INTERACTIONS BETWEEN STEM CELLS AND THE MICROENVIRONMENT IN VIVO

RELEASE DATE:  September 16, 2003

PA NUMBER:  PAS-03-172 (This PA has been reissued, see PAS-05-092)

EXPIRATION DATE: February 1, 2005 

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 on Drug Abuse (NIDA) 
 (http://www.nida.nih.gov)
National Institute of Deafness and Other Communication Disorders (NIDCD)
 (http://www.nidcd.nih.gov)
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov)
National Institute on Aging (NIA)
 (http://www.nia.nih.gov) 

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  
93.853 (NINDS), 93.279 (NIDA), 93.173 (NIDCD), 93.273 (NIAAA), 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 Special Requirements
o Where to Send Inquiries
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA  

National Institute of Neurological Disorders and Stroke (NINDS), the National 
Institute on Drug Abuse (NIDA), the National Institute of Deafness and Other 
Communication Disorders (NIDCD) the National Institute of Alcohol Abuse and 
Alcoholism (NIAAA), and the National Institute on Aging (NIA) invite 
applications for studies on the cellular and molecular signaling between the 
local environment within organisms and stem and progenitor cells that are 
either introduced as transplants or are normally resident within host tissues 
and organs. The objective of this initiative is to promote a thorough 
exploration and characterization of the bi-directional communication between 
multipotent cells and the three-dimensional local milieu or niche that they 
encounter in vivo under normal and compromised states, such as with aging or 
following injury, disease or drug exposure. Of particular interest is the 
rigorous characterization of how interactions with localized cues in space 
and time regulate stem cell survival, migration, replication and 'plasticity' 
in the nervous system and other parts of the body. Projects that address 
comparisons between the responses of stem cells within niches in the 
developing and mature or aging nervous system in vivo, or in host 
microenvironments modified by injury, disease, or by exposure to drugs and 
alcohol would also be directly relevant to this Program Announcement with 
Set-aside (PAS), as are studies to compare different classes of stem cells or 
progeny at progressively more advanced stages of differentiation when placed 
in the same sites in vivo.

RESEARCH OBJECTIVES

Unlike organs such as the skin and the gut that self-renew throughout life, 
the nervous system in adult mammals is restricted in its ability to replace 
neurons and glia that have been lost through injury, disease, alcohol and 
drug abuse or even advancing age.   Stem cell research offers enormous 
potential for treating many congenital, developmental, psychiatric or 
degenerative diseases of the nervous system for which there are no treatments 
or cures.  Under the appropriate tissue culture conditions, a variety of 
multipotent cells appear to acquire many properties of neurons and glia – a 
first step toward developing cell replacement therapies for neurological 
dysfunction.   The discovery of endogenous stem cells, residing either within 
the nervous system or in other tissues raises the possibility that these 
intrinsic systems may be harnessed to restore defective cells and functions.  
In both cases the expectation is that, when exposed to the optimal 
microenvironment in vivo, endogenous or transplanted stem cells will 
differentiate in a manner appropriate to the local brain region, and 
integrate with the existing circuits in the nervous system.

The past decade has seen enormous progress in our understanding of the 
specific requirements of stem cells to proliferate and differentiate along 
specified lineages. This progress has been made possible by the discovery of 
myriad growth factors and substrate conditions followed by careful testing in 
culture. Unfortunately, the behavior of cells in tissue culture does not 
adequately predict how these same cells will behave when transplanted into 
the living host where multiple known and unknown factors converge to 
influence the biological process. We do not know the whole spectrum of 
factors present in vivo that influence cell fate. Effective use of stem and 
progenitor cells for therapeutic purposes hinges on their ability to thrive, 
integrate, and function in a biologically meaningful manner in vivo without 
causing adverse events. Therefore the next stage in developing cell 
restoration therapy requires understanding how the newly generated cells will 
behave within the host.  

Recent reports indicate that the "niche" or local microenvironment that a 
stem cell encounters governs its behavior and fate.  For example, adult 
neural stem cells produced neurons when transplanted into the neurogenic zone 
of the hippocampus, but produced astrocytes in the environment of the spinal 
cord. Further investigation showed that a specific component of the local 
environment, the regional astrocytes from the hippocampus were capable of 
instructing these stem cells to adopt a neuronal fate in vitro.  In addition 
to regional differences within the nervous system, the microenvironment 
encountered by a stem cell may vary as a function of age of the host 
organism. Similarly, alteration of the niche by injury, drugs or other 
circumstances is likely to affect the ability of transplanted stem cells to 
survive, differentiate and integrate into existing neural circuitry. 
Understanding these changes will be important in making decisions about the 
use of cell replacement therapies in very young or elderly patients, in 
patients with a history of alcohol or drug usage, or suffering from injury or 
other neurological conditions. 

