ANCILLARY STUDIES IN HEART, LUNG, AND BLOOD DISEASE TRIALS

Release Date:  June 22, 2000

RFA:  HL-00-012

(See renewal with modifications: RFA-HL-07-009)

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  One month prior to application receipt dates
 Application Receipt Date:  Applications will be accepted every three (3)
 MONTHS on the following receipt dates:  September 11 and December 11 of 2000;
 March 9, June 11, September 10, and December 10 of 2001; and March 11 and June
 10 of 2002.

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN  RESPONSE TO THIS RFA/PA.

PURPOSE

The overall goal of this initiative is to solicit research grant applications 
to conduct mechanistic studies in clinical trials related to heart, lung and 
blood diseases.  Specifically, this initiative focuses on the utilization of 
patients and patient materials from such trials to study the mechanisms 
underlying the interventions, the mechanisms of disease pathogenesis, 
surrogate markers or biomarkers of disease activity and therapeutic effect and 
the mechanisms of human cardiopulmonary and hematologic function.  Studies 
aimed at accelerating the development of new technologies within the context 
of the mechanistic investigations are also encouraged.  Mechanistic studies in 
clinical trials supported by any source (industry, public and private) are 
eligible.  Applications submitted under this program will undergo an expedited 
peer review and award to facilitate the timely conduct of these mechanistic 
studies. 

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 Request for 
Applications(RFA)ANCILLARY STUDIES IN HEART, LUNG AND BLOOD DISEASE TRIALS, is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/.


ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
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 as Principal 
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research project 
grant (R01) award mechanism. Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant. The 
total project period for an application submitted in response to this RFA may 
not exceed four years.  This RFA will be active for two (2) fiscal years (FY 
2001 and 2002)contingent on the availability of funds.  Unsolicited competing 
continuation applications after this 2 year period will compete with all 
investigator-initiated applications according to the customary peer review 
procedures. Highly meritorious applications selected for funding under this 
RFA will receive their awards approximately 15 weeks after the application 
receipt date. 

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

FUNDS AVAILABLE

The NHLBI intends to commit $3.0 million in FY 2001 and $3.0 million in FY 
2002 to fund up to 8-10 new grants each year in response to this RFA. An 
applicant may request a project period of up to four years and a budget for 
direct costs of up to $225,000 (9 modules) per year, including facilities and 
administrative (F&A) costs on consortium arrangements. Because the nature and 
scope of the research proposed in each application may vary, it is anticipated 
that the size of each award will also vary. The parent or core clinical trial 
must be independently funded and will not receive support under this RFA.  
Phase II-IV clinical trials supported by any source (public or private) are 
eligible.  Although the financial plans of the National Heart, Lung, and Blood 
Institute provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds in each fiscal year, and receipt of 
a sufficient number of meritorious applications.

RESEARCH OBJECTIVES

Background

Large numbers of well characterized participants are frequently required to 
conduct clinical trials, especially those that require hard clinical endpoints 
to achieve their primary goals.  These trials constitute a substantial 
investment and provide a unique resource of potential subjects and patient 
materials for studies to better understand disease mechanisms or how responses 
to therapy are mediated.  There is general agreement within the scientific 
community that our understanding of many of the mechanisms underlying 
interventions for treatment of heart, lung, and blood diseases are limited, 
even in cases where efficacy has been shown.  In addition, clinical trials 
supported by industry and other sources, including NIH, often do not 
incorporate studies of underlying mechanisms.  Therefore, it is necessary to 
consider novel approaches to capitalize on these valuable and expensive 
clinical trials to utilize patient information and samples from clinical 
trials of heart, lung, and blood diseases for study of the basic mechanisms of 
therapeutic effect, physiologic/cellular function and disease pathogenesis.  
These mechanistic studies not only offer an opportunity to elucidate disease 
pathogenesis and correlate this information with clinical course and outcome, 
but a means to investigate new mechanisms and obtain new information.  This 
information will be crucial to identifying effective surrogate markers that 
can be used to predict which patients are at high risk, or to design 
treatments, or the timing of treatments that can be targeted to patients with 
specific responses or characteristics. 


