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SPECIALIZED CENTERS OF CLINICALLY ORIENTED RESEARCH (SCCOR) IN VASCULAR INJURY,
REPAIR, AND REMODELING
RELEASE DATE: August 17, 2004
RFA Number: RFA-HL-05-001
EXPIRATION DATE: May 12, 2005
Department of Health and Human Services (DHHS)
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)
COMPONENT OF PARTICIPATING ORGANIZATION:
National Heart, Lung, and Blood Institute (NHLBI)
(http://www.nhlbi.nih.gov)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S) 93.837
LETTER OF INTENT RECEIPT DATE: April 11, 2005
APPLICATION RECEIPT DATE: May 11, 2005
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 Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The primary objective of the Specialized Centers of Clinically Oriented Research
(SCCOR) programs is to foster multidisciplinary research on clinically relevant
questions enabling basic science findings to be more rapidly applied to clinical
problems. The clinical and basic research supported through this RFA must focus on
vascular injury, repair, and remodeling. It is expected that the results from the
SCCOR grants will have a positive impact on the prevention, diagnosis, and
treatment of vascular diseases. This program has three major goals:
(1) to stimulate interdependent clinical and multidisciplinary basic research
projects that investigate molecular and cellular mechanisms of vascular injury,
repair, and remodeling, (2) to promote patient-oriented research that will improve
our ability to prevent, detect, characterize, manage, and treat vascular diseases,
and (3) to develop the skills and research capabilities of new clinical
investigators.
RESEARCH OBJECTIVES
The National Heart, Lung, and Blood Institute (NHLBI) revised the Specialized
Centers of Research (SCOR) program, based primarily on recommendations from the
National Heart, Lung, and Blood Advisory Council. The new program is called the
Specialized Centers of Clinically Oriented Research (SCCOR) program
http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm. The original SCOR
program required both basic and clinical research, but the preponderance of funded
projects was in the basic science arena. The new title and the revisions to the
program reflect the Institute's desire to capitalize on basic research advances by
encouraging their translation to the clinical arena. The guiding principle of the
new SCCOR program is the central focus on clinically relevant research, and the key
change to achieve this goal is the requirement that at least one-half of funded
projects be clinical. The specific components of the new SCCOR program are
detailed in this RFA. Special instructions for preparing a SCCOR application are
available from the program contact listed under WHERE TO SEND INQUIRIES or at
http://www.nhlbi.nih.gov/funding/policies/sccor_supp.htm.
Vascular Injury, Repair, and Remodeling
Vascular diseases are responsible for the major causes of morbidity and mortality
in the United States. They comprise disorders of arteries, veins, microvessels,
and lymphatics. These disorders include coronary, peripheral, visceral and
cerebral vascular occlusive diseases, restenosis, aortic coarctation, aneurysms and
dissection, vasospasm, vasculitis, arterial and venous thrombosis, venous
insufficiency, and lymphedema. Although vascular disorders are heterogeneous in
their causes and orientation, they share the common denominator of pathological
vascular repair and remodeling in response to underlying injury due to
dyslipidemia, hypertension, mechanical forces, diabetes, obesity,
hypercoagulability, oxidative stress, inflammatory or immunological processes,
advanced age, gender or genetics.
Vascular injury, repair, and remodeling are regulated by a myriad of local events
and stimuli. Repair and remodeling mechanisms are influenced by local availability
and activity of mitogens, differentiation factors, cytokines/chemokines, adhesion
molecules, proteases, matrix components, and vasoactive agents. All of these
factors may represent potential targets for improved diagnosis, patient
stratification, and therapeutic intervention.
The vascular repair can be successful and complete, in which case the systemic
reaction may resolve; but in many situations, the repair is incomplete and
unsuccessful and leads to remodeling of the vascular wall. For some patients the
remodeling of the vascular wall may be functional, while for others it may lead to
enlarging or narrowing of the lumen or thromboembolic complications. For example,
pathological remodeling can lead to aneurysm formation, stenosis, restenosis, or
dissection.
While circulating cytokines and growth factors can lead to accelerated inflammation
of the injured vascular wall, such molecules can also promote the recruitment of
bone marrow-derived progenitor vascular cells, endothelial progenitor cells in
particular, with intrinsic capacity to repair the vascular wall. Such cells are
produced by the marrow in response to signals derived from the injured vascular
wall, released in the systemic circulation and anchored at the level of vascular
lesions. They appear to contribute to the repair of the arterial wall, as their
absence results in more vascular lesions, and their administration to animals
deprived of vascular progenitor cells can retard the onset of vascular disorders.
