CLINICAL RESEARCH CONSORTIUM TO IMPROVE RESUSCITATION OUTCOMES
 
RELEASE DATE:  July 2, 2003 (see NOT-HL-03-012)
 
RFA:  HL-04-001  (Reissued as RFA-HL-10-006)

 
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)
Institute of Circulatory and Respiratory Health (ICRH), 
Canadian Institutes of Health Research (CIHR)
 (http://www.cihr-irsc.gc.ca)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.837 (NHLBI), 
93.853 (NINDS)
 
LETTER OF INTENT RECEIPT DATE:  October 16, 2003
APPLICATION RECEIPT DATE:  November 13, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION:
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

This RFA provides support for the establishment of a Resuscitation 
Research Consortium to conduct clinical research in the areas of 
cardiopulmonary arrest and traumatic injury leading to arrest. This 
Clinical Research Consortium (the Consortium), consisting of up to 
seven Regional Clinical Centers (RCCs) and a Data and Coordinating 
Center (DCC), will provide the necessary infrastructure to conduct 
multiple collaborative trials to aid rapid translation of promising 
scientific and clinical advances to improve resuscitation outcomes. 
Trials may evaluate existing or new therapies (such as pharmacologic 
interventions, strategies of fluid resuscitation, and the use of 
immunomodulators), defined or proposed clinical management strategies 
(such as bleeding control strategies, the use of cerebral protection 
and neurologic preservation, metabolically directed therapies, and 
alternative CPR approaches), or a combination of the two.

For the purpose of this document, cardiopulmonary arrest is defined as 
primary cardiopulmonary collapse. Traumatic arrest is defined as trauma 
leading to or threatening cardiopulmonary collapse. Resuscitation 
research is defined as the field of investigation that attempts to 
provide the best and most effective treatment for arrest patients.

RESEARCH OBJECTIVES

Nature of the Research Problem:

Current resuscitation practice is based largely on empirical 
observation and findings from animal research. Few controlled studies 
have been conducted in people to establish the actual benefit of 
interventions presently employed. Results of basic research that have 
improved our understanding of the complex biochemical pathways involved 
in arrest-related ischemia and reperfusion in the heart and brain have 
not yet greatly affected resuscitation procedures and subsequent 
patient outcomes. Both the immediate pre- and post-resuscitation 
dysfunctional periods represent critical periods that are under-
investigated and that may be amenable to therapeutic interventions to 
improve patient survival. The timing and selection of resuscitative 
interventions and the ability to administer them effectively pose 
scientific and logistic challenges shared by both trauma and 
cardiopulmonary arrest investigators.

Pertinent Background Information Establishing Need for the Research:

To date, resuscitation-oriented research in people has failed to 
fulfill expectations generated by recent promising animal results. 
Translating the results of basic science and enabling technology 
research that hold promise for reducing arrest-related morbidity and 
mortality into clinical research and practice is vital for improving 
public health. In recognition of the need to improve resuscitation 
outcomes and to decrease the public health burden associated with 
traumatic injury and cardiopulmonary arrest, the NHLBI, NICHD, NIGMS, 
NINDS, FDA and DOD cosponsored the Post-Resuscitation and Initial 
Utility in Life Saving Efforts (PULSE) workshop on June 29-30, 2000 
(http://www.nhlbi.nih.gov/meetings/pulse/). A major recommendation of 
this workshop was to form a research consortium that would allow for 
the rapid testing of promising therapeutic strategies in appropriate 
populations of arrest patients. 

In response to this workshop recommendation, NHLBI released a Request 
for Information (RFI) [Collaborative Clinical Research Consortium To 
Improve Resuscitation Outcomes NOT-HL-02-002 
(http://grants.nih.gov/grants/guide/notice-files/NOT-HL-02-002.html)] 
soliciting comments to identify obstacles to clinical resuscitation 
research. Responses received from professional organizations, 
established research groups, and individual scientists indicated that 
testing of resuscitation strategies requires both targeted pilot 
studies and randomized controlled trials. Respondents felt that current 
clinical resuscitation research is impeded by a lack of infrastructure 
to allow enrollment of an adequate number of patients and overcome the 
substantial initial investment required for conducting patient-oriented 
research. Other barriers to resuscitation research include the lack of 
mechanisms to facilitate rapid testing and implementation of promising 
experimental approaches in the clinical arena, the absence of a uniform 
definition of successful resuscitation outcomes, and issues of 
obtaining informed consent from arrest patients.  

The ICRH has also recognized the need to invest in research concerning 
clinical resuscitation strategies. Traumatic injuries continue to be a 
huge burden on the Canadian health care system, especially when leading 
to cardiopulmonary arrest. In those circumstances where cardiopulmonary 
arrest occurs outside of the hospital, early and effective 
resuscitation is key to improving patient survival and rehabilitation. 
ICRH supports the recommendations of the PULSE report and recent work 
by the NHLBI to conceptualize the Clinical Research Consortium 
initiative. In order to promote collaboration between Canada and the 
United States on clinical resuscitation trials, ICRH will also support 
the initiative.

In sum, the recommendation of the PULSE workshop and responses to the 
RFI indicate that success in performing clinical resuscitation research 
requires both infrastructure and project support. The major advantages 
of establishing a consortium include: a) coordination between community 
emergency services and research centers; b) development of uniform 
methods for diagnosis and monitoring to more precisely characterize the 
natural history and presentation of cardiopulmonary and traumatic 
arrest; c) development and implementation of standard definitions; d) 
enhancement of patient and facility resources to ensure rapid, 
efficient, and cost-effective patient recruitment and enrollment; e) 
cooperative sharing of data and the use of central core laboratories; 
f) close scientific and administrative collaboration among 
participating centers; g) effective monitoring by the data and 
coordination center for quality, timeliness and adherence to protocols; 
and h) effective monitoring by the DSMB for patient safety. Lastly, the 
Consortium provides a vehicle to rapidly disseminate results to the 
research and practice communities.  

Scientific Knowledge to be Achieved Through Research Supported by this 
Program:

The general aim of this Consortium will be to conduct multiple 
collaborative clinical protocols to evaluate strategies to treat arrest 
patients, with an emphasis on out-of-hospital arrest. 

Objectives of this Research Program:

The primary objective of each study conducted by the Consortium will be to:

o Provide a knowledge base that will improve therapeutic decision-
making by testing approaches to management of cardiopulmonary arrest 
and life-threatening trauma.

