SCOR: Molecular Genetics of Hypertension

Release Date:  November 2, 1999

RFA:  HL-00-002

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date: February 1, 2000
Application Receipt Date: March 28, 2000

PURPOSE

The objective of this initiative is to establish or continue to support 
closely interacting, multiproject Specialized Centers of Research (SCORs) to 
study the molecular genetics of hypertension.  This initiative represents the 
recompetition of an existing SCOR program and covers the second five-year 
funding period of a ten-year program.  Three broad areas will be considered 
responsive to the initiative: (1) mapping and identification of genes 
responsible for high blood pressure or its complications in humans and in 
experimental animal models; (2) mechanistic studies on the biological 
consequences of variations in genes linked to hypertension or its 
complications; and, (3) studies utilizing molecular genetic techniques to 
elucidate basic mechanisms of normal and altered regulation of blood 
pressure.  Collaboration and interaction among centers are encouraged.

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 Request for 
Applications (RFA),  entitled "Specialized Centers of Research on Molecular 
Genetics of Hypertension", is related to the priority area of heart disease 
and stroke.  Potential applicants may obtain a copy of "Healthy People 2000" 
at "http://odphp.osophs.dhhs.gov/pubs/hp2000".

ELIGIBILITY REQUIREMENTS

Applications may be submitted by for-profit and non-profit domestic 
institutions, public and private, such as universities, colleges, hospitals, 
laboratories, units of state or local governments, and eligible agencies of 
the Federal government.  This RFA is intended to support SCOR grants for 
basic and clinical investigations; therefore, applications that include only 
basic or only clinical research will not be responsive to this announcement.  
In addition, clinical research projects focused on large epidemiologic 
studies or large clinical trials will be considered unresponsive to this RFA.  
Awards will not be made to foreign institutions.  However, under exceptional 
circumstances, a foreign component critical to a project may be included as a 
part of that project.  Racial/ethnic minority individuals, women, and persons 
with disabilities are encouraged to apply as principal investigators.

The Principal Investigator should be an established research scientist with 
the ability to ensure high quality research and the experience to administer 
effectively and integrate all components of the program.  A minimum time 
commitment of 25 percent is expected for this individual.  The Principal 
Investigator must also be the project leader of one of the component research 
projects.  If, through peer review, this project is not recommended for 
further consideration, the overall SCOR application will not be considered 
further.  If this project is judged by peer review to be of low scientific 
merit, it will markedly reduce the overall scientific merit ranking assigned 
to the entire application by the review committee.  Project leaders must 
agree to commit at least 20 percent effort to each project for which they are 
responsible.

MECHANISM OF SUPPORT

This RFA will use the National Heart, Lung, and Blood Institute (NHLBI) SCOR 
(P50) grant award mechanism.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.  All 
current policies and requirements that govern the research grant programs of 
the NIH will apply to grants awarded under this RFA.  The anticipated award 
date is February 1, 2001.

Basic and Clinical Research

The overall concept of a SCOR program focuses on scientific issues related to 
diseases relevant to the mission of the NHLBI.  It is essential, therefore, 
that all applications include both basic and clinical research projects.  
Interactions between basic and clinical scientists are expected to strengthen 
the research, enhance transfer of fundamental research findings to the 
clinical setting, and identify new research directions.  Plans for transfer 
of findings from basic to clinical studies should be described.

Each SCOR grant application and award must include research involving human 
patients/subjects.  Support may be provided for human biomedical and 
behavioral studies of etiology, pathogenesis, prevention and prevention 
strategies, diagnostic approaches, and treatment of diseases, disorders, or 
conditions.  Small population-based studies, where the research can be 
completed within five years, may also be proposed.  In addition, basic 
research projects must be included that relate to the clinical focus.  A SCOR 
may also contain one or more core units that support the research projects.

Length of SCOR Programs

Each NHLBI SCOR program is limited to 10 years of support. The current SCOR 
program on Molecular Genetics of Hypertension was funded in 1996 and, 
therefore, this RFA covers the second five-year funding period.  Under this 
policy, SCOR grants funded in response to this RFA will only be for five 
years without the possibility of renewal.  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 SCOR program.

