HEART FAILURE RESEARCH: NEW APPROACHES TO PATHOGENESIS

NIH Guide, Volume 26, Number 37, November 7, 1997

RFA:  HL-97-012

P.T.

National Heart, Lung, and Blood Institute
National Institute on Aging

Letter of Intent Receipt Date:  January 9, 1998
Application Receipt Date:  February 20, 1998

THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" PROCEDURES. THIS
RFA INCLUDES THE MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS
THAT MUST BE USED WHEN PREPARING APPLICATIONS TO THIS RFA.

PURPOSE

The National Heart, Lung, and Blood Institute (NHLBI) and the
National Institute on Aging (NIA) invite applications to
investigate the cellular and molecular underpinnings of heart
failure, as well as the multiple tissue interactions leading to the
symptoms of this condition.  This Request for Applications (RFA) is
intended to promote and support research teams with diverse,
complementary expertise in molecular, cellular, physiological, and
clinical approaches to heart failure research.  The overall goal is
to stimulate innovative multidisciplinary research to expedite
progress in understanding the pathogenesis of heart failure and to
facilitate rapid application of new findings to better recognition
and treatment of the condition.

The objectives of this program are to:  1) encourage outstanding
investigators from various disciplines to apply their expertise to
develop experimental techniques and strategies to understand and
combat heart failure; 2) foster collaborations (teams of physician
and non-physician scientists with different skills, abilities, and
talents, who may be from different institutions, and partner to
solve problems which require a multifaceted approach and diverse
technological skills not typically possessed by a single
investigator or department; see MECHANISMS OF SUPPORT for more
information on collaborations); 3) expedite evaluation and
dissemination of emerging findings, methods, and technologies; and
4) promote the standardization of key definitions and assessments
in clinical and experimental research methods.

This RFA is to support collaborations in the basic and clinical
sciences.  The collaborations should focus on a common hypothesis
with all component projects contributing scientifically to the
central theme.  The collaborative projects may include shared
resources, and need to demonstrate the interdependence and
multidisciplinary nature of the individual components.

Although not an active participant in this RFA, the National
Institute on Environmental Health Sciences (NIEHS) has an interest
in environmental diseases, including heart failure. Referral
guidelines of the NIH will prevail, especially for secondary
assignments to NIEHS.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the
health promotion and disease prevention objectives of "Healthy
People 2000", a PHS led national activity for setting priority
areas.  This RFA, Heart Failure Research:  New Approaches to
Pathogenesis, is related to the priority areas of heart disease and
stroke and diabetes and chronic disabling conditions. Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report: 
Stock No. 017-001-00474-0 or Summary Report:  Stock
017-001-00474-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic non-profit and for-profit
organizations, public and private, such as universities, colleges,
companies, hospitals, laboratories, units of state and local
governments, and eligible agencies of the Federal Government. 
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply.  Applications from foreign
institutions will not be accepted.  However, subcontracts to
foreign institutions are allowable, with sufficient justification.

MECHANISM OF SUPPORT

Support of this program will be through NHLBI and NIA.  The
mechanisms available for support of applications to this RFA
include individual research project grants (R01) and collaborative
R01 projects.  In the case of collaborative R01 projects, a group
of investigators may submit simultaneously at least two, and no
more than five, research project grants (R01s) with a common theme. 
Collaborative R01 projects may be from a single institution or
several institutions, may include shared resources, and are to
demonstrate the interdependence of the individual components.  All
R01 applications, both collaborative and individual, should provide
evidence that the research will be multidisciplinary in nature;
applicants are encouraged to specify how the research will further
the objectives of this RFA.

Specific R01 application instructions are modified to include
"MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being
examined by the NIH.  The modular grant concept establishes
specific modules in which direct costs may be requested as well as
a maximum required under this approach.  The just-in-time procedure
allows applicants to submit certain information only when there is
a possibility for an award.  It is anticipated that these changes
will reduce the administrative burden for the applicants, applicant
institutions, reviewers, and NIH staff.