Understanding the production of cells involved in the repair of the vessel wall
from a distance (bone marrow) is nascent, potentially important and a great
opportunity for advancing the field of vascular disorders.
Both the susceptibility of blood vessels to injury and their amenability to repair
and/or remodel are profoundly affected by vascular cell heterogeneity. Vascular
cell morphology can differ dramatically from one vascular bed to another, according
to specific functional requirements. Endothelial cells destined to reside within
the arterial or venous vascular beds, moreover, follow diverging differentiation
pathways, and those assigned to these specific locations express characteristic
molecular markers. Vessel size, anatomic location, and geometry, in addition,
determine the quality and magnitude of hemodynamic forces to which vascular cells
are exposed. Finally, vascular cells are subject to regional molecular cues and
signals derived from specialized surrounding tissues. As a result, vascular cell
gene expression profiles and functional responses vary significantly from one
setting to another and profoundly influence the cell’s remodeling and repair
capabilities.
While normal tissues maintain equilibrium between vascular growth and cellular
demands, the loss of such balance may lead to either excessive or insufficient
angiogenesis and neovascularization. Although numerous pathways and molecular
players that relate to vascular proliferation have been identified, their
integrated function and co-regulation are poorly understood. Further studies in
this area are expected to reveal a host of opportunities for defining the molecular
basis and treatment of ischemic myocardium and limbs and to prevent the progression
of atherosclerosis.
A complication of vascular inflammation is thrombosis and thromboembolic
complications. The occlusion of an arterial vessel by a thrombus can lead to the
damage of end-organs, such as myocardial infarction and stroke. While hemostasis
at the level of sectioned vessels can be lifesaving, the coagulation system was not
designed to differentiate vascular wall disruption resulting from a traumatic
injury versus the spontaneous fracture of an atherosclerotic plaque at the level of
a coronary vessel. Hence, excess and misguided coagulation can be detrimental,
whereas some degree of thrombosis may enhance the repair process. The dual role of
platelets and coagulation in the process of vascular injury and repair represents
another opportunity for investigations.
This dual role is perhaps particularly true at the level of branching vessels,
where atherosclerotic lesions occur earlier, and hemodynamic conditions are
particularly stringent. Such hemodynamic strain might prevent the successful
repair of vascular injuries. For example, it might be challenging for progenitor
cells to anchor on the surface of damaged arteries. The presence of adhering
platelets might facilitate the attachment of progenitor cells, and further
participation into the repair process.
Hypertension exerts a profound effect upon blood vessel structure and function.
Vascular alterations that occur in this setting may include reconfiguration of
vessel wall matrix components, dysregulation of cellular proliferation profiles,
arterial stiffening, and microvessel rarefaction. A detailed appreciation of these
mechanisms, particularly as they relate to individual genomic and proteomic
profiles, will likely lead to new opportunities for diagnostic and therapeutic
interventions.
Measures of the functional and structural properties of blood vessels can be used
to assess preclinical vascular disturbances such as endothelial dysfunction and
increased vascular stiffness. Abnormalities of endothelial function have been
identified in patients with dyslipidemia, hypertension, diabetes, metabolic
disorders, obesity and atherosclerosis, and have been shown to predict future
vascular events. Vascular compliance decreases with aging and is altered in
patients with hypertension. Moreover, increased vascular stiffness contributes to
systolic hypertension and adversely affects cardiac function. The relationship
between vascular stiffness and arterial diseases is not well defined.
Aortic aneurysms and dissections are examples of vascular diseases characterized by
serious distortions in arterial architecture due to remodeling. Recent research on
the pathophysiology of abdominal aortic aneurysms (AAAs) has highlighted the
importance of chronic inflammation and immune responses, enzymatic destruction of
aortic elastin and collagen, and depletion of vascular smooth muscle cells from the
aortic media. Numerous therapeutic opportunities may exist to influence the
biology and natural history of AAAs, as well as the development of non-surgical
treatments for small AAAs.
A variety of established and emerging imaging technologies will be important in
providing qualitative and quantitative measures of vascular wall dysfunction that
will be especially applicable to clinical studies. Applications of nanotechnology
and molecular imaging are encouraged as a means to facilitate longitudinal studies
in patients, both in detecting and stratifying vascular disease, assessing the
functional characteristics of vascular lesions over time, and in assessing the
results of various interventions.