Transplanted cells can act to influence and change host cells in their 
vicinity. Stem cells may release agents that alter the activity or resiliency 
of damaged host cells. These dynamic interactions are inevitable as living 
cells and tissue contact, react and respond to each other in time and space. 
Teasing out and understanding these interactions poses a major challenge that 
must be faced in order to develop realistic cell replacement therapies and 
enhance normal tissue regeneration. 

Objectives and Scope

This Program Announcement with Set-Aside is intended to promote studies that 
establish and identify the nature and action of microenvironmental cues in 
the nervous system that regulate stem cell fate.  This Program Announcement 
specifically targets cellular, molecular and genetic mechanisms that act in 
vivo to influence stem cell survival, homing/migration, adhesion, 
differentiation, plasticity and tumorigenicity in both the central and 
peripheral nervous systems.  Applications that only propose in vitro studies 
will not be responsive to this initiative.

The following examples illustrate areas that are of high interest; other 
innovative projects are also encouraged. These examples of research 
approaches are not meant to be all-inclusive or restrictive. Plans for data 
and/or reagent sharing and promulgation of results will be integral to the 
applications.  

o Identification, localization and comparison of known or novel cues within 
the developing, adult and aging nervous system that influence the mitotic 
potential, cell cycle and differentiation of stem and progenitor cells along 
specific lineages.

o Characterization of the cell-extrinsic and cell-intrinsic signaling 
pathways and components involved in transducing the action of local cues on 
stem and progenitor cells in vivo.

o Investigation of the causal relationship between site-specific changes of 
endogenous cues resulting from injury, disease, exposure to alcohol, drugs of 
treatment or abuse, and any resulting alterations of stem cell activity.

o Evaluation of the effects of external factors such as stress, exercise, or 
an enriched versus impoverished living conditions on the microenvironment 
within the host organism, and how these changes in microenvironment influence 
the behavior of stem cells at different periods throughout the life span of 
the organism.   

o Investigation of local cellular interactions that determine and maintain 
the structural and functional integration of progenitor cells into the host 
nervous system and existing circuitry. 
 
o Development of assays facilitating the discovery of novel endogenous 
signals that modulate stem cell behavior and fate, as well as signals 
generated by stem cells that regulate components of the local host tissue.  
These may include the development of measures (physiological, behavioral, 
neurochemical, imaging) to evaluate the integration and function of 
progenitor cells in the developing, adult and aging nervous system.

o Assessment of the short and long-term local effects of the interactions 
between the immune system and glial reactions gendered in response to the 
infiltration of stem cells and their progeny in the host.

The NIDA is interested in how drugs of abuse and factors such as stress and
environment affect the behavior of stem cells and the functional consequences
of such alterations, which might be related to the cognitive impairments,
developmental deficits, neuroadaption and addictive behaviors seen in drug
abuse.  The NIDCD is particularly interested in stem cell research
targeting the various peripheral components of the auditory (hearing),
olfaction (smell) and gustatory (taste) systems.  The NIAAA is interested in 
how alcohol exposure alters the biochemical environment of tissues, thus
interfering with the capacity of stem cells to establish contact,
differentiate and function in target tissue.  The NIA is interested in stem
cell research and neurogenesis in the aging nervous system with emphasis on
basic neurobiology, motor and sensory systems, integrative neurobiology,
cognition and the dementias of aging, particularly Alzheimer's disease. 

