OSTEOARTHRITIS BIOMARKERS NETWORK
RELEASE DATE: February 14, 2003
RFA: AR-03-006
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
(http://www.nih.gov/niams/)
Letter of Intent Receipt Date: March 17, 2003
Application Receipt Date: April 17, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Cooperative Agreement Terms and Conditions of Award
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 National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) invites applications for cooperative agreements for the development
and characterization of new or refinement of existing osteoarthritis (OA)
biomarkers. The Principal Investigators of each project will become members
of a national OA Biomarkers Network that the NIAMS will establish immediately
following award. Investigators in the Network will work collaboratively and
share resources for the development, evaluation, and validation of
biochemical markers for osteoarthritis onset, severity, progression, and
response to treatment. A Network Steering Committee (NSC) composed of the
Principal Investigators in the Network and appropriate NIAMS staff (such as a
Science Officer or Program Officer) will coordinate the work of the Network
and with other ongoing NIH sponsored OA studies. If appropriate, the NIAMS
will issue subsequent RFAs for Biomarker Validation and a Data Management and
Coordinating Center.
RESEARCH OBJECTIVES
Background
Osteoarthritis is the most common joint disorder, producing pain and
disability, and ultimately resulting in the destruction of articular
cartilage. Abnormal metabolic processes begin in the articular cartilage
several years before destruction of the articular surface can be detected
radiologically. The development and validation of standardized, sensitive
assays for disease markers in blood/urine may facilitate the ability to
diagnose the disease during the pre-radiologic stages, to monitor disease
progression and the effects of surgical or pharmacological treatment, and to
accelerate the pace of drug discovery.
Biomarkers are defined as molecules that reflect a specific biological or
pathological process, consequence of a process, or a response to therapeutic
intervention. Biochemical studies indicate that in OA there are marked
increases in the breakdown and biosynthesis of the major cartilage matrix
molecules, the collagens and proteoglycans. Exploration of the mechanisms
responsible for breakdown and biosynthesis of articular cartilage in OA has
prompted interest in the potential use of cartilage-derived molecules as
markers of cartilage metabolism in OA. Also, the enhanced synthesis and
degradation of matrix molecules in OA cartilage involves not only accelerated
turnover but also the upregulation of molecules synthesized in immature
cartilage but not in healthy adult articular cartilage. In addition, early
changes in OA have been shown to involve significant changes in markers of
bone turnover. Some of these molecules may be of value for further
investigation and are included in this RFA. A current assessment of the
research needs in OA biomarker research is presented in the NIH
Osteoarthritis Initiative White Paper on Biomarkers, which can be located at
the following web address: http://www.niams.nih.gov/ne/oi/oabiomarwhipap.htm
Among the technical approaches that can be exploited are the identification
of cellular and molecular markers of inflammation, tissue destruction and
repair, and their detection using sera, peripheral blood cells or tissue.
New assay systems have been developed to measure intracellular cytokines, to
identify and isolate cells (such as chondrocytes and synovial cells) and to
simultaneously measure the expression of thousands of genes. An additional
technology applicable to such questions is that of differential gene
expression, detected by the use of microchip array presentation of cDNAs from
affected vs. unaffected tissues, active vs. inactive time points, or affected
vs. unaffected individuals. Experimental studies correlating outcomes
measured by imaging technologies (spectral techniques, bioluminescent
approaches, multiphoton imaging) with current or new biomarkers would
dramatically improve our understanding about their interactions and their
responses to mechanical and inflammatory stimuli, and would potentially
identify targets for pharmacologic agents, especially disease modifying
agents. All or any of these markers would assist in the clinical management
of patients with OA for diagnostic, prognostic, and response-to-treatment
assessment purposes.