Translation of basic science findings into improvements in the diagnosis and
treatment of vascular disease is important. It is apparent that there is
significant human variability in the rate of vascular disease or its progression,
for example, in the growth of aortic aneurysms or in atherosclerotic plaque burden.
Furthermore, clinical heterogeneity exists in the response to treatment, whether
pharmacological, endovascular or surgical. Improved methods for detecting those at
increased risk for vascular disease progression will permit initiation of
preventive and therapeutic measures at an earlier, sub-clinical stage. Better
stratification of individuals into those likely to respond versus those likely to
fail therapy will permit more effective therapy and tailored approach in the
management of vascular disease in the individual patient.
The need for clinical trials to investigate the efficacy, safety and durability of
new treatment methods for vascular disease is critical. Examples include cell- and
gene-based therapies, endovascular and novel pharmacological interventions, as well
as development of durable bioprosthetic devices to treat vascular disorders such as
coronary, peripheral, visceral, and cerebral vascular occlusive diseases.
RESEARCH TOPICS
The objective of the SCCOR in vascular injury, repair, and remodeling is to
stimulate clinically relevant, multidisciplinary collaborations leading to clinical
and basic science research efforts on important public health problems for
individuals with vascular diseases. The translation of knowledge into clinical
practice should be a goal of applications submitted in response to this initiative.
Recent advances in understanding the genetic, molecular, and physiologic
underpinnings of vascular function and pathophysiology of disease offer new
directions to study normal and abnormal vascular function, to develop early
diagnostic tools and markers, and to stratify patients based on genetic and
molecular markers.
The research encompassed by this program will (1) emphasize the development and
translation of basic discoveries to understand the mechanisms of vascular disease;
(2) improve the detection, characterization, staging, and management of vascular
disease by using cutting-edge methodologies, such as nanotechnology, molecular
imaging, genomics, proteomics, quantitative systems analysis; and (3) develop new
methods to treat vascular diseases such as cell- and gene-based therapies for
regenerative medicine.
The SCCOR mechanism provides both the incentive and the structure to maintain
critical collaborative cores or other resources necessary for translational
research. For example, the SCCOR mechanism affords the ability to establish and
maintain a large clinical/DNA sample database of patients with various types of
vascular disease.
The following examples of research topics are intended to provide a perspective on
the scope of research that would meet the objectives of this program. It is not
required that all or any of these topics be included. Applicants are encouraged to
consider other topics that are relevant to the goals of the Vascular Injury,
Repair, and Remodeling SCCOR program. A unified program of clinical and basic
research is needed to address such topics as:
o Define cellular and molecular factors and signals involved in vascular injury,
repair, and remodeling including inflammatory, immune and humoral responses, high-
blood-pressure and lipid effects, and biochemical and biomechanical interactions
o Study mechanisms involved in the vascular injury, repair, and remodeling due to
diabetes, the metabolic syndrome, and obesity
o Identify the origin of cells and mechanisms that contribute to the repair and
remodeling of vascular lesions, and examine the use of stem or progenitor cells to
repair, regenerate, or replace defective or damaged vascular tissue
o Determine how vascular cell heterogeneity contributes to the susceptibility of
blood vessels to injury, repair, and remodeling
o Investigate the role of blood components (e.g., platelets, leukocytes, red blood
cells) in the process of vascular injury, repair, and remodeling
o Determine biological mechanisms responsible for variation in human susceptibility
and progression of vascular diseases, and response to therapy as it relates to
vascular, injury, repair and remodeling
o Apply emerging noninvasive or minimally invasive technologies (e.g.,
nanotechnology and molecular imaging) to study vascular injury, repair, and
remodeling, and use that knowledge and technology to detect and stratify vascular
diseases, to assess the functional characteristics of vascular lesions over time
and the results of therapeutic interventions
o Apply state-of-the-art global technologies such as proteomics and genomics to
understand the mechanisms of vascular injury, repair, and remodeling, and how gene
and protein variations influence therapeutic success.
o Develop novel and improved markers of subclinical vascular disease, including
genetic and proteomic determinants, that can enhance our ability to detect and
diagnose vascular diseases early in the disease process.
o Develop and test: (1) novel drugs to prevent, treat or manage vascular diseases;
(2) novel therapeutic approaches to treat vascular diseases, including cell- and
gene-based therapies; and (3) novel surgical interventions.