Other objectives of the Consortium will be to:

o Develop methods for predicting individual response to interventions. 
o Evaluate and correlate various measures of functional outcome for 
resuscitation survivors.
o Develop collaborations between community emergency service providers 
and clinical research centers to permit out-of-hospital resuscitation 
research.
o Facilitate the training of resuscitation and emergency medicine 
physicians in clinical investigation. 

Types of Research and Experimental Approaches:

Each RCC applicant must demonstrate the capability to implement out-of-
hospital research protocols and enroll the required number of 
cardiopulmonary arrest and trauma patients. It is expected that the 
Consortium will test equal numbers of cardiopulmonary arrest and trauma 
resuscitation protocols. For the purposes of the RCC application, two 
well-developed intervention protocols must be proposed.  One protocol 
must focus on cardiopulmonary arrest, and the other on trauma.  Both 
protocol proposals must aim to significantly improve clinical outcomes. 
Protocols will be of relatively short duration (on average less than two 
years) and well focused. Many therapeutic trials will include phase I 
and/or II clinical trials. Final protocols will be selected by majority 
vote of the Steering Committee. Studies conducted by the Consortium may 
respond to urgent needs by testing new treatment strategies, providing 
data for planning larger trials or addressing conflicting results of 
previous clinical investigations. 

Examples of Research Topics:

Relevant areas may include, but are not limited to, the following 
scientific needs and considerations: 

o Evaluation of pharmacologic interventions to address a three-phase 
(electrical, circulatory, and metabolic) approach to resuscitation. 
o Evaluation of optimal strategies of fluid resuscitation including 
permissive hypotension, timing of initiation of infusion, and use of 
alternative fluids.
o Use of immunomodulators in improving clinical outcomes by altering 
systemic and/or regional inflammatory responses accompanying shock or 
shock-like states.
o Evaluation of bleeding control strategies.
o Use of cerebral protection and neurologic preservation, with an 
emphasis on functional outcome.
o Evaluation of metabolically directed therapies, such as a rapid 
induction of moderate systemic hypothermia and other novel methods to 
reduce metabolic demands in the immediate post-arrest/resuscitation 
interval.
o Evaluation of alternative CPR approaches including device-assisted CPR.
o Evaluation of oxygen delivery systems and methods for airway protection.  

Project Organization:

The Clinical Research Consortium will consist of the following 
components:  the NIH in cooperation with ICRH, up to seven Regional 
Clinical Centers (RCCs), a Data and Coordinating Center (DCC), a Study 
Chair, a Steering Committee and its subcommittees, a Protocol Review 
Committee (PRC), and a Data and Safety Monitoring Board (DSMB). The 
responsibilities of each component of the consortium are described 
below.  

NIH:

NHLBI will be responsible for overseeing the organization of the 
Consortium and thus will be substantially involved with the awardees in 
a partnership, consistent with the cooperative agreement support 
mechanism. NHBLI will routinely consult ICRH staff on management of the 
Consortium and will on a regular basis discuss progress, documentation, 
and shared goals related to this initiative. The NHLBI Program Official 
will monitor patient recruitment and study progress, and ensure 
disclosure of conflicts of interest and adherence to NHLBI policies. 
NHLBI will appoint the Study Chair and all members of the PRC and the 
DSMB. The Study Chair, who may or may not be a PI from one of the RCCs, 
will be responsible for ensuring that there are well-documented 
policies, procedures, and bylaws to guide all aspects of Consortium 
activities and operations. The Study Chair will also be ultimately 
responsible for the prioritization and finalization of study protocols. 
The Consortium leadership (NHLBI, NINDS and ICRH Program Officials, 
Consortium Study Chair, and all PIs from the RCCs and DCC) will 
establish procedures to: a) assure adequate protection of the rights and 
safety of patients involved in the research; b) guarantee the quality 
and integrity of the resulting data; c) maintain accurate and timely 
information on each study; and d) provide interim study summaries to the 
DSMB as requested. This oversight must be in compliance with all federal 
regulations and NIH/NHLBI policies. 

CIHR:

ICRH will provide and administer a portion of the funds for RCCs 
awarded to successful principal investigators located in Canada. ICRH 
staff will work with NHLBI to assess responsiveness, collaborate with 
the NHLBI concerning peer review process and administration, and advise 
the NHLBI on matters related to the management of the Clinical Research 
Consortium.

Regional Clinical Centers (RCCs):

As a group, RCCs will likely represent major medical centers with an 
established associated network of clinical sites or field centers. It is 
expected that individual RCCs will vary in nature and experience, and 
thus may represent both different patient populations and expertise in 
the area of resuscitation medicine. Therefore, the primary center must 
demonstrate both clinical science excellence and expertise in either 
cardiopulmonary arrest or trauma resuscitation, and a proven ability to 
recruit a population that includes patients from either urban or rural 
areas. As a whole, the Consortium intends to enroll patients from both 
urban and rural communities, and to perform research in the areas of 
both cardiopulmonary and trauma arrest resuscitation. However, for 
practical reasons, it is not required that each RCC represent all 
aspects of the arrest population, or demonstrate a facility in all areas 
of arrest investigation.

The Principal Investigator (PI) at each RCC will be responsible for 
proposing protocols, estimating their costs, participating in their 
overall development, conducting the research, assuring quality of 
patient care and protocol adherence, assuring the accurate and timely 
transmission of data collected in conjunction with the DCC, and 
disseminating research findings.

To provide peer reviewers and NHLBI/ICRH staff with sufficient 
information regarding the capabilities of the investigators, each 
applicant for a RCC must submit two protocol proposals. A proposed study 
may or may not ultimately be adopted by the Consortium as one of its 
protocols. The proposals are requested to serve as an indicator of the 
applicant's ability to participate in the development and design of 
protocols for cooperative clinical investigations. It is anticipated 
that the Steering Committee will include the protocols submitted by the 
funded RCCs in their consideration of topics for actual studies.    

