Part I Overview Information

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: Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) for Year 2009 (P50)

Announcement Type
This is a reissue of PAR-07-351

Program Announcement (PA) Number: PAR-09-254

Catalog of Federal Domestic Assistance Number(s)
93.853

Key Dates
Release Date: August 14, 2009
Letters of Intent Receipt Date: September 1, 2009
Application Submission Date: October 1, 2009
AIDS Application Submission Date: Not applicable
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 1, 2010.
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: October 2,, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Neurological Disorders and Stroke (NINDS) invite new and renewal grant applications for Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS). The intent of the SPOTRIAS is to support a collaboration of clinical researchers from different specialties whose collective efforts will lead to new approaches to early diagnosis and treatment of acute stroke patients. The goal of the SPOTRIAS will be to reduce the disability of and mortality in stroke patients by promoting rapid diagnosis and effective interventions.
• Mechanism of Support. This Funding Opportunity Announcement (FOA) will utilize the P50 grant mechanism.
• Funds Available and Anticipated Number of Awards. 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. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.
• Budget and Project Period. The maximum allowable direct cost per year for a SPOTRIAS will be $1,500,000. The total number of years that may be requested for this program is 4 years.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization 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.
• Number of PDs/PIs. Only one PD/PI may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
• Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
• Renewals. Applicants may submit a renewal application
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY (301) 451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism 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. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
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

Despite enormous research efforts including many clinical trials, tissue plasminogen activator (tPA) remains the only FDA-approved treatment for acute ischemic stroke. Clinical trials that demonstrated the efficacy of tPA showed an improved outcome when tPA was given within three hours of stroke onset. The requirement for administration within three hours of stroke onset has proven to be a major obstacle to the widespread use of tPA. Delays in the response to stroke by medical personnel and the risks inherent in the use of tPA, which require careful patient evaluation before treatment, contribute to the inability to extend its benefits to many stroke victims. Dramatic improvements in stroke outcomes could be achieved by reducing the time necessary to respond to and diagnose stroke and by identifying new interventions that could be safely and expeditiously administered to a wider range of patients.

The objective of the SPOTRIAS is to facilitate translation of basic research findings into clinical practice in settings where patients with acute ischemic and hemorrhagic stroke are evaluated and treated very rapidly after the onset of their symptoms. This program seeks to encourage clinical research directed toward improved treatments and treatment strategies for stroke. This translational program may include laboratory or technological research that is directly related to the proposed collaborative clinical research. Because of the importance of early treatment in translational research, SPOTRIAS will be established at institutions with a strong commitment to the rapid treatment of acute stroke patients and which have demonstrated an active collaboration between emergency medical services, emergency physicians, neurologists, and radiologists. Because of the emphasis on translational research, SPOTRIAS will be established at institutions with a strong commitment to bringing discoveries from basic stroke research to clinical practice.

Using its shared resources, a SPOTRIAS will add to the scientific information base and maintain state-of-the-art research that contributes to improved rapid treatment of acute ischemic and hemorrhagic stroke. Components of each SPOTRIAS will include a special stroke response group that treats patients in the emergency department, a biostatistical and data management core, and a human tissue core (blood and genetic samples). SPOTRIAS are expected to conduct a wide spectrum of research activities, and to contribute significantly to the development of specialized research resources, to the development of improved research model systems and to the expansion of the research base through collaborative research with scientists and clinicians in other institutions locally and nationwide. The research supported through this program must have translational potential or significance, i.e., it must apply information developed in basic research laboratories to the design of clinical research that will test interventions or methods for improving the outcomes for patients with acute hemorrhagic or ischemic stroke. Translational research bridges the gap between the discoveries of basic scientists and definitive phase III trials of efficacy for specific treatments.

Projects encouraged within the SPOTRIAS include:

• phase I and phase II studies to evaluate novel stroke treatments;
• development and testing of innovative systems for delivery of emergency medical services;
• development and evaluation of clinical tools useful for rapid stroke treatment;
• tests of potential biomarkers, surrogate outcomes, and clinical stroke scales useful in acute stroke research;
• development and evaluation of new treatments and practices within critical care units for patients immediately after initial emergency department management;
• tests of strategies for rehabilitation of acute stroke patients;
• long term quality-of-life research for patients treated early for acute stroke.

