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 Program of Translational Research in Acute Stroke

Announcement Type
This is a modification of PAS-01-092 which was previously released May 10, 2001.

Update: The following update relating to this announcement has been issued:

Program Announcement (PA) Number: PAR-05-084

Catalog of Federal Domestic Assistance Number(s)
93.853

Key Dates
Release Date: April 8, 2005
Letters of Intent Receipt Date(s): One month prior to submission. Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Application Receipt Dates(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Earliest Anticipated Start Date: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: April 4, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

The National Institute of Neurological Disorders and Stroke (NINDS) invite 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. Eligible institutions must be able to deliver rapid treatment for acute stroke and to conduct the highest quality translational research on the diagnosis and treatment of acute ischemic and hemorrhagic stroke. SPOTRIAS grants will require that a minimum number of stroke patients be treated two hours after the onset of their symptoms. Another important function of SPOTRIAS is to establish a program to recruit and train the next generation of stroke researchers. Eligible organizations include: For-profit or non-profit domestic organizations, public or private institutions, such as universities, colleges, hospitals, and laboratories, Units of State and local governments, and eligible agencies of the Federal government. 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. The support for SPOTRIAS is through an NIH specialized center grant (P50) mechanism. The maximum allowable direct cost per year for a SPOTRIAS will be $1,500,000.

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.

An individual may submit only one application and up to two amendments of it in response to this announcement.

The applicants will follow the instructions for the PHS 398 form (available at http://grants.nih.gov/grants/funding/phs398/phs398.html) and the current Program Announcement (PAR). For further assistance, contact GrantsInfo, Telephone: (301) 710-0267, Email: GrantsInfo@nih.gov. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Because of the size and complexity of the SPOTRIAS Network, prospective applicants are urged to consult with the staff of the NINDS Clinical Trials Group early in the preparation of the application (see Section VII. Agency Contacts). Special instructions are needed for preparing a SPOTRIAS application and are available from the program contact listed under Section VII. Agency Contacts.

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(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


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. Basic research will be included if it will add to the overall progress made by the collaborative translational program. 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.

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, genetic samples, and any autopsy material). 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:

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

Each SPOTRIAS and the network of SPOTRIAS is 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 PAR will lead to significant changes in the care of stroke patients. Examples are:

1) There must be a core that provides 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.

2) 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/stroke_proceedings/sayre.htm). 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.

3) No treatment protocol performed as part of the SPOTRIAS will delay, for any amount of time, the delivery of standard care for acute stroke patients.

4) Three or more translational research projects will be required at each SPOTRIAS, including at least one phase 1 or phase 2 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. In some cases, collaboration with a manufacturer will be required to provide therapeutic agents. Each SPOTRIAS must develop specific safety monitoring plans to ensure the safety of this phase 1 or phase 2 study, but overall data and safety monitoring will be done by a NINDS-appointed DSMB that will oversee the phase 1 and phase 2 studies in all SPOTRIAS in the network. 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/funding/research/clinical_research/dsm.htm.

5) 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. If the meeting is not hosted by NINDS in Rockville, MD, the host center will be chosen based on the number of patients treated within two hours of stroke onset.

6) Besides the annual meetings, monthly conference calls will be scheduled with the NINDS Program Director and the Principal Investigators of all the SPOTRIAS.

7) 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/research_training.htm.

8) There will be a central facility in each SPOTRIAS for collecting and sharing relevant tissue and blood samples collected in the projects. Particularly important will be samples for genetic studies. Some of the samples may be requested by other SPOTRIAS in the network. 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. Some SPOTRIAS may wish to share autopsy material.

9) A biostatistical and data management core 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.

10) Each SPOTRIAS will collect and share specifically defined common data elements for all screened and fully evaluated participants for all SPOTRIAS related projects.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity 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 five 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, http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html).

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://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.

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.

A SPOTRIAS grant application may be submitted for up to 5 years of funding. 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 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 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

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

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 programs.

2. Cost Sharing or Matching

Not applicable

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria
Foreign institutions are not eligible for P50 grants.

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: 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.

The applicant is strongly encouraged to refer to the NINDS guidelines for research program projects when preparing the application. This format is described at http://www.ninds.nih.gov/funding/ppg_guidelines.htm.

3. Submission Dates and Times
Applications must be mailed 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(s): One month prior to submission. Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Application Receipt Dates(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Earliest Anticipated Start Date: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent 30 days before the application receipt date that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

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
E email: sj151t@nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed 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
(For express/courier use Bethesda, MD 20817)

At the time of submission, two additional copies of the application and all copies of the appendix materials must also 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

3.C. Application Processing

Applications must be submitted on or before the application receipt dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm. Upon receipt, applications will be evaluated for completeness by CSR.

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. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

Pre-Award Costs are allowable. A grantee may, at their own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

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.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

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

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to NINDS on the basis of established PHS referral guidelines.

Appropriate scientific review groups convened by NINDS in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

The following will be considered in making funding decisions:

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.

1. 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?

For proposed phase I and phase II trials: Is there adequate preliminary data from laboratory research or an adequate rationale for proposed interventions based on prior clinical experience? Do proposed phase one and phase two studies have a clearly defined place in the process of developing a new intervention? Will the proposed projects be likely to add significant information important to further steps in the development of a clinical intervention?

2. 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 phase I and phase II trials: Are the phase one and phase two studies appropriately designed? Are there appropriate data collection procedures (considering the budget limitations) and a reasonable design?

3. 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?

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Do the investigators demonstrate the capability to modify and refine projects to achieve the specific aims of the research proposed? Will the investigators appropriately modify their projects in response to intermediate results of ongoing projects and in response to results from other centers in the SPOTRIAS network? For phase I and phase II trials: Do the investigators demonstrate understanding that phase one and phase two trials provide limited preliminary data and are not definitive trials of efficacy?

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? Is there evidence that at least twelve eligible patients are treated each year with tissue plasminogen activator within two hours of the onset of their symptoms?

PAR Specific Review Criteria

General Review Criteria for Cores:

Review Criteria for the Biostatistical and Data Management Core

Review Criteria for the Career Development Core

Review Criteria for the Blood and Tissue Specimen Core

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

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

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.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

The NGA will be sent via email to the administrative official whose name is listed in Block 12 on the Face Page of the Form PHS 398 or may be retrieved by the institution through its NIH eRA Commons account. If a grantee is not e-mail enabled, a hard copy of the NGA will be mailed to the institutional official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA 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

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 grant 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

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Scott Janis, Ph.D.
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: sj151t@nih.gov

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: nindsreview.nih.gov@mail.nih.gov

3. Financial or Grants Management Contacts:

Rita Sisco
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 3290
6001 Executive Blvd.
Bethesda , MD 20892
Telephone: (301) 496-7488
FAX: (301) 451-5635
Email: siscor@ninds.nih.gov

Section VIII. Other Information

Required Federal Citations

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

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

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

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Public Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

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

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

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

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


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