BETA CELL BIOLOGY CONSORTIUM (U19)
 
RELEASE DATE:  June 21, 2004
 
RFA Number:  RFA-DK-04-017  (see addendum NOT-DK-04-016)

EXPIRATION DATE:  November 20, 2004

Department of Health and Human Services (DHHS)

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

COMPONENT OF PARTICIPATING ORGANIZATION: 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
 (http://www.niddk.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S) 93.847

LETTER OF INTENT RECEIPT DATE: October 19, 2004  
APPLICATION RECEIPT DATE:  November 19, 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 Supplementary Instructions
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 Institute of Diabetes and Digestive and Kidney Diseases invites 
new and the competitive continuation of applications to participate in an 
international consortium of investigators and institutions, the Beta Cell 
Biology Consortium (BCBC).  The BCBC will work collaboratively to conduct 
research to 1) understand how endogenous beta cells are made by studying 
pancreatic development, with the hope of making pancreatic islets in culture, 
2) explore the potential of animal and/or human stem cells (embryonic or 
adult; if human embryonic, only NIH-approved hES cell lines as a source for 
making pancreatic islets may be used), and 3) determine the basic mechanisms 
underlying beta cell regeneration in the adult as a basis for producing new 
cellular therapies for diabetes.  The BCBC will be responsible for 
collaboratively generating necessary reagents, mouse strains, antibodies, 
assays, protocols, and technologies that are beyond the scope of any single 
research effort. 
 
RESEARCH OBJECTIVES

Background

Type 1 and type 2 diabetes result from the anatomical or functional loss of 
insulin-producing beta cells of the pancreas.  Replacement of these cells 
through transplantation could offer lifelong treatment for diabetes.  A major 
obstacle in implementing treatment is the lack of sufficient islet cell 
tissue for transplantation.  The generation of an alternative source of 
pancreatic islet cells derived from human stem/progenitor cells (adult or 
embryonic) could provide a limitless source of islet cells for 
transplantation therapies.  

The Beta Cell Biology Consortium (BCBC) is a basic science consortium of 
cooperative agreements that originated in 2001 through an RFA DK-01-014 
http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-01-014.html.  In addition 
to investigator initiated research projects, consisting of 5 U19s and 1 U01, 
the BCBC supports an administrative infrastructure located at Vanderbilt 
University that oversees collaborative research cores designed to coordinate 
efforts in creating key research tools that will support studies in 
pancreatic development and function (http://www.betacell.org).  These resources were 
created to substantially accelerate efforts to efficiently differentiate 
animal and human embryonic and adult stem cells into pancreatic 
progenitor/islet tissue appropriate for transplantation.  

The BCBC was created in 2001 by RFA DK-01-014 as a direct response to 
recommendations of the Congressionally-established Diabetes Research Working 
Group http://www.niddk.nih.gov/federal/dwg/dwgsummary.htm that developed a 
strategic plan for research in diabetes.  Two of the extraordinary research 
opportunities recommended by the plan were “to increase basic research 
opportunities on the control and regulation of islet cell differentiation, 
growth and development” and “to create interdisciplinary centers for Beta 
Cell Biology to expand current efforts and bring new investigators into the 
field”.  

At a May 2002 NIH advisory committee meeting on the Use of Special 
Congressional Funds for Type 1 Diabetes Research, the advisory panel 
emphasized “continued investment in cellular therapy as a high priority”   
http://www.niddk.nih.gov/federal/planning/type1_specialfund/

A companion RFA, DK-04-018, will request new U01 grants.  The BCBC will be 
comprised of awardees from both RFA solicitations as well as the existing 
BCBC Coordinating Center located at Vanderbilt University and an existing U01 
at the University of Pennsylvania (U01 DK056947).  A U01 is a single project 
similar to an R01, and can have multiple collaborators. A U19 is composed of 
at least 3 subprojects and 1 or more cores similar to a P01.  

Research objectives

This RFA is intended to provide continuing support for the BCBC, focusing on 
research to understand the control and regulation of pancreatic development, 
as well as islet cell growth and regeneration.  Major scientific advances and 
technological breakthroughs in basic disciplines such as developmental 
biology, stem cell biology, mouse genetics, and bioinformatics demand that a 
multifaceted, interdisciplinary, coordinated and collaborative approach on 
several fronts be utilized to generate key reagents, assays and new 
strategies for the development of novel cellular therapies in diabetes.  
Therefore, at least 50% of the overall application should be directly related 
to the generation of these novel resources and approaches, and could include 
development of new assays or protocols, development of new animal models, 
and/or application of a new technology or new technologies.  