Beyond specific hypothesis testing projects, the network of SPOTRIAS will share several broad goals to:

• provide career development opportunities for new investigators who wish to pursue active research careers in translational acute stroke research; a training component will recruit promising junior physicians for further career development activities supported through the network and NIH grants. The development of collaborative training within the SPOTRIAS network will be encouraged. The success of trainees in obtaining independent research funding will be carefully considered on a yearly basis and at the time that any competing renewal is reviewed.
• share human tissue resources that will benefit both basic and translational acute stroke research;
• share data collection elements that will be included in a common SPOTRIAS clinical and neuroimaging database;
• develop collaborations in critical areas of research need with basic and clinical scientists within and across institutions;
• meet with other SPOTRIAS on a monthly basis to share information, assess scientific progress in the field, identify new research opportunities, and promote inter-SPOTRIAS research collaborations to resolve areas of scientific controversy.

Each SPOTRIAS and the network of SPOTRIAS are expected to conduct research that will have immediate impact on reducing disability and mortality in acute stroke by intervening as rapidly as possible after the onset of symptoms. It is expected that the national network of acute stroke research centers formed as a result of this FOA will lead to significant changes in the care of stroke patients. Examples are:

• physicians early in their careers would be trained to react promptly to stroke and be given experience in the complex process of running an acute stroke treatment center;
• the acute stroke treatment centers would allow stroke fellows to develop clinical research careers by providing them access to stroke patients at the time when stroke can be treated;
• new treatments could be developed in phase one and phase two studies;
• therapies with little commercial interest could be developed;
• collaboration between SPOTRIAS and inclusion of non-SPOTRIAS clinical sites on clinical research projects;
• the emergency treatment of stroke could be further refined and developed;
• basic research could be more directly tied to the critical acute periods of stroke

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

Section II. Award Information

1. Mechanism of Support

This FOA will use the NIH specialized center (P50) award mechanism, which provides funding for multidisciplinary and multi-investigator approaches to the investigation of specific and complex research problems requiring the application of diverse expertise and methodologies. These grants differ from program project grants in that they are more complex and flexible in terms of the activities that can be supported. In addition to support for multidisciplinary research projects, the P50 provides for career development, pilot research projects, specialized resources and shared core facilities. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Applicants may request support for a period of up to four years. The maximum allowable direct cost per year for a SPOTRIAS will be $1,500,000.

Direct costs are limited to $1.5 million in any one year. This limit applies to new grants, their non-competitive continuations, and any subsequent competitive renewals. Since the best scientific talent and resources are expected to be brought to bear on questions posed in each Center, and since these may not all be available at any single institution, projects constituting a given Center may be based at multiple institutions. In an effort to allow for such multi-institutional involvement

Facility and Administrative (F&A) costs for consortium activity at collaborating institutions will not be counted against the $1.5 million limit to direct costs (but these costs should be delineated as instructed in form PHS 398 (see NOT-OD-05-004).

The applicant will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

2. Funds Available

Applications received in response to this program announcement will compete for funds in the general funding pool of the NINDS. No specific funds have been set aside for this announcement. The number and size of the awards will depend on the number of applications received, their relative scientific merit, and the general availability of funds for investigator-initiated research.

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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

Foreign institutions are not eligible for Center P50 grants.

Eligible institutions may include Foreign components as full research projects, or cores, or as part of a research project or core, but Foreign institutions and organizations are not eligible to submit SPOTRIAS applications. SPOTRIAS may also use developmental funds to establish collaborative research efforts with foreign entities. Consortia agreements with Foreign institutions must include provisions that ensure adequate representation of women, minorities, and children in all research components that involve clinical trials or any other type of human intervention and must be in compliance with NIH policies.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her 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

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.

Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications will be permitted only a single amendment (A1).  See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016. Original new and competing renewal applications that were submitted prior to January 25, 2009 will be permitted two amendments (A1 and A2).  For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

Renewals. Applicants may submit a renewal application.

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 GrantsInfo, 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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

SPECIAL INSTRUCTIONS

The application should be prepared in the format required by NINDS for research program projects. This format is described at http://www.ninds.nih.gov/funding/ppg_guidelines.htm.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review and Anticipated Start Dates
Letters of Intent Receipt Date: September 1, 2009
Application Submission Date: October 1, 2009
AIDS Application Submission Date: Not applicable
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date(s): July 1, 2010

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 in Section IV.3.A.

