NEUROVASCULAR MECHANISMS OF BRAIN FUNCTION AND DISEASE

RELEASE DATE:  March 5, 2004

PA NUMBER:  PAS-04-072 

The R01 portion of this funding opportunity has been replaced by PAS-07-197,
which now uses the electronic SF424 (R&R) application for February 5, 2007 
submission dates and beyond.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Accordingly, the R21 portion of this funding opportunity 
expires on the date indicated below. Other mechanisms relating to this announcement will continue to 
be accepted using paper PHS 398 applications until the stated expiration date below, or transition 
to electronic application submission. A replacement R21 (PAS-06-200) funding opportunity announcement 
has been issued for the submission date of June 1, 2006 and submission dates thereafter.

EXPIRATION DATE: for R21 Applications: March 2, 2006
Expiration Date for R01 Non-AIDS Applications: November 2, 2006 
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

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

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)
National Institute on Aging (NIA)
 (http://www.nia.nih.gov)
 
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.853 (NINDS), 93.866 (NIA) 

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Funds Available 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THE PA  

The goal of this Program Announcement with set-aside funds (PAS) is to 
invite applications for studying the integration of neurobiological and 
cerebrovascular mechanisms in the adult, aged and pediatric brain in 
health and disease.  This PAS encourages studies focused on improving our 
understanding of the dynamic interactions within the neurovascular unit 
(NVU), a construct consisting of brain microvascular endothelium, glia, 
neurons and the extracellular matrix that maintains spatial relations 
among them.  Knowledge of these interactions has the potential to 
stimulate new strategies for basic, translational and clinical research in 
many neurological disorders, including stroke, vascular dementia, and 
intracerebral hemorrhage.  Among the challenges to be addressed are: 
generate new hypotheses and conduct exploratory work on microvessel–neuron 
communication; increase our knowledge about cell-cell signaling and how 
insults to the endothelium affect parenchymal cell damage, which applies 
not only to stroke, but may also contribute to understanding neurological 
disorders in which vascular changes are observed; and, elucidate 
mechanisms by which neurons communicate with blood vessels through 
interactions with non-neuronal cells in the microenvironment including 
endothelium, pericytes, astrocytes, oligodendrocytes and microglia.

RESEARCH OBJECTIVES

Background

Stroke is widely recognized as a major cause of premature mortality and 
disability, particularly cognitive and motor impairment.  Significant 
progress has been made in dissecting the molecular pathways of 
excitotoxicity, oxidative stress and apoptosis in ischemic neuronal cell 
death.  However, translation of these laboratory results into clinically 
effective stroke treatments remains a major challenge for the stroke 
community today.  To address this issue and the prediction that strokes 
will increase in our aging population, Congress requested the NINDS to 
develop a stroke research action plan. The leadership of the Institute 
responded by implementing a major planning effort called the Stroke 
Progress Review Group (SPRG).  

The SPRG identified research on the cellular and functional interactions 
among the capillaries, glia, and neurons of the brain, termed the 
"neurovascular unit” (NVU), as a top priority.  The term "neurovascular 
unit" is intended to focus attention on the interactions among cerebral 
blood vessels and the neurons they serve.  It refers to the composite of 
the endothelium, extracellular matrix, astrocytes, pericytes and neurons.  
The term emphasizes the roles that the microvessel and the vascular 
compartment play in neuronal responses and emphasizes the dynamics of 
vascular, cellular and matrix signaling in both the grey and white matter.  
The NVU strategy looks beyond the single cell for a more integrative 
answer to ischemic brain damage which may be closer to modeling the 
clinical reality. 
 
After ischemia, perturbations in neurovascular functional integrity 
initiate several cascades of injury.  Upstream signals such as oxidative 
stress, together with neutrophil and/or platelet interactions with 
activated endothelium, upregulate matrix metalloproteinases (MMPs), 
plasminogen activators and other proteases, which degrade matrix and lead 
to blood–brain barrier leakage.  Inflammatory infiltrates through the 
damaged blood–brain barrier amplify brain tissue injury.  Additionally, 
disruption of cell-matrix homeostasis might also trigger cell death 
pathways in both vascular and parenchymal compartments.  Excitotoxicity 
has also been shown through tissue plasminogen activator (tPA)-mediated 
interactions with the NMDA (N-methyl-D-aspartate) receptor, which augment 
ionic imbalance and cell death.  Neuronal cell death ultimately underlies 
ischemic brain injury and the neurovascular unit concept suggests that 
proximal triggers in endothelium play an important upstream role. 
Refocusing research on how endothelial injury affects parenchymal damage 
applies not only to stroke, but may also contribute to understanding 
neurodegenerative disorders, like vascular dementia, Alzheimer’s disease, 
MS and ALS, in which vascular changes are observed.  Studying 
neurovascular changes as a function of aging may also help in 
understanding how the NVU contributes to age-related changes in brain 
structure and function, particularly motor and cognitive decline. 

