**DIABETES ENDOCRINOLOGY RESEARCH CENTERS**

DIABETES RESEARCH AND TRAINING CENTERS

ADMINISTRATIVE GUIDELINES

NATIONAL INSTITUTE OF DIABETES AND

DIGESTIVE AND KIDNEY DISEASES

**August 2001**

**TABLE OF CONTENTS**

I. Description 4

Background 4

General Description 4

Basic Requirements 5

II\. Administrative Core Component 6

Description 6

Requirements 6

III\. Biomedical Research Component 7

Research Base 7

Biomedical Research Cores 8

Definition

Justification for proposing a core

Personnel

Facilities, space, and special arrangements

Management of the core

Relation of core services to individual research project grants

Renewal applications

Pilot and Feasibility Program 10

Definition

Requirements

Eligibility and related guidelines

Initial review and management of the pilot and feasibility program

Review of the pilot and feasibility program in renewal applications

> Funding levels for the pilot and feasibility program on renewal
> applications

Research Training 14

IV\. Pre-application Process 14

V. Preparation of Application 15

Description 15

Content Order for Applications 15

VI\. Budget Considerations 18

VII\. Review Process and Criteria 19

VIII\. Evaluation and Reporting Requirements 21

IX\. Special Considerations 22

Illustration I Consolidated Budget for 1st Year

of Requested Support 23

Illustration II Distribution of Professional Effort (%) on This

Application 24

Illustration III Summary of Total Current and Pending Support of

All Center Participants 25

Illustration IV Publications Citing Support from this Core Center 26

Illustration V Use of Core Facilities 27

**I. DESCRIPTION**

##### Background

The NIDDK-supported Diabetes Endocrinology Research Centers (DERCs) and
Diabetes Research and Training Centers (DRTCs) are part of an integrated
program of diabetes and related endocrinology and metabolism research.
Centers provide increased, cost effective, collaboration among
multidisciplinary groups of investigators at institutions with an
established, comprehensive research base in diabetes and related areas
of endocrinology and metabolism. DERCs and DRTCs are intended to improve
the quality and multidisciplinary nature of research on diabetes by
providing shared access to specialized technical resources and
expertise.

##### General Description

Both DERCs and DRTCs are intended to facilitate progress in research
with the goal of developing new methods to treat, prevent and ultimately
cure diabetes mellitus and its complications. Both DERCs and DTRCs
support research cores that provide shared resources to enhance the
efficiency of biomedical research and foster collaborations within and
among institutions with established, comprehensive bases of research
relevant to diabetes mellitus. Both types of center also support a Pilot
and Feasibility Program and an Enrichment Program. DRTCs differ from
DERCs in that they provide additional support for cores and pilot and
feasibility projects directed at prevention and control of diabetes.
These should focus on translation of research advances into clinical
practice.

The objectives of the Centers are to bring together investigators from
relevant disciplines in a manner that will enhance and extend the
effectiveness of their research. In addition to collaborations between
scientists within an institution, core centers can foster interaction
and collaborations between investigators at multiple institutions to
promote a multifaceted approach to a common goal. A core center must be
an identifiable unit within a single university medical center or a
consortium of cooperative institutions, including an affiliated
university. An outstanding existing program of biomedical research in
the area of diabetes is required. This research should be in the form of
NIH-funded research projects (R01), program projects (P01), or other
peer-reviewed research, such as that supported by the American Diabetes
Association and the Juvenile Diabetes Foundation. This established
research program must be in existence at the time of submission of a
center application. Research programs outside the primary institution
where the center is based may utilize the core resources. The base of
research projects to be served by the cores must be clearly defined and
justified in the application. The research base for the Center must
consist of at least \$2,000,000 of peer reviewed research projects.
Efficient management of resources and close cooperation, communication,
and collaboration among involved personnel in multiple professional
disciplines are ultimate objectives of core centers.

##### Basic Requirements for a P30 Core Center

To be eligible for a Core Center grant, the potential applicant
institution must already have a substantial base of ongoing,
independently-supported, high-quality research in diabetes and related
areas of endocrinology and metabolism. The research base for a core
center is made up of investigators with individually-funded research
projects who can benefit from shared resources. Core center funding will
provide core facilities (shared resources), pilot and feasibility
studies (new initiatives), and program enrichment activities. Except for
pilot and feasibility studies, core center funds are not intended to
support individual biomedical research projects other than through core
usage. The major source of support for biomedical research projects
associated with the Center should be derived from separately-funded
projects of the participating investigators. Similarly, professional
trainee stipends are not to be supported through core center funding.

A Core Center may serve a single institution or a consortium of
institutions engaged in a collaborative approach to research on
diabetes. Cores may be based solely at the applicant institution or at
multiple institutions through subcontracts. If subcontracts are to be
utilized the applicant must clearly demonstrate how a cohesive and
integrated operation will be ensured and describe the advantages of this
approach to performance of Core functions. The Core Center may also
provide resources for funded projects at collaborating institutions
without a subcontractual arrangement with the parent institution. If
such projects are to be included in the research base, the applicant
must clearly describe and justify the reasons why it is appropriate for
these projects to be included in the research base and the advantages to
be derived from the collective utilization of the Core Center.

At the time of initial submission, the applicant institution or
consortium of institutions must have an active program of excellence in
basic and clinical biomedical research in the area of diabetes and
related areas of endocrinology and metabolism. **The biomedical research
base will be given primary consideration in the peer review process**.
There should be a focus on diabetes, however, related endocrinology and
metabolism research relevant to diabetes may also be supported and
included in the research base. Focus, relevance, interrelationships,
quality, and to some extent quantity, are all considerations in judging
the adequacy of the research base.

##### Basic Requirements for a P60 Core Center

All the elements (see above) required for a P30 Core Centers are also
required for a P60 Core Center. The following additional requirements
for DRTCs should be noted. The research base of the DRTC must include a
substantial focus on research directed at translation of research
advances in the area of diabetes into clinical practice. DRTCs must
request substantial support for cores and pilot and feasibility projects
directed at prevention and control of diabetes. The cores and pilot and
feasibility projects directed at prevention and control of diabetes
should focus on translation of research advances into clinical practice.
This includes the identification of barriers to widespread adoption of
new science and the development and testing of interventions to overcome
these barriers under real world conditions. Applicants are encouraged to
focus on underserved populations disproportionately affected by diabetes
in the cores and pilot and feasibility projects directed at prevention
and control of diabetes.

