and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National
Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National
Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov)
Title: Neurological Emergencies Treatment Trials (NETT)
Network Clinical Site Hubs (U10)
Announcement Type
New
Updates: The following updates relating to this announcement have been issued:
Due Dates for E.O. 12372
Not
Applicable
Additional Overview
Content
Executive Summary
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.
Table of Contents
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research
Objectives
2. NETT
Network Organization and Timeline
A. Clinical
Coordinating Center
B. Statistical
and Data Management Center
C. Clinical
Site Hubs
D. Proposed
NETT Timeline
Section II. Award Information
1. Mechanism(s)
of Support
2. Funds
Available
Section III. Eligibility
Information
1. Eligible
Applicants
A. Eligible
Institutions
B. Eligible
Individuals
2. Cost
Sharing or Matching
3. Other -
Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address
to Request Application Information
2. Content
and Form of Application Submission
3. Submission
Dates and Times
A. Receipt,
Review and Anticipated Start Dates
1. Letter
of Intent
B. Sending
an Application to the NIH
C.Application
Processing
4. Intergovernmental
Review
5. Funding
Restrictions
6. Other
Submission Requirements
A. Supplemental
Application Information
B. Plan
for Sharing Research Data
C. Sharing
Research Resources
Section V. Application Review
Information
1. Criteria
2. Review
and Selection Process
A. Additional
Review Criteria
B. Additional
Review Considerations
C. Sharing
Research Data
D. Sharing Research Resources
3. Anticipated
Announcement and Award Dates
Section VI. Award Administration
Information
1. Award
Notices
2. Administrative
and National Policy Requirements
A.Cooperative
Agreement Terms and Conditions of Award
1. Principal
Investigator Rights and Responsibilities
2. NIH
Responsibilities
3. Collaborative
Responsibilities
4. Arbitration
Process
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research
Contact(s)
2. Peer
Review Contact(s)
3. Financial/
Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
PURPOSE OF THIS RFA
In order to improve outcomes for patients with neurological emergencies through research aimed at new therapies and their more effective implementation, the National Institute of Neurological Disorders and Stroke (NINDS) seeks to develop a Neurological Emergencies Treatment Trials (NETT) Network, comprising three essential components: a clinical Coordinating Center, a statistical and data management center, and a network of clinical sites. The purpose of this RFA is to request applications for the NETT Network Clinical Site Hubs to serve as Hubs for regional emergency department consortia. Applications for a NETT Network Clinical Coordinating Center (RFA NS-06-002, release date November 1, 2005 - http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-06-002.html) and for the Statistical and Data Management Center (RFA NS-06-008) are being sought in separate solicitations. Funding for two large, streamlined phase III clinical trials is included in the developmental phase of the NETT Network initiative.
BACKGROUND
Fifteen million adults and children are seen in U.S. emergency departments annually for acute neurological disorders that vary in seriousness from trivial to life threatening. Most patients are initially evaluated and treated by emergency medicine physicians, not by specialists in neurological diseases. Optimal management in the first hours of neurological emergencies is often critical to recovery; the window of opportunity cannot be reopened later due to the unique vulnerability of the central nervous system.
In order to improve outcomes for patients with neurological emergencies through research aimed at new therapies and their more effective implementation, the NINDS seeks to develop the Neurological Emergencies Treatment Trials (NETT) Network. The goals of the NETT Network are: 1) to facilitate high-quality clinical trials in several different types of emergency neurological disorders afflicting adults or children; 2) to encourage collaboration between emergency medicine physicians and neurological disease specialists in trial design and execution; and 3) to facilitate the implementation of new therapies into clinical practice. Once established, the NETT Network is intended to serve as a resource for investigator-initiated clinical research in acute neurological disorders. Following the initial trials funded through this initiative during the development phase, subsequent trials will be funded through traditional NINDS peer-review mechanisms.
OBJECTIVES OF NEUROLOGICAL EMERGENCIES TREATMENT TRIALS NETWORK
Overall Goal: To develop and widely implement efficacious treatments for patients with a broad spectrum of neurological emergencies in order to decrease the morbidity and mortality associated with neurological disease.
