and Human Services (HHS)
EXPIRED
COOPERATIVE MULTICENTER TRAUMATIC BRAIN INJURY CLINICAL TRIALS NETWORK
Release Date: March 26, 2001
RFA: RFA-HD-01-007
National Institute of Child Health and Human Development
(http://www.nichd.nih.gov)
Letter of Intent Receipt Date: August 10, 2001
Application Receipt Date: October 17, 2001
PURPOSE
The National Center for Medical Rehabilitation Research (NCMRR) at the
National Institute of Child Health and Human Development (NICHD) invites
applications from investigators interested in participating with the NICHD
under a Cooperative Agreement (U01) in a multicenter clinical trials research
Network program. This research Network is focused on Traumatic Brain Injury
(TBI), and is designed to evaluate the relationship between acute care
practice and rehabilitation strategies, to the long-term functional outcome
of TBI patients. The objective of this program is to facilitate study of
these clinical practices by establishing a Network of Clinical Network Sites
and a Data Coordinating Center (DCC) that, by rigorous patient evaluation
using common protocols, can study the required numbers of patients and can
provide answers more rapidly than individual centers acting alone.
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 priority areas. Potential
applicants may obtain "Healthy People 2010" at
http://www.health.gov/healthypeople.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic, 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 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
Research Project Grant (U01) 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 studies to be funded under cooperative
agreements are
discussed below under Terms and Conditions of Award.
FUNDS AVAILABLE
The NICHD intends to commit approximately $5 million in total costs [direct
plus Facilities and Administrative (F&A) costs] in FY 2002 to support up to
eight Clinical Network Sites and one Data Coordinating Center Site.
Applicants for the DCC may request a project period of up to five years and a
budget for direct costs of up to $1.2 million for the first year. For Years
02 through 05, applications for the DCC may request direct costs of up to
$750,000 per year. Applicants for the Clinical Network Sites may request a
project period of up to five years and a budget for direct costs of up to
$150,000 per year.
Because the nature and scope of the research proposed may vary, it is
anticipated that the size of awards also will vary. Although the financial
plans of NICHD 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. At this time, the NICHD has not
determined whether or how this program will be continued beyond the present
solicitation.
RESEARCH OBJECTIVES
Background
Traumatic Brain Injury (TBI) is a leading cause of death and disability in
children and adults. An estimated two million head injuries occur in the
United States each year. The number of treated cases of TBI has increased
over the past 25 years as earlier and more specialized emergency treatment,
especially at the accident scene, has saved individuals who might otherwise
have died before reaching the hospital. Approximately 50 thousand of these
individuals will have persistent physical, cognitive, behavioral and social
deficits that may compromise their quality of life, as a result of their
injury. This increase in the rate of survival from severe brain injury means
that there will be an increasing number of patients in need of effective
treatment to help them attain a satisfactory long-term life adjustment and
quality of life following their injury. The size of this population argues
for the importance of determining the most effective treatment and
rehabilitation practices.
During the past two decades, understanding of the pathophysiology of TBI has
increased dramatically. It is now recognized that all neurologic damage does
not occur at the moment of injury, but rather evolves over the ensuing
minutes, hours and days. It is well established that a combination of early
imaging in the emergency room, removal of extra-axial masses, support of
blood pressure, ventilation as well as monitoring of intracranial pressure
(American Association of Neurological Surgeons and the American Academy of
Neurology, 1995) produces improved survival rates. Equally well established
is the role of aggressive follow-on intensive care treatment. In addition, a
growing literature suggests that adjunctive pharmacological treatment
facilitates behavioral management during the rehabilitation process, and may
result in a better functional outcome. Despite these advances, much remains
to be learned about the underlying damage and pathophysiology of the deficits
associated with TBI, and to link acute care, rehabilitation and long term
patient outcomes.
Because of the subtle and delayed sequelae associated with TBI, determining
the most appropriate medical, rehabilitative and educational services for
children and young adults with brain injury is especially difficult.
Personality changes that appear to be independent of severity of injury are
common long-term consequences of TBI, and may become more pronounced over
time. Such long-term residual psychiatric sequelae pose challenges to
community re-entry and to quality of life and are often viewed as more
seriously handicapping than the cognitive and physical aspects of the injury
itself.