**II. ADMINISTRATIVE CORE COMPONENT**

##### Description

The DERC or DRTC must be an identifiable organizational unit within a
university medical center or a consortium of cooperating institutions
including the university-affiliated center. Such a Center will involve
the interaction of broad and diverse elements; thus, lines of authority
and approval by the appropriate institutional officials must be clearly
specified. The administrative core plays a key role in the coordination
and functioning of the center.

##### Requirements

Each applicant institution specifies a Core Center Director to be
responsible for the scientific and administrative leadership of the
Center. The Director should be an experienced and respected scientist
with a proven track record for obtaining NIH funding. He/she must be
able to coordinate, integrate, and provide guidance in the establishment
of new programs in diabetes and related research. The Core Center
Director should provide at least 10% effort on the Administrative Core
and a total of 20% effort distributed among the Administrative and other
components of the Center. One or more Associate Directors should be
named who will be involved in the administrative, scientific, or
training efforts of the center and will serve as Acting Center Director
in the absence of the Director. An administrative assistant may also be
proposed.

It is expected that the organization of the Administrative core should
encompass a supportive structure sufficient to ensure accomplishment of
the following: coordinating and integrating the Center components and
activities; overseeing the solicitation, review and selection of pilot
and feasibility studies; reviewing the utilization and quality of core
resources; interacting with the scientific and lay communities and the
NIDDK in order to develop relevant goals for the Center; and interacting
with the administrative and scientific leadership at the applicant
institution(s) to enhance the visibility and effectiveness of the center
as a focus for diabetes research.

The final administrative structure of the Center will be left largely to
the discretion of the applicant institution (subject to review by NIH
peer review mechanisms). However, NIH\'s experience has demonstrated
that the effective development of the Center programs require close
interaction between the Center director, the principal investigators,
appropriate institutional administrative personnel, the staff of the
awarding agency, and the members of the community in which the Center is
located. Therefore, each Center applicant should establish an
administrative structure which will permit the development of such
interaction. Within this structure, each applicant institution must also
establish a mechanism to oversee the use of funds for the proposed pilot
and feasibility program. This mechanism must include the use of
appropriate consultants for review from the scientific community outside
the Center institution. Consultants who will serve on advisory
committees should not be specifically identified in the application but
the process by which they will be selected should be described. These
same consultants may be utilized, if desired, for review of other
activities of the Center. The mechanism for reviewing the use of the
pilot and feasibility funds will be considered by the initial review
groups in the evaluation of the Center applications. Further details
regarding this mechanism will be found below in the discussion of the
pilot and feasibility program. The projects selected to receive these
funds will be described by the Centers in their annual reports and will
be given special attention by the NIDDK in its annual evaluation of the
Center program. The Center grant may also include limited funds for
program enrichment (i.e., seminars, etc.) that should be included in
this core.

The initial base of research projects to be served by the cores must be
clearly defined in the application. The process by which additional
projects will be selected to utilize the core resources and by which
selected projects will be prioritized must be delineated. There should
be well- defined criteria for designating an investigator as a Center
participant. Each Center, however, is expected to formulate these
definitions based on its own situation.

Although facilities available should be described for each element of
the application, a more general description of overall facilities and a
statement regarding institutional commitment to the Center should also
be included here.

**III. BIOMEDICAL RESEARCH COMPONENT**

##### Research Base

The Core Center Grant provides a mechanism for fostering
interdisciplinary cooperation within a group of established
investigators conducting high quality research on diabetes and related
areas of endocrinology and metabolism. Therefore, existence of a strong
research base in this area is a fundamental requirement for and the most
important aspect in the establishment of a Core Center.

Applicants should include an overview of current research in diabetes
and related areas being conducted at their institution in sufficient
detail to allow reviewers to judge its extent and the interrelationship
of ongoing research. There should be a substantial body of ongoing
research on diabetes and/or its complications. The relevance to diabetes
of all research included in the research base should be described.
Projects at other institutions may also be included if collaborations
exist with scientists at the applicant institutions. Applicants should
indicate how the establishment of a Center will provide added
dimensions, such as greater focus and increased cooperation,
communication and collaboration.

Presentation of the research base in the application should be done in
two ways: (1) by completing a Table like the one shown in Illustration
III, and (2) by a full description of the diabetes and related research
activities at the applicant institution and any collaborating
institutions. This presentation should be organized into several areas
of emphasis that demonstrate the research focus of the Center. The
research of each Center participant should be discussed and
interrelationships of research being conducted by Center participants
should be highlighted. Since most, if not all, of the research base will
have undergone separate peer review, the quality of the individual
funded projects is already established. The more important aspects are:
(1) interactions and interrelationships of the research efforts; (2)
uses and benefits of core services; and (3) plans to develop productive
collaborations among Center investigators.

For renewal applications, consideration will be given to progress and
accomplishments in the research base, to development of
multidisciplinary, collaborative, and cooperative interrelationships,
and to alteration in the original Center design in order to meet the
evolving needs of the research base. This should be described in a
narrative fashion accompanied by a Table like the one shown in
Illustration IV that documents the contribution of individual cores to
the publications by the research base. Since one of the objectives of
the Center is to extend research relevant to diabetes, new areas of
research and acquisition of new funding should be highlighted.

There is obviously insufficient space in the application for a detailed
presentation of the research base. However, significant research should
be cited and it may be helpful to include up to 10 reprints as an
appendix to the application. Appropriate presentation of the research
base is very important since its assessment is a primary criterion in
the evaluation of an application.