Unfortunately, the time currently required for review and award of new grant 
applications is often incompatible with the time-line of a clinical trial.  
Specifically, when a clinical protocol is finalized (which is required for 
applications submitted under this RFA), investigators are often ready to begin 
once approval is obtained from the clinical trial governing body and  
Institutional Review Board.  The standard time frame for submission to award 
for a NIH investigator-initiated research grant application does not generally 
work well for supporting ancillary mechanistic studies and often critical time 
points are missed.  This RFA would fill two important needs.  The first would 
be to encourage basic scientists and clinical investigators from academia and 
industry to work together on ongoing clinical protocols to enable more in 
depth study of mechanisms of disease pathogenesis.  Secondly, it will provide 
a means of rapidly responding to opportunities to study underlying mechanisms 
and surrogate markers.  This approach should provide a cost efficient means of 
conducting mechanistic ancillary studies of disease pathogenesis within the 
larger context of ongoing clinical trials.

The overall goal of this RFA is to support mechanistic research in clinical 
trials of cardiovascular, respiratory or hematologic diseases.  Specifically, 
the goal is to utilize patients and patient materials from such trials for the 
evaluation of the relevant parameters to study the underlying mechanisms of 
disease activity and therapeutic effect, and mechanisms of human 
cardiopulmonary and hematologic function.  Such studies would not be part of 
the parent or core clinical trial and are commonly referred to as ancillary 
studies.  These studies would consist of measurements not being conducted as 
part of the parent clinical trial.  For example, such ancillary studies might 
be done on the entire participant cohort or on subsets of the participants 
depending on the sample size required to answer the questions.  They may 
involve physiologic or biochemical measures, imaging techniques or analyses of 
biological specimens from the subjects for potential genetic studies, or for 
other factors thought to bear on the pathogenesis of the condition or on the 
mechanism of the intervention.  The primary objective is to help elucidate the 
mechanism of action, or the pathogenesis of the condition, or the validity of 
potential cardiopulmonary or hematologic biomarkers.

These studies must not interfere with or over burden participants in the 
parent study.  Appropriate sample size calculations are required, and all 
ancillary study policies from the parent study must be followed.  The parent 
or core clinical trial must be independently funded and will not receive 
support under this RFA.  Phase II-IV clinical trials supported by any source 
(public or private) are eligible.  This program will utilize an expedited 
application process, rapid review and feedback to the Institute and applicant 
and modular funding to simplify budget negotiations. 

Research Scope

The following are examples of the kinds of areas that might be studied.  
However, these are only examples and are not meant to be limiting. A number of 
potential mechanistic studies of cardiovascular disease pathogenesis are open 
for investigation.  For example, in trials of cardiovascular and diabetes, 
studies might determine the validity of biomarkers or surrogate endpoints to 
assess disease progression. Studies of cardiac energetics (MRI, PET) before 
and after control of metabolic abnormalities and studies to evaluate changes 
in coagulation factors or inflammation with improved control of glucose or 
other risk factors would be appropriate. Similarly, in trials of heart failure 
or sudden death, imaging studies might contribute to the understanding of 
disease progression or mechanism of action of the intervention.

Pathophysiological mechanisms of inflammatory lung diseases such as asthma, 
chronic obstructive pulmonary disease (COPD), cystic fibrosis, acute 
respiratory distress syndrome (ARDS), interstitial pulmonary fibrosis, and 
bronchopulmonary dysplasia (BPD) may differ depending on the initial insult 
and may be further complicated by the patient's underlying condition.  The 
inflammatory cascades initiated by these disease processes are complex and may 
result in activation of different inflammatory mechanisms.  Studies are 
encouraged to explore the underlying mechanisms of airway injury and repair, 
vascular remodeling, regulation of vessel tone, airway/tissue remodeling, 
individual host response to lung injury, role of genetic factors in clinical 
heterogeneity, mechanisms underlying the maintenance and severity of asthma, 
and identification of surrogate markers for rejection and infection in 
transplant patients.