Scope of This RFA
The purpose of this solicitation is to encourage the submission of
applications from qualified investigators interested in research and
development projects designed to identify and characterize biochemical
markers to assess OA disease risk, onset, progression, and response to
treatment. Areas of interest include:
o Small scale studies to evaluate promising biomarkers or technologies,
including evaluation of diagnostic predictive accuracy, sensitivity,
specificity, and whenever possible, medical benefits, of known and
newly identified potential biomarkers;
o Development of biomarkers and biomarker expression patterns, sometimes
of multiple markers simultaneously, which will serve as background
information for subsequent large definitive validation studies;
o Collaborative approaches among academic and industrial leaders in
molecular biology, molecular genetics, biochemistry, rheumatology,
computer science, public health, etc., for the development of high
throughput, sensitive assay methods for biomarkers from an early
diagnosis, risk assessment treatment response monitoring viewpoint;
o Translational research in the biology and pathogenesis of OA that
directly leads to development, characterization, and testing of
biomarkers for early disease diagnosis, assessment of disease risk,
evaluation of disease course, and treatment responses (the search for
new markers should reflect new information about the biology of tissues
and organs involved in OA as well as new knowledge on disease etiology
and pathogenesis, such as apoptosis, cell cycle control, etc.);
o Identification of biomarkers based on advances on the genetic
epidemiology of OA;
o Identification of biomarkers that can potentially be useful to define
disease subsets and risk for severe disease or response to treatments;
Identification of biomarkers that may inform therapeutic approaches in
relation to symptoms, such as pain or structural change;
o Use of new technologies and approaches to identify new potential
targets for the development of biomarkers;
o Development of new assays and technologies for the rapid and accurate
measurement of biomarkers in OA;
o Use of animal models and other experimental systems to identify
biomarkers of loading and other physical properties and changes in
structures affected by OA that may be indicators of disease onset or
evolution;
o Exploratory, small scale ancillary studies to existing cohorts to
determine feasibility of an assay or approach for the identification or
use of biomarkers in the context of ongoing OA studies in patients.
Research of a fundamental nature, such as studies on basic inflammatory
processes, growth regulation, cell cycle control, or other basic studies that
are not explicitly focused on identification of target process or mediators
for biomarker development are NOT included under the scope of this RFA. This
RFA will not support large-scale evaluation studies of new or existing
biomarkers.
Network Goals
This research initiative also seeks to promote the interactions of
investigators with scientific expertise, facilities, and capabilities to
conduct controlled studies through the establishment of the OA Biomarkers
Network. Principal Investigators of the individual cooperative agreements
must actively participate in the OA Biomarkers Network. The purpose of the
Network is to establish a scientific consortium of investigators, academic as
well as industrial, with resources for basic, translational, and clinical
research. The goals of the Network will be to discover and to coordinate the
evaluation of biomarkers for the earlier detection of OA and for the
assessment of risk and response to treatments. Because early diagnosis and
treatment issues are often related, the Network will need meaningful
participation from various medical organizations. In some of its activities,
the Network may need to relate programmatically to the research
infrastructures supported by NIAMS and other NIH components (for example,
Specialized Centers of Research in OA, Multidisciplinary Clinical Research
Centers, Osteoarthritis Initiative), with ongoing NIH clinical research
programs/trials (for example, Glucosamine in OA Trial), or with other
agencies, such as Food and Drug Administration.
MECHANISM OF SUPPORT
This RFA will use a Cooperative Agreement (U01) mechanism. The NIH U01 is a
cooperative agreement award mechanism in which the Principal Investigator
retains the primary responsibility and dominant role for planning, directing,
and executing the proposed project, with NIH staff being substantially
involved as a partner with the Principal Investigator, as described under the
section "Cooperative Agreement Terms and Conditions of Award. At present,
the plans for extending the cooperative agreement projects beyond the initial
award period are indefinite. Future plans will be based on evaluation of
scientific progress achieved by awardees during the initial funding period.
The anticipated award date is September 30, 2003.
This RFA is a one-time solicitation. At this time the NIAMS does not
anticipate that there will be a renewed competition after five years. If the
NIAMS does not continue the program, awardees may submit grant applications
through the usual investigator-initiated grants program. However, before
submitting such applications, applicants are advised to contact the Program
Director listed under INQUIRIES.
FUNDS AVAILABLE
The NIAMS intends to commit an estimated $1,000,000 total costs in FY 2003 to
fund approximately 3 to 4 new grants in response to this RFA. An applicant
may request a project period of up to 5 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 NIAMS provide support for this program, awards
pursuant to this RFA 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
o Faith-based or community-based 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
COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD
Within 90 days of award the NIAMS will establish the OA Biomarkers Network.
As part of the U01 Cooperative Agreement Grant process, the following Terms
and Conditions of Award and details of the arbitration procedures pertaining
to the scope and nature of the interaction between the NIH staff and the
participating awardees will be incorporated into the Notice of Grant Award
and provided to the Principal Investigator and the institutional official at
the time of award. These procedures will be in addition to the customary
programmatic and financial negotiations that occur in the administration of
grants.