##### Biomedical Research Cores

***Definition*:** A biomedical research core is a shared facility that
provides a needed service to Center investigators enabling them to
conduct their funded individual research projects more efficiently
and/or more effectively. Cores should be designed to furnish a group of
investigators with materials, techniques, determinations,
instrumentations, and/or quality control to enhance research and
contribute to cost effectiveness. A charge back mechanism is acceptable
to help defray costs to the Center. If such a cost recovery system is
developed, a detailed charge justification must be presented.
Participating Center members must also be informed to include such costs
with their full budget justifications in their applications for
individual grant support. Cores may be proposed to support any research
activity of the Center, but usually fall into one of five categories:
(1) provision of a technology that lends itself to automation or
preparation in large batches; (2) complex instrumentation; (3) animal
preparation and care; (4) clinical resources; and (5) service and
training. Limited developmental research is also an appropriate function
of a core facility. Such activities, however, must be directly related
to enhancing the function or utility of the core.

***Justification for proposing a core:*** The establishment and
continued support of biomedical research cores within a Center is
justified on the basis of use by independently-funded Center
investigators. The minimum requirement for establishing a core is
significant usage by two or more investigators with
independently-funded, peer-reviewed projects. While investigators
holding awards from the Center pilot and feasibility program are
appropriate users of the core facilities, their use does not contribute
to justification for establishment or continued support of a core.
Additionally, the minimum of two independently funded users does not in
itself provide sufficient justification and will receive close scrutiny
in review.

***Personnel:*** A director must be named for each core. Core directors
may be acknowledged experts with independently-funded research programs
which will use the core services. In such cases, the percent effort on
the grant is usually relatively low. The minimum effort for a core
director is 5%. A core director with requisite expertise may devote a
greater effort to the core and with justification could devote up to 100
percent effort. Where appropriate, an established expert in the core
activities could also be included as a consultant to the core.
Technicians, etc. are allowable in accordance with the volume and type
of work in the core.

***Facilities, space, and special arrangements:*** Particularly in
initial applications, the description of the physical arrangements and
instrumentation for the cores should be given special attention. In
renewal applications, any changes should be carefully documented. Cores
are encouraged, whenever possible, to enter into cooperative
arrangements with established cores in other Centers or resources
offering a similar type of service. However, it should be clear that
DERC or DRTC cores can function independently.

***Management of the core:*** The organization and proposed mode of
operation of each core should be presented. Included should be a plan
for prioritizing investigator use of the core as well as a definition of
qualified users. If use by investigators outside the parent institution
is proposed the mechanism by which such investigators will apply and be
evaluated and selected should be detailed. The definition of qualified
users should not be too narrow. Some minor core use could serve to
entice established investigators in other fields into the field of
diabetes research. Any proposed, ongoing or completed developmental
efforts should be described. If the core is used to train investigators
in special techniques, the mechanism for this training should be
included.

***Relation of core services to individual research project grants:***
When a Center is first established, individual investigator-initiated
research project grants may include funds for a part of the services
which will ultimately be available from the cores. At the time of
renewal (competitive and noncompetitive) the budgets of individual
research project grants must be reduced to reflect the costs supported
by the Center grant. If there are charge backs, these should be detailed
in the submitted budget justification and described as allowable
budgetary items in the investigator\'s individual grants. Some mechanism
should be proposed in the Center application to monitor these budgetary
adjustments and to ensure that Center core users describe their relation
to the Center in their individual grants.

***Renewal applications:*** Information relative to cores in renewal
applications should generally cover all of the same points as initial
applications. In addition, past performance and accomplishments should
be described. The effect of the service provided by a core on
investigator productivity and cost effectiveness should also be
addressed.

##### Pilot and Feasibility Program

Research projects associated with a Core Center will in general be
funded from other resources, such as R01 or P01 grants from NIH, similar
project funding from other Federal agencies, or nonfederal sources.
There is one exception\--pilot and feasibility studies.

***Definition:*** The Pilot and Feasibility Program provides modest
research support for a limited time (one to two years) to enable
eligible investigators to explore the feasibility of a concept related
to the mission of the Center and generate sufficient data to pursue it
through other funding mechanisms. The pilot and feasibility studies are
intended to: (1) provide initial support for new investigators; (2)
allow exploration of possible innovative new leads or new directions for
established investigators in diabetes and (3) stimulate investigators
from other areas to lend their expertise to research in this area. Pilot
and feasibility study support is not intended for large projects by
established investigators that would otherwise be submitted as separate
research grant applications. Pilot and feasibility funds are also not
intended to support or supplement ongoing funded research of an
investigator.

***Requirements:*** Each Center must propose a minimum of 2 pilot and
feasibility studies to be supported from NIDDK funds.

***Eligibility and related guidelines:*** Investigators eligible for
pilot and feasibility funding generally fall into three categories: (1)
new investigators without current or past NIH research support as a
principal investigator (current or past support from other sources
should have been modest); (2) established investigators with no previous
work in diabetes who wish to apply their expertise to a problem in this
area; and (3) established investigators in diabetes who propose testing
innovative ideas that represent clear departure from ongoing research
interests. It is expected that the majority of the investigators will
fall into the first category. All eligible investigators, however, must
have faculty appointments and be independent investigators. Postdoctoral
fellows or their equivalent are not eligible. Each pilot and feasibility
study proposal should state clearly the justification for eligibility of
the investigator under one of the above three criteria.

A proposed pilot and feasibility study should present a testable
hypothesis and clearly delineate the question being asked, detail the
procedures to be followed, and discuss how the data will be analyzed. It
must be on a topic related to the objectives of the Core Center.
Projects should be focused, since funding for these studies is modest
(less than \$50,000 direct costs per year per project) and is limited to
two years or less. Any one investigator is eligible only once for this
support, unless the additional proposed pilot and feasibility study
constitutes a real departure from his/her ongoing research.

Use a separate Form PHS 398 for each project, and number each project
sequentially. Each pilot and feasibility project should be identified
clearly by the same title as that provided in the Table of Contents.
Each project should begin with a face page, abstract, and budget pages,
followed by information requested in Sections A through I of the
instructions for Form PHS 398. It should be submitted generally using
the NIH research project application format, but the description of the
proposed research should be limited to five pages.

