NEUROPROTECTIVE CNS BARRIERS IN NEUROLOGICAL DISEASES

RELEASE DATE:  August 28, 2003

PA NUMBER:  PAS-03-165 

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. Parent R03 (PA-06-180) and R21 (PA-06-181) 
funding opportunity announcements have been issued for the submission date of 
June 1, 2006 and submission dates thereafter. Applications relating to R33 and R34 
activities must be in response to NIH Institute/Center (IC)-specific announcements.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for All R01 Applications: May 1, 2006, unless reissued

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS:  

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

COMPONENTS OF PARTICIPATING ORGANIZATIONS:

National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)  
National Institute on Aging (NIA)
 (http://www.nia.nih.gov/)    

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.853 
(NINDS), 93.242 (NIMH), 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 neurobiological and cerebrovascular mechanisms 
through which the neuroprotective blood-brain and blood-csf barriers function 
in the healthy and diseased adult, aged and pediatric brain.  Blood-Brain 
Barrier (BBB) research embodies the true meaning of a "translational model" 
of neuroscience wherein breakthroughs in basic neuroscience are delivered to 
the clinic and require an agent delivery strategy and/or the ability to 
target specific areas of the brain.  This PAS encourages studies focused on 
improving our understanding of the neuroprotective CNS barriers and enhancing 
the effectiveness of drug and gene delivery strategies for treatment of 
neurological diseases.  Chief among the challenges to be addressed is the 
need to increase our knowledge about the molecular and cellular biology, 
cells of origin, gene and protein expression, and the regional differences of 
brain microvascular endothelial cells and pericytes and their interactions 
with adjacent brain cells.  
 
RESEARCH OBJECTIVES

Background

A major challenge for treatment of most brain disorders is overcoming the 
difficulty of delivering therapeutic agents to specific regions of the brain. 
In its neuroprotective role, the blood-brain barrier (BBB) functions to 
hinder the delivery of many potentially important diagnostic and therapeutic 
agents to the brain. Therapeutic molecules and genes that might otherwise be 
effective in diagnosis and therapy do not cross the BBB into the brain in 
adequate amounts. Improving our knowledge of the molecular and cellular 
biology of the brain microvasculature and their interactions with surrounding 
brain cells, which constitutes the BBB in vivo, could lead to innovative 
strategies for drug and gene targeting to injured or disease tissue.  Also, 
research is needed on the role of the brain microvasculature in protecting 
the brain from toxic agents and how damage to the BBB leads to long-term 
neurological toxicity in the development of many neurological diseases.  
Understanding the basic biology of how the BBB works under normal and disease 
conditions across the lifespan may also provide insight on the integrative 
function of the brain. Research focused on cerebrovascular endothelial cell 
biology may provide insight into the "neurovascular unit", a conceptual model 
that considers brain function from the perspective of interactions among 
blood cells, endothelium, glia, pericytes, extracellular matrix and neurons.
  
This initiative was identified as the top research priority of the Brain 
Tumor Progress Review Group (PRG).  The Stroke Progress Review Group has also 
identified neurovascular research and BBB biology as a high priority for 
advancing our understanding of stroke and brain function.  Both Progress 
Review Groups are responsive to Congressional requests for planning in these 
areas.  Also, the NINDS Neuroscience at the New Millennium Plan clearly 
identifies research on the blood-brain barrier as a scientific priority.  The 
scientific support for this initiative can be found in these reports on the 
NINDS homepage at: 
(http://www.ninds.nih.gov/funding/areas/neural_environment/index.htm)

Scope

This Program announcement is intended to achieve a better understanding of 
the effects of neurological disorders on the blood-brain barrier (BBB), 
improve our knowledge of BBB biology and how it may contribute to the 
initiation and/or progression of neurological disease over the lifespan and 
develop new approaches for targeting the BBB, based on biological 
considerations, in order to improve drug delivery and target treatment of one 
or more such disorders.   

Applications that address gene and protein expression for microvascular 
endothelial cells within normal, aging, and diseased brain such as gliomas or 
the ischemic penumbra are encouraged.  Cerebrovascular genomics is considered 
a high priority.  Because only very abundant BBB-specific transcripts will be 
detected with whole-brain gene microarrays, cerebrovascular genomics research 
needs to start with the initial isolation of brain capillaries from animal or 
human brain, both normal and perturbed. Comparison of capillaries from normal 
brain and perturbed tissue can help to elucidate the tissue-specific gene 
expression.  Pattern-specific tissue expression could provide the platform 
for further investigations on overall brain vascular biology as it pertains 
to conditions such as angiogenesis, cell adhesion, antigen presentation, 
metastasis, cell-cell communication and local inflammation.  