Scott Janis, Ph.D.
Neuroscience Center, Room 2191, MSC 9520
6001 Executive Boulevard
Rockville, MD 20852 (courier)
Bethesda, MD 20892-9520
Phone: 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 application forms 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 http://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 materials 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: [email protected]

3.C. Application Processing

Applications must be submitted on or before the application receipt/submission dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

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.

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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 renewal 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

SPOTRIAS applications must fulfill the following requirements:

(1) Institutional Support. A statement must be provided that addresses how the institutional commitment will be established and sustained, how the institution will maintain accountability for promoting scientific excellence, and how the SPOTRIAS research effort will be given a high priority within the institution (relative to other research efforts and non-NIH supported programs). The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the SPOTRIAS Director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution. The primary institution is strongly encouraged to demonstrate its commitment to SPOTRIAS by providing financial support to the Developmental Research and Career Development Programs on an awarded SPOTRIAS, as well as other programmatic needs identified as high priority on the original application. Letters from a high-level institution official(s) (e.g., Dean of the School of Medicine, Hospital President, and Vice President for Research) should be attached confirming this commitment. In the case of a SPOTRIAS that involves a consortium arrangement between two or more institutions, the institution that submits the P50 application must receive a formal written agreement(s) from the other participant organization(s). This agreement should clearly delineate the institutional commitment of the participating organization(s) (in the ways outlined above) to the Program.

(2) Access to acute stroke patient population. Each SPOTRIAS must have access to patients very soon after the onset of stroke. Standard care of stroke now includes intravenous tPA given to eligible ischemic stroke patients three hours or less after the onset of stroke symptoms. Three hours is an upper limit and basic research data would indicate that earlier treatment would have additional benefit. Testing treatments early after stroke onset allows more opportunity for the treatments to show a measurable benefit when less of the brain is irreversibly injured. For this reason, each SPOTRIAS will be required to treat at least twelve eligible patients each year of the grant with tissue plasminogen activator within two hours of the onset of their symptoms. In order to fulfill this requirement, patients that have hemorrhagic stroke or do not meet the strict requirements for tPA will have to be screened for eligibility. This will assure that ample early hemorrhagic and early ischemic stroke patients are available for clinical research studies. If a SPOTRIAS is not able to treat twelve patients with intravenous thrombolytic therapy within two hours of symptom onset each year, the SPOTRIAS will be terminated, the billing arrangement modified, and participation in the SPOTRIAS network limited. Terms for continuation of the SPOTRIAS that fails to treat the required number of patients may be modified to allow follow-up of patients already enrolled in SPOTRIAS studies and to complete any formal training obligations. Other cores and projects will be deleted.

(3) Involvement of Emergency Medicine: Emergency medicine must be fully integrated into the leadership of the SPOTRIAS and the patient access core. It is likely that many individuals representing different medical specialties, organizations and hospital departments will be part of a successful SPOTRIAS patient access core. These include: the emergency medical system, the hospital emergency departments, radiology facilities, intensive care units, patient coordinators, neurologists, neurosurgeons, radiologists, patient advocates, and patient educators. Central to the treatment of acute stroke is the emergency department where initial contact with most patients is made and the early diagnostic and treatment activities occur. Hence, involvement of the leadership of participating emergency departments in the patient access core as well as in the SPOTRIAS projects and the SPOTRIAS itself is a requirement. Naturally, the organization best suited to rapidly evaluate and treat stroke patients varies according to the local availability of resources, and therefore, a specific emergency physician role is not specified. What is required is clear evidence of involvement of emergency physicians that will ensure the most rapid possible treatment of stroke patients and the development of new procedures and treatment that are broadly applicable. This requirement is consistent with recommendations for organizing the rapid treatment of acute stroke patients that were published in the Proceedings of a National Symposium on Rapid Identification and Treatment of Acute Stroke December 12-13, 1996 (http://www.ninds.nih.gov/news_and_events/proceedings/strokeworkshop.htm#prehosp). These recommendations emphasize the importance of coordinating pre-hospital emergency medical care systems, emergency departments, and acute hospital care. A coordinated rural network or local network of cooperating hospitals may be part of the stroke care system if organized and lead by the SPOTRIAS.