The application should clearly describe and justify the pool from which
potential pilot and feasibility applications will be selected. This can
be limited to investigators at the parent institution or expanded to
include investigators at institutions with a well defined affiliation
with the Core Center. Such an affiliation can occur either through a
subcontractual relationship for support of core resources or through
inclusion of funded projects at a collaborating institution in the
research base utilizing the shared resources of the Core Center. The
mechanisms by which information on the availability of pilot and
feasibility awards will be disseminated and by which applicants will
apply and be selected for these awards must be described and will be an
important element in the review of the pilot and feasibility component
of the Core Center.

***Initial review and management of the pilot and feasibility
program:*** By the very nature of this program, a significant
responsibility for its management will be left to the Center
administration during the project periods. For new Center grant
applications, the pilot and feasibility proposals are reviewed for
scientific merit and eligibility by the initial review group. These
initial pilot and feasibility studies must have been reviewed by the
Center in the manner proposed for review of future studies so that only
those considered to be the highest quality are included in the grant
application. The amount of pilot and feasibility funds provided for the
first year will be based on the review of the proposed studies. The
budget for future years is recommended by the initial review group based
on the quality of the proposed pilot and feasibility studies, and the
proposed method for management and review (as evidenced by this set of
projects). Also considered will be review group\'s evaluation of the
future justification for continued pilot and feasibility support.

Since pilot and feasibility studies can be awarded for any period of
time up to two years, studies end at various times. In addition, the
studies may also be terminated by the Center administration before their
approved time limit for various reasons: e.g., (1) the investigator may
receive outside funding for the project; (2) the project was found not
to be feasible; (3) the investigator may leave the Center institution;
etc. When this occurs, the Center may make new awards for pilot and
feasibility studies with the remaining funds.

While a Center\'s administrative framework for management of the pilot
and feasibility program is basically left up to each Center (subject to
NIH peer review), certain minimal requirements must be met. The program
must have a director who is an established investigator in diabetes.
There must also be a committee representing all the aspects of the
Center to assist the director in the management of the program. The
major responsibilities of the director and the committee will be to:

> \(1\) Maintain oversight and review of ongoing pilot and feasibility
> studies;
>
> \(2\) Make recommendations regarding termination or other actions to
> the Center Executive Committee (or equivalent);
>
> \(3\) Prepare and ensure appropriate distribution of announcements of
> the availability of pilot and feasibility funding;
>
> \(4\) Arrange and preside over the scientific merit review of
> proposals. At least one reviewer from outside the parent institution
> must be used for each proposal. All reviewers should assign priority
> scores in accordance with the NIH system. Copies of all of the
> proposals with written documentation of their reviews, priority
> scores, and final action must be retained by the Center. These records
> must be made available to reviewers if requested at the time of a
> renewal application;
>
> \(5\) Maintain, insofar as is possible, a record of subsequent career
> events of each pilot and feasibility study recipient. This record must
> also be made available to reviewers at the time of the renewal
> application;
>
> \(6\) Make recommendations to the Center Executive Committee (or
> equivalent) for final decisions. A record of actions by this committee
> must be documented and be available if requested by the initial review
> group.

All applicants should describe how these requirements will be met and
have been met in the case of renewal applications. Also included should
be an assessment of the relevancy of the proposed individual pilot and
feasibility studies and of the program as a whole to research on
diabetes and related areas of research and to the specific goals and
objectives of the individual Center and of the Center program generally.

***Review of the pilot and feasibility program in renewal
applications:*** After the initial review of pilot and feasibility
proposals as described above, all responsibility for review and funding
during the remainder of the project period will reside within the Center
itself. This approach provides each Center with the needed flexibility
for effective and efficient management of the program. In competing
renewal applications, the review of this program will be based on the
past track record, the management of the program, and an assessment of
overall potential needs and opportunities.

In general, a competing renewal application will include: (1) an
historical overview; (2) a description of Center management of the
program; (3) a description of the method for solicitation for pilot and
feasibility projects and the number of respondents received for each
solicitation; (4) a listing of all previous, ongoing and approved
proposed pilot and feasibility studies with reports on those which were
supported by the Center during the last project period; and (5) a
statement of the benefits of the program to the Center as well as the
contribution of the uniqueness of the Center environment to the program.
These points are detailed in the following paragraphs.

The historical overview will cover the pilot and feasibility program
since the inception of the Center. This should include, in summary
format, all pilot and feasibility projects ever awarded. For each
project listed, the following should be included: (1) publications as a
result of the studies; (2) peer-reviewed funding as a result of the
studies; and (3) whether the recipient is still active in the area of
diabetes. The pilot and feasibility program director may wish to
highlight certain studies or certain aspects of the past studies.
Collaborations which resulted in lasting relationships, acquisition of
new skills by the study recipient, or other significant outcomes should
be identified. The relationship of the scope of the various studies to
that of the Center should be emphasized. Details such as back-up
documentation (described earlier in relation to the arrangement of the
pilot and feasibility program) should not be included, but should be
available for examination by the reviewers if requested.

The description of center management of the program will present in
detail the current system used to manage the pilot and feasibility
program, including its integration with and relationship to the rest of
the administrative structure. The use of outside consultants for review
should be included in the discussion. Important features of the
solicitation process should be provided including the distribution and
the number of respondents.

The historical review of all pilot and feasibility studies ever awarded
should include a report on each pilot and feasibility study conducted
during the last project period. These reports should be brief (1‑2
pages) and contain (1) the name of the investigator, degree(s),
professional career status at the time awarded, and current professional
career status (if known); (2) an overview of the project including its
significance and salient results; (3) a list of resulting publications;
and (4) peer-reviewed subsequent funding in the same or related area.
The proposals should be available, if requested by the reviewers.

The recommendation of the initial review group will be based on the
overall performance of the center\'s pilot and feasibility program as
documented in the application. This recommendation will be based on: (1)
the extent to which awarded funds were fully utilized during the
previous project period; (2) awards were made to investigators who fully
met the eligibility criteria for pilot and feasibility support as
outlined above; (3) Center-relatedness; and (4) success of previously
supported pilot and feasibility studies (e.g., publications, subsequent
independent R01 or other peer-reviewed support, and/or attraction of new
investigator into Center related research).

