HIGH RISK RHEUMATIC AND MUSCULOSKELETAL AND SKIN DISEASES RESEARCH

RELEASE DATE:  January 7, 2003

RFA: AR-03-009

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
 (http://www.niams.nih.gov/)

LETTER OF INTENT RECEIPT DATE: February 18, 2003
APPLICATION RECEIPT DATE: March 18, 2003

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
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 Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The purpose of this initiative is to broaden the base of inquiry in 
fundamental biomedical, bio-behavioral, and biomedical technology 
research by encouraging applications for research projects that involve 
an especially high degree of innovation and novelty and, therefore, 
require a preliminary test of feasibility.  The goal is to solicit 
research applications with the potential for developing ground-breaking 
technology or methodology that may lead to significant expansion of 
biomedical research horizons, precipitate a paradigm shift in research, 
or lead to substantial improvements in human health.  Research projects 
proposed under this Request for Applications (RFA) may involve 
substantial experimental risks such that their potential for highly 
significant outcomes may be difficult to judge by the standard criteria 
used in evaluating investigator initiated (R01) proposals.  Preliminary 
data are not required.  The work proposed may not overlap with the aims 
of currently supported projects or those in which the Principal 
Investigator has participated during the past five years.  Proposed 
projects must support the mission of the National Institute of 
Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Two kinds of experienced and established investigators are sought.  
First, experienced and established investigators in rheumatic or 
musculoskeletal or skin diseases are encouraged to present a proposal 
for testing the feasibility of a novel idea, resource or technology.  
The project should represent a clear and distinctly different approach 
from the investigator's current and previous (past 5 years) research.  
Second, experienced and established investigators with no previous work 
in rheumatic or musculoskeletal or skin diseases are encouraged to 
apply their expertise to research that is relevant to rheumatic or 
musculoskeletal or skin diseases.  This request for applications should 
not be considered for new investigators without previous grant 
experience.

RESEARCH OBJECTIVES

The NIAMS seeks to broaden the base of inquiry in fundamental 
biomedical, bio-behavioral, and biomedical technology research by 
encouraging research projects that involve a high degree of innovation 
and novelty.  Because innovative projects may require a preliminary 
test of feasibility, this initiative will provide short-term support 
for such preliminary work.  Each research plan should include a brief 
description of how the proposed project represents a high degree of 
innovation and novelty that complements but does not duplicate the 
applicant's currently funded research. The projects must support the 
NIAMS mission as detailed in the NIAMS Web page, which can be found at 
http://www.nih.gov/niams/about/ep1.htm.  In brief, the NIAMS supports 
research in:  a) rheumatic diseases; b) cartilage biology and diseases; 
c) bone biology and diseases (e.g., osteogenesis imperfecta, Paget's 
disease); d) skin biology and skin diseases; e) autoimmune diseases 
(e.g., lupus, rheumatoid arthritis); f) connective tissue diseases; g) 
musculoskeletal diseases (e.g., osteoarthritis, osteoporosis) h) 
musculoskeletal imaging; i) injuries and disorders of the 
musculoskeletal system; j) muscle biology and diseases (e.g., muscular 
dystrophy); k) exercise physiology and musculoskeletal fitness; l) 
sports injuries; m) occupational diseases and injuries; and n) 
orthopaedic and bioengineering topics.

MECHANISM(S) OF SUPPORT

This RFA will use the National Institutes of Health (NIH) 
exploratory/developmental research grant, R21, award mechanism.  
Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  Applicants may 
request up to $50,000 (direct costs) per year for up to two years.  
These awards are not renewable.  If desired, the specific aims of the 
R21 project may be expanded and serve as the basis for a larger 
research grant application (R01) submitted prior to the termination of 
the R21 award. This RFA is a one-time solicitation.

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting format. (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   
Specifically, when an application is submitted with direct costs in 
each year of $250,000 or less, the modular format should be used.

FUNDS AVAILABLE

It is anticipated that for FY 2003, approximately $1,200,000 total 
costs will be available for the first year of support for this 
initiative.  Award of grants is contingent upon the receipt of such 
funds for this purpose.  It is anticipated that up to 20 new grants 
will be awarded under this program.  The specific number to be funded 
will depend on the merit and scope of the applications received and on 
the availability of funds.  Direct costs are limited to $50,000 and 
will be awarded in modules of $25,000, less any overlap or other 
necessary administrative adjustments.  Facilities and Administrative 
costs will be awarded based on the negotiated rates.  Applicants may 
request up to two years of support.

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

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

For this solicitation, individuals with an established research career 
and the skills, knowledge, and resources necessary to carry out the 
proposed research are invited to work with their institutions to 
develop an application for support.  Individuals from underrepresented 
racial and ethnic groups as well as individuals with disabilities are 
strongly encouraged to apply for support from NIAMS programs.

SPECIAL REQUIREMENTS

The Background and Significance Section of application must include a 
brief section (one page or less) entitled "Eligibility for High Risk 
RFA" that states the innovative and high risk aspects of the project 
that distinguish it from currently funded projects in the PI's and 
collaborators' laboratories. The following concerns should be 
specifically addressed:
     1) Innovation & Novelty: Does the proposed project represent a high 
        degree of innovation and novelty?
     2) Lack of overlap with current work:  Does the proposed project
        have specific overlap with current work from the PI?  If
        the proposed work is complementary to on-going research, 
        why couldn't it be carried out within the framework of 
        currently funded studies?
     3) High risk: Explain how the high gain potential of the project, if 
        successful, offsets the high  risk of failure.
     4) Justification of eligibility of PI: Provide evidence of PI's 
        established research career.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  programmatic/general, peer review, and financial or 
grants management issues:

Direct inquiries regarding programmatic issues to the most appropriate 
person listed on the web site 
(http://www.niams.nih.gov/rtac/prog_staff/director.htm) according to 
scientific area.