THE FOLLOWING TOPICS ARE OUTSIDE THE SCOPE OF THIS SCCOR AND ITS INDIVIDUAL
PROJECTS:
o Studies that focus on basic or clinical science only
o Phase III clinical trials
o Epidemiological studies
o Studies that are focused purely on stem cell characterization without
consideration of vascular repair and remodeling
o Studies in coronary artery disease that focus on the injury of the myocardium
CLINICAL RESEARCH SKILLS DEVELOPMENT CORE
The newly developed Specialized Centers of Clinically Oriented Research (SCCOR)
program mechanism requires clinical and basic scientists with a broad range of
skills to work together on a unified theme. It, therefore, presents a rich
environment for young clinical investigators to be exposed to and develop
additional research skills. The individual centers can be expected to include among
their research staff clinical personnel who are newly trained and relatively
inexperienced in research. To assist the SCCOR grants in enhancing the
developmental environment for their new clinical investigators, the NHLBI will
permit applicants for a SCCOR to request up to an additional $100,000 in direct
costs per year for a Clinical Research Skills Development Core. The objective of
the Core is to support activities to assist new clinical investigators in
progressing to more senior status by enhancing their research skills. This support
is in addition to the usual cap on the SCCOR mechanism that is updated annually. A
Clinical Research Skills Development Core is not required, however, and its absence
will not disadvantage an applicant. The quality of the Clinical Research Skills
Development Core, if proposed, will be evaluated based on the specific components
listed below. The priority score on the Core will have no effect on the overall
score of an application.
Developmental opportunities that provide experience with new technologies and
skills are encouraged for inclusion in the Core. Innovative strategies should be
proposed for cross-disciplinary career development to achieve the goal of exposing
new clinical investigators to additional research techniques and opportunities.
Examples include a program of seminars focusing on scientific topics that include
an integration of basic and clinical studies or an "exchange" program, wherein
clinical investigators spend time in basic science laboratories. In addition to
developing the research skills of new clinical investigators, the Cores must ensure
that the participating new clinical investigators receive the mentoring they need
to foster their research careers. The Clinical Research Skills Development Core is
intended for staff investigators with limited clinical research experience,
including fellows and junior faculty members. Investigators who have had a previous
K series award are not eligible to participate as new investigators under this
program. Individuals with an active K grant can participate until the end of the
award period for the K grant, but may not receive salary on the Skills Development
Core. The Core should also address other skills necessary for a successful research
career, such as grant writing, ethical conduct of research, and clinical trial
design. Additional information about the Clinical Research Skills Development Core
can be found at http://www.nhlbi.nih.gov/funding/policies/sccor_skill.htm
If a Clinical Research Skills Development Core is proposed, it must be directed by
an investigator with strong educational and mentoring credentials who will devote a
minimum of 5 percent effort as its Leader. To facilitate mentoring and
multidisciplinary developmental activities, active involvement by the principal
investigator and other senior investigators within the SCCOR is strongly
encouraged. An application for a Clinical Research Skills Development Core will be
evaluated in terms of its potential effectiveness in developing the skills and
research capabilities of new clinical investigators as reflected in the following
required elements of the application:
o A summary of the types of skills that would be developed and a description of
proposed project-specific activities.
o A detailed discussion of how mentoring and the professional development of the
new clinical investigators will be achieved, including their progression to more
independent status.
o The credentials and track records of the Clinical Research Skills Development
Core Leader, the Principal Investigator, and other participating senior staff in
developing new investigators.
o A plan for coordinating the activities of participating senior investigators.
o A plan for monitoring the progress of the new clinical investigators.
o A description of existing opportunities within the applicant's institution for
supporting investigator development and steps taken to avoid overlap with or
duplication of these efforts.
o A detailed development plan for each proposed new investigator (or a
representative plan and proposals for tailoring it to needs of multiple new
investigators) including required course work and scientific enrichment activities
such as special lectures, visiting scientist symposia, seminars, and workshops.
Costs allowable for inclusion within the $100,000 direct costs per year limit for
the Clinical Research Skills Development Core include salary support for the Core
Leader and other participating senior investigators and staff, travel costs for new
investigators, supplies and equipment to be used in support of developmental
activities, and costs for courses, seminars, workshops, and other activities
directly related to the development plan. All costs requested in this Core must be
justified with respect to developmental activities and may not be used to
supplement the costs of research proposed in the rest of the SCCOR.