Research plans should propose questions that could be examined 
cooperatively. Protocols should be written specifically for this 
Consortium to serve as a key factor in evaluation of the application. 
Applicants should outline the rationale and background of each proposed 
study, study design and protocol, eligibility criteria and initial 
sample size and power calculations. In order to avoid speculation about 
the enrollment potential of other RCCs in the actual Consortium, study 
design should be based on the available local patient population, not on 
the potential recruitment to be afforded by the Consortium as a whole. 
Furthermore, RCC applicants should indicate how their disciplinary and 
methodological perspectives could contribute to such a cooperative 
research effort. A protocol budget should be included with each proposal 
and should include an estimated per-patient enrollment cost; however, 
protocol costs should be excluded from the requested RCC budget. 

Data and Coordinating Center (DCC):

The DCC will be responsible for the coordination, administration, and 
support of all clinical research activities at the direction of NIH 
program staff. These activities include, but are not limited to, 
administrative support for the Consortium Study Chair, scientific 
leadership and committees, reimbursement for patient accrual, and 
organization of investigator meetings. The DCC will assist in final 
protocol development, provide statistical leadership for study design, 
and prepare operational timetables. The DCC will develop data collection 
system and manuals of operations, determine sampling and randomization 
schemes, and assist in defining primary and secondary outcomes and 
analytical approaches for the protocols. The DCC will subcontract to 
external laboratories as needed, coordinate with suppliers of drugs, and 
arrange for the preparation and packaging of medications. The DCC will 
manage and distribute all protocol funds.

The DCC will develop procedures for quality control, training and 
certification, and data management. It will monitor the quality and 
quantity of data received from the RCCs, provide relevant reports to the 
NHLBI, RCCs, and Steering Committee, and serve as a central repository 
for study data. The DCC will prepare protocols for submission to the 
PRC, and to the FDA, CMS, or other government agencies as required, and 
prepare confidential data analyses and reports for the DSMB. The DSMB, 
with DCC support, will develop stopping rules. The DCC will support 
manuscript preparation through data analysis, statistical consultation, 
editorial support, and meeting coordination. It will schedule and make 
arrangements for all meetings of established committees and boards. The 
DCC will be subject to annual administrative review.

The Consortium will require an interactive information technology 
system for identifying eligible arrest patients, evaluating 
investigator performance and protocol adherence, maintaining real time 
data accuracy and quality, training of personnel on a regular basis and 
in remote locations, and, most importantly, for assuring the highest 
quality of medical care for patients involved in Consortium protocols. 
This approach to information management provides the benefit of 
instant, reliable communication channels, accelerates the inclusion of 
key participants and medical experts, and reduces non-productive time 
spent traveling. Such a system will be based on teleconferencing and 
will allow for multi-site participants to effectively and precisely 
share and compare both research data and medical information. It must 
be modifiable as protocols demand and medical technology advances. 
Thus, a high degree of technical flexibility is both a priority and a 
requirement. Plans for an information technology system must be 
included in the DCC application and must be universally implemented 
across RCCs. Up to $275,000 total costs will be provided to the DCC in 
the first year for acquisition, installation, and other costs 
associated with necessary information technology equipment and 
software. Up to $250,000 total costs will be available with NHLBI 
approval over the following four years for system upgrades and 
maintenance.     

Steering Committee:

The Steering Committee will be the main governing body of the 
Consortium. Voting members of the Steering Committee include, at a 
minimum, the Study Chair, and the PIs of the RCCs and the DCC (or their 
designated alternate). The NHLBI and NINDS Program Officials and an ICRH 
designate will be non-voting members of the Steering Committee. The 
Study Chair will be appointed by NHLBI and may or may not be a PI at a 
participating RCC or the DCC. The Study Chair will plan network 
activities, oversee its functions, conduct SC meetings, and cast tie-
breaking votes in that committee. The Steering Committee will develop 
and ensure compliance with Consortium policies and procedures, identify 
and prioritize topics for investigation, evaluate protocols proposed by 
the RCCs, and develop consensus protocols for submission to the PRC. The 
Steering Committee will ensure that studies are properly conducted and 
monitored, that data are appropriately analyzed and interpreted, and 
that study results are reported in the scientific literature in a timely 
manner and disseminated to those directly involved in the care of arrest 
patients. Subcommittees consisting of qualified individuals from the 
RCCs, DCC, and NHLBI/NINDS/ICRH may be established by the Steering 
Committee to perform specific functions such as publications and 
presentations or quality control.

Protocol Review Committee (PRC):

The PRC will be appointed by, and responsible to, NHLBI in consultation 
with ICRH. It will consist of a Chairperson and scientists with 
expertise in basic and clinical research, clinical trial design, 
biostatistics, enabling technologies, outcome measures, and other areas 
of expertise as needed. The exact number and duration of protocols 
supported in the five-year program will depend on the nature and extent 
of the investigations proposed by the Consortium's Steering Committee. 
The PRC will evaluate protocols proposed by the Steering Committee based 
on the importance of the question to be addressed, scientific merit of 
the experimental design and approach, feasibility, appropriateness for 
the consortium, and consistency with NHLBI/ICRH missions and policies. 
The PRC will provide a written critique of each proposal and a final 
recommendation to the NHLBI/ICRH. All study protocols performed by the 
Consortium must be recommended by the PRC and approved by the NHLBI/ICRH 
before initiation. Each RCC is expected to participate in at least two 
protocols per year after the first year. 

Data and Safety Monitoring Board (DSMB):

NHLBI, in consultation with ICRH, will establish a DSMB in accordance 
with established policies to ensure data quality and participant safety 
and to provide independent advice to the NHLBI regarding progress and 
the appropriateness of continuing each study (see 
http://www.nhlbi.nih.gov/funding/policies/dsmb_inst.htm ).

Suggested Time Table for Research Agenda Administration:

Phase I (3 months) will be devoted to planning and development of the 
Consortium organizational infrastructure (including committee 
structure), and to protocol selection, development and prioritization, 
thus establishing a cohesive research agenda. Objectives for the 
planning and development stage are to select the Study Chair and 
Steering Committee leadership, determine patient eligibility criteria 
for initial clinical trials, develop data acquisition and consent 
forms, define terms and outcome measures, develop a manual of 
operations, questionnaires, procedures for quality control, determine 
priorities for protocol development, and begin to develop specific 
protocols. The PIs, through the Steering Committee, will lead the 
planning effort, with the assistance of the NHLBI Program Official. 

Phase II (3-6 months) will consist of staff training in data 
acquisition procedures, protocol completion, IRB approval, and initial 
enrollment for the first study. 