For this RFA, funds must be requested in $25,000 direct cost
modules per year, per R01, up to a maximum of 10 modules ($250,000
direct costs per year) whether individual or collaborative.  A
feature of the modular grant is that no escalation is provided for
future years, and all anticipated expenses for all years of the
project must be included within the number of modules being
requested.  Only limited budgetary information will be required and
any budget adjustments made by the Initial Review Group will be in
modules of $25,000.  Instructions for completing the Biographical
Sketch have also been modified.  In addition, Other Support
information and the application Checklist page are not required as
part of the initial application.  If there is a possibility for an
award, necessary budget, Other Support and Checklist information
will be requested by NHLBI or NIA staff following the initial
review.  The APPLICATIONS PROCEDURES section of the RFA provides
specific details of modifications to standard PHS application kit
procedures. In the unusual event that the number of modules
requested must change in a future year due to the nature of the
research proposed, appropriate justifications must be provided.

Applicants for collaborative R01s may request funds to facilitate
the logistics of collaboration.  Such requests may include shared
equipment or resources, communications strategies, shared
consultations or seminars with experts complementing the project,
or other mechanisms to cement and enhance the relationships between
investigators.  As a guideline, these funds are not expected to
exceed 10% of the total collaboration request.  The justification
for such equipment or activities needs to be clearly made that they
are designed to promote collaborations and do not replicate ongoing
activities or research.  Core support for collaborative R01s is
permissible and needs to be justified on the basis of providing
cohesion to collaborations or providing essential resources. 
Administrative cores will not be accepted.  Core costs will
contribute to the total limits on costs described below. 
Applications for all cores should be submitted as a single separate
R01 application and submitted with the complete collaborative
project.

Upon initiation of the program, annual meetings will be held to
encourage exchange of information among investigators who
participate in this program.  In considering the number of modules
to request budget projections should include travel funds that will
allow principal investigators, other key research scientists, and
young investigators to participate in these meetings.

This RFA is a one-time solicitation.  Future unsolicited
applications for continuation will compete with all investigator-
initiated applications and will be peer reviewed by the Center for
Scientific Review according to customary peer review procedures. 
It is anticipated that support for this program will begin in
September, 1998. Administrative adjustments in project period
and/or dollar amount may be required at the time of the award.

Applicants are expected to furnish their own estimates of time
required to achieve the objectives of the proposed research
project.  Since a variety of approaches would represent valid
responses to this RFA, it is anticipated that there will be a range
of costs among individual grants awarded.

FUNDS AVAILABLE

NHLBI will allocate approximately $3.4 million in direct costs
(approximately $5 million in total costs) and NIA will allocate
approximately $340,000 in direct costs (approximately $0.5 million
in total costs) to support projects from this RFA during FY 98. 
Costs for core resources that are part of a collaborative R01
proposal should be submitted as a separate modular grant
application.  A maximum of ten modules of $25,000 ($250,000 direct
costs) per year per R01, up to a limit of $1,000,000 (direct costs)
per collaborative R01 project, may be requested.  Facilities and
administrative (indirect) costs will be awarded based on the
negotiated rate.  Applicants may request up to five years of
support. Although this program is provided for in the financial
plans of NHLBI and NIA, the award of grants pursuant to this RFA is
contingent upon the receipt of a sufficient number of high quality
applications and the availability of funds for this purpose. 
Policies that govern research grant programs of the National
Institutes of Health will prevail.

RESEARCH OBJECTIVES

Background

Heart failure is a particularly complex disorder which can be
either primary in nature or secondary to various diseases,
including hypertension, ischemic heart disease, valvular heart
diseases, diabetes, and atherosclerosis. Pathogenesis appears to
result, in part, from extensive abnormal interactions among
tissues, such as the heart, vasculature, kidney, lungs, and
skeletal muscle. Improvements in understanding this complex
disorder will require an interdisciplinary approach so that more
complete models of the progression of heart failure can be
constructed to serve as the basis for future therapies.