Specific Objectives:
Specific Aims:
2. NETT Network Organization and Timeline
The basic structure of the NETT Network consists of a Clinical Coordinating Center, a Statistical and Data Management Center, both of which have been solicited under separate RFAs, and eleven Clinical Site Hubs , to be solicited in the current RFA. In addition, three key Committees will be established that will collaborate in the development of the network and the oversight of two clinical trials during the award period. In order to understand the interacting roles of each component, each will be described below.
2.A. Clinical Coordinating Center
The NETT Network Coordinating Center will provide overall leadership for the project, including coordinating the activities of the 11 NETT Clinical Site Hubs, particularly recruitment, follow-up, and data quality. It will initiate investigator training and certification, supervise quality control measures, organize limited on-site monitoring, and coordinate meetings and teleconferences as appropriate among all study investigators. The Clinical Coordinating Center will develop and manage the trial protocols, monitor eligibility of participants, assure compliance with regulations and monitor the informed consent process, supervise and encourage recruitment, prepare blinded reports on adverse events, monitor study execution at sites, and arrange the supply of study medication for the trials. In addition, the Clinical Coordinating Center will collaborate with the Statistical and Data Management Center in developing and implementing data management procedures. The Clinical Coordinating Center will be responsible for quarterly progress reports to the NINDS, the NINDS-appointed NETT Network Advisory Group, and one or more DSMBs.
During the initial development phase of the network, funding will be awarded to the NETT Network Coordinating Center to carry out two large, streamlined phase III clinical trials (see http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-06-002.html). High-visibility, high-interest clinical trials will be important in order to stimulate initial interest in the NETT Network and engender enthusiastic participation of emergency medicine physicians.
2.B. Statistical and Data Management Center
The NETT Network Statistical and Data Management Center (SDMC) will work with the network leadership to design and implement data entry systems, develop study forms, receive data from the Clinical Site Hubs, perform data checks/queries, undertake interim monitoring, analyses and reporting for the Clinical Coordinating Center, NINDS, and Data and Safety Monitoring Boards (DSMBs). Biostatistical analyses and trial reporting for the network trials will be done through collaboration with the Steering Committee.
2.C. Clinical Site Hubs
The11 regional Clinical Site Hubs (for which applications are being solicited in the current RFA) will each coordinate activities at 2-10 emergency departments (or spokes in a hub-and-spoke model) involving 18-25 emergency medicine physicians, neurologists, neurointensivists, physiatrists, and neurosurgeons, and other surgeons and subspecialists, varying depending on local circumstances. Typical Hubs are envisioned as regional academic medical centers or tertiary care facilities capable of providing research support for the spokes. Spokes will vary in institutional format from academic emergency centers to community hospitals, with the latter serving to expand patient access, to allow assessment of the intervention in a real world practice setting, and to facilitate dissemination of the research results. Depending on the specific trial design, the spokes could either enroll patients on-site, using the Hub for research support, or identify participants for transfer to the Hub for specialty care. The Hubs will provide clinical leadership, research support, and local neurological expertise, coordinate IRB activities and human subject protections, enter data, and manage contracts. Involvement of nonacademic-affiliated hospitals, non-urban hospitals, and hospitals serving minority populations will be considered in Hub selection. Funding for Hubs will be closely linked to research productivity (e.g. recruitment, data quality); the costs of maintaining the infrastructure will be minimized. Representatives of Clinical Site Hubs will selectively participate on the Steering Committee. During the trial, Hubs may be added, deactivated, or placed in a follow-up mode with budget reduction, depending on performance and recruitment requirements and requirements for protecting human subjects.
Hubs will attempt to recruit all eligible patients with entry and follow-up according to the final, approved trial protocols. Training in good research practices is required of all investigators involved at the hub and measures to protect human subjects must be in place. Hubs will cooperate with data audits and other quality control procedures established by Steering Committee and trial protocols. Hubs will ensure timely transmission of all data to the Statistical and Data Management Center and agree to publish NETT Network generated data only with permission of the NETT Network Steering Committee.