A number of important mechanistic questions in the area of sickle cell disease 
could be studied in ongoing clinical trials.  These include determining the 
mechanism of action of hydroxyurea in ameliorating sickle cell crises, 
including investigation of its effects on fetal hemoglobin levels, on adhesion 
of sickle red blood cells and white blood cells to endothelium in various 
organs, post-translational modifications of hemoglobin, identification of 
biomarkers for a sickle cell crisis, biomarkers to quantify graft vs. host 
disease in blood and marrow transplantation, and the mechanisms responsible 
for first-time stroke.  Studies could explore thrombosis resulting from 
hormone replacement therapy in post-menopausal women or identify newly 
recognized transfusion-transmitted agents and antibodies to these agents.  

SPECIAL REQUIREMENTS

In order to be considered responsive to this announcement, applications must 
propose mechanistic (not clinical) studies using ongoing heart, lung and blood 
related clinical trials. The use of epidemiology studies or existing cohorts 
for mechanistic studies are not eligible under this RFA.  Applications focused 
solely on the development of methodology without plans for addressing the 
goals of this RFA will not be accepted. Studies needed to develop biomarkers 
or to overcome barriers such as the development of instrumentation should be 
integrated into the proposed research program.  For information related to 
ongoing clinical trials supported by the NHLBI prospective applicants may wish 
to refer to the NHLBI clinical trials data base at: 
http://apps.nhlbi.nih.gov/clinicaltrials/ 


Prospective applicants for this RFA may or may not be investigators of the 
parent clinical trial(s)whose data and/or materials and/or subjects they 
propose to use.  It is expected that applicants who are not parent study 
investigators will work together with the parent study investigators in 
developing their applications. All ancillary study applications MUST include a 
letter or statement documenting that patients, samples, data and/or materials 
are available from the parent clinical trial and the proposed ancillary study 
has the approval of the parent study's organization/leadership.  Applications 
not containing such documentation will be considered non-responsive to this 
RFA.  Applicants must submit a time line in their application demonstrating 
that the ancillary study can be completed within a reasonable time frame. 

Upon initiation of the program, periodic meetings may be organized to 
encourage the exchange of information among investigators who participate in 
this program. Travel funds for a one day meeting each year, most likely to be 
held in Bethesda, Maryland, must be included in the module calculation. 
Applicants must include a statement indicating their willingness to 
participate in these meetings.

In addition to yearly progress reports, the Principal Investigators of grants 
funded under this RFA will provide brief (1-2 pages) summary reports of the 
outcomes of the research at the conclusion of the funding period and one year 
later.  The reports will summarize the major scientific knowledge gained and 
identify other substantive outcomes such as publications, patents, and new 
grants, contracts, or research studies based on this mechanistic research.

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 published in the Federal Register of March 28, 1994 (FR 
59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 
11, March 18, 1994, available on the web at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html. 



NIH POLICY AND GUIDELINES ON THE 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 clear and compelling scientific and ethical reasons not 
to include them. This policy applies to all initial (Type 1) applications 
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects" that 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 

URLS IN NIH GRANTS 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. Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site. 

LETTER OF INTENT

Prospective applicants are asked to submit one month prior to the application 
receipt dates a letter of intent that includes: a descriptive title of the 
proposed research; the title of the parent clinical trial; 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 this 
RFA.  Although the letter of intent is not required, is not binding, does not 
commit the sender to submit an application, and does not enter into the review 
of subsequent applications, the information that it contains allows review to 
estimate the potential review workload and to plan the review.  IT IS HIGHLY 
RECOMMENDED THAT THE LETTER OF INTENT BE SUBMITTED, and it should be sent to 
Dr. Scheirer at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applicants are strongly encouraged to call program staff listed in INQUIRES 
below with any questions regarding the responsiveness of their proposed 
project to the goals of this RFA.  


Applications are to be submitted on the grant application form PHS 398 (rev. 
4/98). These forms are available at most institutional offices of sponsored 
research and 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: GrantsInfo@nih.gov and 
on the internet at: http://grants.nih.gov/grants/funding/phs398/phs398.html

For purposes of identification and processing, item 2a on the face page of the 
application must be marked "YES" and the RFA number "HL-00-012" and the words 
"ANCILLARY STUDIES IN HEART, LUNG, AND BLOOD DISEASE TRIALS" must be entered 
on the face page.

