Part I Overview Information

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Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Canadian Stroke Network (CSN), (http://www.canadianstrokenetwork.ca)

Components of Participating Organizations
National Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov)

Title:  Stroke Preclinical Trials Consortia (U01)  

Announcement Type
New

Request For Applications (RFA) Number: RFA-NS-08-001

Catalog of Federal Domestic Assistance Number(s)
93.853

Key Dates
Release Date:  November 27, 2007
Letters of Intent Receipt Date: January 15, 2008
Application Receipt Date: February 15, 2008
Peer Review Date(s): June-July, 2008
Council Review Date: August 2008
Earliest Anticipated Start Date: September 30, 2008
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: February 16, 2008

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

• The National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) have developed a partnership to facilitate the development of multi-institutional, multidisciplinary collaborations to address the pre-clinical translational challenges in stroke research and to conduct pre-clinical trials.
• Applications must have a consortium structure comprised of at least 3 participating laboratories at different institutions and a coordinating center that is responsible for data coordination, site and steering committee communication. Each preclinical site should have two (2) stroke models (species) available with one model common to all sites within the consortium. A steering committee of external advisors, NIH staff and consortium investigators will be responsible for protocol development.  
• The NINDS intends to commit approximately $1.5 million in total costs in FY 2008 for this announcement to support a total of 2 meritorious applications.  A consortium may request a project period of up to four years and a budget for direct costs up to $500,000 in each year. The CSN is currently funding one Canadian consortium at the level of $1.10 million per year for a 2 year period with the opportunity to extend for an additional 2 year period.
• This funding opportunity will use the NIH cooperative agreement research grant (U01) award mechanism.
• Eligible organizations include Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Eligible agencies of the Federal government; Faith-based or community based organizations. 
• Eligible principal investigators include any individual with the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Applicants may submit more than one application, provided they are scientifically distinct.
• Competing renewal (formerly “competing continuation”) and resubmission applications will not be accepted under this FOA. At this time, it is not known if this FOA will be reissued.
• More than one PD/PI, or multiple PDs/PIs, may be designated on the application.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936
• Initial merit review will be convened by NINDS.
• Special  Receipt Date: February 15, 2008

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

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 and 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

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

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose and Objectives

The National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) recognize the need to address the translational barriers that exist today in stroke research. Therefore, this RFA announces the availability of funds to facilitate the development of interdisciplinary teams to address the translational challenges in stroke research and conduct multi-institutional pre-clinical trials. The NINDS and the CSN invite applications that evaluate why research translation for stroke has not been successful, propose a multi-institutional, multidisciplinary strategy to address these issues and identify the research resources needed to facilitate validation and replication of promising therapies by conducting milestone-driven pre-clinical trials.  

The intent of this funding opportunity is to facilitate the translation of laboratory discoveries to clinical application in stroke patients and to address translational barriers through multi-institutional, interdisciplinary teams of scientists and clinicians organized through a consortium.  The purpose of the consortium approach is to facilitate the validation and replication of promising pre-clinical treatment candidates that would increase confidence in candidate selection for further clinical development.  Consortium proposals focused on addressing translational issues in ischemic or hemorrhagic stroke research in adult or pediatric populations would be responsive to this announcement.

Successful outcomes of pre-clinical trials conducted within a consortium could result in an FDA IND application, clinical evaluation through the “Preliminary Investigations Leading To Optimal Trials In Neurology (R01)” (PAR-07-294), the “NINDS Clinical Trial Planning Grant” (PAR-06-460) , industry-sponsored clinical trials, the “Specialized Program of Translational Research in Acute Stroke” (SPOTRIAS) (PAR-07-351), or further preclinical therapeutic development  through the “Exploratory/Developmental Program for Translational Research (R21)” (PAR-06-189),  “NINDS Cooperative Program in Translational Research (PAR-05-158)  or the NINDS Cooperative Small Business Awards in Translational Research (SBIR/U44) (PAR-06-005).  This RFA invites proposals designed to advance preclinical translation of promising stroke therapeutic candidates evaluated through a multi-institutional consortium.  Mechanistic studies of stroke, brain hypoxia/ischemia or hemorrhage, or single site studies that are solely for preclinical therapeutic development or clinical trials are not responsive to this RFA.  

