CONSORTIUM FOR IDENTIFICATION OF ENVIRONMENTAL TRIGGERS OF TYPE 1 DIABETES

RELEASE DATE:  January 22, 2002

RFA:  RFA-DK-02-029 

June 21, 2007 - (Reissued as RFA-DK-07-500)

(Reissued as RFA-DK-06-016)

PARTICIPATING INSTITUTES AND CENTERS (ICs):

National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov/)
National Institute of Allergy and Infectious Disease
 (http://www.niaid.nih.gov/)
National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov/)
National Institute of Environmental Health Sciences
 (http://www.niehs.nih.gov/)
Centers for Disease Control and Prevention
 (http://www.cdc.gov/)

Letter of Intent Receipt Date:  March 5, 2002
Application Receipt Date:       April 15, 2002

THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 
National Institute of Allergy and Infectious Disease (NIAID), National 
Institute of Child Health and Human Development (NICHD), National Institute of 
Environmental Health Sciences (NIEHS) and Centers for Disease Control and 
Prevention (CDC) invite Cooperative Agreement Applications for a single Data 
Coordinating Center (DCC) and for up to six Clinical Centers (CC) to 
participate in the development and implementation of studies to identify 
environmental factors which trigger the development of type 1 diabetes in 
genetically susceptible individuals. The DCC and CCs will work together 
cooperatively as a Consortium.

The primary objective(s) of this investigation will be identification of 
infectious agents, dietary factors, or other environmental factors that are 
associated with increased risk of type 1 diabetes, with specific phenotypic 
manifestations such as early age of onset or rate of progression, or with 
protection from the development of type 1 diabetes.  Currently several 
independent population based studies are underway to achieve this objective.  
Other newly initiated studies will identify and follow neonates with genotypes 
that confer increased risk of type 1 diabetes, these might incorporate into 
their study design collection of information and samples for identification of 
environmental triggers of type 1 diabetes through participation in this 
Consortium. Creation of a Consortium of collaborating investigators following 
common protocol(s) will allow for a coordinated, multi-disciplinary approach 
to this complex problem, collection of information and samples in a 
standardized manner, greater statistical power than can be achieved in smaller 
independent investigations, and creation of a central repository of data and 
biologic samples for subsequent hypothesis based research.

There will be a single Data Coordinating Center (DCC).  This center will be 
responsible for support of development of the study protocol and manual of 
operations, for communication and coordination among the CCs, and for managing 
the collection and analysis of genetic, immunologic, pathogen, and clinical 
data.  It is anticipated that subcontracts for laboratory support and a 
repository for specimens will be required.   The DCC may apply both existing 
and novel methods for data collection and analysis.  The DCC will play a key 
role in the logistics of the planning and development stage. In addition to 
assisting the CCs in finalizing the study protocols, the DCC will establish 
the data acquisition, transfer, and management system, develop procedures for 
ensuring subject confidentiality and safety, develop procedures for quality 
control, training, and certification, develop and produce a manual of 
operations and other study materials, and supervise the orderly collection and 
transmission of data.  In addition, the DCC may propose cost-efficient methods 
to provide services, such as genotyping, to CCs.  Although a DCC and CC may 
exist at the same institution, the two types of centers will require separate 
applications and these will be evaluated independently, by criteria 
outlined below.

The CCs will be composed of one or more sites having investigators with 
expertise in several of the following areas:  genetics, epidemiology, 
immunology, infectious disease, pediatrics, and type 1 diabetes. The CCs will 
recruit and enroll subjects, including obtaining informed consent from parents 
prior to or shortly after birth and study data, obtain genetic and other 
samples from neonates and parents, and prospectively follow selected neonates 
throughout childhood or until development of type 1 diabetes.  It is 
envisioned that the CCs, together with the DCC, consultants with specific 
relevant expertise, and institute and center staff, will develop the study 
design, including the development of realistic estimates of the appropriate 
number of well-characterized selected subjects required to achieve the goals 
of the study. The CCs will have full responsibility for identifying, 
recruiting and enrolling the necessary number of study participants to meet 
the study goals and bring the study to completion. The CCs will collect and 
transmit genetic and other samples and familial and clinical data as 
delineated in the Manual of Operation. As a part of this solicitation, each CC 
will propose at least one study which is aimed at the overall objective, 
stated above, and which will effectively use the resources of the consortium.

RESEARCH OBJECTIVES

Background 

An estimated one million Americans have type 1 diabetes.  Type 1 diabetes is 
one of the most common and serious chronic diseases in children and appears to 
be increasing globally, particularly in the very young.  The etiology of the 
disease however remains unclear.  There is a substantial genetic component to 
susceptibility to type 1 diabetes.  High risk HLA class II alleles appears to 
contribute 40-45% of genetic risk and other genes have also been identified as 
providing more modest contributions to risk.  However only about 1 in 15 
children in the general population with the high risk HLA alleles and one in 
five with a first degree relative with type 1 diabetes and with the high risk 
HLA will develop type 1 diabetes.  Thus, additional unidentified factors are 
important in the etiology of this disease.  Epidemiologic patterns suggest 
that viruses, nutrition, toxic agents and/or socioeconomic factors may 
contribute.  However, definitive identification of environmental factors that 
precipitate type 1 diabetes has proven difficult.  Investigation is confounded 
by the long interval between exposure and onset of clinical disease and the 
multiple genes, and possibly multiple insults, that interact in a complex 
manner.  Numerous studies have investigated environmental influences but have 
yielded conflicting results, in part perhaps due to a failure to account for 
genetic susceptibility, a failure to begin observation of individuals at very 
early ages or in utero, and the inability to follow a sufficient sample of 
individuals long-term on a frequent basis incorporating methods that can 
detect potential pathogens and other environmental influences.  
 