Applications must be received by the receipt date.  Receipt dates are 
September 11 and December 11 of 2000; March 9, June 11, September 10, and 
December 10 of 2001; and March 11 and June 10 of 2002. Applications which are 
received after the deadline will automatically be processed for the next 
receipt date.  Applications not received as a single package (See Special 
Instructions Section below) on the receipt date or not conforming to the 
instructions contained in PHS 398 (rev. 4/98) Application Kit (as modified in, 
and superseded by, the special instructions below, for the purposes of this 
RFA), will be judged non-responsive and will be returned to the applicant.  

The RFA label available in the application form PHS 398 must be affixed to the 
bottom of the face page.  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. A sample RFA label is available at the following site: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is 
in pdf format.
If the application submitted in response to this RFA is substantially similar 
to a grant application already submitted to the NIH for review, but that has 
not yet been reviewed, the applicant will be asked to withdraw either the 
pending application or the new one.  Simultaneous submission of identical 
applications will not be allowed, nor will essentially identical applications 
be reviewed by different review committees.  Therefore, an application that is 
essentially identical to one that has already been reviewed cannot be 
submitted in response to this RFA.  This does not preclude the submission of 
substantial revisions of applications already reviewed, but such applications 
must include an introduction addressing the previous critique.  

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


PLEASE NOTE THAT THIS ADDRESS IS DIFFERENT FROM THE INSTRUCTIONS IN THE 398 
APPLICATION PACKAGE AND FAILURE TO COMPLY WILL RESULT IN DEFERRAL OF REVIEW. 

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 2030 - MSC 7720
Bethesda, MD  20892-7720
Bethesda, MD  20817 (for express mail or courier service)

At the time of submission, two additional copies of the application plus all 
five copies/sets of the appendix material must be sent to Dr. C. James 
Scheirer listed under INQUIRIES.

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.

SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA

The research plan in the application should be limited to 15 pages, excluding 
references.  The research plan includes specific aims, background and 
significance, preliminary studies, and research design and methods (Sections A 
to D).  In the research plan, include a justification for why the proposed 
studies require the use of patients in this clinical trial as opposed to using 
patients with the same disease state but not in a trial. 

Methods of data analysis and power calculations must be included as well as a 
justification for the required sample size.  A restatement of the sample size 
calculations from the parent clinical trial is insufficient.  If appropriate 
to your application, discuss whether it is necessary to perform the 
mechanistic studies on all patients enrolled in the parent trial or whether a 
sub-sample would be sufficient.  There must be a discussion of the statistical 
procedures that will be used to analyze the data.  The manner in which 
mechanistic approaches will be related to the clinical outcomes in the main 
study should also be discussed. 


The protocol and the investigators' brochure for the parent or core clinical 
trial should be included with the application as part of the human subjects 
section. Inclusion of the complete clinical protocol within the PHS 398 grant 
application is intended to simplify the application process by eliminating the 
need to duplicate protocol details in the Research Plan section. Informed 
Consent form(s) from the parent clinical trial must also be included as part 
of this section.  While drafts of the consent forms for the proposed study 
from all participating sites are not required, it would be useful to include 
them if they are available.  NIH will treat as confidential any scientific, 
preclinical, clinical, or formulation data and information that the sponsor 
deems to be proprietary and confidential.

To facilitate the accelerated award schedule, applicants will be notified of 
the need to obtain Institutional Review Board (IRB) approval for the 
mechanistic studies when there is the potential for an award and to provide 
documentation that the parent clinical trial also has IRB approval.

Amended applications will be accepted for ANCILLARY STUDIES IN HEART, LUNG, 
AND BLOOD DISEASE TRIALS ONLY if invited by NHLBI.  Applicants with minor or 
easily corrected problems will be invited to submit an abbreviated amendment 
(5 page limit and one time only) which directly addresses the questions and 
concerns raised in the initial review.

In order to ensure coordination between the mechanistic studies and the parent 
or core clinical trial, the principal investigator and the sponsor of the 
parent or core clinical trial MUST provide written agreement for the conduct 
of the mechanistic studies as presented in the application.  Applications 
submitted without this documentation will be considered non-responsive to this 
RFA.  All procedures to protect the subject's privacy rights must be clearly 
described in the mechanistic study application.

