CELLULAR AND MOLECULAR IMAGING OF THE CARDIOVASCULAR, PULMONARY, AND 
HEMATOPOIETIC SYSTEMS
 
RELEASE DATE:  August 1, 2003
 
RFA Number:  RFA-HL-04-003
 
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov/)
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
 (http://www.nibib.nih.gov/)
Institute of Circulatory and Respiratory Health (ICRH), Canadian Institutes 
of Health Research (CIHR)
 (http://www.cihr-irsc.gc.ca)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):
93.837, 93.838, 93.839  
 
LETTER OF INTENT RECEIPT DATE:  December 22, 2003
APPLICATION RECEIPT DATE:  January 22, 2004
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The National Heart, Lung and Blood Institute (NHLBI), in collaboration with 
the National Institute for Biomedical Imaging and Bioengineering (NIBIB)and 
the Institute of Circulatory and Respiratory Health (ICRH), invites 
applications for the development and application of novel cellular and 
molecular imaging probes and technologies to image the cardiovascular, 
pulmonary, and hematopoietic systems in vivo.  This initiative seeks to take 
advantage of the rapid advances that have taken place in imaging technology, 
allowing normal and pathological processes to be studied in vivo at the 
molecular and cellular level.  The initiative has two related goals. The 
first goal is to detect and quantify at the molecular and cellular level the 
cellular pathways that regulate heart, lung and blood function, and the 
abnormalities in these pathways occurring in heart, lung, blood and sleep 
disorders. The second goal is to develop new methods for cell tracking to 
monitor the movement and location of specific cell populations in vivo for 
application in cell-based therapeutics. 
 
RESEARCH OBJECTIVES

Background

Current methods for imaging the cardiovascular, pulmonary, and hematopoietic 
systems, such as CT, MRI, and ultrasound focus predominantly on anatomical 
and functional measurements.  Molecular imaging is a growing research area 
aimed at developing and testing novel tools, reagents, and methods to image 
specific molecular pathways in vivo, particularly those that are key targets 
in disease processes. In contradistinction to "classical" diagnostic imaging, 
molecular imaging probes the molecular abnormalities that are the basis of 
disease rather than imaging the result of these molecular alterations. 
Molecular imaging can be broadly defined as the in vivo characterization and 
measurement of biologic processes at the cellular and molecular level. While 
the underlying biology represents a new arena for many imaging specialists, 
efforts such as development of novel agents, signal amplification strategies, 
and imaging technologies clearly dovetail with prior research efforts in the 
area of imaging.  

The full potential for molecular and cellular imaging has not yet been 
realized for imaging heart, lung, and blood.  Development of new molecular 
probes for conventional imaging techniques such as MRI and ultrasound, and 
application of new technologies such as optical imaging show great promise, 
but their use in the cardiovascular, pulmonary, and hematopoietic systems is 
still limited.  While there has been limited use of imaging techniques that 
may be defined as "molecular" for imaging heart, lung, and blood,(e.g., 
imaging with monoclonal antibodies or receptor imaging with nuclear 
techniques), it is only recently that needed adjunct basic research tools 
have become routinely available. The availability of these basic science 
tools enhances the capacity of molecular imaging to address basic biologic 
questions in vivo and to do this in a high-throughput fashion. 

The need for the development of improved methods for molecular and cellular 
imaging and for cell tracking was identified at several NIH-sponsored 
workshops and meetings. The 1999 NIH Bioengineering Consortium (BECON) 
"Biomedical Imaging Symposium: Visualizing the Future of Biology and 
Medicine" identified imaging at the cellular and molecular level as a 
critical need for goals such as the early detection of disease. The 
development of novel cell tracking methodologies for cell localization 
represent part of the Strategic Plan for Cell-based Therapies for Heart, 
Lung, Blood and Sleep Disorders developed by the Working Group on Cell-based 
Therapies in May 2002. The need for improved molecular and cellular imaging 
techniques was a common thread running through recommendations from several 
of the subgroups of the January 2003 NHLBI Spark II Conference 
(http://www.nhlbi.nih.gov/funding/fromdir/spark2web.htm). 