Several studies are either ongoing or beginning with the aim of establishing 
cohorts of newborns from the general population who are identified to be at 
genetic risk for type 1 diabetes.  These cohorts are to be followed for the 
onset of various beta-cell auto-antibodies, with documentation of early 
childhood diet, reported infections, and vaccinations, certain case-control 
studies are planned to investigate selected potential environmental 
determinants.  The power of the existing ongoing population-based studies 
could be enhanced through collaboration and expansion into a national network 
with standardized protocols, a coordinating center and central laboratories. 
The cooperative group should be sufficiently large to allow for analyses of 
gene-environmental interactions using both diabetes and islet autoimmunity as 
endpoints and include appropriate representation of the major 
racial/ethnic groups.
 
Experts attending a recent workshop sponsored by NIH, CDC, the Juvenile 
Diabetes Research Foundation International (JDRF) and the American Diabetes 
Association (ADA) reviewed the information currently available and under 
collection regarding the etiology of type 1 diabetes and the evidence for 
environmental factors contributing to pathogenesis.  Presentations focused on 
what we currently know about genetic risk, the initiation of islet 
autoimmunity and progression to type 1 diabetes, the role of specific 
environmental factors in the pathogenesis of type 1 diabetes, the ontogeny of 
islet tolerance and autoimmunity, and novel methods for pathogen discovery and 
for investigating immunopathogenesis and beta-cell function.  The workshop 
participants concluded that a coordinated approach to identifying 
environmental triggers of type 1 diabetes was a challenging undertaking, but 
feasible and timely.  This group recommended establishment of a large, 
population-based cohort of newborns identified from the general population as 
genetically at risk for type 1 diabetes, this cohort could be followed through 
the high risk age (puberty) to identify environmental influences contributing 
to the risk of diabetes and their interaction with genetic influences. 
Consideration should also be given to developing cohort(s) of neonates at high 
genetic risk identified from families with a member with type 1 diabetes and 
to the possibility of enrolling families during pregnancy to allow studies of 
in utero factors associated with increased risk for type 1 diabetes. 
 
The long term goal of this solicitation is the identification of environmental 
factors which trigger development of type 1 diabetes in genetically 
susceptible individuals or which protect against the disease.  Identification 
of such factors will lead to a better understanding of disease pathogenesis 
and new strategies to prevent, delay or reverse type 1 diabetes.

Note:  The Human Subjects Protection Regulations have been revised effective 
December 11, 2001 to include Neonates (see 45 CFR 46, Subpart B -- Additional 
Protections for Pregnant Women, Human Fetuses and Neonates Involved in 
Research at:  http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

Research Goals and Scope

It is the intent of this solicitation to invite applications from 
investigators with diverse scientific interests, who wish to apply their 
expertise to the discovery of environmental factors associated with the 
development of type 1 diabetes.  The specific goals of this solicitation are:  
(1) to encourage novel approaches to identification of infectious pathogens, 
dietary factors or other environmental influences that contribute to the 
pathogenesis of type 1 diabetes in genetically susceptible individuals, (2) to 
facilitate collaborative interactions among scientists by formation of a 
cooperative consortium to conduct a coordinated multi-center study with a 
sufficient sample size, (3) to facilitate the recruitment of appropriate 
subjects and families for prospective studies to delineate environmental 
factors associated with the development and progression of type 1 diabetes, 
and (4) to establish a resource for studies of pathogenesis of type 1 diabetes 
by creating a biologic specimen repository and clinical database.  Ultimately 
it is anticipated that new information about etiology and pathogenesis of type 
1 diabetes emerging from this research effort will contribute to the 
development of strategies to prevent or delay type 1 diabetes in children at 
increased genetic risk.  

It is anticipated that the study will take place in up to six CCs and one DCC.  
While the initial project period will be five years, if the project is 
successful in development of a cogent research protocol and in recruitment and 
follow-up of an appropriate cohort, it is anticipated that there may be an 
opportunity for extension of the consortium to allow sufficient follow-up of 
the cohort under study for an appropriate duration to identify development 
of diabetes.  

Study Design

The individual CCs and the DCC participating in the cooperative study will 
jointly conduct standardized, mutually agreed upon protocols for initial 
characterization of study subjects using genetic analytic strategies, and for 
collection of data and samples during the follow-up of those enrolled.  The 
Steering Committee (see below) will develop a research plan and implementation 
protocols based on consideration of the evidence to date about the real and 
potential relationship between type 1 diabetes and environmental triggers and 
taking into consideration technologies currently available for identification 
of pathogens and other environmental factors. This information will provide a 
rationale for development of priorities among the various "candidate" triggers 
and selection of the most relevant populations for study.  It is anticipated 
that over the seven-year award period, one or more cohorts of neonates will be 
developed and followed by this Consortium.  These may include neonates 
identified in a population-based screen for increased genetic risk, and 
neonates with family members with type 1 diabetes and increased genetic risk.  
Consideration should also be given to collecting samples before birth to 
identify in utero environmental triggers.  The design of the final research 
protocol for implementation, including the eligibility criteria for the final 
study population and the studies to be undertaken, will be effected by the 
Steering Committee, which will take into consideration protocols submitted and 
evaluated by the Scientific Review Group during the review process.