##### Research Training

Training postdoctoral fellows to conduct research in diabetes is an
associated activity of a Center. While stipends for fellows cannot be
funded from the Center, the establishment of a Center should provide an
enhanced environment for research training. Just as in the case of
funding for individual research projects, funding for fellowships should
be sought from NIH NRSA institutional training grants (T32, T35) and
individual fellowships (F32, F33), and other sources such as private
foundations, and commercial companies.

Although no budgetary items would be included for research training, a
section should be included in both initial and competing renewal
applications documenting the research training program in diabetes its
relationship to the Center, and how the presence of the Center may
enhance the program.

**IV. PRE-APPLICATION PROCESS**

It is the policy of the NIDDK that new and competing continuation Center
applications are only accepted in response to a Request for Applications
(RFA) announced in the NIH Guide for Grants and Contracts. It is
strongly encouraged that potential applicants for a Center submit a
letter of intent. The letter should be sent at least one month prior to
submission to allow NIDDK staff to identify potential opportunities and
problems early in the development of the application. The letter of
intent needs to include only: (1) names of the principal investigators
and principal collaborators, (2) identification of the organization(s)
involved; and (3) announcement to which the potential application is
responsive. The purpose of the letter of intent is to establish
communication between the potential applicant group and NIDDK staff. It
is not part of the peer review material. Upon receipt of the letter, the
appropriate NIDDK program director contacts the prospective principal
investigator to assist in a number of areas that include scientific
content and objectives, organization, and clarifications. However,
applicants should not construe advice given by the NIDDK staff as
assurance of favorable review. The staff will not evaluate or discuss
the merit of the scientific aspects of the application.

**V. PREPARATION OF APPLICATION**

##### Description

Applications must be submitted using PHS Form 398 (Rev. 5/01). The RFA
label contained in the application kit must be affixed to the bottom of
the face page of the original copy of the application. Failure to use
this label could result in delayed processing and review of your
application.

Submit the signed original application, including the Checklist, plus
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 time of submission, two additional copies of the application must be
sent to:

Chief, Review Branch

Division of Extramural Activities, NIDDK

6707 Democracy Boulevard, Rm. 653 MSC 5452

Bethesda, MD 20892-5452

(for express/courier service: Bethesda, MD 20817)

The arrangement of materials should follow both the instructions in the
PHS Form 398 application kit and the more specific guidance detailed
below. Applications not in accordance with Center guidelines will be
returned to the applicant by the Center for Scientific Review.

Applicants should keep in mind that the written application is the basis
for the merit review. Particular attention should be given to the format
of the application. Awards for Center grants are for five-year project
periods. Basic information useful for preparing the application follows.
Applicants may also consult with NIDDK staff concerning the technical
aspects of preparing the application.

##### Content Order for Applications

# SECTION 1: INTRODUCTION

-   Face Page (398-AA) Center applications are only accepted in response
    to an RFA. The RFA label must be affixed to the bottom of the face
    page and the title must be typed on line 2 and the 'yes' box must be
    marked.

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-   Description and Key Personnel (398-BB)

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-   Table of Contents

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-   Budgets

1\. Detailed Budget for Initial Budget Period (398-DD)

2\. Budget for Entire Proposed Project Period (398- EE)

> 3\. Consolidated budget for first year of requested support (such as
> the one shown in Illustration I) (Budgets for each individual Core
> should immediately precede the narrative for each Core)

-   Biographical Sketches for all Center participants beginning with
    Center Director and Associate Director and followed by other
    participants in alphabetical order (398-FF)

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-   Distribution of Professional Effort (such as the Table shown in
    Illustration II)

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-   Summary of total current and pending support of all Center
    participants including percent efforts. List support related to
    diabetes first, followed by noncenter-related research support.
    (Such as the Table shown in Illustration III)

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```
-   General description of the proposed or established Center

> For Renewals: Changes from the original Center design should be
> highlighted

# SECTION 2: ADMINISTRATIVE COMPONENT

-   Budget with comprehensive budgetary justifications

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-   Director and Associate Director

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-   Presentation of the administrative structure

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-   Relationship and lines of authority and sanction by appropriate
    institutional officials

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-   Committee structure (include committee for the pilot and feasibility
    program)

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-   General overall description of facilities and institutional
    commitment

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-   Description of plans for the enrichment program

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-   Other Considerations

# SECTION 3: BIOMEDICAL RESEARCH COMPONENT

-   Overview of ongoing research and impact of Center on this research.
    Description of Research Base - Grouped into areas of emphasis for
    the Center

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-   For Renewals: Progress Report including description of significant
    findings, new participants and new funding. Publications Citing
    Support from this Core Center (such as the chart shown in
    Illustration IV)

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```
-   Biomedical research cores (present each core separately)

Descriptive Abstract

Budget with justifications

Objectives of the core

Core function, including quality control

Benefits from core

Proposed developmental research or training

> Funded investigators who will use the core and proposed extent of use
> (such as the Table shown in Illustration V)
>
> For Renewal: Core Use during the last grant period (such as the Table
> shown in Illustration V)

-   Pilot and Feasibility Program

> Composite budget with budgetary justifications for future years
>
> Introduction
>
> Director and Committee
>
> Management of the pilot and feasibility program
>
> Description of future of the pilot and feasibility program
>
> In initial applications include: budget and justifications,
> justification of eligibility as well as the scientific proposals with
> their justification for core usage. 
>
> For competing renewal applications, also include: overview;
>
> listing and reports of pilot and feasibility studies; and additional
> pilot and feasibility proposals, if applicable, as requested for an
> initial application.