It is envisioned that core members of the Hub would include emergency medicine physicians, with the collaboration of neurologists and neurosurgeons, although this may vary depending on local circumstances and should be described and justified. Additional potential involvement and collaboration with intensive care and other acute medicine specialists, physiatrists, radiology/neuroradiology and ambulance systems should be described, both for the hub institution and the proposed spokes. Research experience, the availability of research nurse support, blood and biological specimen processing and storage facilities, and research pharmacy services should be described in the application.
Proposed NETT Timeline
Year 1: First 6 months
Year 1: Second 6 months
Year 2: Patient accrual to begin.
Years 3-4: Patient accrual and follow-up in the trials.
Year 5: Trial close-out, data analysis, and preparation of papers for publication.
1. Mechanism(s) of Support
This funding opportunity will
use the clinical research
cooperative agreement (U10) award mechanism.
As an applicant you will be solely responsible for planning, directing, and executing the proposed project.
This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions. A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.
The NIH (U10) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, 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 VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".
This RFA is a one-time solicitation. The anticipated award date is September, 2006.
2. Funds Available
NINDS has committed $2,200,000 in direct costs to fund 11 awards in response to this RFA in FY 2006. An applicant should request a project period of five years and a budget for direct costs up to $200,000 per year.
Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Facilities
and administrative costs requested by consortium participants are not included
in the direct cost limitation, see NOT-OD-05-004.
Section
III. Eligibility Information
1. Eligible Applicants
1.A.
Eligible Institutions
You may submit (an)
application(s) if your organization has any of the following characteristics:
Foreign institutions are not eligible to apply.
1.B. Eligible
Individuals
Any
individual with the skills, knowledge, and resources necessary to carry out the
proposed research is invited to work with their institution to develop an
application for support. Individuals from underrepresented racial and ethnic groups
as well as individuals with disabilities are always encouraged to apply for NIH
support.
2. Cost Sharing or Matching
Cost
sharing is not required.
The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing
3. Other-Special Eligibility Criteria
Not
applicable
Section IV. Application and Submission Information
1. Address to Request Application Information
The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of
the PHS 398. For further assistance contact Grants Info, Telephone (301) 710-0267, Email: [email protected].
Telecommunications for
the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be
prepared using the most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/.
The D&B number should be entered on line 11 of the face page of the PHS 398 form.
The title and number of this funding opportunity must
be typed on line 2 of the face page of the application form and the YES box
must be checked.
3. Submission Dates and Times
Applications must be
received on or before the receipt date described below (Section
IV.3.A). Submission times N/A.
3.A.
Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt
Date: May 29, 2006
Application
Receipt Date(s): June 28, 2006
Peer Review Date: August 2006
Council Review
Date: September 2006
Earliest
Anticipated Start Date: September 2006
3.A.1. Letter of Intent
Prospective applicants
are asked to submit a letter of intent that includes the following information:
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 to:
Robin
Conwit, M.D.
Clinical Trials Group
National Institute of
Neurological Disorders and Stroke
6001 Executive Blvd., Room
2181
Bethesda, MD 20892
Telephone: (301) 496-9135
FAX: (301)480-1080
Email: [email protected]
3.B. Sending an
Application to the NIH
Applications must be
prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. 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 (U.S. Postal Service Express
or regular mail)
Bethesda, MD 20817 (for express/courier service;
non-USPS service)
Personal deliveries of
applications are no longer permitted (seehttp://grants.nih.gov/grants/guide/noticefiles/NOT-OD-03-040.html).
At the time of
submission, two additional copies of the application and all copies of the
appendix material must be sent to:
Chief,
Scientific Review Branch
National Institute of
Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Blvd.
Bethesda, MD
20892-9529 (Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: [email protected]
Using the RFA Label: The RFA label available in
the PHS 398 application instructions 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/labels.pdf.
3.C. Application
Processing
Applications must be received on or before the
application receipt date(s) described above (Section IV.3.A.).
If an application is received after that date, it will be returned to the
applicant without review. Upon receipt, applications will be evaluated for
completeness by the CSR and responsiveness by the NINDS. Incomplete and non-responsive
applications will not be reviewed.