Thrombolysis trials firmly establish the idea that timely reperfusion can 
salvage the ischemic brain.  The efficacy of hypothermia so far confirms 
that multiple molecular cascades are indeed operational in human brain and 
that neuroprotection is an achievable goal.  Ultimately, combination 
therapies that target the entire neurovascular unit, promote cell survival 
mechanisms and extend the therapeutic time-window for reperfusion therapy 
will provide the required opportunities to meet the challenges for stroke.  
Moreover, developing therapies that maintain proper NVU function or that 
prevent age-associated alterations in the NVU may find use in the 
prevention or treatment of age-related neurodegenerative or neurovascular 
conditions.

The Stroke Progress Review Group is responsive to Congressional requests 
for planning in this area. The scientific support for this initiative can 
be found in the report on the NINDS homepage at: 
(http://www.ninds.nih.gov/funding/areas/neural_environment/index.htm)

Scope

This PAS is intended to achieve a better understanding of the integration of 
cerebrovascular and brain mechanisms in the development of the healthy brain, 
in the maintenance of function in the aging brain, and in neurological 
disorders and stroke.  A major goal is to improve our knowledge of cell-cell 
communication within the NVU and how vascular function may contribute to the 
initiation and/or progression of neurological diseases over the lifespan.  
Developing new approaches for targeting the NVU, based on biological 
considerations, in order to improve potential combination or multi-targeted 
treatments for stroke and other neurological disorders is encouraged.   

Research areas appropriate for this announcement and applicable to either 
healthy or disease conditions include, but are not limited by the following 
examples:

o Develop and characterize in vivo and in vitro models that reflect the 
unique features of neurovascular communication in the brain under normal, 
aging, and disease conditions.  Existing in-vivo models, such as those for 
stroke or neurodegenerative diseases, may also prove useful for studying the 
cellular dynamics of the NVU.  Studies that validate in vitro results with in 
vivo models are encouraged.

o Examination of the genes and proteins that are uniquely expressed by the 
NVU and mechanisms by which brain cells regulate endothelial cell gene 
expression and visa versa. This includes endothelial cell changes that occur 
in response to neurological disease, for example, characterization of 
molecular signatures for disease diagnosis and targeting.

o Identify pattern-specific gene and protein expression within the NVU to 
provide a platform for further investigations on integrating brain-vascular 
biology as it pertains to conditions such as angiogenesis, cell adhesion, 
antigen presentation, metastasis, and local inflammation.  

o Explore the genesis and regulation of the NVU, its stem cell origins and 
the interactions of microvessel networks in the regions of the CNS with 
developing neurons and in areas of adult neurogenesis.

o Identify signal transduction pathways of brain and capillary endothelial 
cells in the regulation of the extracellular matrix under normal and disease 
conditions. 

o Identify regional diversity of NVU properties within the brain and the 
microvasculature throughout the lifespan.  Develop treatment strategies that 
target the unique biological properties of the NVU in contrast to single cell 
targeting. 

o Identify changes in NVU integrative functions in vivo and/or in-situ using 
imaging approaches.

o Explore the cell-cell interactions among the cellular and matrix elements 
of the NVU.  Examine cell-cell communication in tri-cultures with matrices of 
different composition.  

o Examine the plasticity of the NVU and the changes in cell-cell and cell-
matrix signaling throughout the lifespan. 
 
Applications should focus on neurological disorders relevant to the research 
missions of NINDS and/or NIA.  A partial list of diseases of interest to 
NINDS is given in Appendix A of the planning document Neuroscience at the New 
Millennium; http://www.ninds.nih.gov/about_ninds/plans/strategic_plan.htm).  These 
include neurological disorders (e.g. stroke, brain tumors, brain and spinal 
cord trauma, epilepsy, multiple sclerosis, neuro-AIDS, vascular dementia, 
ALS, Parkinson’s disease and Alzheimer's disease).  NIA is interested in age-
related neurodegenerative disorders, such as Alzheimer’s disease; impairments 
in cognitive, motor and sensory functions; and mechanisms underlying changes 
in neuroplasticity across the lifespan.  Research areas relevant to the 
mission of the NIA can be found at: http://www.nia.nih.gov/ResearchInformation/
ExtramuralPrograms/NeuroscienceOfAging/Research+Areas.htm

MECHANISMS OF SUPPORT 

A large amount of basic research is needed to significantly change how we 
translate neuroscience research.  This PAS is focused on stimulating new 
concepts on integrating cerebrovascular communication with neurons through 
the exploratory/developmental grant (R21) and the R01 mechanisms.  This PAS 
will remain active for 3 years to address the many gaps in our knowledge of 
how the NVU may function in health and disease and the time needed to explore 
this critically important research area.

As an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  Applicants are encouraged to contact program 
staff for advice about choosing the appropriate grant mechanism.

