COOPERATIVE MULTICENTER RESEARCH NETWORK TO TEST GLUCOSE SENSORS IN CHILDREN
WITH TYPE 1 DIABETES MELLITUS
Release Date: February 22, 2001
RFA: RFA-HD-01-009
National Institute of Child Health and Human Development
(http://www.nichd.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases
(http://www.niddk.nih.gov)
Letter of Intent Receipt Date: March 27, 2001
Application Receipt Date: May 11, 2001
PURPOSE
The National Institute of Child Health and Human Development (NICHD) and the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
invite cooperative agreement applications for participation in a
collaborative research consortium that will utilize new continuous glucose
monitoring devices to: (1) evaluate glycemic control and the incidence,
magnitude, and duration of hypoglycemia in a contemporaneous population of
children with type 1 diabetes mellitus, and (2) to evaluate glucose
homeostasis in children without diabetes. This research consortium may also
evaluate the value of providing data from these devices to health care
professionals with regard to achieving glycemic control and minimizing
hypoglycemia in children with type 1 diabetes mellitus.
In addition to applications for Clinical Centers (CC), which will recruit
subjects, and develop and implement a common protocol, separate applications
are invited for support of a Data Coordinating Center (DCC). The DCC will
have primary responsibility for Clinical Center coordination, and the
biostatistical analyses and data management aspects of the clinical trials.
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 Request for
Applications (RFA) is related to one or more of the priority areas.
Potential applicants may obtain Healthy People 2010 at
http://www.health.gov/healthypeople/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and North American, for-profit and
non-profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. The need for continuous and active
communication among sites dictates that only institutions in the United
States and North America are eligible to apply. Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to apply as
Principal Investigators.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) cooperative
clinical research (U10) award mechanism, 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 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 Terms and Conditions of Award.
FUNDS AVAILABLE
The NICHD and NIDDK intend to commit approximately $2 million in total costs
[Direct plus Facilities and Administrative (F & A) costs] in FY 2001 to fund
four Clinical Center applications and one Data Coordinating Center
application in response to this RFA. Applicants for the Clinical Centers and
for the Data Coordinating Center may request a project period of up to five
years and a budget for total costs of up to $400,000 per year. Although the
financial plans of NICHD and NIDDK provide support for this program, awards
pursuant to this RFA are contingent upon the availability of funds and the
receipt of a sufficient number of meritorious applications.
RESEARCH OBJECTIVES
Background
Hypoglycemia is the major limitation to implementation of intensive glycemic
control, which has been shown to substantially prevent or delay microvascular
complications in adolescents and adults with type 1 diabetes. Intensive
therapy has not been systematically evaluated in children under 13 years with
type 1 diabetes. Younger children may be at increased risk for hypoglycemia
in the setting of intensive therapy and the risk/benefit ratio of intensive
glycemic control achieved with current therapeutic tools may be less
favorable in this population. This RFA will address that concern through
creation of a Type 1 Diabetes in Children Research Consortium. The
Consortium will develop and implement a protocol using continuous monitoring
devices in children with type 1 diabetes, in order to evaluate the utility of
continuous monitoring devices and to determine if these devices are useful in
improving glycemic control and preventing hypoglycemia in children with type
1 diabetes. This protocol might also evaluate and develop distinct, age-
appropriate treatment approaches to type 1 diabetes in children.
The solicitation is part of a multi-faceted research program at the NICHD and
the NIDDK intended to reduce morbidity and mortality from type 1 diabetes in
the U.S. population. Results of the Diabetes Control and Complications Trial
(DCCT) demonstrated that near-normalization of blood glucose levels can be
achieved through intensive therapy, and slows the progression and
significantly reduces the risk of developing the microvascular complications
of diabetes. Although the same regimen and glycemic goals were imposed on
both adults and adolescents, the latter group was distinctive in their
response to the treatment regimen. Intensive treatment in adolescents caused
a three-fold greater risk for severe hypoglycemia and a two-fold risk for
obesity compared to similarly treated adults with diabetes. Additionally,
the hemoglobin A1c levels remained significantly higher in the adolescent
group compared to the adult subjects despite generally higher insulin
dosages. Notwithstanding the striking differences in the adolescents and
adults, the conclusion of the DCCT was that intensive therapy was recommended
for children over the age of 13, since the benefits appeared to outweigh the
risks.