Since the Core is intended to serve new clinical investigators who occupy positions
and receive salary support from the SCCOR grant, salary support for the new
investigators is neither needed nor allowable as a Core cost. All new clinical
investigators supported by the SCCOR grant should be eligible to participate in
Core-sponsored activities so long as they have not attained independent status.
However, attaining independent status should be an objective of the Core
activities. So, participating new investigators should be encouraged to apply for
either a Career Development Award, a patient-oriented regular research grant, or
any other source of independent research or career development support. Although
the participating new investigators will be expected to devote essentially full-
time effort to research during this period, they may devote an appropriate
percentage of their time to maintaining clinical skills.
An application for a Clinical Research Skills Development Core will be evaluated in
terms of its potential effectiveness in developing the skills and research
capabilities of new clinical investigators as reflected in the required application
components identified above.
MECHANISM OF SUPPORT
This RFA will use the NIH P50 award mechanism. All applications received in
response to the Vascular Injury, Repair, and Remodeling SCCOR program will be
considered as new applications and must meet the requirements for the new SCCOR
program (please see http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm). As
an applicant, you will be solely responsible for planning, directing, and executing
the proposed project. The anticipated award date is April 1, 2006.
Applicants should request a 5-year project period when responding to this
announcement. Each NHLBI SCCOR program is limited to 10 years of support.
Exceptions to this policy will be made only if a thorough evaluation of needs and
opportunities, conducted by a committee composed of non-federal experts, determines
that there are extraordinarily important reasons to continue a specific SCCOR
program. Under this policy, a given SCCOR grant is awarded for a 5-year project
period following an open competition. Only one 5-year competing renewal is
permitted, for a total of 10 years of support, unless the SCCOR program is
recommended for extension.
The NHLBI comprehensive evaluation of the Vascular Injury, Repair, and Remodeling
SCCOR program will be conducted during the second project period according to the
following timetable:
Program Announced: FY 2004
Project Period (First Competition): FY 2006 through FY 2010
Program Re-announced: FY 2008
Project Period (Second Competition): FY 2011 through FY 2015
Letter to Principal Investigators
Regarding SCCOR Evaluation Plans: FY 2012 (mid-way through year 02
of 2nd project period)
SCCOR Evaluation Meeting: FY 2012 (late in year 02 of 2nd
project period)
The NHLBI does not limit the number of applications for a given SCCOR program from
one institution. However, each SCCOR application from the institution must have a
different Principal Investigator and must be self-contained and independent of
other SCCOR applications from the same institution. Institutions envisioning more
than one application are encouraged to discuss their plans with the program contact
listed under WHERE TO SEND INQUIRIES.
This RFA uses just-in-time concepts and only non-modular budgeting formats. Follow
the instructions for the non-modular budget research grant applications at
http://grants.nih.gov/grants/funding/phs398/phs398.html. 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.
FUNDS AVAILABLE
The NHLBI intends to commit approximately $20.0 million in FY 2006 to fund 5 to 7
new grants in response to this RFA. An applicant may request a project period of 5
years and a budget for direct costs of up to $2.5 million per year not including
Facilities and Administrative (F&A) costs for collaborating institutions in the
first year (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html).
In addition, applicants for a SCCOR may request up to $100,000 in direct costs per
year above the usual cap ($2.5 million direct costs) for a Clinical Research Skills
Development Core. All applications will be considered as new applications. An
increase of no more than 3 percent may be requested in each additional year.
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 NHLBI 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.
Consortium Arrangements
If a grant application includes research activities that involve institutions other
than the grantee institution, the application will be considered a consortium
effort. Such applications are permitted, but it is imperative that the application
be prepared so that programmatic, fiscal, and administrative considerations are
explained fully. At least 50 percent of projects (including at least one clinical
project) and 50 percent of the cores must be located at the applicant institution.
The NIH published policy governing consortia is available in the business offices
of institutions that are eligible to receive federal grants-in-aid and should be
consulted before developing the application. For clarification of the policy,
contact Mr. Dave Reiter, Grants Operation Branch, NHLBI (301) 435-0177.
Applicants for SCCOR grants should exercise great care in preserving the
interactions of the participants and the integration of the consortium project(s)
with those of parent institution, because synergism and cohesiveness can be
diminished when projects are located outside the group at the parent institution.