The NHLBI comprehensive evaluation of the Molecular Genetics of Hypertension 
SCOR program will be conducted during the second project period according to 
the following timetable:

Program Announced                 October 1999

Project Period 
(Second Competition)              February 2001 to January 2006

Letter to SCOR Directors         
Regarding SCOR Evaluation Plans   September 2002		

SCOR Evaluation Meeting           November 2002

Notification of SCOR Directors	
of NHLBI Decision                 September 2003 
				
The NHLBI does not limit the number of SCOR applications in a given SCOR 
program from one institution provided there is a different SCOR principal 
investigator for each application and each application is self-contained and 
independent of the other(s).  This does not preclude cooperation, planned or 
possible, among participants of SCORs after awards are made.  Scientific 
overlap among applications will not be accepted.  If more than one 
application is envisioned from an institution, the institution is encouraged 
to discuss its plans with the NHLBI SCOR program administrator.

FUNDS AVAILABLE

The NHLBI intends to commit approximately $ 11 million in FY 2001 to fund up 
to six new and/or competitive continuation SCOR grants in response to this 
RFA.  Applicants may request a project period of up to five years and a 
budget for direct cost of up to $1,280,000 or 10% over the final year budget 
of the current funding period, whichever is greater, in the first year.  The 
facilities and administrative costs for collaborating institutions are 
excluded from this ceiling and a maximum increase of no more than three 
percent is allowed in each additional year requested in the application.  
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 sufficient number of applications of outstanding 
scientific and technical merit.

Equipment is included in the budget limitation.  However, requests for major 
equipment that cause an application to exceed this limit may be permitted on 
a case-by-case basis following staff consultation.  Such equipment requires 
in-depth justification.  Final decisions will depend on the nature of the 
justification and the Institute's fiscal situation.

Consortium Arrangements

When a grant application includes research activities that involve 
institutions other than the grantee institution, it is considered a 
consortium effort.  Such activities may be included in a SCOR grant 
application, but it is imperative that a consortium application be prepared 
so that the programmatic, fiscal, and administrative considerations are 
explained fully.  Applicants of SCOR grants should exercise great diligence 
in preserving the interactions of the participants and the integration of the 
consortium project(s) with those of the parent institution, because synergism 
and cohesiveness can be diminished when projects are located outside of the 
group at the parent institution.  Facilities and administrative costs paid as 
part of a consortium agreement are excluded from the limit on the amount of 
direct costs that can be requested.  The published policy governing consortia 
is available in the business offices of institutions that are eligible to 
receive Federal grants-in-aid. Consult the latest published policy governing 
consortia before developing the application.  If clarification of the policy 
is needed, contact Ms. Jane Davis, Grants Operations Branch, NHLBI, 301-435-
0166.

RESEARCH OBJECTIVES

Background

Hypertension, a complex disease that involves the interplay of genetic and 
environmental factors, affects an estimated 50 million Americans and is a 
major predisposing factor for myocardial infarction, heart failure, vascular 
disease, stroke, and renal failure.  Judging from the results from 
segregation analysis and twin studies, genetic factors undoubtedly play a 
major role in the interindividual differences in blood pressure.

The identification of the genes whose variants contribute to high blood 
pressure will have far-reaching effects on the understanding of the 
pathophysiology of the circulation and may suggest new therapeutic approaches 
and preventive measures, and thereby shift the national health focus in 
hypertension from post-onset therapy to prevention.  In addition, the genetic 
approach may lead to the identification of primary molecular defects that 
will form the basis for mechanistic studies in humans and animals on normal 
blood pressure regulation and on the pathophysiology of hypertension.  The 
genetic approach may also offer crucial new insights into the biochemical and 
physiological pathways that link various risk factors to high blood pressure.

The division of the general population suffering from essential hypertension 
into subgroups, defined by genotypes, may allow for the evaluation of 
therapies in more homogeneous groups.  Knowledge of target subgroups can 
provide new targets for specifically-designed therapies.  Additionally, it 
may be possible to use existing therapies in a more directed way to treat 
individuals with specific genotypes.  It may not be necessary to negate the 
effects of all the genes contributing to hypertension to treat the disease in 
an individual.  It is likely that many genetic effects act in concert and 
that neutralizing one or two of the genetic determinants operating in an 
individual may be sufficient to reduce blood pressure to a level that has 
less associated cardiovascular and renal risk.

An understanding of the basis for genetic susceptibility to hypertension and 
its mechanisms would help identify individuals at risk for developing the 
disease before the manifestation of clinical symptoms.  A major challenge of 
the future in the hypertension field will be the development and 
implementation of effective preventive measures.  Furthermore, molecular 
genetic studies will help investigators characterize the prevalence of 
genetic variants associated with hypertension at the population level.  
Interventions based on this information applied in advance of the rise in 
blood pressure have the greatest potential for preventing the disease.