While there has been substantial improvement in the outcome from severe head
injury, there remains a great deal of variability in the care of these
patients across the country. Current medical management of TBI has, in some
instances, adopted principles of care and employed pharmaceuticals and
methodologies without rigorous use of evidence-based research necessary for
their objective evaluation. Clinically important variations may occur
because there is no efficacious standard of practice, linked to long-term
outcomes, to guide treatment. Similarly, there has been little systematic
study of the variables that influence the course and effectiveness of
rehabilitation after brain injury. Comprehensive rehabilitation programs
typically address areas of cognitive processes, behavioral and social
interactions, speech, language and communication, mobility and activities of
daily living. Depending on the particular focus of the program, certain
areas may receive greater emphasis. The precise format and intensity of the
interventions required for a given patient remain highly variable. Few
programs have been subjected to the degree of scientific scrutiny (e.g., case
definition, stratification by age and severity, standardized patient
inclusion criteria, standardized and quantitative measurement of treatment
and outcome) needed to draw conclusions about the efficacy of various
treatment methods. As a result, it is difficult to determine which
approaches are the most effective in returning TBI patients to maximum levels
of community or vocational integration.
Objectives
The primary scientific objective of the TBI Clinical Trials Network will be
to identify which intervention variables result in improvements in long-term
outcome. It is the objective of this RFA to establish a Network of clinical
sites that will work together and, in conjunction with NICHD staff, design
clinical intervention protocols and measures of outcome. Applicants should
describe their ability to identify TBI patient populations, to provide acute
care, and to provide post-rehabilitation follow-up. Additionally, applicants
should describe their approaches to the sharing of data and design of
comprehensive databases that will allow comparisons of procedures and
interventions. Proposed interventions may be designed for multiple points of
care including the accident scene, emergency room, intensive care unit,
rehabilitation and long-term follow up.
Goals of the TBI Clinical Trials Network will include:
o Recruitment of clinical trauma centers and rehabilitation/post
rehabilitation programs to participate in cooperative research.
o Establishment of uniform case definitions and standards of care among
participating centers that will permit quantitative evaluation of
interventions.
o Development of training programs for management of intracranial pressure.
o Development of a database for collection and management of data, including
development of web-based support and data sharing among and between Network
participants.
o Determine if predictor variables ("proxy measures") can predict long-term
outcome.
o Recommend improved treatment methods.
These research goals will be achieved through a TBI Network that will include
approximately eight Clinical Network Sites and a Data Coordinating Center
(DCC), supported by U01 awards. The Clinical Network Sites will recruit,
evaluate and treat the participants in any or all of the clinical studies
supported by the TBI Network. The DCC will have primary responsibility for
data collection and management of each trial. NICHD program staff serving as
a Project Scientist will cooperate with the funded Principal Investigators
(PI) in designing and executing protocols to optimize management in these
areas.
Role of the Clinical Network Sites
The Clinical Network Sites will work in collaboration with each other and
with NICHD staff to:
o Recruit patients into TBI Network clinical studies.
o Evaluate and treat the participants in any or all of the clinical studies
supported by the TBI Network.
o Design clinical intervention protocols.
o Design outcome measures.
Research conducted within the Network will encompass primarily cooperative
Network protocols. It is expected that the composite research plan will
encompass projects that address each aspect of the TBI Clinical Trials
Network goals for acute care treatment, rehabilitation, and long-term
functional outcome. Limited funds may be available during grant Years 04 and
05 to allow the Principal Investigator of each Clinical Network Site to
propose an individual research plan to accomplish his/her personal research
interests. The proposal will be required to have the same degree of
specificity and format as a regular research grant application. The TBI
Network Steering Committee will review these projects and make decisions
regarding approval. Proposals for individual research projects will be
requested at the time funds become available. They should not be included in
the applications submitted in response to this RFA.
Role of the Data Coordinating Center
The DCC will work in collaboration with the Clinical Network Site Principal
Investigators to:
o Establish data sets for acute TBI care.
o Establish data sets for rehabilitation.
o Establish data sets for one-year follow-up.
o Establish web-based data tools.
o Establish imaging data collection.
o Establish and conduct education and training procedures for all research
coordinators involved in the Network.
o Provide data analysis for all clinical protocols.