The NIDDK will fund as components of the Beta Cell Biology Consortium 
approximately three to four applications, each supporting a highly 
interactive and synergistic team that will agree to work together to 
establish common research goals and to generate necessary reagents which can 
then be shared.  Each program, consisting of at least three projects and one 
or more cores, must address at least one of the three targeted scientific 
goals described below:  Beta Cell Development, Beta Cell Regeneration, and/or 
Stem Cell Biology.
 
Beta Cell Development
A goal of this RFA and the BCBC is to understand the developmental pathways 
required to produce a fully functioning pancreatic islet. 

Areas of emphasis may include but are not restricted to:

o Characterizing sets of specific mouse strains for genes that would mark 
specific cell lineages in the pancreas and/or regulate fate decisions within 
the organ. New mouse strains should be created through coordination with the 
BCBC Mouse ES and Transgenic Core http://www.betacell.org/php/cc.php;

o Characterizing poly- and monoclonal antibodies to cell surface antigens to 
define critical stages of pancreas development, including cell-specific 
antibodies that would delineate stem/progenitor cells of the pancreas and be 
useful for purification of these cells. New antibodies should be developed 
through coordination with the BCBC Antibody Core 
http://www.betacell.org/php/cc.php;

o Discovering mechanisms that control pancreatic cell fate decisions using 
classical vertebrate embryology; 

o Identifying mesenchymal signals that promote pancreatic growth;
  
o Identifying the signals that regulate the temporal differentiation of islet 
cells during normal endocrine development;

o Identifying the signals that support islet cell morphogenesis, growth, 
function and survival; 

o Combining molecular and computational approaches to identify the 
transcriptional networks that regulate pancreatic development.

Beta Cell Regeneration
A goal of this RFA and the BCBC is to understand the mechanisms of beta cell 
regeneration in the adult animal and human.
 
Areas of emphasis may include but are not restricted to:

o Determining the factors important for beta cell regeneration and designing 
strategies to foster regeneration;

o Developing new animal models, such as non-human primates transplanted with 
human islets that can be used to identify exogenous or endogenous factors 
that might promote beta cell regeneration;

o Characterizing the lineage of cells that may contribute or participate in 
beta cell regeneration by genetic marking;

o Developing assays to screen chemical libraries for modifiers of beta cell 
regeneration, differentiation, and/or expansion.

Stem Cell Biology
A goal of this RFA and the BCBC is to understand the nature of 
stem/progenitor cells during normal pancreatic development and in adult 
islets.

Areas of emphasis may include but are not restricted to:

o Characterizing pancreatic stem/progenitor cells during normal development;

o Providing genetic evidence for stem/progenitor cells in the adult pancreas;

o If pancreatic stem cells exist in the adult, designing strategies to foster 
development of new endocrine cells in vivo; 

o Comparing different sources of human pancreatic progenitor cells at the 
molecular level;
      
o Using existing NIH-approved human ES cell lines or mouse embryonic cells to 
efficiently generate endoderm, pancreatic progenitor cells, or differentiated 
beta cells in culture;

o Developing clonogenic assays for quantitatively assessing the efficacy of 
new cellular replacement therapies.

MECHANISM OF SUPPORT
 
This RFA will use NIH U19 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.  The anticipated award date is 
July 31, 2005. 

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/archive/grants/policy/nihgps_2001/part_i_1.htm.  

The NIH U19 is a cooperative agreement award mechanism. In the cooperative 
agreement mechanism, the Principal Investigator retains the primary 
responsibility and dominant role for planning, directing, and executing the 
proposed project, with NIH staff being substantially involved as a partner 
with the Principal Investigator, as described under the section "Cooperative 
Agreement Terms and Conditions of Award".  Continuation of the cooperative 
agreement project beyond the initially award period of performance will 
require an RFA or other announcement.  

FUNDS AVAILABLE 

The NIDDK intends to commit approximately $5.0 million in FY 2005 to fund 3-4 
grants in response to this RFA. An applicant may request a project period of 
up to 5 years and a budget for direct costs of up to $1.0 million 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 NIDDK 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. The receipt of competing continuation applications is 
anticipated.  These applications will compete together with new applications 
received in response to this announcement. Past involvement in the BCBC is 
not necessary or sufficient to ensure a future award.  
 