Insulin pumps and multiple daily injections, now the mainstays of strict
glycemic control, are being prescribed more frequently in young children.
This treatment approach may be associated with high rates of severe
hypoglycemia, possibly leading to various adverse outcomes in some children.
One problem inherent in the current system of blood glucose monitoring is
that we do not know the true incidence, magnitude or duration of these
hypoglycemic episodes. New continuous monitoring systems for measuring
interstitial glucose concentrations have the potential to revolutionize
diabetes treatment. These systems have been tested in adults but still
require testing in children with type 1 diabetes to determine their value in
improving metabolic control and reducing the risk of hypoglycemia.
This multi-center observational study, using the new continuous monitoring
systems, should complement knowledge gained about the risks and benefits of
intensive therapy in adolescents and adults during and after the DCCT. While
the benefits of intensive glycemic control in reducing complications are
likely to accrue in younger children as well as in the DCCT population, the
risks may be substantially different. The incidence and severity of
hypoglycemia may be increased the younger the age of the child. Also,
children with recurrent episodes of hypoglycemia may be at increased risk for
learning disabilities and behavior problems. Although these issues cannot be
fully addressed in an observational study of this length, they remain the
driving force behind this RFA. Data on the incidence, magnitude, and
duration of hypoglycemia, as well as its sequelae, are needed to arrive at a
clear consensus about the potential risks of contemporaneous treatment
regimens of varying intensity in the pediatric population, especially in
prepubertal children. Data to inform decisions on treatment and monitoring
options for young children and age cutoffs for such options will be developed
through this observational study.
Objectives and Scope
This RFA solicits applications 1) for support of Clinical Centers (CCs) to
evaluate glycemic control in children with Type 1 Diabetes by the use of
continuous glucose monitoring devices and 2) for support of a Data
Coordinating Center (DCC) which will be responsible for providing
administrative, analytical, and statistical support for this study.
The CCs and the DCC will jointly comprise a Type 1 Diabetes in Children
Research Consortium to achieve the following objectives:
o To determine the extent of hypoglycemia (frequency, duration and degree) in
a contemporaneously treated population of children with type 1 diabetes,
o To examine the relationship between intensity of therapy and risk of
hypoglycemia,
o To identify factors, including method of treatment, exercise, nutrition,
other aspects of lifestyle and behavior, age, duration of diabetes, and other
patient characteristics, that affect the risk for hypoglycemia,
o To examine the value of current monitoring capabilities in management of
children with type 1 diabetes,
o To measure the blood glucose levels of children without diabetes who are of
comparable age and studied in the same manner as the study population using
the continuous glucose monitoring devices.
Study Protocol
This RFA solicits investigator-initiated clinical proposals to recruit,
assess, and monitor subjects. Each application for support as a Clinical
Center should propose a protocol that can be carried out in a multi-center
study of continuous glucose monitoring in children with and without diabetes
to accomplish the objectives described above. Investigators are invited to
submit a detailed proposal containing the study design he/she believes best
addresses these objectives. This longitudinal study should provide
information on glucose levels throughout a 24-hour period in normal children
and in children with type 1 diabetes treated by either conventional therapy
or intensive therapy. It should also address opportunities for ascertainment
of the threshold for clinical recognition of hypoglycemia in children with
type 1 diabetes using the continuous monitoring device. The application
should present a rationale for the number of children of each age to be
studied, describe how subjects will be selected to achieve appropriate
representation of patient characteristics including methods of treatment,
describe and justify the anticipated race, ethnic, and gender composition of
the study population, describe and justify the proposed monitoring device to
be used, and the setting, duration, and frequency of monitoring. Emphasis
should also be placed on inclusion of children across age, gender,
socioeconomic, and racial-ethnic groups. Incentives to enhance accrual and
retention should be described in the application.
A common protocol to be used by all CCs will be established by the Steering
Committee during the planning phase (the first six months) of the project.