Indirect costs paid as part of a consortium agreement are excluded from the limit
on the amount of direct costs that can be requested.
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 institutions/organizations
o Foreign institutions are not eligible to apply.
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 under-represented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply for
NIH programs.
SPECIAL REQUIREMENTS
1. The overall concept of a SCCOR program focuses on clinical and basic scientific
issues related to diseases and disorders relevant to the mission of the NHLBI. To
be considered responsive to this announcement, all applications must include both
clinical and basic research. In addition, interactions between clinical and basic
scientists are expected to strengthen the research, enhance the translation of
fundamental research findings to the clinical setting, and identify new research
directions. Translation of findings from basic to clinical studies is an important
focus of the SCCOR program.
2. The number of clinical research projects in each NHLBI SCCOR must be equal to or
greater than the number of basic science projects, at the time of submission,
award, and throughout the 5-year project period. For example, if an application has
a total of three projects, two of the projects must be clinical research projects.
Neither a clinical component in a basic science project nor a clinical core
fulfills the requirement for a clinical project. However, a single project can
integrate basic and clinical research. If the majority of the research within a
project is clinical, it will be considered a clinical project; if the majority of
the research within a project is basic, it will be considered a basic project.
Because a SCCOR grant is a 5-year program, an applicant should submit a 5-year plan
for all the projects.
3. In order for a project to be considered clinical research for the purposes of
responsiveness to this RFA, the research must be patient-oriented research.
Patient-oriented research is research in which an investigator (or colleague)
directly interacts with patients having a disease or condition of interest. Normal
healthy subjects may be included, but only in combination with studies involving
patients. In studies involving the use of human specimens, the investigators must
have direct interaction with the patient from whom the specimen is obtained and
relate the research results to the patient status or outcome for this to be
considered a clinical project. It is intended that the requirement for investigator
interaction with the study participants will eliminate research involving archived
tissue.
Applicants are encouraged to pursue patient-oriented research on topics related to
health disparities and the translation of this research to clinical practice for
affected minority populations. At a minimum, clinical research projects must
include women and minorities in the study population in representative numbers,
unless such inclusion can be demonstrated to be inappropriate. Clinical studies
involving interventions or treatments must give consideration to including
sufficient numbers of women and minorities to conduct valid analyses of subgroup
effects. Epidemiologic studies or Phase III clinical trials will be considered
unresponsive to this RFA.
4. Each awarded SCCOR must consist of three or more projects, all of which are
directly related to the overall clinical focus of the SCCOR. At least 50 percent of
the projects and 50 percent of the cores must be located at the applicant
institution, and at least one of the clinical projects must be at the applicant
institution. Component projects not located at the applicant institution may be at
a foreign institution, but must conform to NIH policy regarding the protection of
human subjects. Each component project, whether clinical or basic, requires a well-
described, clinically relevant hypothesis, preliminary data, and a time-table for
conducting the proposed investigations.
5. The relationship of each core to each component project should be described. A
core must provide services to two or more projects.
6. Each SCCOR must have a well-delineated organizational structure and
administrative mechanism that foster interactions between investigators, accelerate
the pace of research, enable translation of basic research findings to clinical
applications, and ensure a productive research effort.
7. Applicants should provide a detailed data and safety monitoring plan for the
clinical research proposed; the monitoring plan will be considered as part of peer
review of the application. This plan should address informed consent, recruitment,
reporting of adverse events, patient safety, oversight of clinical issues in the
protocols, storage and analysis of confidential data, and dissemination of any
research results. After a decision has been made regarding SCCOR awards, the
Institute will determine whether to convene a Data and Safety Monitoring Board
(DSMB) to oversee one or more clinical projects in a SCCOR program. It is NHLBI
policy to appoint DSMBs for Institute-funded intervention studies when an
independent group is needed to evaluate the data on an ongoing basis to ensure
participant safety and/or study integrity. The decision to establish each board is
made by the relevant Division Director with the concurrence of the NHLBI Director.
In those cases where such interventional studies are proposed, applicants are
encouraged to include funds in the budget for 5 DSMB members for 2 meetings a year
to be held in Bethesda, Maryland.