MECHANISM(S) OF SUPPORT 

This PAS will use the NIH Exploratory/Developmental Grant (R21) and the 
Research Project Grant (R01) award mechanisms.  As an applicant, you will be 
solely responsible for planning, directing, and executing the proposed 
project.  The proposed project period during which the research will be 
conducted should adequately reflect the time required to accomplish the 
stated goals and should be no more than 5 years for R01 grants.  The R21 
grants are one-time awards to support innovative, high impact research 
projects that would either 1) generate pilot data to assess the feasibility 
of a novel avenue of investigation, 2) involve high risk experiments that 
could lead to a breakthrough in a particular field, or 3) demonstrate the 
feasibility of new technologies that could have major impact in a specific 
area.  Support for the R21 grants is limited to two years with a cumulative 
maximum of $275,000 direct costs requested for both years.  This program is 
appropriate both for new investigators seeking to establish independent 
research careers and for established investigators wishing to explore new 
areas of neuroscience or develop novel technologies.  For further information 
on the R21 mechanism, including Institute-specific information, see 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html

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/archive/grants/policy/nihgps_2001/part_i_1.htm.  

FUNDS AVAILABLE 
 
The participating ICs have set aside a total of $2 million dollars per year 
to support this initiative. The amount and timing of awards paid from set 
aside funds will depend on the overall scientific merit of the applications 
and the availability of funds throughout the duration of this solicitation (2 
years). 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 will also vary. Although the financial plans of the IC(s) 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.  

SPECIAL REQUIREMENTS 

Upon initiation of the program, the participating institutes will sponsor an 
annual meeting to encourage the exchange of information among investigators 
who participate in this program.  In the preparation of the budget for the 
grant application, applicants should REQUEST ADDITIONAL TRAVEL FUNDS for one 
meeting each year to be held in Bethesda, Maryland.  Applicants should also 
include a statement in the applications indicating their willingness to 
participate in such meetings. Applicants are also strongly encouraged to 
include plans for data and/or reagent sharing and promulgation of results.  

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:

o Direct your questions about scientific/research issues to:

Arlene Y. Chiu, Ph.D.
Program Director, 
Repair and Plasticity Program
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2207, MSC 9525
Bethesda, MD  20892-9525
Telephone:  (301) 496-1447
FAX: (301) 480-1080
Email:  chiua@ninds.nih.gov

Geraline C. Lin, Ph.D.
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard
Room 4282, MSC 9555
Bethesda, MD 20892-9555
Telephone:  (301) 435-1305
FAX: (301) 594-6043
Email: glin@nida.nih.gov

Barry Davis, Ph.D.
Director, Taste and Smell Program
National Institute of Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC-7180
Rockville, MD. 20892-7180
Telephone:  (301) 402-3464
FAX: (301) 402-6251
Email:  davisb1@nidcd.nih.gov

Sam Zakhari, Ph.D.
Director, Division of Basic Research
National Institute of Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD  20892-7003
Telephone: (301) 443-0799
FAX: (301) 594-0673 
Email: sz14w@nih.gov

Bradley C. Wise, Ph.D.
Program Director, Fundamental Neuroscience
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 350 MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: wiseb@nia.nih.gov

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

Michael J. Loewe
Chief, Grants Management Branch
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Suite 3290, MSC 9537
Bethesda, MD  20892-9537
Telephone: (301) 496-9231 
FAX: (301) 402-0219
Email: ml70m@nih.gov

Or to 

Gavin Wilkom
Grants Management Specialist
Grants Management Branch, DER 
National Institute of Neurological Disorders and Stroke
Neuroscience Center, 6001 Executive Blvd. Room 3250, MSC 9537
Bethesda MD, 20892
Telephone: (301) 496-7480
FAX: 301-402-0219
Email: gw62m@nih.gov

Michael Costa
Grants Management Specialist
Grants Management Branch
National Institute on Drug Abuse 
6001 Executive Boulevard
Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone: (301) 435-1354 
Fax:         (301) 594-6849 
Email: mcosta@nida.nih.gov

Ms. Sara Stone
Chief, Grants Management Branch
Division of Extramural Research
National Institute of Deafness and Other Communication Disorders
Executive Plaza South – 400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 402-0909 
Fax:       (301) 402-0219 
Email:  stones@nidcd.nih.gov

Judy Fox Simons
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism 
6000 Executive Boulevard, Suite 504
Bethesda, MD 20892-7003
Telephone:  (301) 443-4704 
Fax:  (301) 443-3891 
E-mail: jsimons@willco.niaaa.nih.gov

Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212 MSC 9205
Bethesda, MD 20892-9205
Telephone:  (301) 496-1472 
Fax:  (301) 402-3672 
E-mail: 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.

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular budget grant format.  The modular budget 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 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 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 PAS 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, 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?  

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 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

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 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. 
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 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://grants1.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 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


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