The Consortium will jointly analyze data from its study populations.  It is 
also anticipated that a mechanism will be determined by the Steering Committee 
(see below) to solicit research proposals from investigators outside the 
Consortium who may have novel hypotheses about potential environmental 
influences on susceptibility to type 1 diabetes that can be tested using 
resources developed by the Consortium.  The Steering Committee, will also 
develop policies and procedures that permit utilization of the DNA and/or cell 
lines developed from the cohort by other investigators who are not members of 
the Consortium.  It is anticipated that collection of specimens will include 
sufficient material for measurements to be made based on hypotheses developed 
by the Steering Committee and also for storage of sufficient specimens that 
material will be available in the future when new technology or approaches to 
pathogen discovery may become available.

Study Components

1.  Clinical Centers (CCs)

Up to six awards will be made for CCs that will be responsible for the 
recruitment and evaluation of neonates and appropriate family members and for 
the long-term follow-up of study subjects.  The CC should consist of an 
interdisciplinary team of investigators and appropriate personnel, such as a 
research coordinator, recruitment coordinator and clerical staff.  A CC can be 
located at a single institution or may include subcontracts for support of 
research at multiple collaborating sites.  The latter may be particularly 
appropriate when ongoing collaboration in a clinical trial or another related 
project will be expanded to include participation in this Consortium.  When a 
CC includes multiple sites, the application should document how communication, 
coordination of activities and quality control within the CC will be maintained. 

CCs will be required to submit genetic data and/or samples for genetic 
measurement on neonates screened for or enrolled in the study, samples for 
measurement of immunologic parameters, auto-antibodies, infectious agents or 
other factors, diagnostic and medical therapeutic data, blood, stool, urine, 
and other samples as required by the protocol for testing or storage, samples 
for a DNA and/or cell line repository, as well as familial data and samples, 
as appropriate and required by the protocol, to the DCC.  The CC must work in 
concert with the DCC to implement procedures for uniform data collection, 
handling and transmittal of data, as well as data audits and other data 
quality control procedures, as established by the study protocol. The 
Principal Investigator and Co-Investigators in each CC should be skilled in 
collaborative clinical investigation.  

It is anticipated that the Consortium will conduct analyses and will have 
exclusive access to data from its study populations for a period of time to be 
determined by the Steering Committee.  The Consortium will then be required to 
share data and patient specimens derived from collaborative studies with 
investigators outside the Consortium under policies and procedures to be 
determined by the Steering Committee.  The Steering Committee will also 
determine policies under which individual, center-specific projects, 
independently supported as ancillary research projects, may be conducted 
through the auspices of the DCC.  

2. Data Coordinating Center (DCC)

There will be a single DCC.  This center will be responsible for the 
collection, management and analysis of the genetic, immunologic, pathogen, and 
other laboratory data, clinical data, and coordinating communication and 
research with the Clinical Centers. The DCC is encouraged to propose to use 
both existing and novel methods for data and sample collection, storage in a 
repository, and genetic analysis. The DCC will play a key role in the 
logistics of the planning and development stage. It is anticipated that in the 
application, approaches to standardization of patient, family member and 
control population selection criteria and genetic studies, and data collection 
for the investigations to be performed will be outlined.  In addition to 
assisting the Steering Committee in finalizing the study protocols, the DCC 
will establish the data acquisition, transfer, and management system, develop 
procedures for ensuring subject and control confidentiality and safety, 
develop procedures for quality control, training, and certification, develop 
and produce a manual of operations, and supervise the orderly collection and 
transmission of data. The DCC should be prepared to assume a key role in 
overseeing implementation and adherence to the study protocols, and assuring 
quality control of the data collected.  Although a DCC and CC may exist at the 
same institution, the two types of centers will require separate applications 
and these will be evaluated independently, by criteria outlined below.

The NIDDK anticipates creation and support of a repository to store biologic 
samples from this and other clinical trials and clinical research studies 
supported by the Institute.  A separate solicitation will seek proposals for 
this activity.  If this repository is not operational at the inception of 
research protocols supported by this Consortium, the DCC may be required to 
make interim arrangements for storage of specimens.  It is anticipated that 
specimens collected under the research protocols developed by the Consortium 
may include DNA and/or samples for creation of cell lines, as well as blood, 
stool, urine, hair and/or other samples that are required to achieve aims of 
specific research studies.  The DCC will coordinate movement of biologic 
specimens from the CCs to central laboratories for analysis and to the 
repository where samples will be stored for future analyses.  The DCC will 
also develop a system for identification of samples and linkage of samples to 
a central clinical database.  

The Steering Committee will determine how genotyping should best be 
accomplished to allow rapid identification and enrollment of appropriate 
neonates.  If genotyping is done through a central laboratory, the DCC will 
have overall responsibility for genotyping and may propose cost-efficient 
methods to provide services to CCs.  

The DCC will be expected to provide appropriate biostatistical, data 
management, and coordination and analytic expertise.  Sub-contracting of 
various aspects of the DCC to other institutions with special expertise may be 
included in the application. It is anticipated that subcontracts will be 
required for laboratories to perform genetic, immunologic, toxicologic and 
other assays, including identification of infectious agents. The DCC will be 
expected to generate appropriately detailed reports to the Steering Committee 
and to the Data Safety and Monitoring Board, and to the NIDDK staff (see 
below) at regular intervals, and will be responsible for the logistics and 
planning of the meeting of the Steering committee and its subcommittees. The 
application should describe how these tasks and responsibilities will 
be accomplished.  