The identification of hypertension genes provides the basis for an 
understanding of the interactions between genes and environmental factors.  
It is very likely that particular environmental variables exert effects only 
in the presence of certain genotypes.  Moreover, the effects of certain 
environmental factors may be difficult to detect in a genetically 
heterogeneous group.

Several recent advances in technology and analytical methods, together with 
the rapid construction of genetic and physical maps in mice, rats and humans, 
have substantially improved the likelihood of detecting the genetic 
determinants of high blood pressure and for studying the molecular and 
physiological consequences of gene variation.  For example, large-scale 
surveys of human genomic variation is now possible with efficient high-
throughput methods using hybridization to high-density DNA probe arrays.  
Furthermore, polymorphism screening can serve to identify single-nucleotide 
polymorphisms in the identification of complex disease genes.

The identification of hypertension genes and a mechanistic analysis of how 
these genes contribute to blood pressure regulation and to the 
pathophysiology of hypertension will require the collaboration of 
investigators with expertise in genetics, biostatistics, clinical science 
with an emphasis on hypertension, molecular biology, biochemistry, and 
physiology.  Economies of scale can be accomplished by sharing technology, 
data, skills, and biological materials. Although some research centers will 
have access to all necessary resources, many of the investigators critical to 
the success of the project may be located in different institutions.  
Therefore, all of the necessary expertise, resources, and infrastructure need 
not be localized at one geographical site.  The center will provide the 
cohesion and coordination that will link the best people in several 
locations, covering such expenses as the exchange of scientists, travel costs 
of participating groups, shipping costs of samples and probes, data 
transmission and data storage costs, and the costs of regular meetings to 
coordinate the activities of the participants.

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the 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 could be included with the application.

Proposed Research

The principal research aim of this RFA is to encourage basic and clinical 
research that is oriented toward mechanisms of blood pressure control and 
hypertension at the genetic level.  Three broad areas will be considered 
responsive to the initiative:  (1) mapping and identification of genes 
responsible for high blood pressure or its complications in humans and in 
experimental animal models; (2) mechanistic studies on the biological 
consequences of variations in genes linked to hypertension or its 
complications; and (3) studies utilizing molecular genetic techniques to 
elucidate basic mechanisms of normal and altered regulation of blood 
pressure.

Each SCOR will require a close association of basic bench-level and clinical 
research.  At times, the clinical studies will act as the driving force and 
lead the overall direction of the center by identifying genes that are 
closely associated or linked to the hypertension or to an intermediate 
phenotype related to high blood pressure in humans.

However, animal models will continue to play crucial roles.  The expanded 
availability of micro-satellite markers on the rat genome makes possible 
detailed mapping of potential candidate genes.  Tissue-specific knockout, 
mutant and recombinant inbred mice will continue to be the major tools to 
better define the function of putative candidate genes.  During the last few 
years, an increasing number of quantitative trait loci, which exhibit highly 
significant linkage with hypertension, have been identified.  The time is 
ripe to develop congenic strains necessary to narrow the regions and to 
evaluate the functional significance of these regions.  Furthermore, new 
candidate genes within the regions can now be identified in the animal models 
with positional cloning and the translation of these findings to human can be 
achieved by homology mapping.  Animal models might also be used subsequent to 
primary identification of human genes related to high blood pressure as a 
means to clarify pathophysiological mechanisms.  Confirmation of the 
pathophysiology derived from animal studies can then be undertaken in human 
subjects.  Mapping and identification of genes responsible for hypertension, 
whether conducted initially in humans or in animals, will continually provide 
candidate loci and hypotheses for testing in humans.

1.  Mapping and Identification of Genes

Mapping of relevant genetic loci and identification of underlying genetic 
mutations responsible for high blood pressure in humans or in experimental 
animal models of hypertension is an area that may be supported through the 
SCOR mechanism.  Gene mapping and identification will be complementary to 
other scientific efforts to be supported by the NHLBI or through other 
sources.
Two principal approaches may be used to map genes that may be linked to 
hypertension:  the first entails a whole genome search using anonymous highly 
informative genetic markers spread throughout the genome; the second approach 
involves the systematic study of candidate genes.  Mapping can be carried out 
with methodologies such as linkage in affected sib pairs, genetic linkage 
analysis of large pedigrees, and association methods.  To reduce the impact 
of genetic heterogeneity, the study population may be subdivided by defining 
intermediate phenotypes (characteristics that have greater heritability than 
the complex trait itself), or a population may be studied that has originated 
from a restricted founder population or has been isolated in some way as to 
limit the number of genetic variants present.