Phase III (6-54 months) will involve the ongoing process of protocol 
development and implementation. Enrollment for the first study will 
begin as soon as a protocol is approved and resources become available. 
The DCC will oversee the management of data and the distribution of 
protocol funds. It will also support manuscript preparation through 
data analysis, statistical consultation, editorial tasks, and 
coordination of meetings. The main results paper for each clinical 
trial will be collaboratively prepared by the investigators and 
submitted for publication. Complete patient records will be audited by 
the DCC on a regular basis.

Phase IV consists of final data analysis and manuscript preparation.

MECHANISM OF SUPPORT

This RFA will use NIH U01 award mechanism.  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project. This RFA is a one-time solicitation. Future unsolicited, 
competing-continuation applications based on this project will compete 
with all investigator-initiated applications and will be reviewed 
according to the customary peer review procedures. The anticipated 
award date is July 1, 2004. Applications that are not funded in the 
competition described in this RFA may be resubmitted as NEW 
investigator-initiated applications using the standard receipt dates 
for NEW applications described in the instructions to the PHS 398 
application.  

This RFA uses just-in-time concepts. This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.  

The NIH (U01) is a cooperative agreement award mechanism in which the 
Principal Investigator retains the primary responsibility and dominant 
role for planning, directing, and executing the proposed project, with 
NIH staff being substantially involved as a partner with the Principal 
Investigator, as described under the section "Cooperative Agreement 
Terms and Conditions of Award".  

Applications submitted by foreign institutions can request facilities 
and administrative (F&A) costs up to a maximum of eight percent.  
Please see the web site 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html 
for more information on allowable F&A costs 
for foreign grants and domestic grants with foreign components.

FUNDS AVAILABLE

NHLBI intends to commit approximately $7 million (total costs) in FY 
2004, and up to $38 million (total costs) over a five-year period. In 
addition, NINDS intends to commit approximately $5 million (total 
costs) over a five-year period. ICRH intends to commit approximately 
$2.5 million over a five-year period toward meritorious grants from 
Canadian institutions. Applicants who wish to have their projects 
considered for funding by ICRH should include with their application a 
letter stating that their application and summary statement may be 
shared with ICRH. These funds are intended to support up to eight new 
grants in response to this RFA including up to seven RCCs and one DCC 
for a period of five years. Budget information for RCC and DCC 
applicants is contained in the sections on budget requirements below. 
Although the financial plans of the ICs 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, it is not known if this RFA 
will be reissued.
 
ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the 
following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Foreign institutions may apply as primary grantees or may participate 
as part of a domestic application.
o Eligible agencies of the Federal government  

Applicants may choose to apply as a RCC, DCC, or as both a RCC and DCC. 
If an institution is applying for both a RCC and DCC, two separate 
applications from two different PIs should be submitted.  
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with the appropriate 
institution to develop an application for support. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH/CIHR programs.   
 
SPECIAL REQUIREMENTS 

The Consortium will be a collaborative effort that will require 
frequent interactions of awardees among each other and with NHLBI/ICRH.  

Applicants should explicitly indicate their willingness to: 

o Participate in Steering Committee meetings (expected to occur 
approximately four times per year in Bethesda, Maryland), site visits 
required by the NHLBI/ICRH, and regular telephone conference calls;
o Cooperate with other awardees in the development and design of 
research protocols;
o Abide by common definitions, common methods for patient selection and 
enrollment, and common protocols, procedures, tests, and reporting 
forms as chosen by majority vote of the Steering Committee; 
o Actively seek to implement each network-wide protocol approved by the 
PRC and NHLBI/ICRH;
o Comply with study policies and quality assurance measures approved by 
the Steering Committee;
o Agree to oversight of the study by a DSMB;
o Accept awards from the DCC for the support of research based on per-
patient (capitated) rates and actual numbers of subjects enrolled, 
followed, and completing the study (RCCs only);
o Accept, manage and distribute awards for the support of research 
based on the number of protocols developed, initiated, and carried out 
(DCC only);
o Transmit study data to the DCC in a timely and accurate manner (RCCs 
only);
o Report all adverse events in accordance with procedures established 
by the Steering Committee and NHLBI/ICRH policies;
o Cooperate with other awardees in the publication of study results and 
the eventual release to the scientific community of study procedures 
and other resources; 
o Develop and implement plans for the dissemination of study results to 
physicians involved in the care of arrest patients;
o Participate in studies of the cost effectiveness of therapeutic 
interventions should the NHLBI/ICRH choose to implement such research 
within the Consortium; and
o Accept the Cooperative Agreement Terms and Conditions of Award given 
below.