3.  Steering Committee

The primary governing body of the study will be the Steering Committee 
comprised of each of the Principal Investigators of the CCs and the DCC, the 
Chairperson of the Steering Committee, representatives of the central 
laboratories, and the NIDDK Project Scientist (described in detail under Terms 
and Conditions).  The NIDDK staff will initially appoint an interim 
chairperson prior to the first meeting of the Steering Committee.  
Representatives of other institutes and centers supporting and sponsoring the 
Consortium will serve as ex officio members of the steering committee.  

It is anticipated that as its first task the steering committee will develop 
common protocol(s) for implementation by the Consortium. Based on current 
information about potential environmental triggers of type 1 diabetes and the 
feasibility of identification of pathogens with current technology, the 
steering committee will set priorities among candidate triggers and determine 
the optimal populations for study, laboratory measures, intervals for sample 
collection and other parameters of the study design.  The steering committee 
will also develop policies and procedures for the Consortium, including 
procedures for modification of the study design, for use of study samples and 
data, for approval of ancillary studies, for publication and presentation of 
results and for monitoring study progress, completeness and quality of data 
collection, and other performance measures.    

4.  Project Scientist

The NIDDK will appoint a Project Scientist, within the Division of Diabetes, 
Endocrinology and Metabolic Diseases, to assist the Steering Committee in 
carrying out the proposed studies (described in detail under Terms and 
Conditions).  The Project Scientist will provide scientific support to 
awardees" activities, including protocol development, quality control, interim 
data monitoring, final data analysis and interpretation, preparation of 
publications, and overall performance monitoring.

MECHANISM OF SUPPORT

This RFA will use the NIH cooperative clinical research (U01) award mechanism 
of support, an "assistance" mechanism (rather than as "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 stimulate the 
recipients" activity by involvement in the activity and otherwise working 
jointly with the award recipients in a partner role, but it is not to assume 
direction, prime responsibility, or a dominant role in the activity.  Details 
of the responsibilities, relationships and governance of the study to be 
funded under cooperative agreements are discussed below under "Cooperative 
Agreement Terms and Conditions of Award."

The total project period for an application submitted in response to this RFA 
may not exceed 5 years. This is a one time solicitation. At this time, the 
sponsoring institutes and centers have not determined whether or how this 
solicitation will be continued beyond the present RFA. The anticipated award 
date is September 2002. 

Modular Grant applications will NOT be accepted for this RFA. However, the 
standard PHS 398 application instructions apply.

The NIH U01 is a cooperative agreement award mechanism in which 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"

FUNDS AVAILABLE
 
The sponsoring institutes and centers intend to commit approximately $5 
million in total costs (direct plus Facilities and Administrative (F & A) 
costs) in FY 2002 to fund approximately five or six Clinical Center (CC) 
applications and one Data Coordinating Center (DCC) application in response to 
this RFA. It is anticipated that the CC center budgets may vary depending on 
the factors such as the number of subjects to be studied at each CC. 
Applicants for the CCs may request a project period up to five years and a 
budget for total costs (direct plus F & A) of up to $1,000,000/year.  
Applicants for the DCC may request a project period up to five years and a 
budget for total costs (direct plus F & A) of up to $1,500,000/year.  However, 
exceptions to these guidelines will be accepted if, for example, a single CC 
consists of a cooperative group located at multiple clinical sites.  Because 
the nature and scope of the research proposed in response to this RFA may 
vary, it is anticipated that the size of each award may vary in all years.  
Future year costs will be distributed based on the recommended protocols, 
database development, patient sample acquisition costs, and research protocols 
proposed and approved by the Steering Committee.

Although the financial plans of the sponsoring institutes and centers 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 applications 
of outstanding scientific and technical merit.  Designated funding levels are 
subject to change at any time prior to final award, due to unforeseen 
budgetary, administrative, or scientific developments. 

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
 
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.

Among the disciplines and expertise that may be appropriate for this program 
are:  epidemiology, pediatrics, genetics, genomics, infectious disease, 
and immunology. 

Within the Consortium an institution may apply for both a CC and the DCC, 
however, each component must have a separate application with a specific plan 
of how the independent operation of each unit of the CC and DCC will 
be maintained. 

SPECIAL REQUIREMENTS

Cooperative Agreement Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator(s) as well as the 
institutional official at the time of award. 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, 
the NIH Grant Policy statement.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01), 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 it is not to 
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(s) 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 and other supporting institute and centers 
Project Scientists.

1) Awardees Rights and Responsibilities

o The awardee(s) will have lead responsibilities in all aspects of development 
and implementation of the protocols, including any modification of study 
design, conduct of the study, quality control, data analysis and 
interpretation, preparation of publications, and collaboration with other 
investigators, unless otherwise provided for in these terms or by action of 
the Steering Committee.  Modifications of protocols will be approved by the 
Steering Committee.

o Awardees will retain custody of and have primary rights to their data 
developed under these awards, subject to Government rights of access 
consistent with current HHS, PHS, and NIH policies.  The collaborative 
protocol and governance policies will call for the continued submission of 
data centrally to the DCC for a collaborative database, the submission of 
copies of the collaborative data sets to each principal investigator upon 
completion of the study, procedures for data analysis, reporting and 
publication, and procedures to protect and ensure the privacy of medical and 
genetic data (if any) and records of individuals.  The NIDDK Project 
Scientist, on behalf of the NIDDK, will have the same access, privileges and 
responsibilities regarding the collaborative data as the other members of the 
Steering Committee.  The NIDDK expects that biologic samples and associated 
clinical data will be made available to the broader scientific community at an 
appropriate juncture to support further studies related to the prevention and 
etiology of type 1 diabetes and in studies to identify environmental factors 
and/or genes predisposing to type 1 diabetes.  The DCC will be expected to put 
all study materials and procedures manuals in the public domain and/or make 
them available to other investigators.