In 2001, the ICRH/Heart and Stroke Foundation workshop on the Vulnerable 
Atherosclerotic Plaque identified imaging modalities that focus on the 
vulnerable plaque, including methodologies that allow functional assessment 
of plaque tissue should be targeted. Also in 2001, the ICRH/Heart and Stroke 
Foundation sponsored the Canadian Consensus Conference on Acute Stroke 
Imaging of Thrombolytic Therapy. This group observed that there was no easily 
applicable imaging method to assess recovery from stroke and identified the 
development of in-vivo functional, physiological and/or metabolic markers in 
the study of brain plasticity as a high priority. The importance of tracking 
cells throughout the circulatory system, including those of hematopoietic 
origin, derives from the impact of mobile cells on tissue injury and repair, 
and the remote targeting of pathological processes such as inflammatory 
involvement of the heart, lung and blood vessels. Circumstances which 
contribute to alterations in coaguability, including sepsis, systemic 
inflammatory response syndrome, and other disorders pertinent to transfusion 
medicine are also of relevance to this initiative.
 
Research Scope

The emerging field of molecular imaging uses novel reagents and methods to 
image specific cellular and molecular pathways in vivo, particularly those 
that are key targets in disease processes.  The ability to obtain molecular 
information in vivo would help to understand the abnormalities underlying 
cardiovascular, pulmonary, and blood diseases, would have profound impact on 
the diagnosis of these conditions, and could provide rapid and efficient 
assessment of treatment effectiveness.  There is also a need to utilize 
molecular methodologies to monitor non-invasively the movement and location 
of specific cell populations in vivo in pre-clinical and clinical studies 
through the development of innovative, high-resolution cellular tracking 
methods.  Molecular imaging techniques may also provide powerful tools for 
monitoring and tracking gene and cell-based therapies in clinical studies of 
cardiovascular, pulmonary, and blood diseases.  Advances in molecular 
technologies provide the potential for a new generation of imaging agents 
targeted to specific cells, ligands, enzymes or microenvironments.  These 
imaging agents provide unique opportunities for studying normal and 
pathologic processes less invasively at the molecular and cellular level in 
vivo.  The use of targeted imaging agents, in conjunction with conventional 
or novel noninvasive imaging techniques, will provide new opportunities to 
understand cardiovascular, pulmonary, and hematologic pathologies and to 
monitor the effectiveness of therapies.  

Because of the specific nature of targeted imaging agents, there is a need 
for development of molecular imaging agents applicable to the cardiovascular, 
pulmonary, and blood systems.  Imaging the cardiovascular, pulmonary, and 
blood systems poses unique technical problems, such as cardiac and 
respiratory motion, the unique air-filled structure of the lungs, and the 
circulation of myeloid, lymphoid, and inflammatory cells through the body.  
These technical issues impose additional requirements for successful cellular 
and molecular imaging of the heart, lungs and blood, such as the addition of 
gated image acquisition to novel imaging technologies currently being 
developed for static imaging.  Sensitivity needs to be optimized to 
compensate for signal loss due to image gating or cell circulation, and 
improved co-registration of molecular and anatomical images is also required.  
This initiative aims to attract researchers to address these technical 
challenges, facilitating the adaptation of existing imaging methodologies and 
fostering the development of novel technologies to image the cardiovascular, 
pulmonary, and blood systems.  These goals will require a multi-disciplinary 
approach, bringing together chemists, biologists, physicists, engineers and 
physicians to design and synthesize probes, and to develop and validate 
imaging systems and imaging protocols required to achieve functional cellular 
and molecular imaging in vivo.

Current methods for the analysis of cell-based therapies are largely 
restricted to invasive measurements in animal models. There is a need for 
alternative methods to monitor the movement and location of specific cell 
populations in vivo through the development of innovative, high-resolution 
cellular tracking techniques.  Particular emphasis needs to be placed on 
methods enabling the identification and characterization of processes 
involved in cell therapies using stem, progenitor, or differentiated cells, 
including cell mobilization, engraftment, and differentiation.  Integration 
of emerging in vivo cellular and molecular imaging and tracking capabilities 
with advances in stem cell biology and cell-based therapeutics for heart, 
lung, and blood disorders will be required for effective development and 
utilization of cell-based therapies.