Background

Successful translation of pre-clinical studies (e.g., tPA Trial) demonstrates that stroke is treatable in the acute stage of the disorder. However, neuroprotective drugs that worked in animal models for stroke failed in humans trials. This apparent disconnect between laboratory and clinic research is considered a major obstacle to progress toward stroke therapy. The basis for translation failure has been the focus of several stroke conferences and translational research was clearly articulated as a priority through the Stroke Progress Review Group (PRG), http://www.ninds.nih.gov/find_people/groups/stroke_prg/04_2002_stroke_prg_report.htm.

The Stroke PRG emphasized that pre-clinical neuroprotection studies have focused on specific parameters that need to be further evaluated. Animal models focusing on infarct volume, transient ischemia, protection of gray matter, age, gender, short-term outcomes and short treatment windows need to be considered in the context of their translation to the clinical realities. Timing of treatment, dose intensity and drug delivery would also benefit from further investigation. The clinical picture is more complex involving functional outcome, both gray and white matter injury, permanent ischemia, extended treatment windows, and long-term evaluation. The consortium approach to address these stroke translational barriers should facilitate validation and replication of promising candidate drugs or devices aimed at developing prevention strategies, acute stroke therapy and/or improving recovery and chronic behavioral outcomes. Clinically relevant events such as hypertension, diabetes, hypercholesterolemia, age and gender have been difficult to model in laboratory investigations of stroke and may contribute to the apparent differences between “bench” and “bedside” research findings.  Pre-clinical trials that consider these translational issues should more closely represent the variability observed in stroke patients and in conducting human clinical trials. Assessment of combination therapies or a single intervention affecting multiple pathophysiological factors and/or the delivery of experimental drugs across the blood-brain barrier in stroke would also benefit from trials conducted by a consortium.

There are many creative strategies that an ischemic or hemorrhagic stroke consortium could pursue to address many of the translational barriers through preclinical trials. Some possibilities include organizing by a scientific theme such as immunomodulation, neuroprotection, vasoprotection, plasticity, recovery, neurovascular unit or blood-brain barrier could be explored.  Strategies that address translational issues observed during the acute, sub-acute or chronic phases of a stroke could also be considered. This initiative encourages alliances among academic institutions, industry and/or government with convergent perspectives on solving the translational challenges in stroke research and expediting laboratory discoveries to stroke clinical trials.

Consortium Structure

To foster new collaborations and facilitate partnerships among different disciplines and institutions, programs will be comprised of consortium-based grant applications that are focused on addressing the translational barriers and improving the validation and replication of promising therapeutic candidates for stroke by designing pre-clinical trials. A consortium should have at least three (3) participating laboratories at different institutions to validate a promising therapy in several laboratories. A coordinating center that is responsible for data coordination, site and steering committee communication will also be required. The institution identified as the site of the coordinating center could also serve as the site of one of the three required laboratories for the consortium. Within each consortium, a lead Consortium Director/PI must be identified who will be the point of contact to the NINDS and CSN. PIs of the other sites within a consortium will be collaborating PIs. Organizing the consortium under the guidelines of the Multiple Investigator announcement is also acceptable (see http://grants2.nih.gov/grants/multi_pi/). Each of the preclinical sites should have two (2) stroke models (species) available with one model common to all sites within the consortium. The common model will serve to validate a particular therapy among several laboratories. The second stroke model (different specie) will provide replication of the findings in the common model.

A scientific steering committee, consisting of the consortium director, the PIs from each collaborating site in the consortium, NIH staff and external advisors (identified by the NIH staff) will be a component of the consortium organized by the NINDS. The purpose of the scientific steering committee will be to discuss and evaluate progress, concerns, cooperative activities and new preclinical trials of the consortium. A major goal of the committee will be to identify and subsequently prioritize ideas for conducting multi-institutional preclinical trials for stroke. At the meetings, participants will also discuss quality assurance, data collection, project coordination, protocol consistency and training. The committee will meet twice per year to discuss progress on each consortium, develop trial protocols and at one meeting each year, exchange information among the different consortia. The role of the NIH Project Scientist is described under COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF THE AWARD, Section VI. 2.A.2.  The Project Official is responsible for reviewing annual progress of the consortium and signing-off on the Grant Progress Reports.