-   Research Training Program

Description

Other considerations

-   Checklist

**VI. BUDGET CONSIDERATIONS**

Unless otherwise indicated in the Notice of Grant Award, allowable costs
and policies governing the research grant program of the NIH will
prevail. The anticipated award will be for five years. The maximum
dollar request in any budget period is limited to \$1,250,000 in direct
costs for DRTC (P60) and \$1,000,000 in direct costs for DERC (P30)
applications with the following exceptions. Not included in these direct
cost limits are: 1) requests for equipment in the first year of a
competitive award; 2) direct costs on subcontracts for the purpose of
establishing collaborations and providing access to the research
infrastructure to investigators at historically black colleges and
universities (HBCU's), health departments, community health centers or
other agencies that focus on underserved populations and offer special
opportunities to foster research to reduce or eliminate health
disparities in populations disproportionately affected by diabetes; and
3) Facilities and Administrative (F&A) Costs associated with any
subcontract. Approximately 20-25% of the direct costs requested in P30
and P60 applications, exclusive of equipment, should be for support of a
Pilot and Feasibility program. Each pilot/feasibility study is limited
to \$50,000 per year and a two year duration of support Future budget
period escalations may not exceed a 3 percent increase over the previous
budget period.

##### Budget Categories

***Professional Personnel:*** This category may include support for
salaries of key personnel within the Center who contribute to allowable
activities of the Center. The salaries derived from the Center grant
will depend on the effort provided and institutional salary as well as
existing NIH policies; however, current NIDDK practice limits annual
increments to 3 percent. The Center Director is expected to devote at
least 20% of his/her efforts to the Center. The Center application
should include salaries for individual principal investigators only to
the extent that they provide an essential Center function. No overlap of
time or effort between the Center and separately-funded projects is
permitted.

Salaries of professional personnel engaged in research activities
supported by pilot and feasibility funds of the Center are an allowable
cost item as are salaries of professional personnel in core facilities.

***Technical and Support Personnel:*** This may include salaries for
identified positions to be filled in the Center. No overlap of time or
effort between the Center and separately funded projects is permitted.

***Equipment:*** Requests for large equipment costs must include
documentation of similar equipment already available at the institution
and provide a clear justification in terms of core need and service to
Center investigators. General purpose equipment needs should be included
only after surveying the availability of such items within the
institution.

***Supplies:*** Consumable supplies related to the operation of the
Center are allowed and include office materials, as well as scientific
supplies, but should not be supplements to separately funded projects.
The supply budgets of individual projects must be reduced to reflect
cost savings through core usage.

***Research Patient Care Costs:*** Research patient care costs (both
in-patient and out-patient expenses) will be considered in the context
of other existing institutional clinical resources. Attempts should be
made by the applicant institution to utilize existing clinical
facilities, such as General Clinical Research Centers and individually
supported beds. Costs relating to the clinical research efforts of
Center investigators may be funded through the Center, provided there is
no overlap of funding. Costs already budgeted in individual projects
should be appropriately reduced if such costs are to be transferred to
the Center budget. The Center is not intended to be a facility for
health care delivery; thus, only those patient costs directly related to
research activities may be charged to the Center.

***Alteration and Renovation:*** Funds for alteration and renovation of
an existing structure to provide suitable core facilities for the Center
may be made available from the grant under current PHS guidelines.

***Travel:*** Domestic and foreign travel of project personnel directly
related to the core activities of the Center is allowable. Travel of
Center participants for attendance at annual Center directors meetings
is also allowable.

***Consultants:*** Consultants and any associated costs (consultant
fees, per diem, travel) may be included when their services are required
within the Center.

**VII. REVIEW PROCESS AND CRITERIA**

Upon receipt, applications will be initially reviewed by the Center for
Scientific Review (CSR) for completeness. Incomplete applications will
be returned to the applicant without further consideration. Evaluation
of responsiveness to the program requirements and criteria stated in the
RFA is an NIDDK staff function.

Applications that are complete and responsive will be evaluated in
national competition in accordance with the criteria stated below for
scientific/technical merit by an appropriate peer review group convened
by the NIDDK. It is essential that the written application be in a form
to be reviewed on its own merit, since no site-visit is anticipated.
Following this review, the applications will be given a second level
review by the National Diabetes and Digestive and Kidney Diseases
Advisory Council.

Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIDDK. 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 NIDDK in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of the applications under review, will be
discussed, assigned a priority score, and receive a second level review
by the National Diabetes and Digestive and Kidney Diseases Advisory
Council.

Review Criteria

The goals of the DRTCs and DERCs are to advance our understanding of
biological systems relevant to diabetes and its complications, and to
facilitate development of new methods to treat, prevent and ultimately
cure diabetes and its complications. DRTCs have the additional goal of
improving the control and prevention of diabetes and its complications
and enhancing health by facilitating translational research,
particularly in underserved populations and populations
disproportionately affected by diabetes. In the written comments,
reviewers will be asked to discuss the following aspects of the
application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. Each of
these criteria will be addressed and considered in assigning the overall
score, weighing them as appropriate for each application. The most
important component of DRTCs and DERCs is the quality (strengths,
breadth and depth) of its established, independently supported, ongoing
base of diabetes research at the institution(s) to be served by the
center. For the DRTC this research base must include translational
research in addition to the biomedical research base required for DERCs.

Specific review criteria are:

 

o Scientific excellence of the Center\'s research base that must have a
broad and central focus in diabetes and may extend to related research
in metabolism and endocrinology. The relevance of the separately funded
research to the Center objectives (see above) and the likelihood for
meaningful collaboration among Center investigators must be
demonstrated.

 

o Potential of the cores for contribution to ongoing research, including
their appropriateness, impact, relevance, uniqueness, modes of
operation, and suitability of facilities. Renewal applications must
document the use, impact, quality control, and cost effectiveness of
each core, and demonstrate progress of any developmental research in the
cores. Progress will be judged in part by the publications supported by
the cores. While a minimum of two users (exclusive

of Pilot and Feasibility projects) are required to establish a core, a
greater number of users will be considered to be more cost effective.

 

o Scientific and administrative abilities of the Center Director and
Associate Director and their commitment and ability to devote adequate
time to the effective management of the Diabetes Research Center.

 

o The qualifications, experience, accomplishments, and commitment of the
Center investigators and their inter-relatedness and collaborations.

o For new applications, the pilot and feasibility program is judged on
the basis of: (1) scientific merit of the studies as submitted and (2)
the merit of the administrative process for selecting subsequent
studies. The scientific merit of the submitted pilot and feasibility
studies will be evaluated for:

\(1\) Significance: Does this study address an important problem? If the
aims of the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field?