Although the actual protocol to be implemented will ultimately be determined
by the Steering Committee, the protocols proposed will provide the major
basis for peer review of CC applications. The Steering Committee, composed
of the Principal Investigator of each Clinical Center, the Principal
Investigator of the Data Coordinating Center, as well as the NICHD and NIDDK
Project Scientists, will meet during the planning phase of the cooperative
agreement to design the actual study protocol. The Steering Committee will be
the main governing board of this study and will have primary responsibility
for developing common research designs, protocols, and manuals of operations,
facilitating the conduct and monitoring of studies, and reporting study
results.
Composition of Clinical Center Personnel
Applications for Clinical Centers will be strengthened by the participation
of individuals with clinical expertise in pediatric endocrinology, behavioral
research, nutrition, clinical research, and biostatistics.
Approximate Timetable
During the first six months, the Steering Committee and other personnel with
appropriate expertise from the Clinical Centers and the Data Coordinating
Center will work collaboratively to develop the study protocol, manual of
operations, and analysis plan. Enrollment and data collection efforts will
occur in the latter half of the first year and in Years 02-04.5. Data
analysis will occur in the latter part of year five.
SPECIAL REQUIREMENTS
Attendance at Meetings
To promote the development of a collaborative program among awardees,
Principal Investigators are expected to attend Steering Committee meetings
and participate in conference calls on a regular basis. In the first six
months, it is anticipated that at least three meetings will be
required, to design the protocol and to establish common measurements and
outcomes. Once patient recruitment has started, at least two Steering
Committee meetings will occur annually, with additional communication by
conference call on a regular basis to discuss emerging issues. Application
budget requests should include funds to support travel of the PI and one
other investigator to attend scheduled Steering Committee meetings.
In addition, the chairperson of the Steering Committee and the Principal
Investigator of the DCC will be expected to attend Data Safety and Quality
Committee meetings, which will take place at least twice a year.
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 (U10), 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 NICHD and NIDDK Project
Scientists.
1. Awardee Rights and Responsibilities
Awardees will have primary and lead responsibilities for the project as a
whole, including research design and protocol development, participant
recruitment and follow-up, data collection, quality control, interim data and
safety monitoring, final data analysis and interpretation, and preparation of
publications, with assistance from the NICHD and NIDDK Project Scientists.
Clinical Center awardees will collaborate with other investigators
participating in this cooperative agreement and agree to follow common
protocols developed by the Steering Committee. The awardees also agree to
meet patient recruitment goals (as determined by the Steering Committee), to
transmit data in a timely manner to the DCC, and provide progress reports to
the Steering Committee. The inability to meet performance requirements may
result in an adjustment of funding, withholding of support, restriction of
funds already awarded, or termination of the award.
The Steering Committee will develop and maintain specific measures to ensure
the safety and protection of the rights of study patients. The Principal
Investigator of each study site will assume and accept primary responsibility
for ensuring that studies are conducted in compliance with all federal
regulations. These include, but are not limited to, Title 21 CFR 50, 56, 312
and Title 45 CFR 46. All awardees must be able to demonstrate that there is
a current, approved Assurance on file with the Office of Human Research
Protections (OHRP), that each protocol and informed consent is approved and
reviewed annually by the Institutional Review Board (IRB) of record, and that
each subject has given written, informed consent. The Principal Investigator
must agree and assure that adequate records will be available, to enable
outside monitors to assess compliance with applicable federal laws and
regulations.
The Data Coordinating Center (DCC) will have primary responsibility for
Clinical Center coordination, the biostatistical analyses, and data
management aspects of the clinical study. The DCC will have both scientific
and administrative functions. The DCC will review all proposed protocols and
help develop the statistical design for the study, analyze study results and
review all manuscripts for statistical considerations. Based on input from
the Steering Committee, the DCC will prepare and update protocols and manuals
of operation, and will provide materials to aid in patient recruitment. The
DCC will be responsible for establishing a database to accommodate data
generated by the study, developing a data transmission system, and assessing
data quality and completeness throughout the study. The DCC will provide for
central registration of all individuals enrolled in the study. The DCC will
establish, via subcontracts, central laboratories and reading centers, if a
need for such is determined by the Steering Committee. The DCC will provide
statistical reports on the progress of study at Steering Committee meetings,
oversee the patient care cost reimbursement system, and facilitate
communication among investigators, including scheduling meetings and
conference calls, developing agendas and documenting minutes, and maintaining
membership rosters and committee lists. The director of the DCC will be a
member of the Steering Committee and cannot have any responsibility for
recruitment or follow-up of study participants.