The consortium application must clearly describe the management of the collaborative research. Applicants should include the following:

• Outline plans and mechanisms to keep the consortium focused on addressing translational issues in stroke research by conducting preclinical trials.
• Set milestones on a timeline to allow for the evaluation of progress towards the consortium's preclinical trial goals.
• Describe the strengths of the investigative team in addressing the translational barriers for stroke research.
• Explain how collaborators can be added or removed as the expertise, knowledge, and skills necessary to advance the project change. 

Travel funds for the consortium director and site PIs should be budgeted for two meetings each year.  Plans to share research data and unique research resources must be addressed in the application. 

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

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1. Mechanism(s) of Support

This funding opportunity will use the NIH cooperative agreement research grant (U01) award mechanism.

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 (see https://grants.nih.gov/grants/funding/phs398/phs398.html). 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 U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility 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".

Competing renewal (formerly “competing continuation”) and resubmission applications will not be accepted under this FOA. At this time, it is not known if this FOA will be reissued.

2. Funds Available

The NINDS intends to commit approximately $1.5 million in total costs in FY 2008 for this announcement to support a combined total of 2 meritorious applications.  An applicant may request a project period of up to four years and a budget for direct costs up to $500,000 in each year.  The anticipated start date for the NIH awards is September 30, 2008.  In addition, the Canadian Stroke Network (CSN) will provide $1.10 million for a 2 year period starting in FY 2008 for the development of a Canadian Stroke Preclinical Trials Consortium.  This consortium will be developed using this RFA’s research objectives and consortium structure.  A general call for Canadian consortium proposals and peer review will be conducted by the CSN in 2008. 

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NINDS 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

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1. Eligible Applicants

1.A. Eligible Institutions

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

• Public/State Controlled Institution of Higher Education
• Private Institution of Higher Education
• Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
• Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education)
• Small Business
• For-Profit Organization (Other than Small Business)
• State Government
• U.S. Territory or Possession
• Indian/Native American Tribal Government (Federally Recognized)
• Indian/Native American Tribal Government (Other than Federally Recognized)
• Indian/Native American Tribally Designated Organization
• Non-domestic (non-U.S.) Entity (Foreign Organization)
• Hispanic-serving Institution
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Regional Organization
• Eligible agencies of the Federal government
• Faith-based or community based organizations

Applications from non-Canadian foreign institutions will not be considered as the parent application but may serve as a collaboration site within a US or Canadian consortium application.

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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at https://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

As defined in the current NIH Grants Policy Statement, this program does not require cost sharing.

The most current Grants Policy Statement can be found at: https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Applications proposing mechanistic studies of stroke, brain hypoxia/ischemia or hemorrhage, or single site studies that are solely for preclinical therapeutic development or clinical trials will be considered non-responsive.

Section IV. Application and Submission Information

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1. Address to Request Application Information

The PHS 398 application instructions are available at https://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 GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.

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.

Foreign Organizations(Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

• Request budgets in U.S. dollars.
• Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms – not the PHS398 Modular Budget component). See NOT-OD-06-096, August 23, 2006.
• Charge back of customs and import fees is not allowed.
• U.S. Government grants cannot pay taxes in foreign countries, including VAT tax.
• Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF.
• Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.                        
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., “Administrative and National Policy Requirements.”

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS  

Applications with Multiple PDs/PIs

Multiple PD/PI Leadership Plan: For applications designating multiple PD/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section I of the Research Plan in the PHS 398), must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PD/PIs must be delineated in the Leadership Plan.  In the event of an award, the requested allocation may be reflected in a footnote on the NOGA.

When all PDs/PIs are within a single institution, follow the instructions contained in the SF398 (R&R) Application Guide.

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. 