2.  Mechanistic Studies on the Consequences of Genetic Variation

Investigators may select genetic variations for mechanistic studies from a 
number of sources.  For instance, SCOR investigators may choose to study 
allelic variations linked to high blood pressure that have been identified 
and reported in the literature or that have been identified from mapping 
activities within the SCOR program.  In addition, candidate genes that are 
well justified in the application may also be studied, even if they have not 
yet been linked to hypertension in humans or specific animal models.  
Mendelian forms of hypertension, while rare and, perhaps, limited in its 
general application, continue to be useful models for studying the impact of 
single gene mutation.

Studies may be conducted at any level of investigation, from the molecular to 
the whole animal.  For example, consideration may be given to approaches 
examining the implications of genetic mutations on:  cellular function, 
including changes in the processing of genetic information, synthesis or 
degradation of vasoactive substances, signal transduction pathways, receptor 
structure and function, and response to cytokines and growth factors; and 
whole animal integrated function, using genetically altered animals, such as 
congenics, transgenics, and knockouts, to clarify modifications of organ 
function and implications for acute and chronic blood pressure control.

3.  Molecular Genetic Studies on Basic Mechanisms of Normal and Altered Blood 
Pressure Control

Molecular and genetic approaches that focus on the genes for which there is 
ample evidence of possible involvement in blood pressure regulation are 
excellent areas for study.  However, mechanistic studies should address the 
implications of genetic alterations on normal blood pressure regulation and 
the pathophysiology of hypertension.

Understanding the genetic regulation of cellular and organ responses to 
elevated blood pressure is an additional area that may be supported through 
the Hypertension SCORs.  Research on cellular and organ responses to 
hypertension includes studies on the complications associated with the 
disease, such as investigation at a genetic level on conditions such as 
nephropathy or cardiac hypertrophy.  Other topics, such as genetic 
determinants of vascular remodeling as a function of high blood pressure, are 
also appropriate responses.

Other examples of possible research areas are:  development and refinement of 
techniques to introduce and express new genetic information and to abolish or 
modify the expression of endogenous genes; development of more efficient 
tissue-specific vectors; antisense and  ribozyme approaches; recombinant 
inbred animals; model systems comprised of multiple cell types; and, 
isolation, characterization, propagation of embryonic stem cells from rats, 
rabbits, and other species in order to study various forms of blood pressure 
regulation and dysfunction.

Identification of the consequences of long-term hypertension on organ 
adaptation and eventually on end stage target organ disease is another 
important objective of this solicitation.  It will be particularly 
interesting to determine how organ adaptations to high blood pressure are 
affected by predisposing genetic factors.  Some of the sequelae to 
hypertension that may be studied include kidney disease, stroke, myocardial 
infarction, heart failure, vascular disease, and retinal disease. It is 
increasingly recognized that certain cluster of genes are often shared as 
common heritable factors by related diseases.  Examples are the complex 
interplay between insulin resistance, diabetes and hypertension.  
Furthermore, with the completion of the human genome project expected in the 
near future, applicants are encouraged to seize the opportunity and to 
enhance the translation of findings from animal models to human studies.

Biennial Research Meetings

Upon initiation of the program, the NHLBI will sponsor periodic meetings to 
encourage exchange of information among investigators who participate in this 
program and to stimulate collaboration. Applicants should request additional 
travel funds for a two-day meeting every other year, most likely to be held 
in Bethesda, Maryland.  Applicants should also include a statement in their 
applications indicating their willingness to participate in these meetings.

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.  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 read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which was first published in the Federal Register of March 28, 
1994 (FR 14508-14513) and in the NIH Guide for Grants an Contracts, Vol. 23, 
No. 11, March 18, 1994, available on the web at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.  The "NIH Policy and Guidelines" on the 
Inclusion of Children as Participants in Research Involving Human Subjects 
that was published in the NIH Guide for Grants and Contracts, March 6, 1998, 
and is available at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

However, in view of the low prevalence of hypertension in children, 
applications in response to this RFA are not expected to include children as 
participants in study populations.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 1, 2000, a letter of 
intent that includes a descriptive title of the proposed research; the name, 
address, and telephone number of the Principal Investigator; 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.

Although a letter of intent is not required, is not binding, and does not 
enter into the review of subsequent applications, the information that it 
contains allows NHLBI staff to estimate the potential review workload and to 
avoid conflict of interest in the review.