o The DCC will be involved in collaborations with the NIDDK, the cosponsoring 
institutes and centers, and the CCs during all phases of the research studies, 
will maintain the central laboratories through subcontracts, and will arrange 
transmission of specimens to the repository and linkage to the central 
database.  Thus, the awardee is expected to work cooperatively with CCs and 
sponsoring organizations in a multi-center study and oversee the 
implementation of and adherence to a common protocol, as well as assure 
quality control of the data and biologic specimens collected.  In addition to 
organizing and attending regular meetings, the DCC will be expected to 
maintain close communications with the NIDDK Project Scientist, 
representatives of the other co-sponsoring institutes and centers, the NIDDK  
biologic specimen repository, the central laboratories, and the Principal 
Investigators of the CCs.
 
o Awardees are encouraged to publish and to publicly release and disseminate 
results, data and other products of the study, concordant with the study 
protocol and governance and the approved plan for making data and materials 
available to the scientific community and the NIDDK and other co-sponsors.  
However, during or within three years beyond the end date of the project 
period of NIDDK support, unpublished data, unpublished results, data sets not 
previously released, or other study materials or products are to be made 
available to any third party only with the approval of the Steering Committee.

o Support or other involvement of industry or any other third party in any 
study performed by the Consortium-- e.g., participation by the third party, 
involvement of project resources or citing the name of the project or the 
NIDDK and other institute and center support, or special access to project 
results, data, findings or resources -- may be advantageous and appropriate.  
However, except for licensing of patents or copyrights, support or involvement 
of any third party will occur only following notification to, and concurrence 
by, NIDDK.

o Upon completion of the project, the DCC is expected to put all study design 
materials and procedure manuals into the public domain and/or make them 
available to other investigators, according to the approved plan for making 
data and materials available to the scientific community and the NIDDK, for 
the conduct of research at no charge other than the costs of reproduction 
and distribution.

2) NIH and CDC Staff Responsibilities

The NIDDK will name a Project Scientist from within the Division of Diabetes, 
Endocrinology and Metabolic Diseases whose function will be to assist the 
Steering Committee in carrying out the study.  Co-sponsoring institutes and 
centers will also name Project Scientists.  The NIDDK Project Scientist will 
have one vote for all key study group subcommittees. Representatives of other 
institutes and centers supporting and sponsoring the Consortium will serve as 
non-voting ex officio members.  The Project Scientists will have substantial 
scientific-programmatic involvement in quality control, interim data analysis, 
safety monitoring, and final data analysis and interpretation, preparation of 
publications, and coordination and performance monitoring.  The dominant role 
and prime responsibility for these activities 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 Project Scientists.

The NIDDK reserves the right to terminate or curtail the study (or an 
individual award) in the event of (a) failure to develop or implement a 
mutually agreeable collaborative protocol, (b) substantial shortfall in 
participant recruitment, follow-up, data reporting, quality control, or other 
major breach of the protocol, (c) substantive changes in the agreed-upon 
protocol with which NIDDK cannot concur, (d) reaching a major study endpoint 
substantially before schedule with persuasive statistical significance, or (e) 
human subject ethical issues that may dictate a premature termination.

3) Collaborative Responsibilities

The Steering Committee, composed of each of the Principal Investigators of the 
DCC and the CCs, the NIDDK Project Scientist, representatives of the central 
laboratories, and the Chairman of the Steering Committee, will be the main 
governing board of the studies.  Project Scientists from other institutes and 
centers will serve as ex officio members of the Steering Committee.  This 
committee will have the primary responsibility for approval of the common 
protocols, facilitating the conduct of participant follow-up, monitoring 
completeness of data collection and timely transmission of data to the DCC, 
and reporting the study results.  It will also be responsible for establishing 
study policies in such areas as access to patient data, ancillary studies, 
publications and presentations, and performance standards.  Each member of the 
Steering Committee will have one vote and all major scientific decisions will 
be determined by a majority vote of the Steering Committee.  The NIDDK will 
initially appoint an interim chairperson prior to the first meeting of the 
Steering Committee.  A Chairperson will subsequently be chosen from among the 
Steering Committee members (but not the NIDDK Project Scientist), or 
alternatively, from among experts in the field of type 1 diabetes who are not 
participating directly in the study.  Subcommittees will be established for 
specific purposes as needed, such as for ancillary studies, publications and 
presentations, quality control, recruitment, protocol adherence, among others.  

Each Consortium CC awardee and the DCC awardee agree to the governance of the 
study through the Steering Committee.  The Steering Committee voting 
membership shall consist of the Principal Investigators of the CCs and the 
DCC, representatives of the central laboratories, and the NIDDK Project 
Scientist.  Meetings of the steering Committee will ordinarily be held by 
telephone conference calls or in the Washington DC Metropolitan Area. 

The NIDDK Project Scientist (and the other cited NIH and CDC scientists) may 
work with awardees on issues coming before the Steering Committee and, as 
appropriate, other committees, e.g., issues of recruitment, intervention, 
follow-up, quality control, standards and methods, adherence to protocol, 
assessment of problems affecting the study and potential changes in the 
protocol, interim data and safety monitoring, final data analysis and 
interpretation, preparation of publications, and development of solutions to 
major problems such as insufficient participant enrollment.  Regardless of the 
number of NIH and CDC staff participating in technical advisory roles, the NIH 
and CDC will be limited to one vote on the Steering Committee.