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

Letters of Intent Receipt Date: January 15, 2008
Application Receipt Date: February 15, 2008
Peer Review Date(s): June-July, 2008
Council Review Date: August 2008
Earliest Anticipated Start Date: September 30, 2008

3.A.1. Letter of Intent

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

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

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:

Thomas P. Jacobs, Ph.D.
Neural Environment Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2112 
Bethesda, MD 20892 (use Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-1431
FAX: (301) 480-2424
Email: jacobst@ninds.nih.gov

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 (see https://grants.nih.gov/grants/guide/notice-files/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 Boulevard
Bethesda, MD 20892-9529
(Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
Fax: (301) 402-0182
E-mail: nindsreview.nih.gov@mail.nih.gov

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: https://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 https://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 https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants are expected to include a plan for sharing research data in their application. The data sharing policy is available at https://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will 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.

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement https://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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, https://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

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1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

• Scientific merit of the proposed consortium as determined by peer review
• Availability of funds
• Relevance of program priorities

2. Review and Selection Process

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:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Neurological Disorders and Stroke Council.

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.

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? Can this consortium facilitate the resolution of the translational issues in stroke research?

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? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs? Is there a strategy that utilizes successful human clinical trial principles for the proposed preclinical trials?

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? Can the consortium advance translational research for stroke?

Investigators: Are the PD/PI(s) and other key personnel 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 PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? 

Environment:  Do(es) the scientific environment(s) 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?  

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:

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.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

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 will 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 presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. https://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 expects that grant 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 https://grants.nih.gov/archive/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

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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 (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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 (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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 cooperative agreement (U01), 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 below.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for planning, organizing and administering the Stroke Preclinical Trials Consortium activities. He/She will participate as a member of the Scientific Steering Committee with the PIs from the other sites within the consortium, external advisors and NIH staff. This includes planning, organizing and carrying-out administrative and research activities to serve the consortium. The PI agrees to comply with any consortia-wide policies established by the Scientific Steering Committee.

Awardees will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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, as described below. He/She will participate as a member of the Scientific Steering Committee, and will invite scientific and clinical advisors to serve. The NIH Project Scientist will help plan and carry-out consortium activities, and will participate in all reports. He/She will act as a liaison between the consortium and the NIH.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

The Scientific Steering Committee will be the primary governing board of the studies and is responsible for overseeing all aspects of the preclinical trials, including implementation of the study protocol, review of reports from the consortium, and preparing and publishing scientific reports. The Committee will discuss and evaluate progress, concerns, cooperative activities and new preclinical trials of the consortium. A major goal of the committee will be to identify and subsequently prioritize ideas for conducting multi-institutional preclinical trials for stroke.  

The committee will meet twice per year to discuss progress on each consortium, develop trial protocols and at one meeting each year, exchange information among the different consortia.  At the meetings, participants will also discuss quality assurance, data collection, project coordination, protocol consistency and training.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

A change in the Principal Investigator or key personnel at the awardee institution or at a preclinical site participating in the trial requires the prior approval of the NINDS Administrative Program Official.  

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 (https://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.  

Section VII. Agency Contacts

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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:

Thomas P. Jacobs, Ph.D.
Neural Environment Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2112 
Bethesda, MD 20892 (use Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-1431
FAX: (301) 480-2424
Email: jacobst@ninds.nih.gov

Antoine Hakim, M.D., Ph.D.
Canadian Stroke Network
University of Ottawa
451 Smyth Road, Room 2225
Ottawa, Ontario
K1H 8M5
Canada
Telephone: (613) 562-5414
Email: ahakim@ohri.ca

2. Peer Review Contacts:

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Boulevard
Bethesda, MD 20892-9529 (use Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
Fax: (301) 402-0182
Email: nindsreview.nih.gov@mail.nih.gov

3. Financial or Grants Management Contacts:

Tijuanna DeCoster, MPA
Grants Management Officer
Grants Management Branch
Division of Extramural Research
National Institutes of Neurological Disorders and Stroke
6001 Executive Blvd, NINDS/NSC 3258
Bethesda MD 20892 (for overnight courier services, use Rockville, MD 20852)
Telephone: 301-496-9231
FAX: 301-402-0219
Email: decostert@ninds.nih.gov 

Section VIII. Other Information

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Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (https://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

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 (https://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 https://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 https://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 https://grants.nih.gov/archive/archive/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.

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 https://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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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.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 https://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.