Domestic organizations with capacity to maintain close communication with NIH
and with prior expertise as a research support services provider, and as a
statistical coordinating and assistance center for multi-center research
(including randomized controlled trials and observational studies of both
medical and behavioral nature), are encouraged to submit applications under
this RFA for establishment and operation of a DCC.
Guidance and Management Structure
The overall guidance and management of the TBI Network will be provided by a
Steering Committee, a Network Advisory Board, and a Data Safety and
Monitoring Committee (DSMC).
In addition, the Network will establish Policies and Procedures that govern
its operations, including publications. These documents will be reviewed
periodically and may be amended at the discretion of the Steering Committee
and the NICHD.
SPECIAL REQUIREMENTS
Minimum Application Requirements for Clinical Network Site Applications:
o The Principal Investigator and research team at each Clinical Network Site
must have a history of previous successful clinical research.
o Applicant Clinical Network Sites must have a minimum of 100 moderate-to-
severe TBI admissions annually.
o Applicant Clinical Network Sites must have an established follow-up program
with experience in following patients and a designated facility must be in
place. Eighty percent of patients entered into the acute care database must
have rehabilitation follow-up. This must include data related to acute care
rehabilitation, intermediate care, community-based care and long-term care.
In addition, one-year post-trauma center discharge information must be
available.
o Each participating site must designate a research coordinator with adequate
percent effort. Description of this individual’s training, experience and
involvement in clinical research should be provided.
o The Clinical Site must demonstrate willingness and ability to participate
in a cooperative manner with other Clinical Network Sites, with the DCC, and
with NICHD in the delineation of research protocols, statistical methods,
uniform data collection and data transfer.
o The departmental and institutional commitment to collaborative TBI research
should be clearly documented by providing letters to the Principal
Investigator, and by citing evidence of past support.
o The application must provide evidence of recent research productivity by
the applicant Clinical Network Site in previous or present clinical trials,
especially of a cooperative multicenter nature. Specifically, contributions
in key areas such as protocol design, patient recruitment, data analysis and
interpretation, and publication are important.
o Proposed Network Concept Protocol
Because protocols for investigation will not be written until after awards
are made, it is not possible for applications to propose the exact work that
they will carry out if funded. Therefore, to provide peer reviewers and
NICHD staff with sufficient information regarding the capabilities of the
investigators, each applicant for a Clinical Network Site must submit a
concept protocol. The applicant should note carefully that the concept
study proposed may or may not be adopted by the TBI Network as one of its
protocols. The proposal is requested to serve as an indicator of the
applicant’s ability to participate in the development and design of protocols
for cooperative clinical investigations.
Principal Investigators should propose a cooperative research protocol that
reflects research efforts transcending his/her individual research programs.
The protocol should be written specifically for this TBI Network and will be
a key factor in evaluation of the application. Applicants should briefly
(two to three pages) outline the rationale and background of the proposed
study, study design and protocol, eligibility criteria and initial sample
size and power analysis. The cooperative research plan should propose
questions that will be examined cooperatively. Applicants should indicate
how their disciplinary and methodological perspectives could contribute to a
cooperative research effort.
Applicants should also address how they might cooperate in the continuing
business of the TBI Clinical Trials Network described above, and should
propose projects that would expand the research agenda of the Network. It is
anticipated that the Steering Committee and Advisory Board will include the
concept protocols submitted by the funded Clinical Network Sites in their
consideration of topics for actual studies. Research conducted during the
first three years of funding will be limited to common Network protocols.
Minimum Application Requirements for Data Coordinating Center Applications:
o The applicant must have demonstrated prior experience as a coordinating
center in multicenter studies.
o The Principal Investigator, with other staff, must have appropriate
biostatistical, data management and coordination expertise.
o The applicant must have the ability to assist in designing protocols and
the data collection system, including transmission via the Internet.
o The applicant must demonstrate the willingness and ability to cooperate
with the Clinical Network Sites and NICHD staff in all design, data
collection and analysis functions.
o The DCC must have an established data system to collect and tabulate
statistics.
Meetings
Each PI should plan and budget for four Steering Committee meetings per year
in the Washington, DC area. Each meeting will be approximately two days in
length. During these meetings, the Steering Committee will determine the
operating policies of the Network, discuss on-going research, formulate the
collaborative research plan, and discuss the implications of their research
with interested parties outside of the Network who may be invited by the
Steering Committee as the occasion warrants.