The R21 mechanism (see http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html)
is intended to encourage new exploratory/developmental research 
projects by providing support for the early stages of their development.  For 
example, such projects could assess the feasibility of a novel area of 
investigation or a new experimental system that has the potential to enhance 
health-related research.  These studies may involve considerable risk but may 
lead to a breakthrough in a particular area, or to the development of novel 
techniques, agents, methodologies, models or applications that could have 
major impact on a field of biomedical, behavioral, or clinical research.

Applications for R21 awards should describe projects distinct from those 
supported through the traditional R01 mechanism.  For example, long-term 
projects, or projects designed to increase knowledge in a well-established 
area will not be considered for R21 awards.  Applications submitted under 
this mechanism should be exploratory and novel.  These studies should break 
new ground or extend previous discoveries toward new directions or 
applications.

R21 applications may request a project period of up to two years with a 
combined budget for direct costs of up $275,000 for the two-year period.  For 
example, you may request $100,000 in the first year and $175,000 in the 
second year.  The request should be tailored to the needs of your project.  
Normally, no more than $200,000 may be requested in any single year.  

This PAS uses just-in-time concepts.  It also uses the modular 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 format.  Otherwise follow the instructions for non-
modular 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.

Competing continuation applications submitted in response to this PAS will 
compete with all investigator-initiated applications and be referred and 
reviewed according to the customary peer review procedures.  Responsibility 
for the planning, direction, and execution of the proposed project will be 
solely that of the applicant. The earliest anticipated award date is June 1, 
2004.

FUNDS AVAILABLE

NINDS and NIA have set aside $1,100,000 in total costs per year.  NINDS will 
use set-aside funds for applications sent in response to this program 
announcement that score outside the NINDS payline (see NINDS Funding Strategy 
http://www.ninds.nih.gov/funding/ninds_funding_strategy.htm), depending on 
the overall scientific merit of the applications and the availability of 
funds throughout the duration of this solicitation (3 years).  NIA will 
consider programmatic priority, as reflected in this PAS, and scientific 
merit in using set-aside funds for applications assigned to it in response to 
this PAS.

The total project period for an application submitted in response to this PAS 
may not exceed 5 years.  Because the nature and scope of the research 
proposed may vary, it is anticipated that the size of each award will also 
vary.  Although the financial plans of the Institute provide support for this 
program, awards pursuant to this PAS 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

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PAS and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

Direct inquiries regarding scientific/research issues to:

Dr. Thomas P. Jacobs
NINDS
Neuroscience Center, Rm 2112
6001 Executive Blvd.
Bethesda, MD  20892-9527
Telephone:  (301) 496-1431
FAX:  (301) 480-2424
Email:  jacobst@ninds.nih.gov

Dr. Bradley C. Wise
NIA
Gateway Building, Suite 350
7201 Wisconsin Avenue
Bethesda, MD   20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email:  wiseb@nia.nih.gov 

Direct inquiries regarding financial or grants management 
matters to:

Ms. Tina Carlisle
Grants Management Branch
NINDS
6001 Executive Boulevard, Rm 
Bethesda, MD 20892
Telephone:  (301) 496-3938
Email:  carlit@ninds.nih.gov

Ms. Linda Whipp
Grants and Contracts Management Office
NIA
7201 Wisconsin Avenue, Suite 2N212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  WhippL@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 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.

The title and number of this program announcement must be typed 
on line 2 of the face page of the application form and the YES 
box must be checked.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.  Please note 
that AIDS related applications have separate receipt dates.

SUPPLEMENTAL INSTRUCTIONS:  All instructions for the PHS 398 (rev. 5/2001) 
must be followed, with these exceptions:

o   Research Plan

For R21 applications only, items a – d of the Research Plan (Specific Aims, 
Background and Significance, Preliminary Studies, and Research Design and 
Methods) may not exceed a total of 15 pages.  No preliminary data is required 
for R21 proposals, but may be included if it is available.  Please note that 
a Progress Report is not needed for R21 awards; competing continuation 
applications for an exploratory/developmental grant will not be accepted.

Appendix.  Use the instructions for the appendix detailed in the PHS 398 
except that for R21 applications, no more than 5 manuscripts, previously 
accepted for publication, may be included.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in the 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five 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)

APPLICATION PROCESSING: Applications must be received by or mailed on or 
before the receipt dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR will 
not accept any application in response to this PAS 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 a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 
critique.

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.

PEER REVIEW PROCESS

Applications submitted for this PAS will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council 
or board

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 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 these criteria in 
assigning your 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.

(1) SIGNIFICANCE:  Does this study address an important problem?  If the aims 
of the 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?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

(3) 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?

(4) 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 to that of other researchers (if 
any)?

(5) 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 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).
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  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.  

ADDITIONAL REVIEW CONSIDERATIONS 

Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research are expected to 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. 

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

AWARD CRITERIA

Applications submitted in response to a PAS will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program 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 

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.  (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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.  See 
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. 

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

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 may wish to place data collected under this PAS in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, 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 
PAS 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)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.