(4) Research Projects. A minimum of three research projects, representing a balance and diversity of translational approaches.

• Each proposed research project must meet the definition of translational research as described in Section I above. Investigators who are not certain about whether their project fits this definition are advised to consult with NINDS program staff.
• Each proposed research project must be designed to test the relevance and/or potential importance of the research to acute stroke within the 4-year term of the grant (e.g., validation of a new screening mechanism or diagnostic test, early phase therapeutic trial, analysis of human tissues such as blood samples). Basic research projects, such as those employing animal models or cell lines, qualify as translational only if a human application is included in the specific aims of the research.
• For renewal applications, the projects may be extensions or continuation of a translational SPOTRIAS project. However, at least one of the projects must be a new innovative proposal that can be outgrowth of an initial SPOTRIAS study. One unique strength of the SPOTRIAS program is the fostering of multicenter research within an experienced stroke network. For the renewal at least one project, either new or a continuation of a previous SPOTRIAS study, must be a collaborative proposal from two or more SPOTRIAS centers. These proposals should be designed to answer important questions in acute stroke that cannot be answered at a single site and which therefore take advantage of the collaborative network.
• For renewal applications, the Institute reserves the right to fund only those research proposals which are met with enthusiasm by peer review. At least one of the three required research proposals must be approved for funding for the site to continue in the network. In cases in which a site is approved for renewal but one or more of their proposed research proposals are not funded, then the core budget will be adjusted accordingly. Non-funded proposals may be resubmitted as competitive supplements for review but their time for completion must not exceed the expiration date of the SPOTRIAS center(s).
• Each SPOTRIAS application must include at least one early (Phase I and Phase II) clinical trial that will test an intervention intended to improve the outcome of patients who present very early after the onset of ischemic or hemorrhagic stroke that is designed as a demonstrated or proposed collaboration with the other centers in the SPOTRIAS network. In some cases, collaboration with a manufacturer will be required to provide therapeutic agents. A plan for a clinical trial must include provisions for rigorous data management, quality assurance, and safety monitoring. Each SPOTRIAS must develop specific safety monitoring plans to ensure the safety of this phase 1 or phase 2 study: see: http://www.ninds.nih.gov/research/clinical_research/policies/dsm.htm. In addition, each SPOTRIAS will be required to budget for a medical safety monitor as needed for this clinical trial. For NINDS safety monitoring requirements see: http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm. In addition each SPOTRIAS proposal involving multi-center research must evaluate whether relevant conflict of interest issue exist, If any are identified then the proposal should include a plan to prevent conflict of interest issues from adversely affecting the execution of the research.
• No treatment protocol performed as part of the SPOTRIAS will delay the delivery of standard care for acute stroke patients.

(5) Shared Cores. Shared cores designed to support the proposed translational objectives of the SPOTRIAS (including the required human tissue/specimen core for the particular site).

• Patient Access Core (Required). Each SPOTRIAS must have a core to screen and track all patients presenting in the emergency room for acute treatment to ensure that all eligible patients are available for clinical research studies. Further, each will collect and share specifically defined common data elements for all screened and fully evaluated participants for all SPOTRIAS related projects with other centers in the SPOTRIAS network.
• Tissue Sample Core (Required). Each SPOTRIAS must have a dedicated core for collecting and sharing relevant tissue and blood samples collected in the projects. All such studies and the procedures for banking and sharing the specimens within the network will all be subject to approval by local Institutional Review Boards (IRBs) acting to protect human subjects from research risks.
• Biostatistical and data management core (Required): Each site will be required to collect and analyze the data for each of the clinical research projects. For any phase 1 or phase 2 studies, reports summarizing patient safety, interim results, recruitment, and baseline description must be prepared for the NINDS-appointed DSMB as requested. The medical safety monitor must be in close communication with this data center and appropriate safeguards must be established to prevent bias by this core. Each SPOTRIAS will collect and share specifically defined common data elements for all screened and fully evaluated participants for all SPOTRIAS related projects.
• Other Cores (Optional). Additional shared cores (e.g., administrative, neuroimaging, etc.) may also be proposed that are supportive of one or more of the research projects of the SPOTRIAS. These cores should provide essential services to at least one SPOTRIAS project and may also include other analytical or non-hypothesis driven research activities designed to enhance a service.