The ultimate goals of this solicitation are to determine new ways
to influence abnormal mechanisms, improve existing procedures, and
to restore normal or necessary function in heart failure.  The
optimal route to new advances demands collaborations among the best
available experts from multiple disciplines in order to appraise
the various, interactive components of heart failure.  The
investigative teams are encouraged to be creative in their
attitudes to current theories concerning heart failure and to
recruit the ideas and skills of experts in other scientific arenas
in overcoming research hurdles.  This RFA provides an opportunity
for investigators to construct and consolidate the expertise to
realize cutting-edge research that will address the fundamental
mechanisms of heart failure.

The coordination of basic science and clinical knowledge to improve
understanding and treatment of heart failure is a high priority of
this RFA.  New techniques in cellular and molecular biology -
including gene-altered animals - are providing vast amounts of
information about the most basic components of biology.  The intent
of this solicitation is to capitalize on this rapidly expanding
information base to advance progress in human heart failure
research.

One attractive area of opportunity is the cardiac cell cycle. 
Heart failure leads to alterations in gene activation and re-
expression of multiple fetal genes resulting in cardiac remodeling
and, eventually, maladaption.  Research which could facilitate the
understanding of cardiac remodeling is now progressing, but is not
traditionally exploited in heart failure research and is encouraged
by this RFA.  Studies to understand cardiac apoptosis are also
encouraged.

Although a reductionist approach to the study of heart failure
provides many important insights, the critical interactions that
occur in the intact organism or tissue also need further
elucidation.  Organ, tissue, and cellular dysfunction in heart
failure need to be examined in the context of the integrated
environment in which the abnormality occurs.  For example, the
roles of the renin-angiotensin and sympathetic nervous systems have
been studied extensively in heart failure and have provided
clinically-useful therapy.  The mechanisms underlying these
strategies, however, are incompletely understood.  In addition, the
numerous alterations in autocrine and paracrine signaling present
in hypertrophied and failing myocardium are not fully elucidated. 
An integrative approach to better understand cell and tissue
regulation, targets, and signaling systems is needed.

Other basic research themes lend credence to novel improvements for
heart failure.  Recent studies, for example, have shown that both
cardiac myocytes and skeletal myocytes can be grafted into animals
in an attempt to rescue a failing heart and the cells attach to
cardiac lesions in experimentally-induced myocardial infarction. 
Many issues remain to be resolved before such therapy can be moved
into the clinical arena, and this RFA provides the opportunity for
investigators to propose research to achieve that goal. In
constructing a complete research program to achieve cell grafting
in heart failure patients, the perspective of investigators in cell
structure, vascular biology, surgery, etc.  would likely be needed.

In summary, these examples illustrate a need for improved
interdisciplinary cooperation among basic and clinical
investigators to overcome the hurdles to resolving central issues
in understanding and treating heart failure.  It is stressed that
data obtained through studies focused on an individual organ,
tissue, or cell system often lack clear relevance to patients as
their hearts adapt to the physiological stresses which bring on
heart failure. Accelerated progress could be achieved towards
understanding these physiologic adaptations, by tapping the ideas
and skills of experts in disciplines complementary to mainstream
heart failure research, such as developmental biologists,
structural biologists, bioinformaticists, or pathologists.

Rationale

In May 1996, the NHLBI convened a Special Emphasis Panel (SEP) to
advise the Institute on research initiatives in the area of Heart
Failure Research.  The SEP followed up on the 1994 NHLBI Report of
the Task Force on Research in Heart Failure and considered the
current state of the field and emerging ideas.  The SEP prioritized
the opportunities likely to lead to advances in combating heart
failure.  The most promising mechanistic recommendations from the
list, as below in PROPOSED RESEARCH, guide this RFA.  Applicants
are encouraged to review the Report of the NHLBI SEP on Heart
Failure Research (J.N. Cohn, et al., Circ.  1997; 95: 766-770).  In
spite of current promising research opportunities, an overriding
concern of the SEP was that geographic and institutional practices
impeded interdisciplinary cooperation among the researchers
required to apply emerging concepts.  An important feature of this
RFA is to encourage development of research teams with broad
scientific expertise focused o n the fundamental aspects of human
heart failure.  Competitive applications will take advantage of
this opportunity to collaborate across disciplines and, where
necessary, among institutions.

