AGING MUSCULOSKELETAL AND SKIN EXTRACELLULAR MATRIX

RELEASE DATE:  September 4, 2003

PA NUMBER:  PA-03-167 (Change in expiration date, see NOT-AG-06-004)

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. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
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 (PA-06-242) funding opportunity announcement has been issued 
for the submission date of June 1, 2006 and submission dates for AIDS and 
non-AIDS applications thereafter.

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: July 2, 2006

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS:

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

COMPONENTS OF PARTICIPATING ORGANIZATIONS:

National Institute on Aging (NIA)
 (http://www.nia.nih.gov)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
 (http://www.niams.nih.gov/)
National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.866, 93.846 and 93.929

THIS PA CONTAINS THE FOLLOWING INFORMATION

o  Purpose of the PA
o  Research Objectives
o  Mechanism(s) of Support
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 THIS PA

The purpose of this PA is to solicit grant applications for basic research 
projects to investigate how changes in the extracellular matrix with age 
affect the function of the tissues of the musculoskeletal system and skin.  
Projects are encouraged that determine how cellular aging processes lead to 
altered matrix production and maintenance, and how aging-related altered 
matrix composition and organization affect the function of these tissues.

RESEARCH OBJECTIVES

Background

The elderly frequently experience problems associated with the 
musculoskeletal system and skin that affect their quality of life.  Some of 
these problems, for example, muscle weakness, are due to changes in tissue 
that are thought to be unavoidably linked to aging.  Other problems are due 
to disease processes accumulation of disabling conditions for which the 
elderly are particularly susceptible, likely due to changes in the diseased 
tissue with age and/or changes in tissues upon which the diseased tissue 
depends.

Cartilage and bone are classified as connective tissues and are composed 
largely of extracellular matrix.  The structural support these tissues give 
to the body depends on the matrix composition and structure; that composition 
and structure being a result of activity of the resident cells (chondrocytes, 
osteoblasts, osteocytes, and osteoclasts).  Reciprocally, the matrix and the 
mechanical and biochemical processes it is subject to, affect the cells.  
Muscle and skin are not connective tissue, but each depends on connective 
tissue for function:  the dermis and subcutaneous fat in the case of skin, 
and the endo- peri- and epimesium layers and tendons in the case of muscle.  
The interaction of the epidermis and the muscle fibers with their associated 
connective tissue and, in particular, the extracellular matrix, is 
fundamental to the function of these tissues.  In most of these tissues there 
is evidence of increased turnover of extracellular matrix with age as well as 
changes in composition of the matrix with age.  Paradoxically, however, the 
matrix can become increasingly insoluble, less digestible and more cross-
linked with age.  Because these tissues depend on matrix for function and 
cell viability, these aging-associated changes in matrix are likely key to 
altered integrity and function of the musculoskeletal tissues and skin in the 
elderly.

More needs to be done to understand the changes that take place in 
extracellular matrix composition and structure with age, why those changes 
occur and the mechanisms by which they result in altered tissue function.  
Changes include both collagenous and non-collagenous proteins, as well as the 
post-translational modifications that may be different in aged vs. younger 
tissues.  Important post-translational modifications may include 
glycosylation, phosphorylation and sulfation, as well as glycation and 
formation of cross-linkages.  Some of these modifications play specific roles 
in specific tissues and have been shown to change with age.  Furthermore, 
there is evidence that the extracellular matrix acts as a reservoir of 
humoral factors such as hormones and growth factors, and mediates cell 
interactions with these factors.  Thus, changes in matrix composition with 
age could lead to altered local balances or effects of these factors.

The extracellular matrix is involved in normal tissue function on a number of 
levels, including regulation of cell fate, growth and function within the 
tissue.  The matrix is a mediator of signals for cell proliferation and 
differentiation, and for apoptosis.  Cell adhesion to extracellular matrix, 
may, in and of itself, help prevent apoptosis.  The extracellular matrix may 
have an influence on vascular function and neurological function, and the 
converse may also be true.  Work in cancer shows that the matrix influences 
angiogenesis.  Thus, matrix influences on blood vessels and nerves in aging 
tissues of the musculoskeletal system and skin may be important to 
understand, as vascular and neural function change.  Because stem cells may 
play a role in maintaining cell numbers and function and in healing of aging 
tissues, it is also important to understand how the matrix microenvironment 
of these tissues affects recruitment, differentiation, and functional 
integration of stem cells.

The structural support lent by the matrix is critical to the structure and 
function of tissues of the musculoskeletal system and skin.  The 
extracellular matrix is the medium through which mechanotransduction takes 
place, which is vital to the health of cartilage, bone and muscle.    
Furthermore, the ability to generate force (in the case of muscle) or respond 
to forces with appropriate structure (in the case of cartilage, skin and 
bone) is inherent in the arrangement of the extracellular matrix.

Within the musculoskeletal system, and to some degree where there is 
mechanical action on skin, the health of the tissue is dependent on 
interaction with associated tissues, notably through the extracellular 
matrix.  These interactions can be endocrine, paracrine, or mechanical.  In 
some cases, changes in one tissue may result in changes in the extracellular 
matrix and resulting tissue health of another associated tissue.  For 
example, in osteoarthritis changes occur in the quality and quantity of 
cartilage matrix, and the underlying bone is also affected, but it is unclear 
whether these are interdependent changes.

Expertise on several tissues may need to be integrated to investigate tissue 
interactions as they affect, and are affected by, altered extracellular 
matrix with age.  Research is needed on interdependent aging changes in bone, 
skin, muscle, and cartilage, and the role of extracellular matrix in these 
changes.  The biomechanical and biochemical signals from these tissues and 
how the extracellular matrix mediates these effects may be critical to our 
understanding of interdependent changes in tissues with age.