There are several modalities for drug and gene delivery through the BBB.  
They include: BBB disruption; the use of endogenous transport systems, 
including carrier-mediated transporters such as glucose and amino acid 
carriers; receptor-mediated transcytosis, systems such as the insulin or 
transferrin receptor; and active efflux transporters such as p-glycoprotein 
and the associated anti-porters. Studies to determine which strategies are 
most effective and how they can be improved for patients with neurological 
diseases are encouraged. 

Research areas appropriate for this announcement 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 the BBB as translational models of neurological disease. 
Existing in-vivo models, such as those for stroke or lysosomal storage 
diseases, may also prove useful for studying the structure and dynamics of 
the BBB.  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 
intact BBB and mechanisms by which brain cells regulate endothelial cell gene 
expression. This includes changes that occur in response to neurological 
disease or the aging process, for example, characterization of molecular 
signatures for disease diagnosis and targeting.

o Explore the genesis and regulation of the BBB, its stem cell origins and 
remodeling of the (diseased/damaged/aged) brain microvasculature.

o Identify signal transduction pathways of brain capillary endothelial 
transcytosis and tight junction regulation under normal and disease 
conditions.

o Characterize endogenous influx and efflux properties of the barriers 
including transporters in luminal and abluminal membranes of brain 
endothelium and epithelium.

o Identify regional diversity of barrier properties within the brain and 
spinal cord microvasculature.

o Characterize brain endothelial tight junction proteins in normal and 
disease states.

o Investigate the various enzymatic barrier mechanisms. 

o Characterize membrane protein expression by cells of the BBB.

o Development of novel brain drug and gene delivery methods based on unique 
properties of the BBB including gene therapy via vectors or via modified 
autologous cell transfer.

o Explore the molecular basis of microbial interactions with brain 
endothelium.

o Develop neuroimaging tools to identify changes in BBB permeability in vivo.

o Examination of the molecular and cellular mechanisms of leukocyte migration 
at the BBB throughout the lifespan.

o Comparison of transport systems in brain endothelia with choroids plexus 
epithelium as well as systemic epithelial cells.

o Explore the interactions among the cellular and matrix elements of the BBB, 
for example, the microvascular basement membrane.

o Examine the plasticity of the blood-brain and blood-CSF interfaces 
throughout the lifespan.
 
Applications should focus on neurological disorders relevant to the research 
missions of NINDS, NIMH 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, Parkinson's 
disease, brain and spinal cord trauma, epilepsy, multiple sclerosis, brain 
lysosomal storage disorders, neuro-AIDS and Alzheimer's disease).  The NIMH 
is interested in mechanistic studies of trafficking of cells, immune 
molecules and drugs across the blood-brain and blood-csf barriers during 
development and adulthood and how these processes impact the pathogenesis of 
neuroAIDS and mental disorders http://www.nimh.nih.gov/research/nimhwebs.cfm.
NIA is interested in age-related neurodegenerative disorders, such as 
Alzheimer's disease, brain injury, and impairments in cognitive, motor and 
sensory functions.  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 bidirectionally.  This PAS is focused on 
stimulating new concepts in the BBB field through the 
exploratory/developmental grant (R21) and the R01 mechanisms.  The current 
workforce in the BBB field is small relative to the scientific and clinical 
needs for improved understanding of the BBB and progress will require 
collaboration among current investigators and scientists from disciplines not 
currently working in this area.  Therefore, training and early career 
development will be encouraged (please contact Program Staff for additional 
information).  This PAS will remain active for 3 years to address the many 
gaps in our knowledge of how the neuroprotective barriers function and the 
time needed to increase the workforce in this critically important 
translational 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 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_2001/part_i_1.htm.

Competing continuation applications submitted in response to this PA 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, NIMH, and NIA have set aside $2,000,000 in total costs per year, in 
addition to funds available for applications sent in response to this program 
announcement that score within 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).  Applications 
submitted in response to this PA will compete with all investigator-initiated 
applications for funding.  

The total project period for an application submitted in response to this PA 
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 PA 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 PA 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. Jeymohan Joseph
NIMH
Neuroscience Center, Rm 6202
6001 Executive Blvd.
Bethesda, MD  20892-9527
Telephone:  (301) 443-3012
FAX:  (301) 443-9719
Email: jjeymoha@mail.nih.gov

Dr. Bradley C. Wise
National Institute on Aging
7201 Wisconsin Avenue, Suite 350
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

Brian Albertini
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-0004
FAX:  (301) 443-0219
Email:  albertinib2@mail.nih.gov

Ms. Linda Whipp
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:  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.

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 PA 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 unfunded version 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 PA will be assigned on the basis of 
established PHS referral guidelines.  Appropriate scientific review groups 
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 evaluate 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, 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, your 
application will also be reviewed with respect to the following:

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

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).

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 PA 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. 

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $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.

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).

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 AMENDMENT "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 PA 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 PA 
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 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.