Proposed Research

The goal of this RFA is to encourage multi-disciplinary programs
that will attract premier scientists in complementary fields to
heart failure research and to pioneer directions leading to better
understanding and treatment.  As indicated in the PURPOSE section,
applicants are encouraged to make full use of the mechanisms of
support available in this RFA by including outstanding
investigators from varied disciplines and to relate all components
of the project to a central unifying theme of relevance to human
heart failure.  Applicants are encouraged to include outstanding
investigators with technologies and cogent views not typically
expressed in mainstream heart failure research.  The collaborative
R01 project needs to outline strategies and request funds to
demonstrate how it will promote synergies within the research team,
such as sharing ideas and facilities, jointly designing and
performing experiments, and evaluating data.

The projects are to have a unifying theme to create cohesion,
provide scientific focus, and to facilitate meaningful interactions
among the members of the research team.  Both single and
collaborative projects need to be multidisciplinary in nature and
a critically-important evaluation element is whether the research
team includes an effective combination of scientific disciplines. 
Rationale for specific expertise included in the research team and
how the project will achieve the goals in the RFA should be clearly
stated.  Ideally, basic and clinical investigators will collaborate
to develop a clearly-targeted, hypothesis-driven project drawing on
multiple disciplines to address major issues and potential
treatments for heart failure.  Applicants are urged to include
studies involving subjects, patients, or tissue to support the
project's relevance to the human condition.

Applications for individual R01s are expected to pursue the goals
of multi-disciplinary, innovative science as indicated above.  All
applicants are expected to explain how their proposal will achieve
the objectives of this RFA.  Rationale for how the proposed
research will further recognition, prevention and treatment of
human heart failure should be clearly stated in the application.

This RFA supports the highest priorities of the SEP on Heart
Failure Research:

o perform studies designed to understand and regulate cardiac
apoptosis;

o examine the cardiac cell cycle and determine how to control cell
proliferation and growth;

o encourage studies encompassing physiological, molecular,
biochemical and multi-organ factors and relate these factors to in
vivo situation and human heart failure.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority
groups and their subpopulations must be included in all NIH
supported biomedical and behavioral research projects involving
human subjects, unless a clear and compelling rationale and
justification is provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the
research.  Protection of human subjects must be addressed and the
expected number of subjects from each gender and minority group
must be included.  This policy results from the NIH Revitalization
Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects
should follow the "NIH Guidelines for Inclusion of Women and
Minorities as Subjects in Clinical Research", which have been
published in the Federal Register of March 28, 1994 (FR 59
14508-14513), and in the NIH Guide for Grants and Contracts of
March 18, 1994, Volume 23, Number 11.

LETTER OF INTENT

Prospective applicants are asked to submit,by January 9, 1998, a
letter of intent that includes a descriptive title of the proposed
research, the names, addresses, and telephone numbers of the
Principal Investigator(s), the identities of other key personnel
and participating institutions, and the number and title of the RFA
in response to which the application may be submitted.  A letter of
intent is not required, is not binding, and does not enter into the
review of a subsequent application. However, the information it
contains is helpful to NHLBI staff in estimating workload, avoiding
conflicts of interest, and in planning and conducting higher
quality reviews.

The letter of intent is to be sent to Dr. Scheirer at the address
listed under APPLICATION PROCEDURES.

APPLICATION PROCEDURES

Prospective applicants are encouraged to communicate with program
and grants management staff of either Institute as early as
possible in the planning phase of application preparation.