(6) A fellowship training and career development program (with a minimum required allocated budget of $50,000 in direct costs per year). The SPOTRIAS must demonstrate a consistent and significant commitment to a training program in translational acute stroke research. The NINDS is committed to the career development of clinically trained research scientists. The Institute supports several programs to advance the careers of clinician-scientists by: (1) encouraging the interest of outstanding physicians early in their career; (2) accelerating entry to independent research; (3) encouraging translational research; and (4) fostering research training by especially competent laboratories. SPOTRIAS will propose and carry out career development plans. SPOTRIAS will select candidates for career development who demonstrate potential for independent research careers or who are established investigators and are changing the direction of their research careers. In this selection process the SPOTRIAS will seek out and include qualified minorities, women, and persons with disabilities for inclusion in the career development program. After an individual is selected, a specific plan will be developed and facilitated by the leadership of the SPOTRIAS. A budget will be proposed for sustaining a significant activity in career development for a maximum of one year while applications for any further support are prepared. Further support would have to come from career development grants from NIH or other organizations. For example, the NINDS sponsors career development awards, minority career development supplements, and fellowships. For a description of these programs, please consult the NINDS training and career development website: http://www.ninds.nih.gov/funding/areas/training_and_career_development/index.htm.

(7) Evidence of collaboration with an existing center in the SPOTRIAS network. Each site is expected to share ideas and communicate with other centers in the SPOTRIAS network. SPOTRIAS will provide resources required for their centers to participate in annual three-day meetings of the SPOTRIAS network. This participation will include travel for up to ten individuals to Rockville, Maryland, or to an institution hosting a meeting. Included will be the SPOTRIAS Principal Investigator, the Principal Investigator for each SPOTRIAS project, the clinical coordinators, and the lead statistician. The SPOTRIAS will be responsible for advance planning to ensure the fullest possible attendance at the network meetings. Besides the annual meetings, monthly conference calls will be scheduled with the NINDS Program Director and the Principal Investigators of all the SPOTRIAS.

New centers are expected to demonstrate some level of existing collaboration with a currently funded SPOTRAIS center. Collaboration may be in the form of a collaborative SPOTRIAS project with an existing center (e.g., this may include a project that is submitted as a collaborative project with another center) or evidence of participation in an ongoing SPOTRIAS project.

(8) For renewal applications, include a Progress Report. This report should: 1) list the progress and achievements specific to the application and relevant to translational research since the previous competitive review; 2) address the major scientific achievements in research on acute stroke and related topics carried out by Center personnel and by projects utilizing Center resources in the last funding period; 3) identify significant findings in acute stroke research that were facilitated or supported directly through Center resources; 4) include summaries of progress in achieving the major aims of the Center and its projects and highlight major publications; and 5) describe how the presence of the Center has facilitated and improved translational acute stroke research at the Institution and within the network of translational SPOTRIAS centers.

When a project or optional core has terminated, include a final report with a summary of results and publications. If an optional core is continuing, include a progress report in that component write-up. Applicants should include tables detailing 1) Publications and grants (source, amount and title) resulting from each component funded by the SPOTRIAS, 2) Publications and grants (source amount and title) resulting from pilot projects, 3) Involvement in collaborative projects with other Centers including those funded by SPOTRIAS, and 4) minority enrollment into research projects or clinical trials and specifically, into any research projects addressing minority issues.

In addition to text summaries, applicants should also include summary tables detailing:

1. A list of all active Clinical trial protocols during the previous grant period being conducted in the Center including trial name, sponsor, number of patients enrolled and randomized, and dates. Detail separately currently active and completed trials and NIH and pharmaceutical industry sponsored trials. If multiple trials are selecting from the same patient population, describe process for determine trial eligibility and priority.

2. Collaborations with other acute stroke researchers, other Centers, cooperative studies, and with biotechnology and pharmaceutical companies. Identify non-SPOTRIAS sub-sites used to contribute patients to a SPOTRIAS study.

Research Plan Page Limitations

Projects and cores are limited to 25 pages each.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance, research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

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

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by NINDS and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/) using the review criteria stated below.

As part of the scientific peer review, all applications will:

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

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications.

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed). 