Cooperative Agreement Terms and Conditions of Award

The cooperative agreement is an award instrument establishing an 
"assistance" relationship (in contrast to an "acquisition" 
relationship) between NHLBI and a recipient, in which substantial NHLBI 
scientific and/or programmatic involvement with the recipient is 
anticipated during performance of the activity. The purpose of NHLBI 
involvement is to support and/or stimulate the recipient's activity by 
acting as a "partner", while avoiding a dominant role, direction, or 
prime responsibility. The terms and conditions below, elaborate on 
these actions and responsibilities, and the awardee agrees to these 
collaborative actions with the NHLBI Project Scientist to achieve the 
project objectives. It is anticipated that these terms and conditions 
will enhance the relationship between the NHLBI staff and the principal 
investigator(s), and will facilitate the successful conduct and 
completion of the study. These agreements will be in addition to, and 
not in lieu of, the relevant NIH procedures for grants administration. 
The terms will be as follows:
1.  The awardee(s) will have lead responsibilities in all aspects of the 
study, including any modification of study design, conduct of the 
study, quality control, data analysis and interpretation, preparation 
of publications, and collaboration with other investigators, unless 
otherwise provided for in these terms or by action of the Steering 
Committee.
2.  The NHLBI Project Scientist will serve on the Steering Committee; 
he/she or other NHLBI scientists may serve on other study committees, 
when appropriate. The NHLBI Project Scientist (and other NHLBI 
scientists) may work with awardees on issues coming before the Steering 
Committee and, as appropriate, other committees, e.g., recruitment, 
intervention, follow-up, quality control, adherence to protocol, 
assessment of problems affecting the study and possible changes in 
protocol, interim data and safety monitoring, final data analysis and 
interpretation, preparation of publications, and development of 
solutions to major problems such as insufficient participant 
enrollment.
3.  Awardee(s) agree to the governance of the study through a Steering 
Committee. Steering Committee voting membership shall consist of the 
principal investigators (i.e., cooperative agreement awardees), the 
NHLBI Project Scientist, and the Chairperson. Meetings of the Steering 
Committee will ordinarily be held by telephone conference call or in 
the metropolitan Washington Area.
4.  A Data and Safety Monitoring Board will be appointed by the 
Director, NHLBI to provide overall monitoring of interim data and 
safety issues; the Steering Committee will nominate members for this 
Board. Meetings of the Data and Safety Monitoring Board will ordinarily 
be held in Bethesda. An NHLBI scientist other than the NHLBI Project 
Scientist shall serve as Executive Secretary to the Board. An 
independent Protocol Review Committee, established by the NHLBI, will 
provide peer review for each network protocol.  Because the Board 
serves as an independent group advisory to the NHLBI, study 
investigators will not communicate with Board members regarding study 
issues, except as authorized by the Board's Executive Secretary.
5.  Awardees will retain custody of and have primary rights to their 
data developed under these awards, subject to Government rights of 
access consistent with current HHS, PHS, and NIH policies. The 
collaborative protocol and governance policies will call for the 
continued submission of data centrally to the coordinating center for a 
collaborative database; the submittal of copies of the collaborative 
datasets to each principal investigator upon completion of the study; 
procedures for data analysis, reporting and publication; and procedures 
to protect and ensure the privacy of medical and genetic data and 
records of individuals. The NHLBI Project Scientist, on behalf of the 
NHLBI, will have the same access, privileges and responsibilities 
regarding the collaborative data as the other members of the Steering 
Committee.
6.  Support or other involvement of industry or any other third party in 
the study -- e.g., participation by the third party; involvement of 
study resources or citing the name of the study or NHLBI support; or 
special access to study results, data, findings or resources -- may be 
advantageous and appropriate. However, except for licensing of patents 
or copyrights, support or involvement of any third party will occur 
only following notification of and concurrence by NHLBI.
7.  Study investigators are encouraged to publish and to release 
publicly and disseminate results and other products of the study, in 
accordance with study protocols and governance.  Within three years of 
the end of the period of NHLBI support for the project, data not 
previously released and other study materials or products not 
previously distributed, are to be made available to individuals who are 
not study investigators, provided such release is consistent with the 
study protocol and governance and with paragraph 6.  In addition, study 
investigators must establish a plan for making data sets and materials 
available to the scientific community and to the NHLBI immediately upon 
completion of the three year period following the end of the period of 
NHLBI support.
8.  The NHLBI reserves the right to terminate or curtail the study (or 
an individual award) in the event of (a) failure to develop or 
implement a mutually agreeable collaborative protocol, (b) substantial 
shortfall in participant recruitment, follow-up, data reporting, or 
quality control, (c) major breach of the protocol or substantive 
changes in the agreed-upon protocol with which NHLBI cannot concur, (d) 
attaining of a major study endpoint before schedule with persuasive 
statistical significance, or (e) human subject ethical issues that may 
dictate a premature termination.
9.  Upon completion of the project, awardees are expected to put their 
intervention materials and procedure manuals into the public domain 
and/or make them available to other investigators, according to the 
approved plan for making data and materials available to the scientific 
community and the NHLBI, for the conduct of research at no charge other 
than the costs of reproduction and distribution.
10.  Any disagreement that may arise in scientific/programmatic matters 
(within the scope of the award), between award recipients and the NHLBI 
may be brought to arbitration. An arbitration panel will be composed of 
three members--one selected by the Steering Committee (with the NHLBI 
member not voting) or by the individual awardee in the event of an 
individual disagreement, a second member selected by NHLBI, and the 
third member selected by the two prior members. This special 
arbitration procedure in no way affects the awardee's right to appeal 
an adverse action that is otherwise appealable in accordance with the 
PHS regulations at 42 CFR part 50, Subpart D and HHS regulation at 45 
CFR part 16, or the rights of NHLBI under applicable statutes, 
regulations and terms of the award.
11.  These special terms of award are in addition to and not in lieu of 
otherwise applicable OMB administrative guidelines, HHS Grant 
Administration Regulations at 45 CFR part 74, and other HHS, PHS, and 
NIH grant administration policy statements.

Awards made from ICRH will be held to similar terms and conditions as 
outlined above. 

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants. Inquiries may fall into 
three areas: scientific/research; peer review; and financial or grants 
management issues.

o Direct your questions about scientific/research issues to:

Tracey Hoke, M.D., Sc.M.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9198
Bethesda, MD  20892-7940
Telephone:  (301) 435-0515
FAX:  (301) 480-1454
Email: hoket@nhlbi.nih.gov

Mary Ellen Michel, Ph.D.
NINDS/NIH
Neuroscience Center, Room 2209, MSC 9525
6001 Executive Boulevard
Bethesda, MD 20892-9525
(301) 496-1447
Email: mm108w@nih.gov

o Direct your questions about peer review issues to:

Anne Clark, Ph.D.
Chief, Review Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD  20892 (20817 for express/courier service)
Telephone:  (301) 435 0270
FAX:  (301) 480 3541
Email: clarka@nhlbi.nih.gov

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

David Reiter
Grants Operations Branch 
National Heart, Lung, and Blood Institute 
6701 Rockledge Drive, Room 
Bethesda, MD  20892
Telephone:  (301) 435-0144
Email: reiterd@nhlbi.nih.gov

For any questions directed to ICRH please contact:
Elissa Hines Reimer
Senior Associate
Institute of Circulatory and Respiratory Health
Telephone: (613) 954-0544
Email: ehinesreimer@cihr.gc.ca

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document. The letter of intent should be sent by mail or email 
to Anne Clark at the above address.

In addition, for this RFA, principal investigators located in Canada 
are requested to notify ICRH of their intent to apply by sending an 
email to icrh@cihr.gc.ca by 10/16/2003. 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact Grants Info, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

SUPPLEMENTAL INSTRUCTIONS

EXPECTATION OF COOPERATION

Applicants should indicate their willingness and ability to participate 
in the stated aspects of the Consortium. 

Departmental and Institutional Commitments:

The local department and institutional commitment to collaborative 
resuscitation research and to the prioritization of Consortium research 
must be clearly documented by providing letters to the PI 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 and should include IRB assurance of a willingness to consider 
participation in resuscitation research.