Applications are to be submitted on grant application form PHS 398
(rev. 5/95). Application kits are available at most institutional
offices of sponsored research; from the Division of Extramural
Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
(301) 435-0714, email ASKNIH@od.nih.gov; and are on the internet at
http://grants.nih.gov/grants/funding/phs398/phs398.html.  The instructions
accompanying Form PHS 398 must be followed as far as possible.

The RFA label found in the PHS 398 application form must be affixed
to the bottom of the face page of the application.  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,"Heart Failure Research:  New
Approaches to Pathogenesis" HL-97-012," must be typed on line 2 of
the face page of the application form and the YES box must be
marked.

This RFA is restricted to R01 grants.  Applicants must indicate on
the Face Page, Title Line (line 1), whether the application is for
a "Individual R01" or a "Collaborative R01".  In the case of
collaborative R01 projects, the individual components and cores
must be submitted as one packet accompanied by a cover letter that
lists the principal investigators of each R01, their institution,
and their project title.  To facilitate proper processing and
review, include this letter with each of the individual R01s, and,
in each R01, list the collaborating projects and principal
investigators on page 2, under Performance Sites.  In addition, the
RESEARCH PLAN section for each R01 within a collaborative R01
should be the same and the applicants should define how and why the
individual participants propose to collaborate.  Applicants should
elaborate on the significance and the nature of the collaboration
in an Introduction section of the Research Plan of each component
R01.

All applications must be submitted as modular grants.  Only limited
budgetary information is required in the application.  A detailed
budget need not be provided.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT Do not complete
the categorical budget tables on Form page 5 of the PHS 398 (rev. 
5/95).  Only the requested direct costs line for each year must be
completed based on the number of $25,000 modules being requested. 
Be certain to complete the direct and total cost lines (7a,b -
8a,b) on the face page. A maximum of ten modules of $25,000
($250,000 direct costs) per year per R01, up to a limit of
$1,000,000 (direct costs) per collaborative R01, may be requested. 
Continuing direct cost budgets (excluding equipment) will be
constant throughout the life of the project.  Any necessary
escalation should be built into the number of modules requested. 
Applicants may not request a change in the number of modules after
review.  Each applicant may request up to five years of support for
this RFA.  Total Direct Costs for the Entire Proposed Project
Period should be shown in the box provided.

Follow the directions, below, for modified application procedures. 
If there is a possibility for an award, necessary Budget, Other
Support, and Checklist information will be requested by NIH staff
following the initial review.

The total direct costs must be requested in accordance with the
program guidelines and the modifications made to the standard PHS
398 application instructions described below:

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD Do not complete
Form Page 4 of the PHS 398 (rev 5/95).  It is not required nor will
it be accepted at the time of application.

o BUDGET JUSTIFICATION

Budget justifications should be provided under "Justifications" on
Form Page 5 of the PHS 398.

List the names, role on the project and proposed percent effort for
all project personnel (salaried or unsalaried) and provide a
narrative justification for each person based on his/her role on
the project.  Identify all consultants by name and organizational
affiliation and describe the services to be performed.

Provide a general narrative justification for individual categories
(equipment, supplies, etc.) required to complete the work proposed. 
More detailed justifications should be provided for high cost
items.  Any large one-time purchases, such as equipment requests in
excess of $25,000, must be accommodated within these limits.

The budget should include a request for funds to attend an annual
meeting specifically convened to update the NHLBI, the NIA, and the
other awardees in the RFA.  The principal investigators and other
key investigators including young investigators and investigators
new to the field would be expected to attend and share their data.