Objectives and Scope

This PA is intended to encourage basic research into aging effects on 
extracellular matrix and how those changes in extracellular matrix 
composition and organization contribute to the altered function seen with 
aging in the musculoskeletal system and skin.  While some descriptive work 
may be justified to document changes that take place in extracellular matrix 
with age, studies are especially encouraged to investigate the mechanisms 
whereby aging leads to these changes and by which altered matrix affects cell 
and tissue function.  The following examples illustrate areas of research 
that are of interest, but serve as examples only, and are not exclusive.  
Basic biology studies on aging that use animal models or human tissues are of 
interest.  However, clinical studies in humans, beyond collection of tissues 
or cells for in vitro use, are outside the scope of this PA.

o  The mechanisms by which altered composition of the matrix seen with age 
affects mechanotransduction and the response of cells to loading

o  Effect of age-related changes in matrix structure/function on the 
susceptibility of cells to altered apoptosis

o  Effect of age-related changes in matrix structure/function on cell 
proliferation

o  Interactions between cells and matrix that lead to characteristic 
alterations in cell or tissue morphology and function with age.  For example, 
thinning of epidermis or change in fiber type in muscle.

o  How cell senescence affects matrix synthesis, secretion, assembly, or 
turnover 

o  How altered matrix composition or structure may predispose tissues to 
diseases commonly associated with aging, such as Paget's disease or 
osteoarthritis.

o  How alterations in matrix composition or structure with age affect normal 
tissue repair or cell turnover, including involvement of stem cells in these 
processes

o  How the changing extracellular matrix environment with age affects the 
local bioavailability of growth factors or hormones that influence tissue 
health and function

o  Mechanisms by which changes in one tissue, lead to altered structure and 
function in another tissue.  For example, how muscle weakness of sarcopenia 
affects the structure and integrity of the associated bone.  Such interaction 
could be effected through mechanotransduction, through soluble factors such 
as IL-6, or through other mechanisms.

o  How alterations in activity levels or function affect matrix structure and 
function, particular in the context of disabling conditions; this may include 
studies of muscle atrophy and contractures or osteoporosis.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH R01 Research Project and R21 
Exploratory/Developmental Research Grant award mechanisms.  As an applicant, 
you will be solely responsible for planning, directing, and executing the 
proposed project.

R21 applications for Exploratory/Developmental Research Grants may request up 
to two years of support with a combined budget for direct costs of up to $275 
for the two year period.  For example, the applicant may request $100,000 in 
the first year and $175,000 in the second year.  The request should be 
tailored to the needs of the project.  Normally, no more than $200,000 may be 
requested in any single year.  Exploratory/development grant support is for 
new projects only; competing continuation applications will not be accepted 
for this mechanism.  Two revisions of a previously reviewed 
exploratory/developmental grant application may be submitted as defined in 
NIH Policy at http://grants.nih.gov/grants/policy/amendedapps.htm. A general 
announcement for R21 applications can be found at 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html.

This PA 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.

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:

o  Direct your questions about scientific/research issues to:

Jill L. Carrington, Ph.D.
Director, Musculoskeletal Biology
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-2210
Email: Carringtonj@nia.nih.gov

William J. Sharrock, Ph.D.
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIH, DHHS 
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-5055
FAX:  (301) 480-4543
Email: ws19h@nih.gov

Ralph Nitkin, Ph.D.
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 2A03, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 402-4206
FAX:  (301) 402-0832
Email:  rn21e@nih.gov

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

Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD   20892
Telephone:  (301) 496-1472
FAX:  (301) 402-1758
Email: whippl@nia.nih.gov

Michael G. Morse
Deputy Chief, Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIH/DHHS
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
Phone:  (301)594-3506
E-mail:  morsem@mail.nih.gov

Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915
Email:  kh246t@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.

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

For R21 Exploratory/Developmental Grants 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 are required but may be included if available.  Please note 
that a Progress Report is not needed; competing continuation applications for 
an exploratory/developmental grant will not be accepted.  In addition, for 
appendix materials, use the instructions for the appendix detailed in the PHS 
398 except that no more than 5 manuscripts, previously accepted for 
publication, may be included.

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 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 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.

The NIH R21 Exploratory/Developmental grant is a mechanism for supporting 
novel scientific ideas or new model systems, tools, or technologies that have 
the potential to significantly advance our knowledge or the status of health-
related research.  Because the research plan is limited to 15 pages, an 
Exploratory/Developmental grant application need not have extensive 
background material or preliminary information as one might normally expect 
in an R01 application.  Accordingly, reviewers will focus their evaluation on 
the conceptual framework, the level of innovation, and the potential to 
significantly advance our knowledge or understanding.  Reviewers will place 
less emphasis on methodological details and certain indicators traditionally 
used in evaluating the scientific merit of R01 applications including 
supportive preliminary data.  Appropriate justification for the proposed work 
can be provided through literature citations, data from other sources, or, 
when available, from investigator-generated data.  Preliminary data are not 
required for R21 applications.

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 the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals.  The scientific review 
group will address and consider each of the following criteria in assigning 
the application's overall score, weighting them as appropriate for each 
application. 

o  Significance 
o  Approach 
o  Innovation
o  Investigator
o  Environment

The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

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

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

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

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

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in 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 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. The NIH policy on data-
sharing is described at: 
http://grants.nih.gov/grants/policy/data_sharing/.

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.

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)
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