REGIONAL CLINICAL CENTERS

Minimum Application Requirements for Regional Clinical Center (RCC) 
Applications:

o The PI and research team at each RCC must have a history of previous 
successful clinical research.
o The applicant must provide evidence of recent research productivity in 
previous or present clinical trials, especially of a cooperative, multi-
center nature. Specifically, contributions in key areas such as protocol 
design, patient recruitment, data analysis and interpretation, and 
publication are important.  
o The applicant must have a minimum of 500 arrest (cardiopulmonary 
and/or trauma) cases annually. These cases must be suitable for 
resuscitation research. Applicants are expected to provide information 
regarding the nature of the available patient population including 
numbers of arrest cases over the past five years, type of arrest 
(cardiopulmonary vs. traumatic), average response time (both in terms of 
time from 911 call to patient contact and from patient contact to 
arrival at hospital), percent achieving return of spontaneous 
circulation, and percent admitted to hospital, and percent discharged 
from the hospital. 
o The applicant must have an established program with experience in 
identifying and treating arrest and trauma patients and a designated 
facility for this purpose. 
o Each RCC 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 applicant must demonstrate the willingness and ability to 
participate in a cooperative manner with other RCCs, the DCC, and the 
NHLBI and ICRH in the development of research protocols, statistical 
methods, uniform data collection and data transfer.
o The departmental and institutional commitment to collaborative 
consortium research should be clearly documented by providing letters to 
the PI and by citing evidence of past support.
o The applicant must provide a plan for community representation in 
Consortium activities. This may include both lay people as well 
representatives of various organizations involved in local emergency 
medical systems. The plan should address how the representatives' 
inclusion will make a substantive contribution to the overall success of 
the Consortium.
o The applicant should plan and budget for two members of the 
investigative team to attend four Steering Committee meetings per year 
in Bethesda, MD. Each meeting will be approximately two days in length. 
During these meetings, the Steering Committee will determine the 
operating policies of the Consortium, discuss on-going research, 
formulate the collaborative research plan, and discuss the implications 
of their research with interested parties outside of the Consortium who 
may be invited by the Steering Committee as the occasion warrants.

Clinical Trial Agreement (CTA): 

When a pharmaceutical or device collaborator (third party) provides a 
study agent/device to the Consortium, a CTA will be negotiated 
describing respective responsibilities and rights. The agreement will 
include, but is not limited to, IND/IDE sponsorship, safety and data 
monitoring, and access to data. Third party agreements must be developed 
and implemented by the NHLBI/ICRH.

Informed Consent:

Patients who meet the eligibility criteria for a protocol may be 
unresponsive and incapable of providing consent at the time of 
enrollment. Further, the interventions being evaluated may need to be 
applied immediately (or have a small therapeutic window) to be 
effective, prohibiting any delay to obtain consent from next of kin. 
Therefore, NHLBI anticipates that certain protocols will be conducted 
under the regulations for exception from informed consent for emergency 
research (21 CFR 50.24) (see 
http://www.fda.gov/oc/ohrt/irbs/appendixb.html). These regulations have 
obligations for the investigators, the IRBs and NHLBI. The activities 
associated with fulfilling the requirements of those regulations can be 
substantial and vary by community. Applicants should anticipate 
undertaking research requiring an exception from informed consent and 
should allocate sufficient time and resources for the process, plan to 
work proactively with their IRBs, and develop community contacts, which 
can facilitate public input.

Applicants for each RCC should present the following information:  

For each year, each RCCs should request core budget costs only. 
Estimated protocol implementation costs should be based on the 
proposals presented in the applicant's research plan, but should not be 
included in the RCC budget request. A table should be included showing 
estimated costs per patient for conducting each proposed protocol. The 
budget for each protocol should be developed on a cost-per-patient 
basis and include all direct costs and the associated protocol 
facilities and administrative costs. 

Costs of drugs or laboratory tests that are not clinically indicated 
(i.e., are not eligible for third-party reimbursement as part of 
routine clinical care) should be part of the per-patient cost of 
conducting a protocol. Applications should identify the potential 
source(s) for any drugs or substances that are being considered for 
clinical protocols that are currently unavailable commercially. It 
should be noted that funds will not be provided for the purchase of 
expensive medical equipment such as echocardiographic or magnetic 
resonance imaging systems. If any of the protocols proposed by RCC 
applicants includes obtaining blood or tissue samples, the applicant 
should delineate how such specimens will be handled and analyzed. In 
the event that a central laboratory is required to analyze specimens, 
the RCCs will be responsible for obtaining the sample(s) and the cost 
of obtaining them will be part of the RCCs per-patient expense. The 
cost of shipping, analyzing, and storage, as well as training of 
personnel and quality control will be the responsibility of the DCC. 

All protocol proposals should include implementation budgets; however, 
costs for protocols should not be included in the RCC core budget 
request. Investigators should prepare budgets only for their own RCC to 
conduct the proposed protocols, and not for the entire Consortium. The 
yearly protocol budget for the applicant's center should include: a) 
the number of patients available for each of the proposed protocol at 
the applicant's center; b) costs per patient for obtaining community 
consent in order to facilitate emergency research; and c) costs for 
recruitment and retention of the specified number of patients. Note 
that ongoing annual budgets for protocols will be based on the 
protocols approved by the PRC and the Consortium Steering Committee. 
Continuation and level of funding for each RCC will be based on actual 
recruitment and overall performance. Awards will be subject to annual 
administrative review.  

Budget Requirements for RCC Applications:

RCC applicants should consider the following additional issues 
regarding budgets. The underlying concept of the Consortium is that a 
RCC core effort is essential to maintain the infrastructure required to 
perform multiple clinical trials. Based on this approach, it is 
estimated that the individual RCC will require a minimum level of 
effort to sustain the organizational aspects of the Consortium. It is 
also expected that the type and complexity of each RCC will vary. RCCs 
may represent compact urban clinical centers or extensive rural 
networks, and may require individualized staffing models in order to 
operate effectively. Therefore, each RCC applicant should submit a 
request for a CORE BUDGET between $350,000 and $500,000 total costs per 
year. Requests must be submitted with appropriate justification. It is 
anticipated that this core budget will include the following personnel 
categories: PI and Co-Investigators, Study Coordinators, Data 
Management/Teaching and Training Coordinator, Secretary/Administrator, 
Community/Policy Leadership Liaison, and EMS Leadership Liaison.