Prior to award, the applicant must provide to the NHLBI a memorandum of 
understanding signed by the applicant, an appropriate representative of the 
applicant institution, the principal investigator of the parent or core 
clinical trial, and an appropriate representative of the sponsor of the parent 
or core clinical trial.  This memorandum will indicate agreement and will 
outline the specifics of the agreement for the following areas: 1) data from 
the mechanistic studies (including ownership, analysis, access, and release), 
2) access to the data from the parent or core clinical trial (how/when) which 
is needed to analyze the mechanistic studies, including procedures for 
prevention of unblinding of the parent trial and informed consent/privacy 
issues for patient samples, 3) documentation of quality assurance procedures 
for both the parent trial and the mechanistic studies, and documentation of 
Data Safety Monitoring procedures for the parent trial, especially for 
efficacy trials, 4) ownership of intellectual property developed during the 
mechanistic studies, and 5) publication of the results of the mechanistic 
studies.

MODULAR APPLICATION DETAILS:

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach. The 
just-in-time concept 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, reviewers and Institute 
staff. The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for these grants, with the modifications noted below.

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to 
a total direct cost request of $225,000 (9 modules) per year including F&A 
costs on consortium arrangements. 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:

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $225,000) and Total Costs [Modular Total 
Direct plus F&A costs] for the initial budget period Items 8a and 8b should be 
completed indicating the Direct and Total Costs for the entire proposed period 
of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 
of the PHS 398. It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398. It is not required and 
will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. 
(See http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages.) At the top of the page, enter the total direct costs requested for 
each year. This is not a Form page.

o Under Personnel, List key project personnel, including their names, percent 
of effort, and roles on the project. No individual salary information should 
be provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus F&A costs) for each year, each rounded to the nearest $1,000. List the 
individuals/organizations with whom consortium or contractual arrangements 
have been made, the percent effort of key personnel, and the role on the 
project. Indicate whether the collaborating institution is foreign or 
domestic. The total cost for a consortium/contractual arrangement is included 
in the overall requested modular direct cost amount. Include the Letter of 
Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch is required for all 
key personnel, following the instructions below. No more than three pages may 
be used for each person. A sample biographical sketch may be viewed at: 
http://grants.nih.gov/grants/funding/modular/modular.htm

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the type 
of agreement and the date. All appropriate exclusions must be applied in the 
calculation of the F&A costs for the initial budget period and all future 
budget years.

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. 

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI. Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.


Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NHLBI in accordance with the review criteria stated below. As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National 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)?


(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) Is there adequate documentation that patients, samples, data and/or 
materials are available from the parent clinical trial?

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. If the proposed research includes studies in human subjects, 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

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

o scientific merit (as determined by peer review)

o availability of funds

o program balance.

INQUIRIES

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:

James Kiley, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Rockledge 2, Suite 10018
Bethesda, MD 20892-7952
Telephone: (301) 435-0233
FAX: (301) 480-3547
Email: Kileyj@nih.gov

Peter Savage, M.D.

Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 8104 (MSC 7938)
Bethesda, MD 20892-7950
Telephone:  (301) 435-0422
FAX:  (301) 480-0868
Email: Savagep@nih.gov 

Carol Letendre, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10152 (MSC 7950)
Bethesda, MD 20892-7950
Telephone:  (301) 435-0055
FAX:  (301) 480-0868
Email: Ledendrc@nih.gov 

David Gordon, M.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9152 (MSC 7956)
Bethesda, MD 20892-7956
Telephone:  (301) 435-0555
FAX:  (301)480-2858
Email: GordonD@nih.gov

Direct inquiries regarding review matters to:

C. James Scheirer, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Dr.,Room 7216 (MSC 7924)
Bethesda, MD 20892-7924 (20817 for Courier)
Telephone: (301) 435-0266
Fax: (301) 480-3460
Email: js110j@nih.gov 

Direct inquiries regarding fiscal matters to:

Raymond Zimmerman
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7154, MSC 7926
Bethesda, Maryland  20892-7926						
Telephone:  301 435-0171
FAX:  301 480-3310
E-mail: ZimmermR@nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.837, 93.838, 93.839. 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 NIH grants policies and 
Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


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