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. 

The Principal Investigator may apply for either a U01 (RFA-DK-04-018) or a 
U19, but not both.

SPECIAL REQUIREMENTS 

To promote the development of a collaborative program among the award 
recipients, the Principal Investigator and a Co-Principal Investigator or 
other senior investigator are expected to attend BCBC Steering Committee 
meetings twice a year.  A major goal of these meetings is to facilitate 
progress by providing a forum that will lead to sharing skills, ideas, 
technology, data, and biological reagents.  At the meetings, participants 
will discuss quality assurance, bioinformatics, coordination, sharing, and a 
means of informing the community about progress made by the Consortium.  
Funds should be requested to attend Steering Committee meetings as well as 
other collaborative meetings of the BCBC. 

During the course of the funding period, technologies will improve and the 
rate of progress and scope of the research may change.  It is expected that 
the Principal Investigators, in consultation with NIDDK program staff, will 
make necessary adjustments to accommodate the changing research environment, 
to remain focused on appropriate goals, to maintain excellent coordination 
with the other projects funded under this RFA and the companion RFA,
RFA-DK-04-018, and to incorporate new technological advances.

HESC requirements

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).   

Data and Reagent Sharing:

All applications submitted through this announcement and the companion 
RFA (RFA-DK-04-018) must include technology transfer and sharing plans for 
both data and unique research resources that are generated by the projects in 
concordance with the BCBC policies 
http://www.betacell.org/php/about.php#policies.  It is expected that 
resources developed by the BCBC will be made available to the broader 
scientific community, after a propriety period, at no charge other than the 
cost of reproduction and distribution. Applicants must indicate their 
willingness to distribute research tools to the wider community including 
antibodies, transgenic mouse strains, mouse ES cell lines, and other 
reagents.  A distribution plan should be included.  Likewise the applicants 
must describe their willingness to submit microarray data generated through 
this project to EPConDB http://www.betacell.org/php/epcondb.php and other 
pertinent information about research resources generated through this U19 to 
the BCBC Coordinating Center http://www.betacell.org/php/cc.php.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF THE AWARD

A.  Applicability.  
These special Terms of Award are in addition to and not in lieu of otherwise 
applicable OMB administrative guidelines, HHS Grant Administration 
Regulations at 45 CFR Parts 74 and 92, and other HHS and NIH Grant 
Administration policy statements.  

The administrative and funding instrument used for this program is a 
cooperative agreement (U19), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance 
of the activity. 
 
Under the cooperative agreement, the NIH purpose is to support and/or 
stimulate the recipient's activity by involvement in and otherwise working 
jointly with the award recipient in a partner role, but NIH will not assume 
direction, prime responsibility, or a dominant role in the activity.  

Consistent with this concept, the dominant role and prime responsibility for 
the activity resides with the awardee for the project as a whole, although 
specific tasks and activities in carrying out the studies will be shared 
among the awardees and the NIDDK Project Scientist or designee.

Under the cooperative agreement, a relationship will exist between the 
recipient of these awards and the NIDDK, in which the performers of the 
activities are responsible for the requirements and conditions described 
below, and agree to accept program technical assistance, advice and/or other 
coordination above and beyond normal program stewardship from a named NIDDK 
Project Scientist in achieving the project objectives.

Failure of an awardee to meet the performance requirements, including these 
special terms and conditions of award, or significant changes in the level of 
performance, may result in a reduction of budget, withholding of support, 
suspension and/or termination of the award.

B.  Awardee Rights and Responsibilities

The Awardee is a member of the Beta Cell Biology Consortium (BCBC) and is 
responsible for:

o Defining objectives and approaches, and planning, conducting, analyzing, 
and publishing results, interpretations, and conclusions of studies conducted 
under the terms and conditions of the cooperative agreement award;

o Conducting the research supported by the project in accordance with the 
terms and conditions of the award;

o Participating as a permanent, voting member(s) of the Steering Committee;

o Contributing to and implementing the goals, priorities, procedures, and 
policies agreed upon by the Steering Committee;

o Coordinating and collaborating with the other components of the BCBC and 
with the NIDDK staff;

o Contributing to BCBC Core resources and serving on BCBC subcommittees as 
needed;

o Sharing both data and unique research resources that are generated by the 
projects in concordance with the BCBC policies;

o Awardees will retain custody of, and have primary rights to, the data 
developed under these awards, subject to Government rights of access 
consistent with current HHS and NIH policies.