A minimum of 25% effort for the PI at each RCC is required. Appropriate 
effort for other key personnel, travel costs for two people to attend 
approximately four trips each year to attend Steering Committee 
meetings in Bethesda, MD, and other travel related to Consortium 
operations (such as DSMB meetings and site visits) should be included 
with appropriate justification. 

In addition to the RCC core budget, each RCC will be provided funds for 
protocol implementation and participation (enrollment) by the DCC. This 
support will be provided for each protocol on a per-patient basis. The 
precise number of protocols conducted over the five years will be 
determined by the Consortium Steering Committee and will depend on a 
number of factors including scientific priority, availability of funds, 
length of the protocols, and ease of enrollment. It is anticipated that 
after the first year, at least two protocols may be active each year. 

Clinical Research Skills Development Core (Core):

The Consortium presents a rich environment for young investigators to 
be exposed to and develop additional research skills. To assist the 
Consortium awards in enhancing the developmental environment for their 
new clinical investigators, NHLBI will permit applicants for a RCC to 
request up to $100,000 in total costs per year for a Clinical Research 
Skills Development Core. A Core is not a required component of an RCC 
and its absence will not disadvantage an applicant. The priority score 
on the Core will have no effect on the overall score of an application. 
If a Consortium application includes an application for a Core, then 
the Core should be mentioned in both the Abstract and the Table of 
Contents. Up to four additional pages may be used to describe the 
proposed Clinical Research Skills Development Core. The Core proposal 
should be inserted in the Consortium application at the end of the 
Research Plan. This text will not be counted toward the 25-page limit 
for the total Research Plan specified by the Form 398 instructions. 
Requests for Core funds should not be included in the body of 
Consortium applications as it is expected that this aspect of the 
Consortium will be supported by supplemental funds. Thus, applicants 
should provide a separate budget page for the Core and add the cost of 
the Core as a line item into the total request for funds. Applicants 
should read the specific requirements and other instructions for 
applying at http://www.nhlbi.nih.gov/funding/policies/ntwk_skill.htm.

DATA AND COORDINATING CENTER:

Minimum Application Requirements for Data and Coordinating Center 
Applications:

o The applicant must have demonstrated prior experience as a 
coordinating center in multi-center studies.
o The PI, with other staff, must have appropriate biostatistical, 
enabling technologies, data management and coordination expertise.
o The applicant must have the ability to assist in designing protocols 
and the data collection system, including secure transmission via the 
Internet.
o The applicant must demonstrate the willingness and ability to 
cooperate with the Consortium and NHLBI/ICRH staff in all design, data 
collection and analysis functions.
o The applicant must have an established data system to collect and 
tabulate and analyze statistics.
o The applicant should demonstrate the ability to provide multimedia 
conferencing and collaboration.
o The applicant must demonstrate and ability to manage and distribute 
protocol funds.

Budget Requirements for DCC Applications:

Applicants for the DCC should prepare budgets for five one-year periods 
with maximum total allowable costs for the DCC limited to $1,500,000 in 
the first year and $2,500,000 in years two through five. In addition, 
the Consortium has budgeted $525,000 total costs during the project 
period for information technology (multimedia conferencing and 
collaboration), and $3,000,000 total costs per year for protocols. This 
cost structure may be modified once the Consortium is finalized and 
protocols are underway. It is expected that patient care costs will be 
greatest in years two through five. Total costs may be escalated at 
three percent annually for future years. 

For budget purposes, DCC applicants should assume that in the first 
year all administrative aspects of the Consortium will be organized and 
at least one protocol will be developed and enrollment started. For 
subsequent years, applicants may assume that at least two protocols a 
year will be active (either in the protocol development, 
implementation, or analysis and writing phase).  

DCC applicants should include costs for managing the DSMB, the PRC, and 
the Steering Committee including the cost of DSMB calls and meetings 
(DSMB meetings will be held two times per year in Bethesda, MD), the 
cost of PRC conference calls and meetings, and the administrative 
expenses of weekly Steering Committee conference calls and the four 
Steering Committee meetings in Bethesda, MD. Costs allowed for the 
participation of the Study Chair include salary support (up to 20% of 
the NIH cap), travel expenses and administrative support. The DCC also 
should include costs for site visits of each of the RCCs over the five-
year study period, assuming up to six RCCs and a five-member site visit 
team for purposes of budget preparation. Cost for financial 
administration to prepare protocol budgets and to distribute and 
monitor funds should also be addressed. 

In addition, RCC applicants must include a statement of willingness to 
work collaboratively after award with the other funded sites to prepare 
a joint dissemination plan. DCC applications/proposals should describe 
methods to coordinate the dissemination planning and implementation. 
The DCC must include a budget and justification for any additional 
costs of this collaborative effort.
Applications that do not include a dissemination plan will be 
considered non-responsive and not eligible for review.      

The awards will be subject to annual administrative review. It is 
expected that all protocols will be performed in a manner consistent 
with United States Food and Drug Administration guidelines.   

USING THE RFA LABEL 

The RFA label available in the PHS 398 (rev. 5/2001) application form 
must be affixed to the bottom of the face page of the application.  
Type the RFA number on the label.  Failure to use this label could 
result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA 
title and number must be typed on line 2 of the face page of the 
application form and the YES box must be marked. The RFA label is also 
available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH 

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:
 
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and 
all five collated sets of appendix material must be sent to Anne Clark 
at the above address.
 
APPLICATION PROCESSING 

Applications must be received on or before the application receipt date 
listed in the heading of this RFA.  If an application is received after 
that date, it will be returned to the applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within eight weeks.
 
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.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes.  While the investigator may 
still benefit from the previous review, the RFA application is not to 
state explicitly how.

PEER REVIEW PROCESS 

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NHLBI/ICRH. 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 Division of Extramural Affairs, NHLBI, in 
consultation with ICRH, and in accordance with the review criteria 
stated below. The roster of the initial review group will be posted on 
the NHLBI/ICRH home page approximately two weeks prior to the review. 
As part of the initial merit review, all applications will receive a 
written critique and undergo a review in which only those applications 
deemed to have the highest scientific merit, generally the top half of 
the applications under review, will be discussed, assigned a priority 
score, and receive a second-level review by the National Heart, Lung, 
and Blood Advisory Council.  
 