Study investigators must agree to implement an adverse event tracking system,
as designed by the Steering Committee. Awardees must conform to the
guidelines pertaining to the accrual of women, children and minorities as
subjects in clinical research, and the reporting of results in these
subgroups.
In addition to periodic financial and administrative reports required by NIH
for administration of cooperative agreements, awardees must agree to furnish
reports documenting recruitment and follow-up activity.
Prompt presentation and publication in the scientific literature of study
findings is required. Awardees must agree to acknowledge NICHD and NIDDK
support in the publications and oral presentations resulting from research
conducted under this cooperative agreement. Manuscripts and presentations
will be written and reviewed according to policies established by the
Steering Committee.
Awardees will retain custody of and have primary rights to the data developed
under these awards, subject to Government rights of access consistent with
current HHS, PHS, and NIH policies. The DCC will be expected to put all
study materials and procedure manuals in the public domain and/or make them
available to other investigators.
A study site and its institution may not be involved simultaneously in other
studies involving the testing of glucose sensors in children with and without
diabetes if enrollment criteria overlap between the studies and if the
studies are actively recruiting participants. Applicants will forego
participation in studies that would compete for recruitment of the same study
population.
2. NICHD and NIDDK Staff Responsibilities
The NICHD and NIDDK Project Scientists will provide scientific assistance to
the awardees activities, including protocol development and modification,
quality control and performance monitoring, interim data monitoring, final
analysis, and preparation of publications. Consistent with the cooperative
agreement nature of this study, the NICHD and NIDDK Project Scientists
will be substantially involved as an active partner in those aspects of the
scientific and technical management of the study stated in these Terms and
Conditions. This level of involvement will be above and beyond the level
required for administration of traditional research grants.
The NICHD and NIDDK Project Scientists will have voting membership on the
Steering Committee and, as appropriate, will participate in its
subcommittees.
The NICHD and NIDDK reserve the right to terminate or curtail the study (or
an individual award) in the event of substantial shortfall in participant
recruitment, follow-up, data reporting, quality control, or other major
breach of the protocol. The NICHD and NIDDK can also terminate or curtail a
study if a major study endpoint is reached substantially before schedule with
persuasive statistical significance, if futility in reaching a significant
difference between the treatment groups is realized, if there is emergence of
new information that diminishes the scientific importance of the study, or if
human subject safety or ethical issues dictate a premature termination. The
NICHD and NIDDK may also terminate the project if there is failure to develop
or implement a mutually agreeable collaborative protocol.
3. Collaborative Responsibilities
The Steering Committee, which will be the main governing board of the study,
will be composed of the Principal Investigator of each Clinical Center, the
Principal Investigator of the DCC, and the NICHD and NIDDK Project Scientists
(one vote combined). The Steering Committee will have primary responsibility
for developing common research designs, protocols and manuals, facilitating
the conduct and monitoring of the study, and reporting study results. The
Steering Committee will design the protocol, and develop standardized methods
and measurements to be utilized in the study. The Steering Committee will
approve the protocol, changes to the protocol, and the manual of operation.
Responsibility for the execution of the study will rest with the Principal
Investigator of each study site, who will provide progress reports to the
Steering Committee. The Steering Committee will also develop policies
relating to access to patient data and specimens, and ancillary studies. The
Steering Committee will establish guidelines for presentations at scientific
meetings and for writing and publishing manuscripts on the findings of the
study. The Steering Committee will meet initially to develop the protocol
and subsequently to discuss the progress of the study. The NICHD and the
NIDDK will select a chairperson from among the non-federal Steering Committee
members or other experts in diabetes clinical research. If a study
investigator is chosen as chairperson, he/she must designate a replacement
investigator at his/her institution. The chairperson must have proven
evidence of leadership ability and be able to make an adequate time
commitment to the cooperative agreement.