Departmental and Institutional Commitments
The department and institutional commitment to collaborative TBI research and
to prioritization of TBI Network research should be clearly documented by
providing letters to the Principal Investigator and by citing evidence of
past support. This institutional assurance to provide support should address
areas such as fiscal administration, personnel management, space allocation,
procurement, planning, equipment and budgeting.
Expectation of Cooperation
Applicants should indicate their willingness and ability to participate in
these stated aspects of the Network. The statement of willingness to
cooperate should be included under Consortium/Contractual Arrangements, item
h of the Research Plan in the application.
Budget Requirements
All applications must include an adequately justified year-by-year budget,
reflecting the changes in proposed activities as the studies progress. In
addition, a composite budget should be submitted. Applicable facilities and
administrative costs will be provided. Budgets will be reviewed on the basis
of appropriateness for the work proposed. Allowable costs and policies
governing the research grant program of the NIH will prevail.
Budget Requirements for the Clinical Network Site Applications:
o For Clinical Network Sites, the first-year budget at the time of
application will be limited to a BASE BUDGET. This budget should reflect
Base Budget support for the minimum number of full-time and/or part-time
staff necessary to successfully carry out the proposed trial. The personnel
list should include a Principal Investigator, co-investigator(s), study
coordinator, and data entry staff.
When an application has been funded, the Principal Investigator will be
required to complete protocol budgets for those studies planned within the
TBI Network. These budgets will consist of specific protocol-related costs
and the anticipated number of subjects to be enrolled in the study at the
applicant Clinical Network Site. The Principal Investigator will be required
to project patient enrollment for a specific protocol during a specified time
frame. Ongoing annual budgets of each Clinical Network Site will be based on
specific protocols. Protocol funds will be awarded separately.
Future years budgets should be limited to base budget costs, with an annual
increment of base salary and travel costs not to exceed three percent (the
maximum amount available for equipment and supplies will not increase).
Applicants shall use the negotiated rates for Facilities and Administrative
(F&A) costs in effect at the time of the initial award throughout the each
competitive segment of the project. Award levels for sponsored agreements
may not be adjusted in future years as a result of changes in negotiated
rates.
o Each investigator should budget for travel costs and related expenses for
travel to required meetings (four meetings a year) in the Washington, DC
area. Each meeting will be approximately two days in length.
Budget Requirements for DCC Applications:
DCC applicants should provide a BASE BUDGET, presented with precision and
clarity, that includes at a minimum, the following:
o Salary and administrative support for the Principal Investigator, Project
Coordinator, and other staff as required to meet the first-year
responsibilities of the DCC.
o Estimated travel costs and related expenses for the Principal Investigator
and other DCC staff for travel to required meetings.
o Travel and logistical support expenses for members of the DSMC and the
Network Advisory Group. For the purposes of this RFA, applicants should
estimate three meetings per year for the DSMC and one meeting per year for
the Network Advisory Group.
o Expenses related to communications, supplies, equipment, and other items
identified as essential to the establishment and operation of the DCC.
o Clearly specified plans and procedures for monitoring of DCC budgetary
expenditures.
Terms and Conditions of Award
Cooperative agreements are assistance mechanisms and are subject to the same
administrative requirements as grants. The following terms and conditions
will be incorporated into the award statement and provided to each Principal
Investigator as well as the institutional officials at the time of the award.
These terms are in addition to, and not in lieu of, otherwise applicable OMB
guidelines, HHS Grant Administration Regulations at 45 CFR Part 74 and 92,
and other HHS, HS, and NIH grant administration policies. The NICHD Grants
Management Branch in accordance with HHS, PHS, and NIH Grant Administration
policies will administer business management aspects of these awards.
The cooperative agreement funding mechanism will require collaboration among
the NICHD Project Scientist, the DCC Principal Investigator, and the
Principal Investigators of the TBI Clinical Network Sites. The NICHD Project
Scientist will coordinate the activities of the TBI Network, and will
facilitate communication and the exchange of information.
