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 301-435-0714, E-mail: Grantsinfo@nih.gov. 

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:  Beth_Ansel@nih.gov 

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:  cm143g@nih.gov 

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.


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