The Data Safety and Quality Monitoring Group (DSQ) is an external oversight
committee which will be appointed by the NICHD and the NIDDK. It will be
composed of pediatric and diabetes and clinical research experts not directly
involved in the protocol. Prior to the initiation of the study, the DSQ will
review the protocol to ensure proper scientific design and protection of
human subjects. The studies will move forward into the recruitment phase
only with the concurrence of the awardees, the DSQ, the NICHD and the NIDDK.
The DSQ will monitor the study for safety and scientific validity, with
authority to recommend protocol or procedural changes or early termination of
the study. The DSQ is advisory to the NICHD, the NIDDK, and the Steering
Committee. The chairperson of the Steering Committee and the Principal
Investigator of the DCC will attend DSQ meetings, which will take place at
least twice a year.
4. Arbitration Process
Any disagreement that may arise on scientific/programmatic matters (within
the scope of the award) between award recipients and the NICHD and NIDDK may
be brought to arbitration. An arbitration panel (with appropriate expertise)
will be formed to review the NICHD and NIDDK decision and recommend a course
of action to the Directors, NICHD and NIDDK. The arbitration panel will be
composed of three members: one selected by the Steering Committee (with the
NICHD and the NIDDK not voting) or by the individual awardee in the event of
an individual disagreement, a second member selected by the NICHD and the
NIDDK, and the third member selected by the two prior selected members.
These special arbitration procedures in no way affects the awardee"s right to
appeal an adverse action that is otherwise appealable in accordance with PHS
regulations 42 CFR Part 50, Subpart D, and DHHS regulations 45 CFR Part 16.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
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 biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification are 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 research involving human subjects should read the
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for Grants and Contracts on
August 2, 2000
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a
complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The
revisions relate to NIH-defined Phase III clinical trials and require: a)
all applications or proposals and/or protocols to 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) all investigators to report accrual, and to conduct and report
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of NIH 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, published in the NIH Guide for Grants
and Contracts, March 6, 1998, and available on the Internet at:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes a
descriptive title of the proposed research, the name, address, and telephone
number of the Principal Investigator, the identities of other key personnel
and participating institutions, and the 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 NICHD staff to estimate the potential review workload and
plan the review.
The letter of intent is to be sent to Dr. Karen K. Winer at the address
listed under INQUIRIES, below, by March 27, 2001.
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. Reviewers are cautioned that their
anonymity may be compromised when they directly access an Internet site.
APPLICATION PROCEDURES
The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants. These forms are available at most institutional
offices of sponsored research, on the Internet at
http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the
Division of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone 301-710-0267, E-mail: grantsinfo@nih.gov.
Application Requirements
To promote the development of a collaborative program among the award
recipients, a number of issues need to be addressed in the grant applications
as discussed below. Applicants should document their ability to recruit a
sufficient number of participants, their ability to interact effectively with
the coordinating center, and their willingness and capability to participate
in monthly meetings during the planning phase (up to six months) and semi-
annual meetings over the duration of the five-year award. It is anticipated
that two investigators (including the PI), from each clinical site will
attend these meetings. Also, applicants should state their willingness to
follow the common protocol that will be agreed upon during the planning
phase.
1. Clinical Center Applications
All applicants should provide a detailed description of the design of the
study and should demonstrate how the continuous monitoring will be
implemented. Additionally, applicants should justify the proposed monitoring
device to be used, along with the setting, duration, and frequency of
monitoring. The application should contain a rationale for the number of
children in each age to be studied and should describe how subjects will be
selected to achieve appropriate representation of patient characteristics,
including methods of treatment. A crucial element of the study design is
specification of the precise methods and timing for collecting data including
the eligibility, baseline, and follow-up testing. Examples of proposed data
forms and questionnaires should be given. The process for sample collection,
storage, and handling needs should be included. A description of the
laboratory tests that are needed with appropriate methods for performing them
should be provided. If multiple tests are available to assess a parameter, a
justification for the chosen method should be included. Also include the
methods that would be used to ensure privacy and maintain confidentiality of
data. There must be a data and safety monitoring plan.