1. The Primary Rights and Responsibilities of the Awardees
All awardees will agree to accept the participatory and cooperative nature of
the group process. All awardees are required to submit annual progress
reports to NICHD, as appropriate and to provide study and site performance
information as stipulated by NICHD.
The Principal Investigator of each Clinical Network Site and the DCC will
play an important role in the design, implementation and execution of the
clinical trial. Each Principal Investigator will have primary responsibility
to define objectives and approaches, and to plan, conduct, analyze, and
publish results, interpretations and conclusions of his/her studies. The TBI
Network will retain custody of, and primary rights to their data developed
under this award, subject to Government rights of access, consistent with
current HHS, PHS, and NIH policies.
Each investigator will have the right to publish based on the work of their
individual research programs. Each Principal Investigator will also propose
a cooperative research plan in which they will identify research questions,
methodological research, protocols and data sets that they propose to work on
cooperatively.
Clinical Network Sites:
The Clinical Network Sites specifically will:
o Develop and implement research protocols, interventions, and evaluation
strategies, with all protocol documents including, at a minimum, an
introduction section with background and rationale, a statement of the study
objectives, criteria for selection of subjects and enrollment procedures,
clinical and laboratory evaluations to be performed, plans for data
collection, management, and monitoring, and for reporting of adverse events,
a complete description of the study treatment, and statistical
considerations, including general design issues, endpoints, sample size,
accrual and power, monitoring and analysis, and stopping rules. Some of
these activities are shared with the DCC.
o As a shared activity with the DCC, when appropriate, collect, analyze, and
interpret data, and disseminate research results from TBI Network studies,
while assuring quality control.
o Be required to project patient enrollment for a specific protocol during a
specified time frame, continuation and level of funding will be contingent on
actual recruitment.
o Present research concepts, plans, progress, and results to the Steering
Committee.
o Publish and disseminate results of both independent and shared research.
When joint protocols are completed, publish in collaboration with other
involved TBI Network Sites.
o Collaborate with other awardees and the NIH.
o Retain custody of and rights to data developed under these awards subject
only to the Government rights of access consistent with current HHS, PHS, and
NIH policies.
o Implement any Network-approved shared study protocols, where feasible,
including the recruitment and monitoring of study participants, associated
data collection, and study-associated quality control measures at the study
sites, in collaboration with the DCC.
o Obtain local institutional review board (IRB) approval of all study
protocols implemented at U.S. or foreign sites and comply with both IRB and
TBI Network policies and procedures.
o Generate, if feasible, additional research proposals, including shared
protocols, for consideration for inclusion in the TBI Network.
o Attend and participate in all Network conference calls and Steering
Committee meetings.
Data Coordinating Center:
The DCC will provide research support services to the TBI Network. These
will include establishment and maintenance of a centralized information
management system to help the TBI Clinical Network Sites collect, edit,
store, analyze, publish, and disseminate results from their individual
projects as well as from shared research. It will assist the program staff
of the NICHD in monitoring research progress, and will work to ensure data
integrity, accuracy, and accessibility among all Network sites. It will
offer technical assistance and analytical support for all sites, as needed.
All activities of the DCC must be closely coordinated with the NICHD Project
Scientist. In support of all research projects undertaken by the TBI
Network, the DCC staff will:
o Support the activities of the Network Advisory Group, Steering Committee,
and the DSMC through provision of materials/documentation support, meeting
planning and logistics, and conference call coordination.
o Provide advice on study design, data collection, data analysis, and
publication development to all TBI Network research projects.
o Prepare, design, and disseminate operations manuals, data collection forms,
databases, and results reporting summaries for TBI Network research projects.
o Compile for the Network Advisory Group and Steering Committee, the DSMC and
the NICHD site visit reports, monthly and quarterly subject enrollment
reports, meeting summaries.
o Prepare quarterly Clinical Network Site performance and progress reports,
and other reports as needed.
o Maintain or assure maintenance of high quality databases resulting from any
collaborative research, supervise all data collection procedures, and arrange
for the most efficient transfer of study data where indicated.
o Ensure that all TBI Clinical Network Sites and investigators fully comply
with NIH regulatory requirements, including informed consent, reporting of
adverse events, human and animal subject safety and welfare provisions, and
the requirements of international collaboration.
o Provide training to all Clinical Network Site personnel as needed on data
management and analysis, and quality control and quality assurance.
o In coordination with the NICHD, provide periodic on-site monitoring of the
Clinical Network Sites for those studies being performed at each site.
o Provide monthly reports detailing the progress in patient recruitment as
well as the percent effort spent on each specific research protocol for each
Clinical Site.
o Provide budget pages for each protocol in non-competing continuation (Type
5) applications.
o Attend and participate in all Network conference calls and Steering
Committee meetings.