The NIH will not accept
any application in response to this funding opportunity 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 a funding opportunity, it is to be prepared as a NEW
application. That is, the application for the funding opportunity must not
include an Introduction describing the changes and improvements made, and the
text must not be marked to indicate the changes from the previous unfunded
version of the application.
Information on the
status of an application should be checked by the Principal Investigator in the
eRA Commons at: https://commons.era.nih.gov/commons/.
4. Intergovernmental Review
This initiative is not subject to intergovernmental
review.
5. Funding Restrictions
All NIH awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement. The Grants Policy Statement can
be found at http://grants.nih.gov/grants/policy/policy.htm.
Pre-Award Costs are allowable. A grantee may, at its own risk and
without NIH prior approval, incur obligations and expenditures to cover costs
up to 90 days before the beginning date of the initial budget period of a new
or competing continuation award if such costs: are necessary to conduct the
project, and would be allowable under the grant, if awarded, without NIH prior
approval. If specific expenditures would otherwise require prior approval, the
grantee must obtain NIH approval before incurring the cost. NIH prior approval
is required for any costs to be incurred more than 90 days before the beginning
date of the initial budget period of a new or competing continuation award.
The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
6. Other Submission
Requirements
6.A. Supplemental application information
For the development phase of the NETT Network, the goal is to establish a model of large, streamlined trials of clear clinical relevance and substantial interest to neuro-clinicians and emergency medicine physicians in order to demonstrate what the Network is capable of accomplishing. Two randomized clinical trials will be conducted as part of network development during the RFA period; the trials will be selected by the NETT Advisory Group, which will also approve the final protocols. Trial design is expected to be simple (i.e. streamlined), thus making the trials amenable to execution at community emergency centers. Selection of trials will consider both high prevalence neurological disorders and lower prevalence disorders with high morbidity. The public health importance, economic impact of the disease, scientific merit, feasibility for completion within the timeframe of the RFA, protocol quality and completeness, and budget will be considered in trial selection.
6.B. Plan for Sharing Research Data
All
data collected as part of the NETT Network trials will be submitted to the
central NETT coordinating center, which will be responsible for data
management, analysis, and distribution. Data sharing requirements will be
the responsibility of the NETT Clinical Coordinating Center and the Statistical
and Data Management Center.
6.C. Sharing
Research Resources
NIH policy requires that
grant awardee recipients make unique research resources readily available for
research purposes to qualified individuals within the scientific community
after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
The adequacy of
the resources sharing plan and any related data sharing plans will be
considered by Program staff of the funding organization when making
recommendations about funding applications. The effectiveness of the resource
sharing will be evaluated as part of the administrative review of each
non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm).
See Section VI.3. Reporting.
Section
V. Application Review Information
1. Criteria
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
The following will also be considered in making funding decisions:
Relevance of program priorities
Upon
receipt, applications will be reviewed for completeness by CSR and
responsiveness by NINDS. Incomplete and/or non-responsive applications will not
be reviewed. 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 NINDS in accordance with the review
criteria stated below.
As part of the initial
merit review, all applications will:
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an 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.
Special Review Criteria for NETT Clinical Site Hubs
The final design for each clinical trial will be developed collaboratively by the Steering Committee relying largely on the expertise of the Clinical Coordinating Center and the Statistical and Data Management Center. The major role of the Hubs is to recruit patients. The peer review group will focus on evidence that the Hub applicant can recruit sufficient numbers of patients and willingly accept the responsibility to meet or exceed all requirements for human subject protection.
Significance: Does this study address an important problem? If the
aims of the application are achieved, how will scientific knowledge or clinical
practice be advanced? What will be the effect of these studies on the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field?
Approach: Are the conceptual or
clinical framework, design, methods, and analyses adequately developed, well
integrated, well reasoned, and appropriate to the aims of the project? Does the
applicant acknowledge potential problem areas and consider alternative tactics?
Innovation: Is the project original and innovative? For example:
Does the project challenge existing paradigms or clinical practice; address an
innovative hypothesis or critical barrier to progress in the field? Does the
project develop or employ novel concepts, approaches, methodologies, tools, or
technologies for this area?