Cooperative agreements are assistance mechanisms subject to the same
administrative requirements as grants. The special Terms and Conditions of
Award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS Grant Administration Regulations at 45 CFR
Part 74 and 92, and other HHS, PHS, and NIH grant administration policies and
procedures. Facilities and Administrative Cost (indirect cost) award
procedures will apply to cooperative agreement awards in the same manner as
for grants.
The administrative and funding instrument used for this program is a
Cooperative Agreement (U01), an "assistance" mechanism (rather than an
"acquisition" mechanism) in which substantial NIAMS scientific and/or
programmatic involvement with the awardee is anticipated during performance
of the activity. Consistent with this concept, the dominant role and prime
responsibility for the activity resides with the awardee(s) for the project
as a whole, although specific tasks and activities in carrying out the
studies will be shared among the awardees and the NIAMS Science Officer.
Failure of the awardees to meet the performance requirements, including these
special terms and conditions of award, or significant changes in level of
performance, may result in a reduction of budget, withholding of support,
suspension and/or termination of the awards.
1. Awardee Rights and Responsibilities
Awardees have primary authorities and responsibilities to define objectives
and approaches, and to plan, conduct, analyze, and publish results,
interpretations, and conclusions of their studies. The primary
responsibilities of the awardees are to:
o Define the research objectives
o Design the necessary research protocols
o Conduct specific studies
o Analyze and interpret research data
o Propose protocol modifications as required
o Participate in Network collaborative activities approved by the Network
Steering Committee (NSC)
o Serve on the NSC
o Agree to sharing of reagents and technologies in accordance with approved
sharing plans
o Provide information to the NIAMS staff concerning progress
o Abide by all scientific, practical and policy decisions of the NSC
Awardees will retain custody of and primary rights to their data and
intellectual property developed under the award, subject to current
government policies regarding rights of access as consistent with current
HHS, PHS, and NIH policies and subject to the terms and conditions of this
RFA. All research publications shall be submitted to NIH for administrative
and policy review prior to submission for publication. This review shall not
be for the purpose of scientific oversight, but rather to ensure that NIH
policies and/or representations that may imply NIH endorsement of clinical or
research standards are not proposed. These reviews may not unreasonably
delay submission for publication.
2. NIAMS Responsibilities
NIAMS Science Officer
NIAMS Science Officer will be NIAMS Program staff member who will have
substantial scientific involvement during the conduct of this activity,
through technical assistance, advice, and coordination above and beyond
normal Program stewardship for grants. The NIAMS Science Officer will be
selected by the NIAMS. The degree of involvement of the NIAMS Science
Officer will include the following:
o Assist in coordinating collaborative research efforts that involve multiple
laboratories and avoiding unwarranted duplication of effort across
laboratories;
o Review and comment on critical stages in the research program before
subsequent stages are implemented;
o Assist in the interaction between the awardee and the FDA, when
appropriate;
o Assist in the interaction between the awardee and investigators of other
institutions, as well as between the awardee and potential commercial
sponsors;
o Retain the option of recommending termination of studies if technical
performance falls below acceptable standards, or when specific lines of
research cannot be effectively pursued in a timely manner;
o Retain the option to recommend additional research endeavors within the
constraints of the approved research and negotiated budget;
o Serve on the NSC.
NIAMS Program Officer:
NIAMS will appoint a Program Officer who will have program oversight
responsibilities for each grant and for the entire Network. The Program
Officer will:
o Exercise the normal stewardship responsibilities of an NIAMS Program
Officer
o Carry out continuous review of all activities to ensure objectives are
being met
o Have the option to recommend withholding support to a participating
institution if technical performance requirements are not met
3. Collaborative Responsibilities/ Network Steering Committee (NSC)
Collaborative activities of the Network, consistent with the stated intent of
the RFA, will be done by a NSC consisting of the Principal Investigators of
each grant and the NIAMS Science Officer. Each Principal Investigator (or
designee) will have one vote, and the NIAMS will have one vote. Membership
on the NSC becomes effective upon issuance of the Notice of Grant Award. The
NSC may establish additional by-laws, subcommittees, or workgroups for
specific tasks. The NIAMS Science Officer may not chair any committee or
subcommittee. During the first year there will be one planning committee
meeting within 6 months of the award date and one NSC meeting in the
Bethesda, MD area. After the first year the NSC meetings will be convened
twice yearly in the Bethesda, MD area. The purpose of these meetings is to
share scientific information, assess scientific progress, identify new
research opportunities, and discuss strategy and potential avenues of
collaborations such as with industry, private foundations and/or NIH
intramural scientists, establish priorities that will accelerate the
translation of preclinical findings into clinical applications, reallocate
resources and conduct the business of the cooperative research program.