8. The principal investigator (SCCOR Director) should be an established research
scientist with the ability to ensure quality control and the experience to
administer both clinical and basic research effectively and integrate all
components of the program. A minimum time commitment of 25 percent is required for
this individual. The Principal Investigator must be the Project Leader of one of
the component research projects. If this project is not recommended by peer review,
the overall SCCOR application will not be considered further. If this project is
judged by peer review to be of low scientific merit, this will markedly reduce the
overall scientific merit ranking assigned to the entire application.
9. Project Leaders should have significant research experience and must agree to
commit at least 20 percent effort to each project for which they are responsible.
Leaders of clinical projects should have experience in clinical research as defined
in Item 2, above. Investigators with minimal research experience, but promising
credentials, may participate; however, it is expected that most of the project
leaders will be investigators with significant research experience.
10. Applicants are encouraged to establish links and utilize existing resources,
including the NHLBI Program in Genomic Applications
(http://www.nhlbi.nih.gov/resources/pga/); NHLBI Proteomics Centers
(http://www.nhlbi.nih.gov/resources/medres/proteomics/index.htm); Programs of
Excellence in Gene Therapy for Heart, Lung, and Blood Diseases with National
Service Cores for Pre-Clinical Grade Vector Production, Cell Morphology,
Hematopoietic Cell Processing, and Non-Human Primate Hematopoietic Transplantation
(http://www.med.cornell.edu/pegt/); NHLBI clinical research networks; and General
Clinical Research Centers, as feasible and appropriate. If applicants propose to
utilize such resources, a letter of agreement from the Program Director or
Principal Investigator of the resource should be included with the application.
11. The applicant should plan and budget for the SCCOR Director and the Project
Leaders of the SCCOR to attend one annual grantee meeting per year in Bethesda,
Maryland.
12. NIH recently reaffirmed support for the concept of timely sharing and
distribution of model organisms for biomedical research. Applicants are expected
to include in the application/proposal a description of a specific plan for sharing
and distributing unique model organism research resources generated using NIH
funding so that other researchers can benefit from these resources. More
information can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html.
Applicants are encouraged to include funds in the budget for this purpose.
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:
H. Eser Tolunay, Ph.D.
Director, Vascular Biology Research Program
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge Centre ll
6701 Rockledge Drive, Room 10190
Bethesda, MD 20892-7956
Telephone: (301) 435-0545
FAX: (301) 480-2858
Email: TolunayE@nhlbi.nih.gov
o Direct your questions about peer review issues to:
Valerie Prenger, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge Centre ll
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Telephone: (301) 435-0270
Fax: (301) 480-3541
Email: prengerv@nhlbi.nih.gov
o Direct your questions about financial or grants management matters to:
David Reiter
Grants Operations Branch
National Heart, Lung, and Blood Institute
Rockledge Centre ll
6701 Rockledge Drive, Room 7172
Bethesda, MD 20892-7926
Telephone: (301) 435-0177
FAX: 301-480-3310
Email: reiterd@nhlbi.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 program
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 NHLBI 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 by mail or email to Dr. Valerie
Prenger at the address listed under “WHERE TO SEND INQUIRIES.”
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 D&B number can be
obtained by calling (866) 705-5711 or through the web site at
http://www.dunandbradstreet.com/. The D&B number should be entered on line 11 of
the face page of the PHS 398 form. The PHS 398 document 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: Because of the size and complexity of a SCCOR,
prospective applicants are urged to consult with the staff of the Division of Heart
and Vascular Diseases early in the preparation of the application (see INQUIRIES
Section). Special instructions are needed for preparing a SCCOR application and
are available from the program contact listed under WHERE TO SEND INQUIRIES or at
http://www.nhlbi.nih.gov/funding/policies/sccor_supp.htm. To provide opportunity
for such interactions, the time frame for implementation of this program includes
an ample interval between the release of this RFA and the receipt date for
applications.
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:
http://grants.nih.gov/grants/funding/phs398/labels.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 and all copies
of the appendix material must be sent to:
Valerie Prenger, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge Centre 11, Room 7214
Bethesda, MD 20817 (express mail)
Telephone: (301) 435-0270
Fax: (301) 480-3541
Email: prengerv@nhlbi.nih.gov
APPLICATION PROCESSING: Applications must be received on or before 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.
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.
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. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to an RFA, it is to be prepared as a
NEW application. That is, the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text must not be
marked to indicate the changes from the previous unfunded version of the
application.