o CONSORTIUM/CONTRACTUAL COSTS - If collaborations or subcontracts
are involved that require transfer of funds from the grantee to
other institutions, it is necessary to establish formal subcontract
agreements with each collaborating institution.  A letter of intent
from each collaborating institution should be submitted with the
application.  Only the percentage of the consortium/contractual
TOTAL COSTS (direct and indirect) relative to the total DIRECT
COSTS of the overall project needs to be stated at this time.  The
following example should be used to indicate the percentage cost of
the consortium, "The consortium agreement represents 27% of overall
$175,000 direct costs requested in the first year.". A budget
justification for the consortium should be provided as described in
the "Budget Justification" section above (no Form Page 5 is
required for the consortium).  Please indicate whether the
consortium will be in place for the entire project period and
identify any future year change s in the percentage relative to the
parent grant.  If there is a possibility for an award, the
applicant will be requested to identify actual direct and indirect
costs for all years of the consortium.  Please note that total
subcontract costs need NOT be calculated in $25,000 modules. 
However, when subcontract funds are added to the parent grant
budget, the total direct cost amount must be included in the number
of $25,000 modules requested.  The total costs for the initial
budget period and the entire project period must be stated on the
application face page (7a,b - 8a,b).

o BIOGRAPHICAL SKETCH - Instructions for completing the
"Biographical Sketch" have also been modified.  A biographical
sketch is required for all key personnel, following the modified
instructions below.  Do not exceed the two-page limit for each
person.

Complete the educational block at the top of the form page. List
current position(s) and those previous positions directly relevant
to the application.  List selected peer-reviewed publications
directly relevant to the proposed project, with full citation.  The
applicant has the option to provide information on research
projects completed and/or research grants participated in during
the last five years that are relevant to the proposed project.

o OTHER SUPPORT - Do not complete the "Other Support" pages (Form
Page 7).  Selected other support information relevant to the
proposed research may be included in the Biographical Sketch as
indicated above.  Complete Other Support information will be
requested by NHLBI or NIA staff if there if there is a possibility
for an award.

o CHECKLIST - No "Checklist" page is required as part of the
initial application.  A completed Checklist will be requested by
staff if there is a possibility for an award.

o The applicant should provide the name and phone number of the
individual to contact concerning fiscal and administrative issues
if additional information is necessary following the initial
review.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for
conducting the proposed research.  If so, a letter of agreement
from either the GCRC program director or principal investigator
should be included with the application.

Applications not conforming to these guidelines will be
considered unresponsive to this RFA and will be returned
without further review.

Submit a signed, typewritten original of the application,
including a cover letter (if appropriate) and three signed
photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
National Institutes of Health
6701 Rockledge Drive, Room 1040-MSC 7710
Bethesda, MD 20892
Bethesda, MD 20817 (for express/courier service)

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

Dr. C. James Scheirer
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220
Bethesda, MD  20892
Telephone:  (301) 435-0266
FAX:  (301) 480-3541
Email:  JS110J@NIH.GOV

Applications must be received by February 20, 1998.  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 applications in response to this RFA that
essentially duplicate ones either already reviewed or pending
initial review unless the latter is first withdrawn by the
applicant.  This does not preclude submission of substantially
revised applications, but these must include an introduction
addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR
and responsiveness by NHLBI and NIA.  Incomplete applications will
be returned to the applicant without further consideration.  If
staff find that the application is not responsive to the RFA, it
will be returned without further consideration.  Remaining
applications may be subjected to a streamlined review process by a
Special Emphasis Panel convened by the NHLBI Division of Extramural
Affairs, to determine their scientific merit relative to other
projects received in response to the RFA.  The roster of reviewers
for the RFA will be available on the NHLBI home page approximately
four weeks prior to the scheduled review date.

Applications determined to be meritorious following the streamlined
review will be evaluated for scientific and technical merit by the
review committee, will be discussed, and will receive a priority
score.  All other applications will not be discussed or scored. 
The SEP will evaluate all R01s, whether individual or
collaborative, as individual, investigator-initiated grant
applications.  Each R01 will receive a priority score.  Cores will
not receive a score, but will be either approved or not approved
based on appropriateness to the proposed research, feasibility, and
expectations of promoting collaboration and innovation.  All
applications will be considered for their multidisciplinary nature
and a critically-important element is whether the project includes
an effective combination of scientific disciplines.  Additionally,
the committee will comment on the overall strength and likelihood
of effective collaboration of each collaborative project reflecting
such issues as interaction, breadth of expertise, synergy,
innovation, and commitment to interaction among the research team.

