NHLBI COMPETITIVE SUPPLEMENTS FOR HUMAN EMBRYONIC STEM CELL RESEARCH 

RELEASE DATE:  December 12, 2003
 
PA NUMBER:  PAR-04-037 (This PA has been reissued, see PAR-05-047)

EXPIRATION DATE:  February 13, 2004.

Department of Health and Human Services (DHHS) 

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Heart, Lung, and Blood Institute (NHLBI) 
 (http://www.nhlbi.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.837, 93.838, 93.839

LETTER OF INTENT RECEIPT DATE:  January 13, 2004
APPLICATION RECEIPT DATE:  February 13, 2004 

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism 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 Supplemental Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA 

The purpose of these supplements is to enable NHLBI grantees with little or 
no prior experience working with human embryonic stem (ES) cell lines to 
conduct research with these cell lines that is directly related to the aims 
of an existing, funded NHLBI grant. The research proposed in the supplement 
should be within the scope of the existing NHLBI grant and may not expand the 
original scope of the parent grant. Only research using human ES cell lines 
listed in the NIH Human Embryonic Stem Cell Registry will be eligible for 
Federal funding (see http://escr.nih.gov/).

RESEARCH OBJECTIVES

On August 9, 2001 President Bush announced his decision to allow Federal 
funds to be used for research on existing eligible human ES cell lines.  In 
order to facilitate research, the NIH Human Embryonic Stem Cell Registry 
lists the human ES cell lines that meet the eligibility criteria (see 
http://escr.nih.gov/).  The availability of human ES cell lines for Federally 
funded research affords a unique opportunity for investigators to use these 
cell lines to address fundamental biomedical research questions.  However, 
most investigators have had little or no prior experience in working with 
human ES cells and have not had the opportunity to propose research aims 
utilizing human ES cells in their grant applications.  This notice provides 
the opportunity for NHLBI grantees to incorporate the use of human ES cells 
into their experimental plan when the proposed supplemental research falls 
within the original scope of the parent grant and is a logical extension of 
the goals and objectives.

MECHANISM OF SUPPORT 

This PA will use the NIH competitive supplement to an existing NHLBI award.  
As an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  This PA is a one-time solicitation.  

This PA uses just-in-time concepts.  It also uses the modular budgeting as well as 
the non-modular budgeting formats (see 
http://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 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.  

FUNDS AVAILABLE
 
The NHLBI intends to commit approximately $1,125,000 in FY 2003 to fund up 
to 15 competitive supplements in response to this PA.  An applicant may 
request a project period of 1 or 2 years and a budget for direct costs of 
up to $50,000 per year.  The supplement award period cannot extend beyond 
the project end date of the parent grant.  Although the financial plans of 
the NHLBI provide support for this program, awards pursuant to this PA 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 institutions/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

The applicant must be the principal investigator on an existing NHLBI funded 
Research Project (R01, R37, or U01), Exploratory/Developmental Project (R03 
or R21), Phase II SBIR (R44), Program Project (P01), or Specialized Center  
(P50, P60, U10 or U54) award.

Competitive supplements are available to NHLBI grantees to conduct research 
using human embryonic stem (ES) cell lines.  All human ES cell lines used 
must be listed on the NIH Human Embryonic Stem Cell Registry 
(http://escr.nih.gov/). Additional guidance on Federal funding of human 
embryonic stem cell research is listed in the citations at the end of this 
announcement.

Competitive supplements can only be awarded for research that is within the 
scope of an existing funded NHLBI Research Project (R01, R37, or U01), 
Exploratory/Developmental Project (R03 or R21), Phase II SBIR (R44), Program 
Project (P01), or Specialized Center (P50, P60, U10, or U54) award. The Principal 
Investigator must be the same person as is the current Principal Investigator on 
the original application.  A supplemental application will not be accepted until 
after the original application has been awarded, and may not extend beyond the term 
of the current grant. Investigators carrying out murine ES cell work may elect to 
request funding to extend their investigations to human ES cell lines.  Other 
investigators carrying out stem cell research, developmental studies, or 
other related studies are also encouraged to apply.  In all cases, a careful 
explanation and justification for the supplement as a logical extension of 
the ongoing research must be included.   

Investigators must contact the human ES cell line providers listed on the NIH 
Registry independently and make arrangements to obtain the cell lines, 
including any required material transfer agreements (MTA).  Applicants must 
indicate which human ES cell line or lines will be used. The NIH registry number 
for all ES cell lines to be used must be in the Description on Page 2.  A letter or 
agreement indicating the provider will supply the human ES cell line must be 
furnished either with the application or prior to issuance of the award.  The 
investigators should also demonstrate prior ability to work with human ES cell 
lines or outline their plans for obtaining training in the culture of human ES 
cells.  The human ES cell line providers, other laboratories with ES cell 
experience, or laboratory training courses on ES cell methods are potential means 
of obtaining this training.  Other means for acquiring human ES cell expertise may 
also be proposed.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA 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:

Dr. John W. Thomas
Division of Blood Diseases and Resources / NHLBI
6701 Rockledge Drive / Room 10154 /Mail Stop 7950
Bethesda, MD  20892-7950
Telephone:  (301) 435-0050
FAX:  (301) 451-5453
E-mail:  ThomasJ@nhlbi.nih.gov

John Fakunding, Ph.D.
Division of Heart and Vascular Diseases / NHLBI
6701 Rockledge Drive / Room 9170 / Mail Stop 7940
Bethesda, MD  20892-7940
Telephone:  (301) 435-0544
FAX:  (301) 480-1336
E-mail:  FakundiJ@nhlbi.nih.gov