The aim of this initiative is to develop in vivo molecular and cellular 
imaging methods. In vitro studies of isolated molecules and cells which are 
not likely to lead to in vivo applications and methods will not be considered 
responsive to the RFA. The following areas would represent appropriate topics 
for proposed projects.  This list is not intended to be all-inclusive, and 
other topics should be considered.

o   Imaging of probes targeted to specific cells or molecules involved in 
cardiovascular, pulmonary, and blood disease processes; e.g., plaque 
components, integrins expressed in angiogenesis, and molecular receptors.

o   Development of new imaging agents allowing identification and tracking of 
specific cell types and detection of specific cell populations derived from 
stem or progenitor cells.      

o   Use of probes activated by specific enzymes involved in cardiovascular or 
pulmonary disease processes to allow regional assessment of enzyme activity; 
e.g., metalloproteinase activation in the development of aneurysms or 
emphysema.

o   Development of new or improved software or hardware approaches to 
compensate for cardiac and pulmonary motion, facilitating quantitative 
measurement of tracers.

o   Development of new or improved software or hardware approaches to 
increase sensitivity and hence facilitate tracking of circulating blood cells 
in vasculature and in tissues.

o   Development and imaging of probes activated by specific environments 
relevant to cardiovascular and pulmonary disease, e.g. redox and pH-sensitive 
probes to detect oxidative stress and hypoxia.

o   Imaging methods for localization of specific cytokines, growth factors, 
or proteases in the heart, lungs, and bone marrow of individuals with 
cardiovascular, pulmonary, and blood diseases.

o   Improved methods for registration of images from different modalities, 
such as techniques for measuring spatial correlations of lung structure, 
(e.g., emphysema by CT) and function (e.g., perfusion and/or ventilation by 
MRI) with molecular indices of lung injury, inflammation, apoptosis, 
fibrosis, or repair.

o   Adaptation of optical techniques (e.g., fluorescence molecular 
tomography) to cardiovascular, pulmonary, and blood cell imaging.

o   Imaging methods aimed at specific molecular targets to visualize the 
anatomical distribution of specific cell types in the heart, vessels, lung, 
bone marrow, and circulation.

o   In situ generation of magnetic resonance probes by biocatalysis to 
monitor gene therapy and gene expression in the cardiovascular, pulmonary, 
and hematopoietic systems. 

o   Development of improved temporal and spatial cell localization using 
novel or existing cellular tracking technologies; e.g., in vivo 
bioluminescence, multiphoton microscopy, and magnetic resonance imaging.

MECHANISM OF SUPPORT
 
This RFA will use the NIH R01 award mechanism.  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  Future unsolicited, 
competing-continuation applications based on this project will compete with 
all investigator-initiated applications and will be reviewed according to the 
customary peer review procedures.  The anticipated award date is September 1, 
2004.  Applications that are not funded in the competition described in this 
RFA may be resubmitted as NEW investigator-initiated applications using the 
standard receipt dates for NEW applications described in the instructions to 
the PHS 398 application. Canadian applicants may apply to the Canadian 
Institutes of Health Research open competition as a new application.

This RFA uses just-in-time concepts.  It also uses the modular budget as well 
as the non-modular budgeting formats (see 
https://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
https://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm. 

Applications submitted by foreign institutions can request facilities and 
administrative (F&A) costs up to a maximum of eight percent.  Please see the 
web site https://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html  
for more information on allowable F&A costs for foreign grants and domestic 
grants with foreign components.

FUNDS AVAILABLE 
 
The NHLBI intends to commit approximately $7.5 million (total costs) in FY 
2004 to fund 10 to 15 new and/or competitive continuation grants, and up to 
$30 million (total costs) over a four year period. NIBIB intends to commit 
approximately $0.5 million (total costs) in FY 2004, and up to $2 million 
(total costs) over a four year period. The ICRH, in collaboration with other 
Canadian organizations, intends to commit approximately $2 million to fund 
meritorious applications, relevant to their mission, involving Canadian 
institutions.  ICRH will make the award of grants for meritorious 
applications of interest to them.  Applicants who wish to have their projects 
considered for funding by ICRH should include with their application a letter 
stating that their application and summary statement may be shared with ICRH.  
An applicant may request a project period of up to 4 years and a budget for 
direct costs of up to $500K per year.  Because the nature and scope of the 
proposed research will vary from application to application, it is 
anticipated that the size and duration of each award will also vary. Although 
the financial plans of the NHLBI provide support for this program, awards 
pursuant to this RFA are contingent upon the availability of funds and the 
receipt of a sufficient number of meritorious applications.
 
ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics: 
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based or community-based organizations 
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   
 
SPECIAL REQUIREMENTS

To be considered responsive to this initiative, projects must either include 
in vivo molecular or cellular imaging studies, or be directly applicable to 
the development of new technologies or improvement of existing techniques for 
in vivo molecular and cellular imaging.  Projects must also be of immediate 
relevance to the study of the cardiovascular, pulmonary, and hematopoietic 
systems.   

Grantees' Meeting

Upon initiation of the program, the NHLBI/NIBIB/ICRH will sponsor periodic 
meetings 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, should be included in the 
modules.  Applicants should also include a statement in their application 
indicating their willingness to participate in these meetings and to interact 
openly with other study participants so as to provide the greatest promise 
for scientific advances from the approved research scope of the awards.
 
WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to the following:

Molecular Imaging

For NHLBI:
Denis Buxton, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9044
Bethesda, MD  20892-7940
Bethesda, MD  20817 (for express delivery)
Telephone:  (301) 435-0516
Fax:  (301) 480-1454
Email: buxtond@nhlbi.nih.gov

For NIBIB:
John W. Haller, Ph.D.
Health Scientist Administrator
National Institute of Biomedical Imaging and Biomedical Engineering
6707 Democracy Blvd., Suite 200
Bethesda MD 20892-5469
Telephone:  301-451-4780
Fax:  301-480-4973
Email: hallerj@mail.nih.gov

Cell Tracking

John W. Thomas, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
Rockledge Two Centre, Room 10154
Bethesda, MD  20892-7950
Bethesda, MD  20817 (for express delivery)
Telephone:  (301) 435-0065
Fax:  (301) 451-5453
Email:  thomasj@nhlbi.nih.gov   

o Direct your questions about peer review issues to:

Anne P. Clark, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD  20892-7924
Bethesda, MD  20817 (for express delivery)
Telephone:  301-435-0270
Fax:    301-480-0730
Email:  clarka@nhlbi.nih.gov

o Direct your questions about financial or grants management matters to:

For NHLBI:

Gene McGeehan
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7142
Bethesda, MD  20892-7926
Bethesda, MD  20817 (for express delivery)
Telephone:  (301) 435-0177
Fax: (301) 480-3310
Email: mcgeehae@nhlbi.nih.gov

For NIBIB:

Florence Turska 
Grants Management Specialist 
National Institute of Biomedical Imaging and Bioengineering
6707 Democracy Blvd., Suite 200
Bethesda, MD 20892-2077
Telephone:  301-451-4782
Fax:  301-451-5735
turskaf2@mail.nih.gov

o   For any questions directed to ICRH please contact:

Elissa Hines Reimer
Senior Associate
Institute of Circulatory and Respiratory Health
Telephone: (613) 954-0544
Email: ehinesreimer@cihr.gc.ca
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent by mail or email to Dr. 
Anne Clark at the address listed under Where to Send Inquiries.

In addition, for this RFA, principal investigators located in Canada are 
requested to notify ICRH of their intent to apply by sending an email to 
icrh@cihr.gc.ca by the LOI deadline.

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.
  
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting 
up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
https://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application must be 
sent to send to Dr. Anne Clark at the address listed under Where to Send 
Inquiries.
  
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the applicant 
without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes.  While the 
investigator may still benefit from the previous review, the RFA application 
is not to state explicitly how.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI/NIBIB/ICRH.  

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/NIBIB/ICRH in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the NHLBI 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: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  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.

SIGNIFICANCE: Does this study address an important problem? If the aims of 
the project were achieved, would the project yield new understanding of 
and/or be clinically applicable to heart, lung, or blood disorders?

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?

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?

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)?

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?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL CONSIDERATIONS 

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  December 22, 2003
Application Receipt Date:  January 22, 2004
Peer Review Date:  May/June 2004
Council Review:  September 2004
Earliest Anticipated Start Date:  September, 2004

AWARD CRITERIA

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

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: https://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
https://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at 
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:   The 
Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003 (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 
2010," a PHS-led national activity for setting priority areas. This RFA is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

ICRH STRATEGIC DOCUMENTS: Applicants are encouraged to visit the ICRH 
website, accessible through the Canadian Institutes of Health Research 
homepage (www.cihr-irsc.gc.ca) for information concerning the ICRH mandate, 
current research initiatives and publications such as the Strategic Plan 
(available in English and French).

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
https://grants.nih.gov/grants/policy/policy.htm

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

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