Investigators: Are the investigators
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? Does the investigative team bring complementary and
integrated expertise to the project (if applicable)?
Environment: Does the scientific
environment in which the work will be done contribute to the probability of
success? Do the proposed studies benefit from unique features of the scientific
environment, or subject populations, or employ useful collaborative
arrangements? Is there evidence of institutional support?
Are there examples of previous success in clinical trials?
2.A.
Additional Review Criteria:
In addition to the above
criteria, the following items will continue to 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 the Research Plan, Section E on Human Subjects in the PHS Form
398).
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 will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated (see the Research Plan, Section E on Human Subjects in
the PHS Form 398).
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
Form 398 research grant application instructions will be assessed.
2.B.
Additional Review Considerations
Budget: The reasonableness of the
proposed budget and the requested period of support in relation to the proposed
research. The priority score should not be affected by the evaluation of the
budget.
2.C. Sharing Research Data
Data Sharing Plan: The reasonableness of the
data sharing plan or the rationale for not sharing research data may be
assessed by the reviewers. However, reviewers will not factor the proposed data
sharing plan into the determination of scientific merit or the priority score.
The funding organization will be responsible for monitoring the data sharing
policy. http://grants.nih.gov/grants/policy/data_sharing.
Program staff will be responsible for the administrative
review of the plan for sharing research data.
2.D.
Sharing Research Resources
NIH policy requires that
grant awardee recipients make unique research resources readily available for
research purposes to qualified individuals within the scientific community
after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html).
Investigators responding to this funding opportunity should include a sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.
Program staff will be
responsible for the administrative review of the plan for sharing research
resources.
The adequacy of the
resources sharing plan will be considered by Program staff of the funding
organization when making recommendations about funding applications. Program
staff may negotiate modifications of the data and resource sharing plans with
the awardee before recommending funding of an application. The final version of
the data and resource sharing plans negotiated by both will become a condition
of the award of the grant. The effectiveness of the resource sharing will be
evaluated as part of the administrative review of each non-competing Grant Progress
Report (PHS 2590). See Section VI.3. Reporting.
3. Anticipated Announcement and Award Dates
Not
applicable
Section VI. Award Administration Information
1. Award Notices
After the peer review of
the application is completed, the PD/PI will be able to access his or her
Summary Statement (written critique) via the eRA Commons.
If the application is under consideration for funding,
NIH will request "just-in-time" information from the applicant. For
details, applicants may refer to the NIH Grants Policy Statement Part II: Terms
and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).
A formal notification in the form of a Notice
of Award (NoA) will be provided to the applicant organization. The NoA
signed by the grants management officer is the authorizing document. Once all
administrative and programmatic issues have been resolved, the NoA will be
generated via email notification from the awarding component to the grantee
business official (designated in item 12 on the Application Face Page). If a
grantee is not email enabled, a hard copy of the NoA will be mailed to the
business official.
Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Also Section
IV.5. Funding Restrictions.
2. Administrative and National
Policy Requirements
All
NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
The following Terms and
Conditions will be incorporated into the award statement and will be provided
to the Principal Investigator as well as to the appropriate institutional
official, at the time of award.
2.A. Cooperative Agreement
Terms and Conditions of Award
The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to
apply), and other HHS, PHS, and NIH grant administration policies.
The administrative and
funding instrument used for this program will be the clinical
research cooperative agreement (U10), an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined above.
2.A.1. Principal Investigator Rights and Responsibilities
The Principal Investigator will have the primary responsibility for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner.