Dr. Mary Ann Berberich
Division of Lung Diseases / NHLBI
6701 Rockledge Drive /Room 10102 / Mail Stop 7952
Bethesda, MD  20892-7952
Telephone:  (301) 435-0222
FAX:  (301) 480-3557
E-mail:  BerberiM@nhlbi.nih.gov

o Direct your questions about peer review issues to:

Sherry Dupere, Ph.D.
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive
MSC 7843, Room 5136
Bethesda, MD 20892
(for express mail use zip 20817 and remove MSC 7843)
Tel. (301) 435-1021
Fax (301) 480-1677
Email:  DupereS@csr.nih.gov 

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

Marsha Mathis 
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7158, MSC 7926
Bethesda, MD 20892-7926
Telephone:  (301) 435-0170
FAX:  (301) 480-3310
Email:  MathisM@nhlbi.nih.gov 

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
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 to:

Sherry Dupere, Ph.D.
Center for Scientific Review
National Institutes of Health
6701 Rockledge  Drive
MSC 7843, Room 5136
Bethesda, MD 20892
(for express mail use zip 20817 and remove MSC 7843)
Tel. (301) 435-1021
Fax (301) 480-1677
Email:  DupereS@csr.nih.gov 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet 
(D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier 
when applying for Federal grants or cooperative agreements. The DUNS number can be 
obtained by calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of 
the face page of the PHS 398 form. The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  
For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.

The title and number of this program announcement must be typed on line 2 of the 
face page of the application form and the YES box must be checked.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted only for the date listed at the beginning of 
this document.

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 
http://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 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SUPPLEMENTARY INSTRUCTIONS

Overview

A competing supplemental application may be submitted to request support for 
a significant expansion of a project's scope or research protocol.  The Principal 
Investigator must be the same person as is the current Principal Investigator on 
the original application. Applications for competitive supplements are not 
appropriate when the sole purpose is to restore awards, administratively reduced by 
the funding agency, to the full SRG-recommended level. A supplemental application 
will not be accepted until after the original application has been awarded, and may 
not extend beyond the term of the current grant. 

Introduction

The Introduction to the supplemental application should provide an overall 
description of the nature of the supplement and how it will influence the 
specific aims, research design, and methods of the current grant. If the 
supplemental application relates to a specific line of investigation 
presented in the original application that was not recommended for approval 
by the SRG, then the applicant must respond to the criticisms in the prior 
summary statement, and substantial revisions must be clearly evident and 
summarized in the introduction. The introduction should not exceed one page.

Research Plan

The body of the application should contain sufficient information from the 
original grant application to allow evaluation of the proposed supplement in 
relation to the goals of the original application.  The regular Research Plan 
format should be followed but is limited to 10 pages excluding references.  
The research plan includes specific aims, background and significance, 
preliminary studies, and research design and methods (Sections A to D).

Progress Report

A progress report is required for supplemental applications. Provide the 
beginning and ending dates for the period covered since the project was last 
reviewed competitively.  Summarize the previous application's specific aims 
and the importance of the findings.  Discuss any changes in the specific aims 
as a result of budget reductions for the current grant.

Modular Budget

If the original application used a modular budget, then Modular Budget Procedures 
apply to competing supplemental applications.  Otherwise follow the instructions 
for non-modular budget research grant applications.   The modules requested should 
reflect the total direct costs only of items for which additional funds are 
requested.  If the initial budget period of the supplemental application is less 
than 12 months, prorate the personnel costs and other appropriate items of the 
detailed budget. Any budgetary changes for the remainder of the project period of 
the current grant should be discussed under the budget justification.

In summary, the application should include:

o A one page Introduction
o The 10-page research plan, excluding references, which includes specific 
aims, background and significance, preliminary studies, and research design 
and methods (Sections A to D).
o A description of the proposed supplemental activity and how it is related 
to the specific aims and objectives of the parent grant
o The significance and potential impact of the supplement on ongoing research 
in the field
o A summary of the expected overall impact of the requested supplement on 
ongoing research results
o The NIH registry number for all ES cell lines to be used must be in the 
Description on Page 2. 
o A description of prior experiences working with human ES cell lines or an 
outline of plans for obtaining training on human ES cell culture methods.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five 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)

APPLICATION PROCESSING: Applications must be received by the application 
receipt date listed at the beginning of this document.  If an application is 
received after that date, it will be returned to the applicant without 
review. 

The CSR will not accept any application in response to this PA that 
is essentially the same as one currently pending initial review unless the 
applicant withdraws the pending application.  The CSR will not accept any 
application that is essentially the same as one already reviewed.  This does 
not preclude the submission of a substantial revision of an application 
already reviewed, but such application must include an Introduction 
addressing the previous critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o 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 your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals.  The scientific review group will address and consider each of these 
criteria in assigning your application's overall score, weighting them as 
appropriate for each application.   

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
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, 
you 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 your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?  Is the proposed supplemental activity related to the 
specific aims and objectives of the parent grant?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR:  Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?  Is a 
description of prior experience working with human ES cell lines or an 
outline of plans for obtaining training on human ES cell culture methods 
provided?

(5) ENVIRONMENT:  Does the scientific environment in which your 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?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  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.

INCLUSION:  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 included in the 
section on Federal Citations, below)

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:  January 13, 2004
Application Receipt Date:  February 13, 2004
Peer Review Date:  June 2004
Council Review:  Not Applicable
Earliest Anticipated Start Date:  July 1, 2004

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities.

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

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

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

Applicants may wish to place data collected under this 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.

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 PA 
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. 

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance No. 93.839, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92. 

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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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