\(2\) Approach: Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the project? Does the applicant acknowledge potential problem
areas and consider alternative tactics?

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

\(4\) Investigator: Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers (if
any)?

\(5\) Environment: Does the scientific environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements? Is there
evidence of institutional support?

In competing renewal applications, emphasis is placed on the pilot and
feasibility program as a whole, including past track record and
management of the program.

 

o The Administrative organization proposed, including: coordination of
ongoing research; establishment and maintenance of internal
communication and cooperation among DRTC investigators; mechanisms for
prioritizing usage of shares resources; mechanisms of selecting and
replacing essential personnel within the Center; mechanisms for
reviewing the use of and administering funds for the pilot and
feasibility program, and management capabilities.

 

o The appropriateness of the DRTC budgets for the proposed and approved
work to be done in core facilities, for pilot and feasibility studies,
and for enrichment in relation to the total Center program.

 

o Institutional commitment to the program, including lines of
accountability regarding management of the DRTC grant and a commitment
to establish new positions as necessary.

 

o Although the DRTCs do not specifically support research training,
demonstration of accomplishments and future plans related to the
training of investigators necessary to conduct research in diabetes and
related metabolic and endocrine disorders will be considered in
assessing the potential to meet Center objectives. The integration of
these efforts into the overall Center, including core facilities is of
particular importance. Efficient and effective use and/or planned use of
the limited enrichment funds, including the contribution of these
activities in enhancing the objectives of the Center will also be
considered.

 

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

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

o The reasonableness of the proposed budget and duration to the proposed
research.

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

o The adequacy of the proposed plan to share data.

Funding decisions will be based on the quality of the proposed Center as
determined by peer review, overall balance in the Diabetes Research
Centers program, and the availability of funds.

**VIII. EVALUATION AND REPORTING REQUIREMENTS**

The annual Application for Continuation Grant (Progress Report), which
is due two months before the anniversary date of the award, should be
submitted as described in the PHS Form 2590 application kit which is
sent automatically to NIH grantees. The following order for presentation
of information in the Continuation Grant Progress Report is suggested:

\(1\) Cumulative Budget

\(2\) Budget for each Core

\(3\) List new Key personnel followed by biosketches

\(4\) Other support for all Key personnel

\(5\) Listing of current Center Investigators, with member\'s name,
department, and area of interest; indicate those who are new to center
in past year and who are collaborative (outside center) members

\(6\) Administrative Core: Highlight significant accomplishments,
evaluation activities, and enrichment activities

\(7\) Biomedical and Translational Research Cores: Highlight significant
changes from previous report; Describe services provided and number of
users; and List publications citing support from the Center which used
this core

\(8\) Pilot and Feasibility Projects: Describe new projects and progress
on ongoing progress and projects that terminated during the previous
funding period; List publications and new peer-reviewed research support
emanating from the pilot and feasibility projects.

**IX. SPECIAL CONSIDERATIONS**

Each Center will be expected to develop its own program in accordance
with local talents, interests, and resources. Each Center must also be
responsive to national needs to develop new approaches to the
prevention, treatment and cure of diabetes and its complications and
must be willing to work with the NIDDK and other organizations in
furthering the overall goals of the Centers Program. In this regard, the
Center Director and selected other Center participants may be invited to
meet periodically with NIDDK staff and its consultants to review
progress, identify emerging needs and opportunities, and plan approached
for future investigations.

Within the context of these guidelines, potential applicants for Center
grants are encouraged to exercise the flexibility necessary to utilize
the strengths of their particular institutions in preparing a plan which
will eventually cover the spectrum of required activities. While types
of activities that should be included are indicated in the guidelines,
specific approaches for their accomplishment are left to the individual
applicant.

Because of resource limitations and in light of the size of the Center
grants, it is unlikely that NIDDK will be in a position to provide
hardship allowances in the event that an application for renewal of
Center support is not funded.

**ILLUSTRATION I**

**CONSOLIDATED BUDGET FOR 1st YEAR OF REQUESTED SUPPORT**

  ------------------- ---------- --------- ---------- ---------- -----------
  Budget Category     Core A     Core B    Core C     P&F 1      Total

  Personnel                                                      

  Consultant Costs                                               

  Equipment                                                      

  Supplies                                                       

  Domestic Travel                                                

  Foreign Travel                                                 

  Patient Care Costs                                             

  Alterations and                                                
  Renovations                                                    

  Other Expenses                                                 

  Contractual Costs                                              

  Total                                                          
  ------------------- ---------- --------- ---------- ---------- -----------

**ILLUSTRATION II**

**DISTRIBUTION OF PROFESSIONAL EFFORT (%) ON THIS APPLICATION**

  ----------------- ------- ------- ------- -------- -------- ------------- ---------
  Participating     Core A  Core B  Core C  Core D   P&F 1    Application   Other
  Investigators\*                                             Total         Support

  Dr. A.            \*10                    10                20            50

  Dr. B.                    10                       \*10     20            40

  Dr. C.            5                                         5             

  Dr. D.                            15      \*10              25            55

  Etc.                                                                      
  ----------------- ------- ------- ------- -------- -------- ------------- ---------

\*Star the percent effort (See Admin) when that individual is the core
director or the principal investigator on a pilot and feasibility study.

Minimum effort for Core Director is 10%. Minimum total effort for Center
Director is 20%.