The awardees for the Clinical Site Hubs will:
a) Participate in the design of the study protocols and the writing of the manual of operations for one or more of the clinical trials,
b) Help develop operational plans and carry out patient recruitment, treatment, and follow-up that is efficient,
c) Carry out complete and accurate data collection and timely transmission of the data to the Coordinating Center,
d) Suggest approaches to the analysis of data and participate in writing manuscripts of the interim and final results of the trials,
e) Ensure adequate representation of women and racial/ethnic minority groups in the trials,
f) Willingly adhere to a common study protocol for each trial,
g) Take all appropriate measures to protect human subjects, setting a superior example in this regard for others to follow in the future,
h) Attend all training meetings and annual investigator’s meeting as outlined in the protocol,
i) If placed on non-recruiting status due to deficiencies in performance, agree to continue follow-up of participants according to the protocol unless follow-up arrangements can be made through an alternate Clinical Site Hub,
j) Agree to publish data collected as part of the trial according to guidelines established by the Steering/Publications Committee,
k) Carry out the other elements of the research project as described in this RFA.
Awardees will retain custody of and primary rights to their data developed under the award, subject to government policies regarding rights of access. In accordance with the policies and procedures established by the Steering Committee, all Clinical Site Hub awardees will be required to provide study data to the Coordinating Center, which will, in turn, transmit all data to the Statistical and Data Management Center. The data will be stored at the end of the trial in a format suitable for archival in a United States national repository at an appropriate time after completion of data collection and publication of primary manuscripts.
2.A.2. NIH Responsibilities
An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NINDS will name the Project Scientist for the NETT Network project. The Project Scientist’s function will be to advise the Steering Committee, the Publication Committee, and other subcommittees in carrying out the trials, including quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and coordination of efforts of all the project centers. The NINDS Project Scientist will have voting membership on the Steering Committee, and as appropriate, other subcommittees of the Steering Committee, including the Publications Committee. To the extent that the NINDS Project Scientist contributes to the scientific content of the trial, authorship may be shared in publications with other investigators in accordance with the same policies of the Publication Committee that apply to other investigators and NIH publication policies.
A second NINDS Program Official will administer the cooperative agreements and will be responsible for the fiscal management and programmatic stewardship of the program at the NIH. In addition, a Clinical Research Project Manager from the NINDS Clinical Trials group will serve as liaison to the Data and Safety Monitoring Board(s).
Other NINDS scientists may, as appropriate, attend meetings and serve on study committees and work with awardees on issues coming before the Steering Committee or its subcommittees. However, in all cases, the NINDS will have only a single vote on study committees, either of the whole or on subcommittees.
The NINDS reserves the right to terminate or curtail the study (or an individual award) in the event of (a) a major breach in the protocol or substantial changes in the agreed-upon protocol with which the Institute does not agree or (b) human subject ethical issues that may dictate a premature termination or (c) failure to pursue the objectives stated in this Request for Applications, or (d) substantial shortfall in recruitment and/or retention of subjects or (e) a recommendation to the NINDS by the DSMB to stop a pilot study or the large trial.
2.A.3. Collaborative Responsibilities
NETT Network Committees
1. Network Advisory Group (NETT-AG) will be organized by NINDS and be composed experts in Emergency Medicine and Neurology, both from within and outside the NETT Network and will include NINDS officials with expertise in clinical trials of neurological emergencies. It will serve as an oversight committee, giving final approval to the trial protocols, modifications to the protocols, the overall budget, and plans for analysis, and will forward reports and recommendations to NINDS.
2. NETT Network Steering Committee will consist of the principal investigator of the Coordinating Center (who will serve as the chair), principal investigator of the Statistical and Data Management Center, the NINDS Scientific Program Director, and selected representatives of the Clinical Site Hubs, to be chosen by the other members and approved by the NETT Advisory Group. The specific membership and charter of the Steering Committee will be proposed by the Coordinating Center and approved by the NETT-AG. The Steering Committee will approve the final protocols, supervise overall execution of the trial, generate and approve study policies, consider modifications of the protocol and operations, and plan and draft study-related publications. The Steering Committee may appoint subcommittees to perform specific tasks. Each full member will have one vote. The Awardee will be required to accept and implement policies approved by the Steering Committee.
3. Data and Safety Monitoring Board (DSMB) will be appointed by NINDS to monitor safety and performance and to review interim analyses in the NETT Network clinical trials. Depending on the specific trials selected, more than one DSMB may be required. The NINDS will appoint and support the travel and other expenses of the members of the Data and Safety Monitoring Board, either directly or through a supplement to the Clinical Coordinating Center award.
