementation, including FAQs,  
is available at: http://grants.nih.gov/grants/policy/data_sharing/. 
 
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_2003/) and the Principles  
and Guidelines for Recipients of NIH Research Grants and Contracts on  
Obtaining and Disseminating Biomedical Research Resources  
(http://www.ott.nih.gov/policy/rt_guide_final.html or 
http://ott.od.nih.gov/NewPages/64FR72090.pdf). 
   
Applicants are encouraged to discuss the plans with their Institutional  
Official and Office of Technology Transfer prior to submission of the  
application.  The applicant organization signature on the application  
indicates the agreement of the organization with the plan in the  
application. 
 
NIA program staff will consider the adequacy of the sharing plan and 
its consistency with NIH and NIA/NINDS 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.

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, Alzheimer’s 
Centers and relationships with NACC to:

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

o Direct your questions regarding scientific/research issues, 
Parkinson’s disease and related disorders, and Udall Centers to:

Diane D. Murphy, Ph.D.
Program Director
Neurodegeneration Group
National Institute of Neurological Disorders and Stroke
NSC Room 2223
6001 Executive Blvd.
Rockville, MD 20852
Telephone:  (301) 496-5680
FAX:  (301) 480-1080
Email: dm152o@nih.gov

o Direct your questions about peer review issues to:

Mary Nekola, Ph.D., Chief
Scientific Review Office
National Institute on Aging 
Gateway Building, Room 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
Lead Grants Management Specialist  
Office of Grants and Contract Management
National Institute on Aging 
Gateway Building, Room 2N212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email: stauffed@nia.nih.gov

Or

Kimberly Campbell
Grants Management Specialist
Grants Management Branch 
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd.  Rm. 3249
Rockville, MD 20892 
Telephone: (301) 496-7809
FAX: (301) 402-0219 
Email: kc274k@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 Institute 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
National Institute on Aging 
Gateway Building, 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 D&B number can be obtained by calling (866) 
705-5711 or through the web site at http://www.dunandbradstreet.com/. 
The D&B 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.
 
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/labels.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)
 
At the time of submission, two additional copies of the application and 
all copies of the appendix material must be sent to:

Mary Nekola, Ph.D., Chief 
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212, MSC 9205
Bethesda, MD 20892-9205
Telephone:  (301) 496-9666
FAX:  (301) 402-0066
Email: NekolaM@nia.nih.gov
 
APPLICATION PROCESSING: Applications must be received on or before 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. Applications must be complete at the time of 
submission.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding 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.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIA and NINDS. Incomplete and/or 
nonresponsive applications will not be reviewed.
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, but possibly more, 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 or the National Advisory Neurological Disorders and Stroke 
Council. 
 
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 evaluate the 
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
  
The 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, an investigator may propose to carry out 
important work that by its nature is not innovative but is essential to 
move a field forward.

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

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project? Does the applicant acknowledge potential problem areas and 
consider alternative tactics?

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

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

ENVIRONMENT: Does the scientific environment in which the 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 determining scientific merit and priority score.

The adequacy of collaborative arrangements as documented by signed 
agreements and a plan to subcontract with NACC to manage data related 
to the project.

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.  

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

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: November 21, 2004
Application Receipt Date: December 21, 2004
Peer Review Date:  March 2005
Council Review: May 2005
Earliest Anticipated Start Date: July 1, 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 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on 
Humane Care and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), 
as mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the 
USDA Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

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

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://escr.nih.gov).   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 Coordinating Center data bank, 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 structure informed consent statements and other human 
subjects procedures for wider use of data collected under this award by 
other qualified researchers.

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).  

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.healthypeople.gov/.

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 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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