The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

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

REVIEW CRITERIA FOR REGIONAL CLINICAL CENTER APPLICATIONS:

o Research plan.  Appropriateness of proposed protocols, need for the 
network to accomplish the proposed protocols, relevance and importance 
of the research questions, preliminary results that justify the 
proposed end points and sample size, and likelihood that accrual could 
be accomplished on time.

o Qualifications and experience.  The expertise, training, and 
experience of the investigators and staff in clinical trials, evidence 
of understanding of randomized, multi-center trials, administrative 
abilities of the Principal Investigator and the level of commitment to 
the program for the effective function of the Clinical Research 
Consortium.

o Patient access and study population.  The access to at least 500 
arrest patients; plans for the recruitment and retention of subjects; 
plans to ensure appropriate representation by ethnic group, age, and 
gender; the description of competing protocols, and the strategy for 
allocating patients between them.

o Willingness and ability to participate in the Consortium.  Applicant 
institution's history of collaborative research, depth of commitment, 
willingness to randomize patients, and ability to work with other 
Consortium Centers and NHLBI.

o Institutional resources for patient care and follow-up.  Adequacy of 
institutional resources including personnel, space, and special 
laboratory facilities.

REVIEW CRITERIA FOR DATA AND COORDINATING CENTER APPLICATIONS 

o Research plan.  Demonstrates understanding of the scientific, 
statistical, logistical, and technical issues underlying multi-center 
studies, including issues relating to assessment of outcomes relating 
to use of novel treatments of arrest patients; and demonstrates 
leadership in study design and statistics, data acquisition and 
management, data quality control, data analysis, handling and quality 
control of laboratory specimens, and consortium coordination.

o Qualifications and experience.  The expertise, training, and 
experience of the investigators and staff, including the administrative 
abilities of the Principal Investigator, co-investigator, and the time 
they plan to devote to the program for the effective coordination of 
the Consortium.

o Study management.  The administrative, supervisory, and collaborative 
arrangements for achieving the goals of the program, including 
willingness to cooperate with the participating RCCs and the NHLBI.  
This includes the ability to assist RCCs with recruitment problems to 
meet enrollment goals.

o Willingness and ability to participate in the Consortium.  Applicant 
institution's history of collaborative research, depth of commitment, 
and ability to work with RCCs and the NHLBI.

o Environment.  Facilities, equipment, and organizational structure to 
effectively coordinate Consortium activities and assist RCCs in 
implementing the Consortium protocols, providing for specialized 
laboratory testing, and collecting data.  This includes but is not 
limited to development of repositories, conduct of lab tests and 
studies, and obtaining study drugs or investigational agents or 
products.

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

o The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research. 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, animals or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.

REVIEW CRITERIA FOR CLINICAL RESEARCH SKILLS DEVELOPMENT CORES

The Clinical Research Skills Development Core will receive a priority 
score based on the review criteria below, but the priority score will 
not enter into the overall Consortium application priority score.    

The Clinical Research Skills Development Core will be evaluated for its 
effectiveness in developing the skills and clinical research 
capabilities of new investigators. This will include an evaluation of:   

o Credentials and track record of the PI, Core Project Leader, and 
other participating senior investigators. 
o Methods by which new investigators are to be recruited and selected 
including plans to recruit women and minority individuals.   
o Plans for developing the skills of new investigators; the types of 
skill and technologic development proposed.  
o Means by which the new investigators' professional development will 
be achieved.

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, and in 
accordance with NIH policy, the following items will be considered in 
the determination of scientific merit and the priority score:
 
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research. Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the 
sections on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  

DATA SHARING AND DISSEMINATION PLAN:  The adequacy of the proposed DCC 
plan to share and disseminate data. Applicants must include in their 
application/proposal a plan for dissemination of research results and 
such a plan should include: 
o Identification and description of target audience of the 
dissemination plan. 
o Description of the methods to be used to reach the audience. 
o Appropriate benchmarks for success. 
o Appropriate additional personnel for developing and implementing the 
dissemination activities. 
o An appropriate budget for the proposed dissemination activities for 
the last year of requested funding.  
o A statement that the investigators agree to discuss and finalize the 
dissemination plan with Institute staff prior to its implementation. 
BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE:

Letter of Intent Receipt Date:  October 16, 2003
Application Receipt Date:  November 13, 2003
Peer Review Date:  March 2004
Council Review:  May 13, 2004
Earliest Anticipated Start Date:  July 1, 2004

AWARD CRITERIA

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

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research 
components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous 
data management, quality assurance, and auditing procedures. In 
addition, it is NIH policy that all clinical trials require data and 
safety monitoring, with the method and degree of monitoring being 
commensurate with the risks (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy 
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health of 
the subjects or the purpose of the research. This policy results from 
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the 
new OMB standards; clarification of language governing NIH-defined 
Phase III clinical trials consistent with the new PHS Form 398; and 
updated roles and responsibilities of NIH staff and the extramural 
community. The policy continues to require for all NIH-defined Phase 
III clinical trials that: a) all applications or proposals and/or 
protocols must provide a description of plans to conduct analyses, as 
appropriate, to address differences by sex/gender and/or racial/ethnic 
groups, including subgroups if applicable; and b) investigators must 
report annual accrual and progress in conducting analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 
1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects. You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances. Data that are (1) first 
produced in a project that is supported in whole or in part with Federal 
funds and (2) cited publicly and officially by a Federal agency in 
support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA. It is important for applicants 
to understand the basic scope of this amendment. NIH has provided 
guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time. If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  
The Department of Health and Human Services (DHHS) issued final 
modification to the "Standards for Privacy of Individually Identifiable 
Health Information", the "Privacy Rule," on August 14, 2002. The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as "covered entities") must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on "Am 
I a covered entity?" Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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

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

ICRH Web Documents: Applicants are encouraged to visit the ICRH website 
available from the Canadian Institutes of Health Research homepage 
(www.cihr-irsc.gc.ca) to view the ICRH mandate and related strategic 
documents. Information about the CIHR Clinical Research initiative is 
also available by visiting the CIHR homepage and choosing, "Strategic 
Initiatives" and Clinical Research (available in English and French). 

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


H H S Department of Health
and Human Services

 
  N I H National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892