## ILLUSTRATION III

**SUMMARY OF TOTAL CURRENT AND PENDING SUPPORT OF ALL CENTER
PARTICIPANTS**

+-----------+-----------+------------+-------+-------+-------+-------+
| DIABETES  |           |            |       |       |       |       |
| RESEARCH  |           |            |       |       |       |       |
| BASE:     |           |            |       |       |       |       |
| Current   |           |            |       |       |       |       |
| Support   |           |            |       |       |       |       |
+-----------+-----------+------------+-------+-------+-------+-------+
| Principal | S         | Title      | Pr    | Total | Cu    | Pe    |
| Inv       | upporting |            | oject | A     | rrent | rcent |
| estigator | Org       |            | P     | mount | A     | E     |
|           | anization |            | eriod |       | nnual | ffort |
| Co-Inves  | and Grant |            |       |       | A     |       |
| tigator\* | Number    |            |       |       | mount |       |
+-----------+-----------+------------+-------+-------+-------+-------+
| Example:  | P01       | Immunopa   | 4/1/  | \$60  | \$12  | 40    |
|           | DK00000   | thogenesis | 90-3/ | 0,000 | 5,261 |       |
| Doe, Joe  |           | of         | 31/96 |       |       | 50    |
|           | K04       | Diabetes   |       | \$10  | \$    |       |
| Jones,    | DK-00000  |            | 6/1/  | 0,000 | 3     | 15    |
| Sam       |           | Cellular   | 92-5/ |       | 5,000 |       |
|           | R01       | Therapy    | 31/98 | \$16  |       |       |
| Lane,     | DK-00000  | for        |       | 2,518 | \$    |       |
| Andrea    |           | Diabetes   | 7/1/  |       | 5     |       |
| (G.       |           |            | 91-6/ |       | 0,000 |       |
| Under)    |           | Genes for  | 30/97 |       |       |       |
|           |           | Type 2     |       |       |       |       |
|           |           | Diabetes   |       |       |       |       |
+-----------+-----------+------------+-------+-------+-------+-------+
| DIABETES  |           |            |       |       |       |       |
| RESEARCH  |           |            |       |       |       |       |
| BASE:     |           |            |       |       |       |       |
| Pending   |           |            |       |       |       |       |
| Support   |           |            |       |       |       |       |
+-----------+-----------+------------+-------+-------+-------+-------+
| Principal | S         | Title      | Pr    | Total | First | Pe    |
| Inv       | upporting |            | oject | A     | Year  | rcent |
| estigator | Org       |            | P     | mount | Su    | E     |
|           | anization |            | eriod | Requ  | pport | ffort |
| Co-Inves  | and Grant |            | Requ  | ested | Requ  | Requ  |
| tigator\* | Number    |            | ested |       | ested | ested |
+-----------+-----------+------------+-------+-------+-------+-------+
| NON-CENTE |           |            |       |       |       |       |
| R-RELATED |           |            |       |       |       |       |
| RESEARCH: |           |            |       |       |       |       |
| Current   |           |            |       |       |       |       |
| Support   |           |            |       |       |       |       |
|           |           |            |       |       |       |       |
| (as       |           |            |       |       |       |       |
| above)    |           |            |       |       |       |       |
|           |           |            |       |       |       |       |
| NON-CENTE |           |            |       |       |       |       |
| R-RELATED |           |            |       |       |       |       |
| RESEARCH: |           |            |       |       |       |       |
| Pending   |           |            |       |       |       |       |
| Support   |           |            |       |       |       |       |
|           |           |            |       |       |       |       |
| (as       |           |            |       |       |       |       |
| above)    |           |            |       |       |       |       |
+-----------+-----------+------------+-------+-------+-------+-------+

\* If co-investigator\'s name is used, put principal investigator\'s
name in parentheses below.

## ILLUSTRATION IV\--FOR COMPETING RENEWALS ONLY 

**PUBLICATIONS CITING SUPPORT FROM THIS CORE CENTER GRANT**

[Core or P&F/P.I. Name]{.underline} [Publications]{.underline} [Core
A]{.underline} [Core B]{.underline}

Core A/ Brown Brown, A.C; Jones R.C.; P

Smith, A.J. Metformin

reduces hepatic glucose output.

Diabetes, 1996

Brown, A.C.; Cheng, A.G.; P S

Anderson, J.C. Results of

Islet Transplantation.

Diabetes, 1994

Core B/ Cheng, Cheng, A.C.; Meyer, G.C. S P

Linkage Studies in Animal

Models for Diabetes

Nature Genetics, 1995.

Smith, F.G.; Cheng, A.C.; P S

Tissue Specific Knockout of Glut 4

PNAS, 1996

\*List each publication only once under the project number most
significantly contributing to the work. The project most significantly
contributing to the work should be signified by a P (primary). All
other contributing projects and cores are designated by an S
(secondary).

**ILLUSTRATION V**

#### USE OF CORE FACILITIES

+-----------------------------------------------------------------------+
| CORE: NAME                                                            |
|                                                                       |
| Determination/Services Rendered                                       |
|                                                                       |
| A.                                                                    |
|                                                                       |
| B.                                                                    |
|                                                                       |
| Funded Projects with Period of Determinations Estimated Use           |
|                                                                       |
| Users Identifying Number Performance Services and Comments            |
|                                                                       |
| 1\.                                                                   |
|                                                                       |
| 2\.                                                                   |
|                                                                       |
| 3\.                                                                   |
+-----------------------------------------------------------------------+
| EXAMPLE                                                               |
|                                                                       |
| Core A: Molecular Biology                                             |
|                                                                       |
| Determination/Services Rendered                                       |
|                                                                       |
| A.                                                                    |
|                                                                       |
| B.                                                                    |
|                                                                       |
| C.                                                                    |
|                                                                       |
| D.                                                                    |
|                                                                       |
| Funded Projects with Period of Determinations Estimated Use           |
|                                                                       |
| Users Identifying Number Performance Services and Comments            |
|                                                                       |
| A B C D E                                                             |
|                                                                       |
| 1\. J. F. Smith R01 DK00000-00 3/7/89-3/7/98 X X A. 5 per month       |
|                                                                       |
| C. 100 per month                                                      |
|                                                                       |
| 2\. S. R. Jones K04 DK00000-00 1/4/92-1/4/98 X B. 40 per week         |
|                                                                       |
| 3\. R. G. Brown R01 GM00000-00 9/1/89-9/1/98 X A. 16 per week for 6   |
|                                                                       |
| months                                                                |
+-----------------------------------------------------------------------+
| Core B: Morphology                                                    |
|                                                                       |
| Determination/Services Rendered                                       |
|                                                                       |
| Same format                                                           |
+-----------------------------------------------------------------------+