Core Review Criteria.  Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

Significance.  Does the project address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the proposed projects likely add significant information important to further steps in the development of a clinical intervention?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? For phase I and phase II trials: Is there adequate preliminary data from laboratory research or adequate rationale for proposed interventions based on prior clinical experience? Do proposed phase one or phase two studies have a clearly defined place in the process of advancing acute stroke treatment?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Is there evidence of effective use of SPOTRIAS cores? Is there evidence of collaboration with the existing SPOTRIAS centers?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/priority score.

PAR Specific Review Criteria

a. Research Projects

• Do the overall scientific objectives and hypothesis of the proposed projects address important gaps in translational research in acute stroke?
• Is there strong evidence for the interrelationship of the individual projects and cores?
• Is the administrative structure of the program, including any internal and external advisory committees, adequate to support a SPOTRIAS project?
• Are the principal investigator/program director’s scientific and administrative qualifications and her/her commitment to the program adequate to support multiple SPOTRIAS projects?
• Is there effective integration of specialists in emergency medicine into the leadership of the SPOTRIAS program, its cores, and the individual projects?
• Are there plans for collaboration with other centers in the SPOTRIAS network?

For renewal applications, is there evidence from the previous grant award period that: 1) progress of the projects made significant scientific contributions; 2) the projects were well supported by their cores; and 3) there was strong evidence of collaborative research within the SPOTRIAS network? If any of the proposed projects in the renewal application are an extension of a previous study, does the application describe adequate progress on the project(s) and are extensions for the project(s) logical and feasible?

b. Cores

1. Patient Access Core (this is a required component of a SPOTRIAS).

• Does the patient access core present evidence of their potential to exceed the minimum requirement to treat more than twelve patients with standard intravenous thrombolytic therapy within 2 hours of acute stroke onset in the manner approved by the FDA?
• Does the applicant provide convincing evidence that within the SPOTRIAS there is 24- hour, seven day availability of a well- trained and organized stroke response system immediately available to all stroke patients with the full support and cooperation of departments of emergency medicine, radiology, neurology, and neurosurgery?
• Is it clear that no project in the SPOTRIAS proposes a protocol, intervention or diagnostic test that delays the delivery of standard thrombolytic treatment for eligible ischemic stroke patients?

2. Biostatistical and Data Management Core (this is a required component of a SPOTRIAS).

• Is the biostatistical and data management core appropriate for the proposed studies? Is there evidence that biostatistical expertise will be available from the design to the reporting phase of all projects?

3. Blood and Tissue Specimen Core (this is a required component of a SPOTRIAS).

• Are the plans and facilities for storing and sharing any collected human blood or tissue specimens adequate?
• Does the proposed plan adequately address and prioritize the distribution of specimens within and outside the SPOTRIAS?
• Does the proposed plan adequately address if and how the investigators will obtain written informed consent for all prospectively collected tissues/specimens in a manner that will protect patient confidentiality?

4. Other Cores

• Does the proposed plan for each other core adequately indicate that it (will) effectively and efficiently support the research of the SPOTRIAS in a manner that can not be supported through other available (institutional or outside) resources?
• Does the proposed plan demonstrate that the activities of the core are essential to one or more SPOTRIAS projects?
• Does the proposed plan demonstrate that the activities of the core are well integrated with those of the projects and the investigators within the projects are working closely with those of the core to meet project objectives?
• If applicable, does the proposed plan demonstrate the activities of the core related to the performance of specialized analyses or development of technologies or methodologies that enhance and benefit the projects?
• Does the proposed plan address the qualifications, past performance (if applicable), and time commitments of the Core Director(s)?

c. Fellowship Training and Career Development Program

• Does the proposed plan for the career developmental plan describe how promising candidates for independent careers (academic, industrial, governmental) in translational stroke research will be selected?
• Does the proposed plan address how the investigators will seek out and include qualified women and minorities for participation in the proposed program?

d. Overall Program Organization, Interaction, and Capability

1. Leadership

Are the scientific qualifications and involvement of the principal investigator as well as his/her scientific and administrative leadership capabilities and time commitment presented and sufficient for the requirements of the proposed SPOTRIAS?

2. Institutional Commitment

Is the institutional commitment for facilitating the research objectives of the SPOTRIAS (e.g., special facilities, recruitments, discretionary resources, such as dollars and space) documented and sufficient?