Applicants should provide a detailed description of the target population to
be studied with justification including a definition of the cohort by age,
sex, and race. The ability to recruit this target population and the methods
to be used should be described, with an estimation of the number of potential
subjects who fit the eligibility criteria and expected accrual rates. Sample
size needs and the assumptions and calculations used to estimate sample size
should be detailed. Emphasis should also be placed on inclusion of children
across age, gender, socioeconomic, and racial-ethnic groups. Incentives to
enhance accrual and retention should be described in the applications.
Because the ultimate study carried out under this RFA will be a collaborative
effort, an investigator may propose a study that requires more subjects than
can be recruited from within his/her institution. The investigator should
provide a detailed description of the total sample size needed as well as the
number of subjects that could be recruited from his/her own site. Applicants
must state their plans for reporting accrual by gender, race, and ethnicity
and for the reporting of results that examine differences in treatment
effects across these subgroups (see section, Inclusion of Women and
Minorities in Research Involving Human Subjects ). The application must
provide a detailed account of the local population pool from which subjects
will be recruited, including the gender and racial/ethnic make-up of the
population and the expected numbers of subjects from each group that could be
recruited. A plan for recruitment and retention of participants must be
provided. Subcontracts may be used to recruit subjects from additional local
sites not a part of the parent institution. In this case, the Principal
Investigator must include a detailed description of the subject pool at these
additional sites, as well as letters of cooperation from potential
subcontractors. It must be made clear that, depending on the final design of
the study, not all potential subcontractors will be needed.
2. Data Coordinating Center (DCC) Applications
A separate complete application is required from institutions applying to be
the DCC for the Type 1 Diabetes in Children Consortium. Applicants for the
DCC component are not required to be a clinical site within the Consortium,
though applicants for clinical sites may also submit an application 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 address the following issues that are
important to the successful development of a collaborative program:
Applicants must 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. Applicants must address the
following responsibilities of the DCC: 1) participation in the
design of the final protocol and development of the manual of operation, data
collection forms, and questionnaires, 2) development and implementation of
systems for communication among Steering Committee members, and among study
sites, 3) data collection, editing, processing, analysis, and reporting, 4)
monitoring of adherence to the protocol and of data quality, and 5)
establishment of procedures that insure the safety and confidentiality of all
records.
Data management and quality control procedures must be detailed. Methods for
assuring privacy and maintaining confidentiality should be included. There
must be a data and safety management plan. Applicants must state their plans
for the reporting of results that examine differences in treatment effects
across these subgroups (see section, Inclusion of Women and Minorities in
Research Involving Human Subjects ).
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.
3. Issues To Be Addressed By All Applicants
Qualifications and Experience: Applicants must include a description of
their experience and expertise to conduct a clinical study and participate in
a multi-center collaborative effort. In addition, the application must
provide evidence of the Principal Investigator’s ability
to contribute to the scientific effort of this cooperative agreement.
Institutional Support: There should be evidence of strong institutional
support for the proposed study, including adequate space, resources, and
facilities for subject care and follow-up.
Willingness to Collaborate: Applicants must document their willingness to
participate in Steering Committee activities, including meetings at the NIH
and regular conference calls, and should state their willingness to follow
the common protocol agreed to during the planning phase.
4. Budget Information
Detailed budget information should be provided for the proposed Clinical
Center or Data Coordinating Center. The budget should be divided into three
phases: 1) planning (first six months), 2) recruitment and study (three -
four years), and 3) analysis (final six months). The application should
contain a detailed budget for each phase.
The planning phase will be for the development of the protocol and the manual
of operation by the Steering Committee. It is anticipated that during the
planning phase, the budget will primarily support the salary and travel of
the Principal Investigator and other key personnel. Once the award is made,
each study site will directly receive costs for personnel, supplies,
equipment, communication, travel, and subject care costs associated with the
study. The application should detail these costs as dictated by the study
that is proposed. The actual budget awarded after the initial project period
will be determined once the Steering Committee finalizes the protocol.
Therefore, the final awards may vary among sites. If any centralized
laboratory assessments are required, costs for laboratory tests will be
reimbursed using subcontracts through the DCC, at rates determined by the
NICHD and the NIDDK.