C. NIDDK Staff Responsibilities

An NIDDK Program Director identified in the Notice of Grant Award will be 
responsible for the normal stewardship and monitoring of the award and will 
serve as the NIDDK Project Scientist.  

The NIDDK Project Scientist will have substantial scientific-programmatic 
involvement during conduct of this activity, through technical assistance, 
advice and coordination.  The dominant role and primary responsibility for 
the activity resides with the awardees for the project as a whole, although 
specific tasks and activities in carrying out the studies will be shared 
among the awardees and the NIDDK Project Scientist. 

An NIDDK Project Scientist will have substantial involvement in the project 
above and beyond normal stewardship and monitoring of the award, as described 
below:

o Being a voting member of the Steering Committee and, as determined by that 
committee, its subcommittees;

o Being the contact point for all facets of the scientific interaction with 
awardee(s).  As required for the coordination of activities and to expedite 
progress, NIDDK may designate additional NIDDK staff to provide advice to the 
awardee on specific scientific issues.  

o Serving as a resource with respect to other ongoing NIDDK activities that 
may be relevant to the research of the BCBC in order to facilitate 
compatibility and avoid unnecessary duplication of effort.

Responsibilities as NIDDK Program Director:

o Retaining overall programmatic responsibility for the award, and will 
clearly specify to the awardee the name(s) and role(s) of any additional 
individuals with substantial involvement in the project and the lines of 
reporting authority

o Interacting with the Principal Investigator(s) on a regular basis to 
monitor research progress.  Monitoring may include:  regular communications 
with the principal investigator and staff, periodic conference calls for 
discussions with awardee research teams, quality control, fiscal review, and 
other relevant matters; as well as attendance at Steering Committee meetings, 
External Advisory Board Meetings, and related meetings.  The NIDDK retains, 
as an option, periodic external review of progress.

o Reviewing and approving applications of the Pilot and Feasibility Program 
to insure that they are within the scope of peer review and NIH guidelines  

o Making recommendations for continued funding based on: a) overall research 
progress, b) cooperation in carrying out the research (e.g. attendance at 
Steering Committee meetings, implementation of group decisions, compliance 
with the terms of award, and c) maintenance of a high quality of research, 
which will allow pooling of data and comparisons across multiple cooperative 
agreement awards for common data elements

D.  Joint Responsibilities
   
BCBC Steering Committee

o The Steering Committee will be composed of the Principal Investigator and a 
Co-Principal Investigator or other senior investigator from each U19 project 
or the Principal Investigator from each U01 project and the NIDDK Project 
Scientist.  The two investigators from each U19 project and the Principal 
Investigator from each U01 project and the NIDDK Project Scientist will each 
have one Steering Committee vote.  The chairperson will be someone other that 
the NIDDK Project Scientist, and will be selected by NIDDK. 

o The Steering Committee has primary responsibility for establishing 
priorities, develop common protocols, and review progress.  The Steering 
Committee will refine the BCBC scientific objectives consistent with progress 
in the BCBC components and other laboratories.  Major scientific decisions 
regarding BCBC core data and resources, as well as setting scientific 
priorities for special programs such as the Pilot and Feasibility Program 
will be determined by the Steering Committee.  The Steering Committee will 
document progress in written reports to the NIDDK Program Director, and will 
provide supplementary reports upon request.  

o There will be two Steering Committee meetings annually, one in the Spring 
and the other in the Fall. 

o The Steering Committee may, when necessary, invite additional, non-voting 
scientific advisors to the meetings at which research priorities and 
opportunities are discussed.  The NIDDK reserves the right to augment the 
scientific expertise of the BCBC when necessary.   

o At the Fall meeting each year, the Steering Committee will formulate plans 
for any additional meetings or symposia to be held.

o The BCBC members will serve on subcommittees, scientifically review 
applications for special programs such as the Pilot and Feasibility Program 
(http://www.betacell.org/php/cc.php), as it is deemed appropriate; the NIDDK 
Project Officer will serve on subcommittees as appropriate.  NIDDK staff with 
special expertise may serve on subcommittees at the request of the Steering 
Committee.  Subcommittee chairs will be selected from the Steering Committee 
and will report progress at Steering Committee Meetings and lead discussions 
at the Annual Investigator’s Retreat (http://www.betacell.org/php/cc.php).