2.A.4. Arbitration Process
Any
disagreements that may arise in scientific or programmatic matters (within the
scope of the award) between award recipients and the NIH may be brought to
arbitration. An Arbitration Panel composed of three members will be convened.
It will have three members: a designee of the Steering Committee chosen without
NIH staff voting, one NIH designee, and a third designee with expertise in the
relevant area who is chosen by the other two; in the case of individual
disagreement, the first member may be chosen by the individual awardee. This
special arbitration procedure in no way affects the awardee's right to appeal an
adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.
3. Reporting
Awardees will be
required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually
(http://grants.nih.gov/grants/funding/2590/2590.htm)
and financial statements as required in the NIH Grants Policy Statement.
Section
VII. Agency Contacts
We encourage your inquiries concerning this funding opportunity 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:
1. Scientific/Research Contacts:
Robin Conwit, M.D.
Clinical Trials Group
National Institute of
Neurological Disorders and Stroke
6001 Executive Blvd., Room 2181
Bethesda, MD 20892
Telephone: (301) 496-9135
FAX: (301)480-1080
Email: [email protected]
2. Peer Review Contacts:
Chief,
Scientific Review Branch
National Institute of
Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Blvd.
Bethesda, MD 20892-9529 (Rockville, MD 20852 for express/courier
service)
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: [email protected]
3. Financial or Grants Management
Contacts:
Gavin T.
Wilkom
Grants Management
National Institute of
Neurological Disorders and Stroke
NSC, Room 3254
6001 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 496-7480
FAX: (301) 451-5635
Email: [email protected]
Section
VIII. Other Information
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).
Data and Safety
Monitoring Plan:
Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should
be commensurate with risk. The establishment of data and safety monitoring
boards (DSMBs) is required for multi-site clinical trials involving
interventions that entail potential risks to the participants (NIH Policy for
Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research
Data:
Investigators submitting
an NIH application seeking $500,000 or more in direct costs in any single year
are expected to include a plan for data sharing or state why this is not
possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their
institutions, on issues related to institutional policies and local IRB rules,
as well as local, State and Federal laws and regulations, including the Privacy
Rule. Reviewers will consider the data sharing plan but will not factor the
plan into the determination of the scientific merit or the priority score.
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 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 funding opportunity 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.
Sharing of Model
Organisms:
NIH is committed to support
efforts that encourage sharing of important research resources including the
sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.
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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is 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 Clinical Research:
The NIH maintains a
policy that children (i.e., individuals under the age of 21) must be included
in all clinical research, conducted or supported by the NIH, unless there are
scientific and ethical reasons not to include them.
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 (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 applications for research involving human subjects and
individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem
Cells (hESC):
Criteria for federal
funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC
line(s)to be used in the proposed research. Applications that do not provide
this information will be returned without review.
NIH Public Access
Policy:
NIH-funded investigators
are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central
(PMC) an electronic version of the author's final manuscript upon acceptance
for publication, resulting from research supported in whole or in part with
direct costs from NIH. The author's final manuscript is defined as the final
version accepted for journal publication, and includes all modifications from
the publishing peer review process.
NIH is requesting that
authors submit manuscripts resulting from 1) currently funded NIH research
projects or 2) previously supported NIH research projects if they are accepted
for publication on or after May 2, 2005. The NIH Public Access Policy applies
to all research grant and career development award mechanisms, cooperative
agreements, contracts, Institutional and Individual Ruth L. Kirschstein
National Research Service Awards, as well as NIH intramural research studies.
The Policy applies to peer-reviewed, original research publications that have
been supported in whole or in part with direct costs from NIH, but it does not
apply to book chapters, editorials, reviews, or conference proceedings.
Publications resulting from non-NIH-supported research projects should not be submitted.
For more information
about the Policy or the submission process please visit the NIH Public Access
Policy Web site at http://publicaccess.nih.gov/ and
view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).
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).
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 PA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.
Authority and
Regulations:
This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections 301
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement. The NIH Grants Policy
Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
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.
Loan Repayment
Programs:
NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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