Submission Instructions
The RFA label available in the PHS 398 (rev. 4/98) application form must be
stapled to the bottom of the face page of the application and must display
the RFA number HD-01-009. A sample RFA label is available at
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this
is in the pdf format. 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.
Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies, in one package, to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application should be
sent to:
L. R. Stanford, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Applications must be received by May 11, 2001. 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 already reviewed, but such applications must
include an introduction addressing the previous critique.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by CSR and for
responsiveness by the NICHD and 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 NICHD in accordance with the review criteria stated below.
As part of the initial merit review, all applications will receive a written
critique and may undergo a process in which only those applications deemed to
have the highest scientific merit will be discussed, assigned a priority
score, and receive a second level review by the National Child Health and
Human Development Advisory Council and the National Diabetes and Digestive
and Kidney Diseases Advisory Council.
Review Criteria
All applications will be reviewed according to the following criteria:
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in assigning the overall
score, weighting them as appropriate for each application. Note that the
application does not need to be strong in all categories to be judged likely
to have major scientific impact and thus deserve a high priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
o Significance: The application should address 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.
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. 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.
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research.
o The reasonableness of the proposed budget and duration in relation to the
proposed research.
o 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.
All applications for the Clinical Centers will also be reviewed with respect
to the following:
o Approach: Plans for the recruitment and retention of subjects will be
evaluated. Evidence of the ability to recruit, enroll and maintain subjects.
This includes an adequate description of the racial, ethnic and gender
composition of the proposed cohort and documentation of access to an
adequate patient population who may be approached in finding potentially
eligible study participants.
o The adequacy of plans to ensure accurate collection and timely transmission
of study data to the DCC.
o The appropriateness of plans to protect confidentiality of data.
o The adequacy of the data and safety monitoring plan.
All applications for the Data Coordinating Center will be reviewed with
respect to the following:
o Data Management System
Demonstrated experience and ability to implement a data management system for
collecting, checking, editing, and correcting data from Clinical Centers and
entry of corrected data into a computer. The system should include
provisions to ensure the accuracy of data entry.
o Quality Control System
Demonstrated ability to implement a quality control system for monitoring
data collection procedures with timely feedback to the individual centers.
o Personnel
Evidence that the proposed Principal Investigator and other personnel have
expertise in all aspects of study coordination including monitoring and
computerizing data, design and implementation of multicenter study protocols,
and the design and execution of appropriate statistical analysis and
reporting of data.
o Facilities
Adequacy of facilities and software for data management, monitoring and
analysis.
AWARD CRITERIA
Applications recommended by the NICHD and NDDK Advisory Council will be
considered for award based on the scientific merit of the proposed project,
as determined by peer review, and the ability of the investigators to meet
the research objectives of this RFA. In addition, program balance, defined
as the scope and variety of research strengths to enable a successful
collaborative program, the racial and ethnic composition of the populations
being studied, and the geographical location of the trial will be considered.
Awards are contingent upon the availability of funds.
SCHEDULE
Letter of Intent Receipt Date: March 27, 2001
Application Receipt Date: May 11, 2001
Peer Review Date: June 2001
Council Review: September 2001
Earliest Anticipated Award Date: September 2001
INQUIRIES
Inquiries concerning this RFA are encouraged. The opportunity to clarify any
issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Karen K. Winer, M.D.
Endocrinology, Nutrition and Growth Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B11, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6877
FAX: (301) 480-9791
E-mail: WinerK@mail.nih.gov
Joan T. Harmon, Ph.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 697, MSC 5460
Bethesda, MD 20892-5460
Telephone: (301) 301-594-8813
FAX: (301) 480-3503
E-mail: harmonj@extra.niddk.nih.gov
Direct inquiries regarding fiscal matters to:
Mary Daley
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17E, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1305
FAX: (301) 402-0915
E-mail: md74u@nih.gov
Kim Law
Division of Extramural Activities
National Institute of Diabetes Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 639, MSC 5456
Bethesda, MD 20892-5456
Telephone: (301) 594-8869
FAX: (301) 480-3504
E-mail: lawk@extra.niddk.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance Nos.
93.865 and 93.847. 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 and Federal Regulations 42 CFR 52 and
45 CFR Parts 74 and 92. This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-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 routing education, library, day care, health care or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
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