2. NICHD Responsibilities
NICHD Project Scientist:
The NICHD TBI Network Project Scientist will be the Director of the Clinical
Practices Research Program of the National Center for Medical Rehabilitation
Research, NICHD. The Project Scientist is a partner within the Network
representing the government"s interest in the substantive work of the
Network. The primary role of the Project Scientist is to facilitate the work
of the Network and to connect the Network to public policy operations within
the government. He/she will:
o Assist in all functions of the Steering Committee, including: reviewing
and commenting on each stage of the program before subsequent stages are
started, exercising the options of adding, modifying or terminating aspects
of the program .
o Assist with the development of common protocols.
o Assist in the analysis, interpretation, and reporting of findings in the
scientific literature and other media to the community at large and the
public policy community within the Federal government.
NICHD Project Officer:
NICHD will appoint a Project Officer, apart from the Project Scientist, who
will:
o Have the option to withhold support to a participating institution if
technical performance requirements, such as compliance with the protocol, are
not met.
o Carry out continuous review of all activities to ensure objectives are
being met.
The above responsibilities are in addition to, not in lieu of, the levels of
involvement normally
required for program stewardship of grants.
3. Collaborative Responsibilities
The overall guidance and management of the TBI Network will be provided by a
Steering Committee, a Network Advisory Board, and a Data Safety and
Monitoring Committee (DSMC), as described below:
Steering Committee Responsibilities
Planning and implementation of the cooperative aspects of the study will be
done by a Steering Committee consisting of the Principal Investigator from
each participating awardee institution and the NICHD Project Scientist. The
Steering Committee will formulate a research plan for cooperative research
that will distill the several individual cooperative research plans into a
coherent plan and will involve allocating resources among the participating
cooperative agreements to implement it. The cooperative research plan will
be agreed upon by majority vote of the Steering Committee, but each Principal
Investigator will have the right of approval for any aspect of the
cooperative research plan involving them. Due publication credit will be
given to all work done cooperatively. The Steering Committee will:
o Plan the design and implementation of the cooperative research protocols.
o Participate in decision-making regarding allocation of funds for
cooperative research protocols.
o Participate in decision-making regarding allocation of funds for individual
research protocols.
o Publish results, conclusions, and interpretations of the cooperative
protocols.
o Formulate publication policy and appoint a Publication Subcommittee, as
judged necessary by the Steering Committee.
o Agree to accept the coordinating role of the committee and the cooperative
nature of the group process.
Network Advisory Board
An Advisory Board will advise the Steering Committee in the identification
and prioritization of topics for Network research. The Advisory Board,
chosen by NICHD, will comprise senior scientists in the areas central to the
work of the Network who are not affiliated with NICHD or part of the Network.
As well as serving in an advisory capacity to the Steering Committee as
deemed necessary, the Advisory Board will serve as the second level of review
for projects approved by the Steering Committee as part of the research
activities of the Network. The Network"s scope is defined as the sum of the
approved individual and cooperative research plans of participating
cooperative agreements in the Network.
Data Safety and Monitoring Committee
A Data Safety and Monitoring Committee (DSMC), established by NICHD, will
advise the NIH and the TBI Network, including the DCC, on research design
issues, data quality and analysis, and ethical and human subject issues. It
also will monitor the safety of any ongoing clinical trials. DSMC membership
will include, but not be limited to, individuals with expertise in clinical
trial design and conduct, relevant basic, medical, rehabilitation and
behavioral sciences research. The DCC will prepare reports and provide
coordination, support, and funding for travel and logistics arrangements
related to DSMC meetings and actions.