Awardees must set aside 20% of their annual budget after the first year for
Network collaborative studies. The NSC will develop the process and review
procedures for handling the 20% funds in future years. The use of these set
aside funds will be restricted and must be reviewed and approved by the NSC
and then recommended to, and approved by the NIAMS for release from the
individual U01 awards. Decisions will be made by a majority vote of a
quorum, with an attempt for consensus when possible. The NSC can convene
through telephone conference or in person. Outside consultants/experts may
be asked to participate in these discussions as nonvoting advisors.
Collaborative projects among the Network members will require NSC approval.
NSC members will abide by all scientific, practical, and policy decisions of
the NSC.
4. Arbitration Process
Any disagreement that may arise on scientific/programmatic matters (within
the scope of the award), between award recipients and the NIAMS may be
brought to arbitration. An arbitration panel consist of one person selected
by the Principal Investigators, one person selected by the NIH, and a third
person selected by both NIH staff and the Principal Investigators. The
decision of the arbitration panel, by majority vote, will be binding. This
special arbitration procedure in no way affects the awardee's right to appeal
an adverse action that is otherwise appealable in accordance with the PHS
regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part
16.
5. Public Domain of Data
All data from collaborative studies will first be available to be analyzed
and interpreted by the collaborators in the project. However, since the
creation of the data set is funded through public monies and because the data
set will constitute a national scientific resource for the research
community, the awardees will make data of all types available to the larger
research community no more than 24 months from the date after which the final
wave of data for a particular project have been collected and cleaned. More
rapid sharing of data is encouraged.
6. Progress Reviews
Progress of the Network projects will be reviewed annually by the NIAMS staff
at the time each continuation application is considered for funding to assure
that satisfactory progress is being made in achieving the project objectives
and that each site is following the procedures recommended and approved by
the NSC. During the first year of funding, and during subsequent years, if
deemed necessary by the Program Officer, reviews will be more frequent.
Should problems arise in the conduct of a project, the NIAMS staff may
require that the awardee submit quarterly reports on progress and fiscal
matters. By acceptance of this award, the awardee agrees to abide by
decisions and policies of the NSC and the other terms and conditions listed
above or referenced in the Notice of Grant Award.
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: scientific/research, peer review, and financial or grants management
issues:
o Direct your questions about scientific/research issues to:
Bernadette Tyree, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Blvd.
Suite 800
Bethesda, MD 20892-6500
Telephone: (301) 594-5032
FAX: (301) 594-4543
Email: tyreeb@ep.niams.nih.gov
o Direct your questions about peer review issues to:
John R. Lymangrover, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-4952
FAX: (301) 402-2406
or (301) 480-4543
Email: lymangrj@ep.niams.nih.gov
o Direct your questions about financial or grants management matters to:
Melinda Nelson
National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIAMS, NIH
6701 Democracy Blvd.
Suite 800
Bethesda MD 20892-6500
Telephone: (301) 594-3535
FAX (301) 480-5450
Email: nelsonm@ep.niams.nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes
the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does not
enter into the review of a subsequent application, the information that it
contains allows NIAMS staff to estimate the potential review workload and
plan the review.
The letter of intent is to be sent by the date listed at the beginning of
this document. The letter of intent should be sent to:
John R. Lymangrover, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-4952
FAX: (301) 402-2406
or (301) 480-4543
Email: lymangrj@ep.niams.nih.gov
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
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact Grants Info, Telephone (301) 710-0267, Email: Grants Info@nih.gov.
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 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:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SPECIAL INSTRUCTIONS FOR PREPARATION OF THE APPLICATION: "The Research Plan"
section must not exceed a total of 35 pages. To promote the development of a
collaborative program among the award recipients, a number of issues need to
be addressed in their applications as discussed below.