The letter of intent is to be mailed, or faxed, by the letter of intent 
receipt date listed in the heading of this RFA to: 

Dr. C. James Scheirer
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220, MSC 7924
Bethesda, MD 20892-7924
Telephone: (301) 435-0266
FAX: (301) 480-3541
Email: js110j@nih.gov.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and  from the Division of Extramural Outreach 
and Information Resources, Center for Scientific Review, National Institutes 
of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
301/435-0714, e-mail: grantsinfo@nih.gov.

Special supplemental instructions for the preparation of grant applications 
for SCORs may be obtained by contacting the Hypertension SCOR Program 
Administrator listed under INQUIRIES.

The RFA label available in the PHS 398 (Rev.4/98) 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, to identify the application as a response 
to this RFA, check "YES", enter the title "Specialized Centers of Research -- 
Molecular Genetics of Hypertension," and the RFA number HL-00-002 on Line 2 
of the face page of the application.

The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the 
checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (FOR EXPRESS/COURIER SERVICE)

At the time of submission, two additional copies of the application must be 
sent to the Chief, Review Branch at the address listed under LETTER OF 
INTENT.  It is important to send these two copies at the same time as the 
original and three copies are sent to the Center for Scientific Review (CSR), 
otherwise the NHLBI cannot guarantee that the application will be reviewed in 
competition for this RFA.

Applications must be received by March 28, 2000.  If an application is 
received after that date, it will be returned to the applicant without 
review. The Center for Scientific Review (CSR) will not accept any 
application in response to this announcement that is essentially the same as 
one currently pending initial review, unless the applicant withdraws the 
pending application.  CSR will not accept any application that is essentially 
the same as one already reviewed.  This does not preclude the submission of 
substantial revisions of applications already reviewed, but such applications 
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR, and 
responsiveness by NHLBI.  Incomplete and/or non-responsive applications will 
be returned to the applicant without further consideration.  Applications 
that are complete and responsive to this RFA may be subjected to a 
streamlined review process by an appropriate peer review group convened by 
the National Heart, Lung, and Blood Institute to determine their scientific 
merit relative to other applications received in response to the RFA.  
Applications determined to be meritorious will be evaluated for scientific 
and technical merit by the review committee, be discussed and receive a 
priority score.  All other applications will not be discussed or scored.  
Secondary review of the applications will be conducted by the National Heart, 
Lung, and Blood Advisory Council.

Review Criteria:

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments reviewers will be asked to discuss the following aspects 
of the application 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 assigning the overall 
score, weighting them as appropriate for each application.  Note that the 
application does not need to be strong in all categories to be judged likely 
to have major scientific impact and thus deserve a high priority score.  For 
example, an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

(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?

(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?

(3) Innovation 
Does the project employ novel concepts, approaches or method? 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 (if any)? Does the Program 
Director have the appropriate scientific statue and proven leadership to 
serve in such capacity ?

(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?

(6) Collaboration
Does the submitted proposal represent collaborative research among 
investigators from basic and clinical research with necessary disciplines? 
What are the likelihood of effective collaboration among the investigators, 
and the likelihood of success of the research objectives proposed?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

AWARD CRITERIA

Applicants should be aware that, in addition to scientific merit, program 
priorities and program balance, the total costs of the proposed project and 
the availability of funds will be considered by NHLBI staff as well as NHLBAC 
in making funding recommendations.  In circumstances in which applications 
have similar scientific merit, but vary in cost competitiveness, NHLBI is 
likely to select the more cost competitive application for funding.

SCHEDULE

Letter of Intent Receipt Date:     February 1, 2000
Application Receipt Date:          March 28, 2000
Peer Review Date:                  June/July 2000
Review by NHLB Advisory Council:   September/October 2000
Anticipated Award Date:            February 1, 2001


INQUIRIES

Inquiries concerning this RFA are encouraged. The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding scientific issues to:

Michael C. Lin, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Drive, MSC 7956
Bethesda, MD  20892
Telephone:  (301) 435-0560
FAX:  (301) 480-2849
E-mail: michael_lin@nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Ms. Jane Davis
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Drive, MSC 7926
Bethesda, MD  20892
Telephone:  (301) 435-0166
FAX:  (301) 480-3310
E-mail: jane_davis@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.837, Heart and Vascular Diseases.  Awards will be made under the 
authorization of the Public Health Service Act, Title V, 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 requirement 
of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant 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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