External Advisory Board

An independent External Advisory Board has been established by the NIDDK.  
The External Advisory Board will review periodically interim progress of the 
BCBC including the Scientific Cores, Pilot and Feasibility Program and any 
other special activities of the BCBC and report to NIDDK.  The External 
Advisory Board will continue to meet annually. An NIDDK staff person other 
than the NIDDK Project Scientist/Program Director will serve on the External 
Advisory Board and organize these meetings. 

E. Arbitration

Any disagreement that may arise on scientific/programmatic matters (within 
the scope of a U01 or U19 award) may be brought to arbitration.  An 
arbitration panel will be composed of three members--one selected by the 
awardee (or Steering Committee, with the NIDDK Project Scientist not voting), 
a second member selected by the NIDDK; and, the third member selected by the 
two prior selected members.  This special arbitration procedure in no way 
affects the awardee's right to appeal an adverse action that is otherwise 
appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart 
D and HHS regulation at 45 CFR Part 16.
 
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:

Sheryl Sato, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 6105
Bethesda, MD  20892-5460
Telephone: (301) 594-8811
FAX: (301) 480-3503
Email:  ss68z@nih.gov 

o Direct your questions about peer review issues to:

Francisco O. Calvo, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: fc15y@nih.gov 

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

Mary K. Rosenberg
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 708
Bethesda, MD  20892-5452
Telephone:  (301) 594-8891
FAX:  (301) 594-9532
Email: mr239@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:

Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505

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 document 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.

SUPPLEMENTARY INSTRUCTIONS

General Application Format Instructions

In preparing a Beta Cell Biology Consortium U19 application, applicants 
should follow the NIDDK administrative guidelines for preparing a Program 
Project Grant that are available at 
(http://www.niddk.nih.gov/fund/divisions/DEA/review_branch/P01guidelines.htm) 
or from staff listed under Inquiries below.  Note however, that budget caps 
for the P01 are not applicable to a Beta Cell Biology U19.  A Beta Cell 
Biology U19 must propose a minimum of 3 projects.  Collectively these 
projects should demonstrate essential elements of unity and interdependence 
and result in a greater contribution to program goals, as well as to BCBC 
goals, than would occur if each project were pursued individually.  The 
relationship and contributions of each research component and core to the 
overall theme of the BCBC should be discussed.  These U19s provide support 
for research projects as well as common resources and facilities (cores) that 
are available to individual projects comprising the U19.  The common 
resources and facilities in an individual U19 should not duplicate or overlap 
with the effort of existing BCBC scientific cores.  Cores must provide 
essential functions, services, techniques, determinations or instrumentation 
that will enhance at least 2 individual research projects.  Subcontract 
budgets should be listed on a separate page, and the subcontract fiscal and 
administrative costs should be calculated and listed in the usual place as 
part of the direct costs of the budget.  However, only the direct costs 
associated with each subcontract will count toward the direct costs cap of $1 
million on the budget for the first year.  The total costs for the 
applications are not capped. 

Competing renewals should include as part of their progress report a 
description of the common resources or data that they have developed and 
shared, as well as their specific contributions to the BCBC steering 
committee, BCBC Scientific Cores and/or subcommittees, the BCBC reagent 
databases (http://www.betacell.org) and/or EPConDB 
http://www.cbil.upenn.edu/EPConDB/, and the BCBC Investigator’s Retreat 
(http://www.betacell.org/php/cc.php).

Applicants must budget for travel and per diem that will allow the Principal 
Investigator, and designated Co-PI or senior investigator of the U19 to 
participate in 2 steering committee meetings each year.  In addition, 
applicants should plan that at least 5 investigators per U19 grant will attend 
the Annual Investigator’s Retreat, as well as Subcommittee meetings throughout 
the year.  There will be at least one interim review meeting conducted by the 
External Scientific Board and NIDDK in which all participating subproject 
leaders and core directors are required to attend, and applicants will be 
expected to include funds for all required meetings in their travel budget.