1. Collaborative Activities
o Applicants must include their specific plans for responding to the "Terms
and Conditions" section. Applicants should state their willingness to
collaborate and share data freely with the others in the Network, to serve on
the NSC and be bound by its decisions, particularly those which relate to
setting priorities for quality assurance and validation phase of the
biomarker development, and to be able and willing to interact with each other
and the NIAMS in an Internet environment. Applicants must describe computer
and Internet resources for this type of interaction. Applicants should also
discuss the interaction with the NIAMS Program Director as to how they will
fulfill the responsibilities of the Network to work together cooperatively.
o Interaction with Industry (Patent Rights): Applicants are strongly
encouraged to forge a partnership with industry/biotechnology firms in
developing biomarkers/reagents. It is anticipated that the creation of the
Network will serve as an attractive collaborator for industry, since it will
provide clinical opportunities for the evaluation of new technologies of
private companies.
o Since basic research and development of new biomarkers/reagents is an
objective of this effort and since active involvement by the industrial
laboratories is often facilitated by the existence of adequate patent
coverage, it is essential that applicants provide plans to assure such
coverage, as appropriate. Since multiple institutions may be involved, the
situation can become complex. Each applicant, therefore, must provide a
description of the approach to be used for obtaining patent coverage, and for
licensing in particular where the inventions may involve investigators from
more than one institution. Attention is drawn to Bayh-Dole Act (Public Law
96-517). Pursuant to Bayh-Dole, inventions made by the extramural
investigators belong to their respective institutions. This may be of
concern to collaborators, especially those who are the source of proprietary
biomarkers/reagents.
2. Budget
o Applicants must budget for travel and per diem expenses for NSC meetings.
In the first year, applicants should plan for two investigators, the
principal investigator and an additional senior investigator, to attend a
planning meeting and one NSC meeting. In the second and subsequent years,
applicants should plan for the PI and another investigator to attend two NSC
meetings per year.
o Applicants must set aside 20% of their annual budget after the first year
for Network collaborative studies. The use of these set aside funds will be
restricted and must be reviewed and approved by the NSC and then recommended
to, and approved by the NIAMS for release from the individual U01 awards.
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:
John R. Lymangrover, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Blvd, Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-4952
FAX: (301) 402-2406
or (301) 480-4543
Email: lymangrj@ep.niams.nih.gov
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.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIAMS. Incomplete and/or non-responsive applications
will be returned to the applicant without further consideration.
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
Upon receipt, each application will be reviewed for completeness by the
Center for Scientific review (CSR) and for responsiveness by the NIAMS.
Incomplete and/or non-responsive applications will be returned to the
applicant without further consideration. 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 scientific merit
review, a process may be used by the initial review group in which
applications receive a written critique and 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, assigned a
priority score, and receive a second level review by the National Arthritis
and Musculoskeletal and Skin Diseases Advisory Council.
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to discuss the following
aspects of 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
The scientific review group will address and consider each of these criteria
in assigning your application's overall score, weighting them as appropriate
for each application. Your application does not need to be strong in all
categories to be judged likely to have major scientific impact and thus
deserve a high priority score. For example, you may propose to carry out
important work that by its nature is not innovative but is essential to move
a field forward.
(1) SIGNIFICANCE: Does your study address an important problem? If the aims
of your application are achieved, how do they advance scientific knowledge?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Do you acknowledge potential problem areas and consider alternative
tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project challenge
existing paradigms or develop new methodologies or technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out
this work? Is the work proposed appropriate to your experience level as the
principal investigator and to that of other researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o INTERACTIONS: Are there adequate plans for effective interaction and
coordination with the Network, the NSC, and the NIAMS? Do the investigators
state their willingness to collaborate and share information? Do the
investigators state their willingness to abide by the priorities and policies
agreed upon by the NSC for collaborative studies? Have the applicants
proposed sound strategies for communication among themselves and with the
NIAMS?
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 reasonableness 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: March 17, 2003
Application Receipt Date: April 17, 2003
Peer Review Date: TBA
Council Review: September 2003
Earliest Anticipated Start Date: September 30, 2003
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
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 (https://grants.nih.gov/grants/guide/notice-
files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are
available at
https://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
https://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
https://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 https://grants.nih.gov/grants/stem_cells.htm and at
https://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
https://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, Osteoarthritis Biomarkers Network, is related to several objectives,
particularly those listed in the chapter "Arthritis, Osteoporosis, and
Chronic Back Conditions." 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
https://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.