The NIDDK expects that biologic samples and associated clinical data will be 
made available to the broader scientific community at an appropriate juncture 
to support further studies related to the prevention and etiology of type 1 
diabetes and in studies to identify environmental factors and/or genes 
predisposing to type 1 diabetes.  The DCC will be expected to put all study 
materials and procedures manuals in the public domain and/or make them 
available to other investigators.

4) Arbitration

Any disagreement that may arise in scientific/programmatic matters (within the 
scope of the award), between award recipients and the NIDDK may be brought to 
arbitration.  An arbitration panel will be composed of three members one 
selected by the Steering Committee (with the NIDDK member not voting) or by 
the individual awardee in the event of an individual disagreement, a second 
member selected by NIDDK, and the third member selected by the two prior 
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, or the rights of NIDDK under applicable statutes, regulations and 
terms of the award.

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:

Beena Akolkar, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd.
Room 681, MSC 5450
Bethesda, MD  20892-5450
Telephone:  (301) 594-8812
FAX:  (301) 480-3503
Email:  [email protected]

Inquiries may also be made to representatives of NIAID, NICHD, NIEHS and CDC,

Elaine Collier, M.D. 
Chief, Autoimmunity Section
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 5135, MSC-7640
6700-B Rockledge Drive
Bethesda, MD  20892-7640
Telephone:  (301) 496-7104
FAX:  (301) 402-2571
E-Mail:  [email protected]

Gilman Grave, M.D.
Chief, Endocrinology Nutrition & Growth Branch
National Institute of Child Health and Human Development
6100 Executive Blvd., Room 4B11A, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5593
FAX:  (301) 480-9791
Email:  [email protected]

Kim Gray Kamins, PhD
Chemical Exposures and Molecular Biology Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
PO Box 12233 MD EC-21
Research Triangle Park, NC  27709
Telephone:  (919) 541-0293
Fax:  (919) 316-4606
Email:  [email protected]
 
Robert F. Vogt, Jr., Ph.D.
Division of Laboratory Sciences
CDC, MailstopF19
4770 Buford Highway
Atlanta, GA  30341
Telephone:  770-488-7895 
FAX:  770-488-4609 FAX
Email:  [email protected]

o Direct your questions about peer review issues to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD  20892-5452
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  [email protected]

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

Cheryl Chick
Senior Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd.
Room 714, MSC 5456
Bethesda, MD  20892-5456
Telephone:  (301) 594-8825
FAX:  (301) 480-3504
Email:  [email protected]

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 NIDDK staff to estimate the potential review workload and 
avoid conflict of interest in the review.

The letter of intent is to be sent to the Chief, Review Branch at the address 
listed under INQUIRIES, above.

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email:  [email protected].
 
SUPPLEMENTAL INSTRUCTIONS:

Applicants must describe plans to accommodate the stated program requirements, 
criteria, and staff involvement.  Applicants must address points discussed in 
the SPECIAL REQUIREMENTS section of this RFA.

1.  CC Applications

Applicants for the CCs should respond with at least one research protocol 
involving multi-center participation to address the objectives of the study 
and to reach the study goals.  The application should discuss: (1) the 
evidence to date about the real and potential relationship between type 1 
diabetes and environmental triggers, (2) priorities among the various 
"candidate" triggers and the rational for their importance, (3) state of the 
art technologies applicable to the analysis of triggers, and (4) the most 
relevant populations for study based on items (1-3). It is anticipated that 
applicants will develop criteria for enrollment of neonates at high genetic 
risk for type 1 diabetes and protocols for obtaining and analyzing samples at 
specified intervals to identify environmental contributors to diabetes risk.  
In addition to outlining the rationale and background of the proposed studies, 
study design and protocols, eligibility criteria, and type of subjects to be 
included in the studies, applicants should discuss sample size needs and 
provide initial power analyses in their applications.  Applicants for CCs 
should consider the economies of scale to be gained and cost effectiveness of 
strategies of research plans involving large numbers of patients.  For each of 
the clinical protocols, the CC applicants should discuss the characteristics 
and number of potential participants that would be available from their own 
geographic region.  CC applicants should propose a research plan within the 25 
page limit.  

Genetic studies involving individual subjects and groups of people necessarily 
involve information that should be kept highly confidential.  It will be 
critical that at all phases of the study, the investigators understand and 
minimize the risks involved in such genetic research, protecting both 
individual subjects and research participants in groups, and optimize 
procedures for obtaining informed consent.  The approach to obtaining informed 
consent should be discussed in the context both of use of samples and data 
collected in protocols developed by the Consortium and of subsequent 
availability of data and samples collected in future investigations by the 
broader scientific community.  

An application for a CC should discuss the number of participants the CC 
anticipates will be recruited for protocols of the Consortium. The application 
should provide evidence that the investigators are capable of recruiting this 
number of participants, and of initiating and completing studies consistent 
with the overall goals of this RFA.  Applicants should describe the target 
population from which they expect to recruit the required number of subjects 
as study participants, and plans for recruitment of women, minorities, and 
children, as required. Proposed provisions to ensure confidentiality and to 
optimize informed consent procedures must be presented in the application.