4. Arbitration Procedures
When agreement between an awardee and NICHD staff cannot be reached on
programmatic and scientific-technical issues that may arise after the award,
an arbitration panel will be formed. The panel will consist of one person
selected by the Principal Investigators, one person selected by the NICHD
staff, and a third person selected by these two members. The decision of the
arbitration panel, by majority vote, will be binding. These special
arbitration procedures in no way affect the awardees right to appeal an
adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart
D, and HHS regulations at 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 subject 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 may obtain copies of the policy from the program staff listed
under INQUIRIES. Program staff also can 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. Beth Ansel, at the address listed
under INQUIRIES, below, by August 10, 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: [email protected].
Application Instructions
Instructions accompanying the PHS 398 (rev. 4/98) are to be followed in
completing these applications. The research plan section of the application
should conform to the guidelines of PHS-398. The cooperative research plan
should be presented and should include Specific Aims, Background and
Significance, Progress Report/Preliminary Studies, and Research Design and
Methods, as in the standard Research Plan section. The budget for the
application should be predicated on the requirements of the cooperative
research plan. The standard 25-page limit for sections a d of the Research
Plan will apply.
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-01-007. 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 5E03F, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Applications must be received by October 17, 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. 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 to this RFA by NICHD. 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 Advisory Child
Health and Human Development Council.
Review Criteria
Criteria for the Evaluation of Clinical Site Applications:
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 review, comments on the following aspects of the application will
be made 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 the assignment of the overall score,
which is to reflect the overall impact of the project on the field, weighing
the criteria appropriately for each application. An application does not
need to be strong in all categories to be judged likely to have a major
scientific impact and thus deserve a high merit rating. For example, an
investigator may propose to carry out important work, which by its nature is
not innovative, but is essential to move a field forward.
(1) Significance: Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be advanced?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? Does the research plan consider and address the course
of TBI treatment and care?
(3) Innovation: Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies?
(4) Investigator: Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the Principal Investigator and other researchers (if any)? Do the
Principal Investigators and associated team members have experience with the
clinical management of TBI patients?
(5) Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed analyses take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?
Have the Clinical Network Centers established a cooperative participation
with acute rehabilitation and long-term care sites?
Criteria for Evaluation of DCC applications:
(1) Does the applicant possess the knowledge necessary to contribute
meaningfully to final study design, including understanding of the
scientific, ethical and practical issues underlying the type of research to
be conducted by the Network?
(2) Does the applicant demonstrate knowledge of the potential problems
associated with the conduct of the research to be conducted by the Network,
and identify solutions or alternatives?
(3) Does the application provide specific evidence of experience and
qualifications of team members who would be responsible for data quality and
management activities?
(4) Does the application document knowledge and experience in areas relevant
to the conduct of collaborative clinical research? This includes the
adequacy of the approach to developing a cooperative relationship among the
Clinical Sites and exercising appropriate leadership in matters of study
design, data acquisition, data management, data quality and data analysis.
(5) Is there evidence of experience of DCC personnel in using procedures
that ensure the safety and confidentiality of all records?
In addition to the above criteria, all applications for the TBI Clinical
Network will also be reviewed with respect to the following:
o Commitment to the cooperative nature of the program.
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
evaluated.
o The reasonableness of the proposed budget and duration in relation to the
proposed research.
o The adequacy of the proposed protection for humans or the environment, to
the extent they may be adversely affected by the project proposed in the
application.
SCHEDULE
Letter of Intent Receipt Date: August 10, 2001
Application Receipt Date: October 17, 2001
Peer Review Date: February/March 2002
Council Review: June 2002
Earliest Anticipated Award Date: July 2002
AWARD CRITERIA
Applications recommended by the National Advisory Child Health and Human
Development Council will be considered for award based primarily on
scientific and technical merit, as determined by peer review. Program
balance, that is, the scope and variety of research strengths to enable a
successful collaborative program, will be considered. Final selection of
Clinical Sites for funding may be based partly on the need for diversity in
the study population. Awards will be contingent upon availability of funds.
INQUIRIES
Written and telephone 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:
Beth M. Ansel, Ph.D., CCC-SLP
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 2A03, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 402-2242
FAX: (301) 402-0832
E-mail: [email protected]
Direct inquiries regarding fiscal matters to:
Christopher Myers
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17H, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6996
FAX: (301) 402-0915
E-mail: [email protected]
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance Nos.
93.929. 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 routine education, library, day care, health care or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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