The personnel category will be reviewed for appropriate staffing
based on the requested percent effort and justification provided. 
The direct costs budget request will be reviewed for consistency
with the proposed methods and specific aims.  Any budgetary
adjustments recommended by the reviewers will be in $25,000
modules.  The duration of support will be reviewed to determine if
it is appropriate to ensure successful completion of the requested
scope of the project.  Secondary review of the applications will be
conducted by the National Heart, Lung and Blood Advisory Council
(NHLBAC) and the National Advisory Council for Aging (NACA).

Review Criteria

The goals of NIH-supported research are to advance our
understanding of biological systems, improve the control of
disease, and enhance health.  In the written review, comments on
the following aspects of the application will be made in order to
judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered in the assignment of the
overall score.

(1) Significance

Does this study address an important problem?  If the aims of the
application are achieved, how will scientific knowledge be
advanced?  What will be the effect of these studies on the concepts
or methods that drive this field? How will the results be applied
to understanding or treating heart failure?

(2) Approach

Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims
of the project?  Does the applicant acknowledge potential problem
areas and consider alternative tactics? Are the approaches
applicable to critical questions in heart failure research or to
cardiac patients?

(3) Innovation

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

(4) Investigator

Is the investigator appropriately trained and well suited to carry
out this work?  Is the work proposed appropriate to the experience
level of the principal investigator and other researchers?

(5) Environment

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

Two additional criteria will be utilized:

(6)  Multi-disciplinary Approach

(a) Individual R01s - Does the project represent effective multi
disciplinary research among appropriate investigators.

(b) Collaborative R01s - Does the group of collaborative R01s
represent effective multi disciplinary collaborative research. 
Will the proposed collaborators interact synergistically to exploit
novel scientific themes or technologies?  Are the breadth and depth
of the research team appropriate to the central theme and
sufficiently extensive to ensure feasibility?

(7) Effectiveness of Collaboration in Collaborative R01 Projects

Is there an indication of breadth of expertise, synergy, and
innovation?  What is the commitment, strength, and likelihood of
effective interaction between collaborating investigators?

AWARD CRITERIA

Applications will receive a secondary level of review by both the
NHLBAC and the NACA in September 1998.  The earliest anticipated
date of award is September 1998.  Applicants should be aware that,
in addition to scientific merit, program priorities and program
balance, the total cost of the proposed project and the
availability of funds will be considered by NIH staff as well as
the NHLBAC and the NACA.  In circumstances in which applications
have similar scientific merit, but vary in cost competitiveness,
NHLBI and NIA are likely to select the more cost competitive
application for funding.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged. 
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Leslie Reinlib
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
Rockledge 2, Room 9188
Bethesda, MD  20892-7940
Telephone:  (301) 435-0504
FAX:  (301) 480-1454
Email:  lr25v@nih.gov

Dr. David B. Finkelstein
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C 231, MSC-9205
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-0010
Email:  finkelsd@exmur.nia.nih.gov

Direct inquiries regarding grants management issues to:

Mr. William Darby
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Dive, Room 7128
Bethesda, MD  20892-7924
Telephone:  (301) 435-0177
FAX:  (301) 480-3310
Email:  darbyw@gwgate.nhlbi.nih.gov

Mr. Robert Pike
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212 - MSC 9205
Bethesda, MD  20892
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  pikeR@gw.nia.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.121, 93.837, 93.838, 93.839, 93.846, and 93.866. 
Awards are made under authorization of the Public Health Service
Act, Title IV, Part A (Public Law 78-410, as amended by Public Law
99-158, 42 USC 241 and 285) and administered under PHS grants
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. 
This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
review.

The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-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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