There should be evidence of strong institutional support for the CC, including 
adequate space in which to conduct clinical and research activities and office 
space for staff. An organizational structure for the CC should be set forth in 
the application, delineating lines of authority and responsibility for dealing 
with problems in all general areas as well as stated willingness to follow 
commonly agreed upon protocols.  The principal investigator should indicate 
his/her willingness to participate in a per patient basis for operational 
costs of patient specimen acquisition and processing.  There must be ability 
to interact with the DCC and transmit and edit data.

The applicant should include a succinct discussion of previous relevant 
research efforts.  The applicant should also discuss in detail the recruitment 
strategies to procure the expected number of study participants.  Specific 
plans for recruitment of minority participants must also be discussed.  

The applicant should indicate willingness to participate in the Consortium 
concept outlined in this solicitation, participate in the Steering Committee 
meetings and abide by its decisions, and indicate prior experience in 
collaborative, multi-center research.  

2. DCC Applications

A separate complete application is required from institutions applying to be 
the DCC.  

Applicants must describe plans to achieve the stated "Objectives and Scope," 
"Special Requirements," and "Terms and Conditions of Award" stated in this 
RFA.  In addition, applicants should document their willingness to participate 
on the Steering Committee and appropriate subcommittees, work cooperatively 
with other members of the Steering Committee, and follow the common protocol 
established cooperatively by the Steering Committee.  It is expected that the 
PI of the DCC would carry out a significant leadership role in the consortium.  

Applicants must also address the following regarding responsibilities and 
requirements for the DCC:  

Participation in the design of the analyses to be undertaken, development of 
research studies and development of the manual of operation, data collection 
forms, questionnaires, and other study materials, 

Development and implementation of systems for communication among Steering 
Committee members, and among study sites, 

Data collection, editing, processing, analysis, and reporting,

Monitoring of adherence to the research plan and of data quality,

Establishment of procedures that insure the safety and confidentiality of 
all records.

Specific experience in coordinating or monitoring studies of diabetes and/or 
studies to identify environmental factors involved in pathogenesis of chronic 
disease is highly desirable, but if this does not exist collaboration with 
experts in diabetes and investigation of environmental agents in disease 
pathogenesis is encouraged.

The applicant for the DCC must delineate a plan for selection and operation of 
subcontracts for laboratory analyses required for this study, possibly 
including central laboratories for genetic testing, measurement of auto-
antibodies to beta cell antigens, assessment of other immune parameters, and 
identification of infectious agents, and development of a repository.  

The applicant for the DCC should also address any issues regarding common 
services, such as genotyping, that could be provided to the various 
participating CCs.

Applications may not exceed 25 pages for sections a - d, excluding appendices, 
which may contain copies of pertinent forms or examples of correspondence 
useful for coordinating tasks.

BUDGET AND RELATED ISSUES

Applicants should complete the budget information as directed in the PHS 398 
application form. 

1. CC Applications 
 
CCs should prepare budgets for five 12 month periods.  Applicants should 
consider the following issues regarding budgets.  A central concept is that a 
core clinical effort will be required to maintain the infrastructure required 
to enroll and follow patients and to acquire clinical specimens.  Therefore, 
individual CCs should submit requests for a CORE BUDGET.  It is anticipated 
that this core budget will cover effort for the principal investigator, and 
co-investigators with relevant expertise, effort for other key personnel 
(research coordinator, recruitment coordinator, technician, secretary), and 
travel costs for two individuals to attend consortium meetings up to four 
times a year in the Washington, DC area.  Depending on the sample size 
requirements, it may be necessary for CCs to subcontract to other clinical 
sites to obtain a sufficient number of patients and specimens for analysis.  
The core budget will include per patient costs for obtaining specimens from 
patients to forward to the central laboratories and repository. These costs 
should be justified appropriately in budgets and may be distributed into 
subcontracts.  Escalation is allowed at three percent for future years.  Costs 
for clinical care are not permitted.

The Consortium awards will be subject to administrative review annually.

2. DCC applications

Applicants for the DCC should prepare budgets for five 12 month periods that 
roughly correspond with the standard coordinating center responsibilities 
outlined in other sections of this RFA.  In the first year, DCC applicants 
should include all costs associated with the organization of all 
administrative aspects of the Consortium to be developed and with the 
initiation of the research protocol.  Funds will subsequently be added for 
central laboraties and respositories as needed.

The DCC will be subject to an annual administrative review. 

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/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed photocopies, in one 
package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At time of submission, two additional copies of the application must be sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD  20892-5452 (Courier use ZIP 20817)
Telephone:  (301) 594-8885
FAX:  (301) 480-3505

APPLICATION PROCESSING: Applications must be received by 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. 

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.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications previously reviewed, but such applications must 
include an introduction addressing the previous critique.

PEER REVIEW PROCESS

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

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the 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 discuss the following aspects 
of your application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals: 

o Significance
o Approach
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these criteria 
in assigning your application"s overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move a 
field forward.

o Significance:  CC applications should include a protocol addressing the 
problem outlined in the RFA.  The application should demonstrate how the study 
will advance scientific and/or medical knowledge.

o Approach:  The adequacy of the proposed conceptual framework, design, 
methods, and analyses.  The acknowledgement of potential problem areas and the 
consideration of alternative tactics.