Additional materials

The “Research Plan” should have a section entitled “Collaboration within the 
BCBC.”  In this section:

o The applicant should describe how they believe their unique expertise can 
contribute to the collective efforts of the BCBC.

o In generating unique research tools, applicants should describe their 
willingness to cooperate and coordinate with the research activities and 
priorities of the BCBC Antibody Core/Database 
(http://www.betacell.org/php/cc.php), the BCBC Mouse/ES Core 
(http://www.betacell.org/php/cc.php) and the Endocrine Pancreas Consortium 
Database (http://www.cbil.upenn.edu/EPConDB).
All protocols, antibodies, vectors, cells, animals and data generated through 
the BCBC will be made freely available to the general scientific community. 
In working with the BCBC Coordinating Center at Vanderbilt 
(http://www.betacell.org), and Steering Committee, applicants must agree to 
distribute unique resources developed through the BCBC.

o The application must reflect adequate time commitment of personnel.  Levels 
of effort that are awarded will vary depending on the requirements of the 
research to be performed and the anticipated contributions to the BCBC.

o The BCBC is a collaborative effort that requires frequent interactions of 
awardees among themselves and with the NIH.  Applicants must explicitly 
indicate their willingness to:  participate in Steering Committee Meetings (2 
times per year), regular telephone conference calls; cooperate with other 
awardees in the development and design of research priorities, especially 
regarding resources, and accept the Cooperative Agreement Terms and 
Conditions of Award given above.

o Budget Information:  The actual award will vary yearly, depending upon the 
work scope of the BCBC scientific cores, and special programs such as the 
Pilot and Feasibility Program.

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: 
http://grants.nih.gov/grants/funding/phs398/labels.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
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and all 
copies of the appendix material must be sent to:

Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
(for express/courier service: Bethesda, MD 20817)

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 from the 
previous unfunded version of the application.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR.  
NIDDK will conduct the review.  The Chief of the Review Branch, assigned SRA, 
and NIDDK Program Staff will conduct an administrative review to determine if 
the application is responsive to the RFA, or missing any information. 
Incomplete applications will not be reviewed and will be returned to the 
applicant.  

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

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 written critique
o Receive a second level review by the National Diabetes and Digestive and 
Kidney Diseases 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 evaluate the 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 the following criteria in assigning the 
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, an investigator may propose to generate important 
reagents or tools that by its nature are not innovative but are essential to 
move a field forward.  The application should focus on generating important 
reagents and tools for the BCBC and general scientific community, and on 
conducting challenging research projects in a cooperative spirit that might 
be considered too descriptive, ambitious, risky, or less likely to succeed as 
an individual program project grant.   
 
SIGNIFICANCE: Does this study address an important problem in beta cell 
biology? 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?  Will the resources or technology 
to be developed be useful to investigators working in pancreatic development 
and stem cell biology and furthermore, benefit the larger beta cell 
biology/diabetes community?  

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? 

COLLABORATION:  Does the applicant provide evidence of sharing and developing 
reagents?  Does the applicant state their intention to cooperate with other 
BCBC members? 
 
ADDITIONAL REVIEW CRITERIA: 

In addition to the above criteria, the following will be considered in the 
determination of scientific merit and the priority score both in new and 
competitive renewals of U19s. 
(http://www.niddk.nih.gov/fund/divisions/DEA/review_branch/P01guidelines.htm; 
SEE IX. REVIEW GUIDELINES C. THROUGH G.) 

The following items will be considered in determination of scientific merit 
and the priority for competitive renewals of U19s:

o Documentation of experience and ability in all aspects of managing and 
coordinating a large basic science Cooperative Agreement;  

o Documentation of participation in BCBC Scientific Cores and/or 
Subcommittees;

o Documentation of contributions to BCBC reagent databases http://www.betacell.org 
and/or EPConDB http://www.cbil.upenn.edu/EPConDB/;

o Documentation of participation in Steering Committee Meetings, Subcommittee 
Meetings, and BCBC Investigator’s Retreat 
(http://www.betacell.org/php/cc.php)

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 REVIEW 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:          October 19, 2004
Application Receipt Date:               November 19, 2004
Peer Review Date:                       March-April 2005
Council Review:                         May 2005 Council
Earliest Anticipated Start Date:        July 31, 2005

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 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on Humane Care 
and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA 
Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

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 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.   (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://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. 

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 
http://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 
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 RFA 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).  

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 
http://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.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ in the following 
citations:  No. 93.847, Diabetes Research, No. 93.855. 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.  This program is not subject to the intergovernmental 
review requirements of Executive Order 123472 or Health Systems Agency 
review. The NIH Grants Policy Statement can be found at 
http://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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NIH Funding Opportunities and Notices


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