3. Integration within the SPOTRIAS

Do the plans for integrating the activities of SPOTRIAS projects with proposed cores, as well as integrating SPOTRIAS research and cores with existing institutional resources, give confidence and sufficient evidence that such efforts are likely to be effective?

4. Hyper-acute Stroke Patient Population

Is the access to patients and populations for conducting current and projected therapeutic, prevention, detection, and control research adequate to ensure likely success of the goals of the program?

5. Planning and Evaluation of Activities

Are the plan(s) and/or track record(s) to evaluate the translational research productivity of existing projects and cores; discontinue activities of low productivity; initiate new activities in response to important translational research opportunities; establish collaborations; and utilize the advice of internal and external advisors presented and sufficient for the requirements of the proposed SPOTRIAS?

6. Collaborations

Is there evidence of tangible interactions with other SPOTRIAS centers? Are the abilities and availabilities of the investigators to interact with other SPOTRIAS and with the NIH/NINDS in sharing information, participating in committees, and collaborating on activities of mutual interest evident and sufficient?

7. Progress (for Competitive Renewal Applications)

Does the application identify progress and achievements specific to translational research since the previous competitive review? Have there been scientific achievements in research on acute stroke and related topics by projects utilizing Center resources in the last funding period? Are significant findings in acute stroke research identified that were facilitated or supported directly through Center resources? Has the progress in achieving the major aims of the Center and its projects been highlighted in major publications? Does the application describe how the presence of the Center has facilitated and improved translational acute stroke research at the Institution and with in the network of translational SPOTRIAS centers?

Additional Review Criteria.  As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission Applications.  When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications.  When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications.  When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project.  If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations.  As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

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.

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.

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.

2. Administrative and National Policy Requirements

Terms and Conditions of Award

The following terms and conditions will be incorporated into the notice of grant 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, and other HHS, PHS, and NIH grant administration policies.

1) The awardees for a SPOTRIAS will treat within two hours of onset of stroke symptoms a minimum of twelve eligible ischemic stroke patients during each year of the project with standard thrombolytic treatment as approved by the FDA. It is the intention of this announcement to facilitate the creation of SPOTRIAS at which more than twelve patients will be treated per year. Therefore if a SPOTRIAS should not be able to achieve this minimum level of performance, then funding will be severely reduced. Noncompliance with the terms of award may result in a reduction of the recommended budget, withholding of support, suspension, or termination of the award.

2) A condition of any award will be the periodic review of the clinical research projects which compose a SPOTRIAS by a Data Safety and Monitoring Board (DSMB) established by and reporting to the NINDS. This DSMB will review research progress in the entire SPOTRIAS as well as the phase I or phase II studies in the SPOTRIAS.

3) Information concerning the number of patients enrolled in each SPOTRIAS protocol, the completeness of follow-up, and other data necessary to assess research progress and to plan expenditure of funds shall be made available to the NINDS on a quarterly basis. The report shall include the number of males and females, and the different ethnic groups, in the study population. Reports are to be sent to the NINDS program administrator, summarizing progress, including data on patient accrual, completeness of data, and patient safety. These will be due March 1, June 1, September 1, and December 1 each year of the grant (or as mutually agreed upon with the NINDS program administrator).

4) The NINDS reserves the right to terminate or curtail a SPOTRIAS (or an individual project or core) in the event of (a) a major breach in a clinical 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 Program Announcement, or (d) shortfall in recruitment and/or retention of subjects or (e) a recommendation to the NINDS by the DSMB to a project.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. 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).

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement. The Progress Report should also address the special programmatic requirements noted above in the Terms and Conditions of Award Section.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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:

Scott Janis, Ph.D.
Office of Clinical Research
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2191
6001 Executive Blvd.
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 Boulevard
Bethesda, MD 20892-9529 (Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
Fax: (301) 402-0182
E-mail: [email protected]

3. Financial or Grants Management Contacts:

Maxine Davis-Vanlue
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 3258
6001 Executive Blvd.
Bethesda , MD 20892
Telephone: (301) 496-5707
FAX: (301) 402-0219
Email: [email protected]

Section VIII. Other Information

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 (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://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.

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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

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.

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.

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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html), investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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. 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 FOA 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. 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/.