Since the final study design(s) will be developed collaboratively by the 
Steering Committee for the protocols, the peer review group will focus on 
evidence that the applicant has carefully thought about the issues involved 
and possesses the knowledge necessary to contribute meaningfully to the final 
design, including understanding of the scientific, ethical, and practical 
issues underlying the proposed study.

o Innovation:  The applicant should demonstrate how the project challenges 
existing paradigms or develops new methodologies or technologies.

o Investigator:  The investigator should be appropriately trained and well 
suited to carry out this work.  For CC applications the proposed study should 
be appropriate to the experience level of the principal investigator and other 
researchers (if any).  There should be evidence of prior experience in working 
collaboratively to carry out a clinical study or standard protocol as well as 
evidence of willingness to work cooperatively on the Steering Committee to 
develop and follow a unified protocol.

o Environment:  The environment in which the work will be done should 
contribute to the probability of success. The proposed protocol should take 
advantage of unique features of the scientific environment and employ useful 
collaborative arrangements. There should be evidence of institutional support.

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

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

o INCLUSION:  The adequacy of plans to include subjects from both genders, all 
racial and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the 
section on Federal Citations, below)

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

o OTHER REVIEW CRITERIA

Applicants are encouraged to submit and describe their own ideas about how 
best to meet the goals of the cooperative study and their specific protocols. 
The evaluation of applications for CCs and the DCC will be based primarily on 
the scientific merit of the proposed studies, as defined above.  Specific 
criteria for review of applications will also include:

For both CCs and the DCC:

1. The scientific merit of the proposed study design(s) to address the 
objectives of the RFA, including strategies for patient identification and 
recruitment, and data collection and management, as outlined in the RFA.

2. Adequacy of the facilities and space.

3. Understanding and awareness of the scientific, ethical, and practical 
issues underlying the proposed studies and appropriateness of plans to deal 
with them.

4. Evidence of the degree of institutional commitment and support for the 
proposed program, including the relative position of the proposed project 
staff within the applicant"s organizational structure.

5. Willingness to carry out a commonly agreed upon study protocol, and to 
share patient data and specimens derived from collaborative studies.

6. Adequacy of plans to ensure accurate collection, confidentiality and 
timely transmission of study data.

7. The organizational and administrative structure of the proposed program.

For CCs:

1. Documentation of the specific competence and previous experience of 
professional, technical, and administrative staff pertinent to the operation 
of a CC in previous collaborative clinical investigations. Evaluation will 
include the following: familiarity with and experience in recruiting 
participants in a study, handling laboratory specimens, 
working in collaboration with other investigators under a common protocol, 
ability to implement study procedures, and meticulous and expeditious handling 
of study data.

2. Documentation of the expertise of the investigators relevant to the goals 
of the RFA as evidenced by past accomplishments and by the proposed protocol(s).

3. Documentation of access to patient population(s) from which a substantial 
number of participants can be recruited in sufficient numbers to meet the 
goals specified in the RFA.

4. Ability to recruit representative minority populations and children, 
as required.

For the DCC:

1. Documentation of the specific competence and experience of professional, 
technical, and administrative staff pertinent to both the molecular biologic, 
biostatistical and data coordination aspects of the proposed study.  Prior 
experience in similar studies, in the collection of data and patient specimens 
from multiple locations, as well as experience in monitoring the quality and 
timeliness of such data, should be demonstrated.

2. Demonstrable knowledge of the potential problems associated with the 
conduct of this study and possible solutions must be demonstrated.

3. Suitability of proposed data management and data analytic plans.

4. Ability to design, implement and maintain a distributed data entry system 
for the CCs.

5. The approach to and likelihood of soliciting cooperation from the 
participating CCs and exercising appropriate leadership in matters of study 
design and protocol revisions, and data acquisition, management, and analysis.  
Specific plans for ensuring standardization and quality 
control of data collection across all study sites are required.

6. The adequacy of the proposed technical hardware.

7. Ability to work with a repository to organize and provide oversight for a 
DNA and cell line collection suitable for the proposed studies for 
the consortium.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    March 5, 2002
Application Receipt Date:         April 15, 2002
Peer Review Date:                 July 2002
Council Review:                   September 2002
Earliest Anticipated Start Date:  September 2002

AWARD CRITERIA

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

o Scientific and technical merit of the application for a CC or a DCC.
o The multi-disciplinary nature of the proposed studies (CC).
o Demonstration of expertise to manage, design and coordinate multi-center 
clinical research studies, including handling and storage of laboratory 
specimens (DCC).
o The quality of response to the special requirements stated in this RFA. 
o Relevance to the overall programmatic balance and priorities of the NIDDK 
and sufficient compatibility of features proposed in the research plan and 
qualifications of the investigators to make a collaborative program within the 
Consortium a reasonable likelihood. 
o Availability of funds.
o Access to patients including women, children and minority individuals.
o A demonstrated willingness on the part of the investigators to work as part 
of the Consortium and with the NIDDK Project Scientist.

REQUIRED FEDERAL CITATIONS

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and 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 AMENDMENT "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. 
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.  
The Human Subjects Protection Regulations have been revised effective December 
11, 2001 to include Neonates (see 45 CFR 46, Subpart B -- Additional 
Protections for Pregnant Women, Human Fetuses and Neonates Involved in 
Research at:  http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.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.

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.

The Steering Committee 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.  To facilitate this, the DCC 
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 include in the application 
a discussion of approaches to structure informed consent statements and other 
human subjects procedures given the potential for wider use of data collected 
under this award.

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

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

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance No. 93.848 and is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review.  
Awards are made under authorization of Sections 301 and 405 of the Public 
Health Service Act as amended (42 USC 241 and 284)and administered under NIH 
grants policies described at http://grants.nih.gov/grants/policy/policy.htm 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.  http://grants.nih.gov/grants/guide/pa-files/PA-02-015.html.

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