Principal Investigators should not send supplementary material without first
contacting the Scientific Review Administrator (SRA). The SRA will be identified in
the letter sent to you indicating that your application has been received. If you
have not received such a letter within three weeks after submitting the
application, contact Dr. Valerie Prenger at the address listed under “WHERE TO SEND
INQUIRIES.”
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NHLBI. Incomplete or unresponsive applications will not be
reviewed.
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
NHLBI in accordance with the review criteria stated below. As part of the initial
merit review, all applications will:
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 written critique.
o Receive a second level review by the NHLBI 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. Factors to be
considered in the evaluation of each application will be similar to those used in
the review of traditional clinical and basic research grant applications and, in
addition, will include overall proposed interactions between clinical and basic
research projects. The review panel will include a majority of clinical
researchers who will receive special instructions to place emphasis on strong
clinical components. Major factors to be considered in the evaluation of
applications include:
o Scientific merit of the proposed clinical and basic research projects including
significance, importance, clinical relevance and appropriateness of the theme;
innovation, originality, and feasibility of the approach; and adequacy of the
experimental design.
o Leadership, scientific expertise, experience, and commitment of the principal
investigator; competence of the investigators to accomplish the proposed research
goals and their time commitment to the program; clinical research experience among
the investigators; and the feasibility and strength of consortium arrangements.
o Collaborative interaction between clinical and basic research components, and
plans for transfer of potential findings from basic to clinical studies.
o Adequacy of the environment for performance of the proposed research including
clinical populations and/or specimens; laboratory facilities; quality of the
support cores; proposed instrumentation; quality controls; administrative
structure; institutional commitment; and, when needed, data management systems.
o Adequacy of the data and safety monitoring plan for the clinical research
proposed.
Each project will receive a priority score. Each core (except the Clinical
Research Skills Development Core) will be Recommended or Not Recommended based on
whether the core is essential for the proposed research and has the capability to
fulfill the proposed function. Reviewers will evaluate the number of projects
serviced by the core; strengths and weaknesses of the proposed approaches,
resources, and interactions; whether the investigators are qualified for their
role(s) in the core; and whether the proposed budget for the core is appropriate.
Each application will receive an overall priority score based on the review
criteria listed above.
The Clinical Research Skills Development Core will receive a priority score based
on the review criteria below, but the priority score will not enter into the
overall priority score.
Review Criteria for Clinical Research Skills Development Core:
The Clinical Research Skills Development Core will be evaluated for its
effectiveness in developing the skills and clinical research capabilities of new
investigators. This will include an evaluation of:
o Credentials and track record of the Principal Investigator, Clinical Research
Skills Development Core Project Leader, and other participating senior
investigators.
o Methods by which new investigators are to be recruited and selected including
plans to recruit women and minority individuals.
o Plans for developing the skills of new investigators; the types of skill and
technologic development proposed.
o Means by which the new investigators' professional development will be achieved.
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.)
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. 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.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: April 11, 2005
Application Receipt Date: May 11, 2005
Peer Review Date: Sept/Oct 2005
Council Review: February 2006
Earliest Anticipated Start Date: April 1, 2006
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
ANIMAL WELFARE PROTECTION: Recipients of PHS support for activities involving
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of
Laboratory Animals
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated
by the Health Research Extension Act of 1985
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal
Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as
applicable.
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: Investigators submitting an NIH application seeking
$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: (1) 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 (2) 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.
All investigators proposing research involving human subjects should read the "NIH
Policy and Guidelines" on the inclusion of children as participants in research
involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy
requires education on the protection of human subject participants for all
investigators submitting NIH proposals for research involving human subjects. You
will find this policy announcement in the NIH Guide for Grants and Contracts
Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on
hESCs can be found at http://stemcells.nih.gov/index.asp and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research
using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry
will be eligible for federal funding (see http://escr.nih.gov). It is the
responsibility of the applicant to provide, in the project description and
elsewhere in the application as appropriate, the official NIH identifier(s) for the
hESC line(s) to be used in the proposed research. Applications that do not provide
this information will be returned without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office
of Management and Budget (OMB) Circular A-110 has been revised to provide public
access to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported in
whole or in part with federal funds and (2) cited publicly and officially by a
federal agency in support of an action that has the force and effect of law (i.e.,
a regulation) may be accessed through FOIA. It is important for applicants to
understand the basic scope of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this 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.
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).
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 RFA is related to one or
more of the priority areas. Potential applicants may obtain a copy of "Healthy
People 2010" at http://www.healthypeople.gov/.
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.
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