For general inquiries about this RFA contact:

Gayle E. Lester, Ph.D.
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-5055
FAX:  (301) 480-4543
Email: [email protected]

Direct your questions about peer review issues to:

Richard Bartlett, Ph.D.
Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza 
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: 301-594-4956 
Fax: 301-402-2406
Email: [email protected]

Direct your questions about financial or grants management matters to:

Melinda Nelson
Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd. Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  [email protected] 

LETTER OF INTENT

Prospective applicants are asked to submit, by February 18, 2003, a 
letter of intent that includes:
 
Descriptive title of the proposed research;
Name, address, and telephone number of the Principal Investigator;
Names of other key personnel;
Other participating institutions
Number and title of this RFA.

Although a letter of intent is not required, is not binding, does not 
commit the sender to submit an application, and does not enter into the 
review of a subsequent application, the information that it contains 
allows IC staff to estimate the potential review workload and plan the 
review.  The letter of intent should be sent to:

Richard Bartlett, Ph.D.
Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza 
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: 301-594-4956 
Fax: 301-402-2406
Email: [email protected]

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  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) 710-0267, Email: [email protected].

SPECIAL APPLICATION PROCEDURES:  The research plan (a-d) is limited to 
10 pages.  APPLICATIONS THAT EXCEED THE PAGE LIMIT WILL BE RETURNED 
WITHOUT REVIEW.  A Preliminary Data section is not required.  If 
included in R21 applications, it should not exceed one page.  The 
Background and Significance Section of application must include, at the 
beginning, a brief section (one page or less) entitled "Eligibility for 
High Risk RFA" in which the PI specifically addresses the following 
concerns:  1) Innovation & Novelty: Does the proposed project represent 
a high degree of innovation and novelty?  2) Lack of overlap with 
current work:  Does the proposed project have specific overlap with 
current work from the PI?  If the proposed work is complementary to on-
going research, why couldn't it be carried out within the framework of 
currently funded studies?  3) High risk: Explain how the high gain 
potential of the project, if successful, offsets the high  risk of 
failure. 4) Justification of eligibility of PI: Provide evidence of 
PI's established research career.  An appendix may be included in the 
application; however, the appendix is not to be used to circumvent the 
page limit of the research plan. 

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in 
a 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.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number (AR-03-009) on the label.  
Failure to use this label could result in delayed processing of the 
application such that it may not reach the review committee in time for 
review.  In addition, the RFA title and number must be typed on line 2 
of the face page of the application form and the YES box must be 
marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application 
must be sent to:

Richard Bartlett, Ph.D.
Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza 
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: 301-594-4956 
Fax: 301-402-2406
Email: [email protected]

APPLICATION PROCESSING: Applications must be received by the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review.

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an Introduction addressing 
the previous critique.  This Introduction SHOULD NOT exceed 1 page.  
Such revised applications will be allotted a total length of 11 pages 
for sections a-d and including the one page Introduction.

PEER REVIEW PROCESS  

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIAMS.  Incomplete applications will be 
returned to the applicant without further consideration.  In addition, 
applications will be reviewed by NIAMS for responsiveness to the RFA 
after receipt of application and prior to review.  If the application 
is not determined to be responsive to the RFA, NIAMS staff will either 
return the application to the applicant or contact the applicant to 
clarify questions of suitability.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIAMS in accordance with the review 
criteria stated below.  As part of the initial merit review, all 
applications will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score
o Receive a second level review by the National Arthritis and 
Musculoskeletal and Skin Diseases Advisory Council. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
For this initiative, the proposed project must have the potential for 
developing ground-breaking technology or methodology that may lead to 
significant expansion of biomedical research horizons, precipitate a 
paradigm shift in research, or lead to substantial improvements in 
human health.  In the written comments, reviewers will be asked to 
discuss the following aspects of your application in order to judge the 
likelihood that the proposed research will have a substantial impact on 
the pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

Each of these criteria will be addressed and considered in the 
assignment of the overall score.

(1) Significance.  Does the proposed study have potential for the 
development of ground-breaking technology or methodology that may lead 
to significant expansion of biomedical research horizons, precipitate a 
paradigm shift in research, or lead to substantial improvements in 
human health?  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?

(2) Approach.  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Does the investigator acknowledge potential 
problem areas and consider alternative tactics?

(3) Innovation.  Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does the project 
challenge existing paradigms or seek to develop new methodologies or 
technologies?  Does the high gain potential of the project, if 
successful, offset the high risk of failure?

(4) 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, your 
application will also be reviewed with respect to the following:

o 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.

o INCLUSION:  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.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria included in the section on Federal Citations, below)

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

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: February 18, 2003
Application Receipt Date: March 18, 2003
Peer Review Date: June/July, 2003
Council Review: September, 2003
Earliest Anticipated Start Date: December, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Novelty, innovation, and high risk nature of the proposal
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research 
components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous 
data management, quality assurance, and auditing procedures.  In 
addition, it is NIH policy that all clinical trials require data and 
safety monitoring, with the method and degree of monitoring being 
commensurate with the risks (NIH Policy for Data Safety and 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 is 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://grants.nih.gov/grants/stem_cells.htm 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 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 RFA 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.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information 
necessary to the review because reviewers are under no obligation to 
view the Internet sites.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 
site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.846, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies described 
at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

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

			Department of Health and Human Services (HHS)
NIH... Turning Discovery Into Health®