Part I Overview Information

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Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)  

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

Title: NINDS Ischemic Stroke Genetics Consortium (U01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-NS-09-002

Catalog of Federal Domestic Assistance Number(s)
93.853

Key Dates
Release Date: February 26, 2009  
Letters of Intent Receipt Date: April 15, 2009  
Application Receipt Date: May 15, 2009
Peer Review Date: July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 30, 2009 
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: May 16, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose.   This funding opportunity announcement (FOA) issued by the National Institute of Neurological Diseases and Stroke (NINDS), the National Institutes of Health (NIH) solicits grant applications from institutions/ organizations that propose to establish a genome-wide association study consortium focused on the goal of identifying genes that influence the risk and outcome of ischemic stroke.  The NINDS will support one such multi-center consortium.  This project will create a permanent global resource, via the Database of Genotype and Phenotype (dbGAP), of genotyping data of rigorously phenotyped ischemic stroke cases.  The proposed study should concentrate on using existing DNA sample sets.  Each application submitted in response to this FOA must include plans to establish:  (i) a Data Coordinating Center (DCC) and (ii) Genetic Research Centers (GRC) that together would be able to make available a sufficient number of genotyped and uniformly phenotyped samples to provide statistical power for a meaningful GWAS analysis (6,000 or more samples is an estimate of an appropriate sample size).  The Consortium should develop standardized, validated, and easily replicated methods to assign stroke subtypes for this GWAS analysis.  The samples submitted for this GWAS should be accompanied by clinical data to support the endophenotyping in this study and more importantly, to enable the utilization of the data from these study in future subtype-specific studies.  The goal of this announcement is not only to enable an initial exploration of genes that affect susceptibility and outcome, but also to create a national resource of high quality information for data mining, replication studies, and future hypothesis generation.
• Mechanism of Support.  This FOA will utilize the NIH cooperative agreement research grant award (U01) grant mechanism
• Funds Available and Anticipated Number of Awards.  The NINDS intends to commit approximately $3.6 million in total costs to fund one award in response to this FOA.
• Budget and Project Period.  The total project period for an application submitted in response to this funding opportunity may not exceed four years.  Direct costs are limited to $450,000/year.
• Application Research Plan Component Length. Applications submitted in response to this FOA are limited to 25 pages for sections 2-5 of PHS 398.
• 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.  More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications.  Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions. Resubmission of applications are not permitted in response to this FOA
• Renewals. Renewal applications are not permitted in response to this FOA. 
• Special Date(s).  This FOA uses non-standard due dates.  See Receipt, Review and Anticipated Start Dates
• Application Materials.  See Section IV.1 for application materials.
• Hearing Impaired.  Telecommunications for the hearing impaired are available at TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
    D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

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
     A. Cooperative Agreement Terms and Conditions of Award
         1. Principal Investigator Rights and Responsibilities
         2. NIH Responsibilities
         3. Collaborative Responsibilities
         4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The primary objective of this FOA is to identify genes or genomic regions that affect either the susceptibility to, or outcome of ischemic stroke.  The genetic risk factors in question may either predispose towards ischemic stroke in general or to specific subtypes of ischemic stroke. The study may consider planning for analysis of genetic association with specific sub-phenotypic manifestations, such as early age of onset, ethnic or population subtype, pathogenic mechanism, variation in severity, brain location, complications, response to therapy, functional recovery, or susceptibility to environmental risk factors.  An additional key objective is to assure that SNP genotyping and associated phenotyping data generated from this project result in a publicly available resource for ongoing stroke and related future research via the Database of Genotype and Phenotype (dbGaP).  The application will consist of a collaborative consortium, which will work together with the NINDS staff to achieve these goals.

Background

Stroke is not a disease but a set of cerebrovascular events that occur due to a wide variety of etiologies.  These range from factors that influence the development of a variety of disorders of the heart, coagulation abnormalities, hypertension-related vascular changes, atherosclerosis and other disorders of the vessel wall.  Though the various stroke subtypes may share certain genetic risk factors, it is likely that others are more influential in specific stroke subtypes, or even specific classes within the subtypes.  Similarly, the outcome of stroke varies significantly even in patients with comparable pre-existing conditions, localization and volume of stroke.  Therefore, careful phenotyping will substantially enhance the value of the GWAS data, especially for future studies.  The consortium should develop standardized, validated, and easily replicated methods to assign stroke subtypes samples for this GWAS analysis.  The samples submitted for this GWAS should be accompanied by clinical data sufficient to support the endophenotyping in this study and to enable the utilization of the data from this study with future subtype-specific studies, which places special emphasis on the standardized unified phenotyping.  This will allow not only the discovery of genetic risk factors for Ischemic Stroke and genetic factors affecting the Ischemic Stroke outcome leveraging resources from already funded studies, but also create a national resource of high quality information for data mining, replication studies, and future hypothesis generation by adding to the National Resource, DbGAP.

Objectives

This FOA will fund one consortium consisting of multiple Genetic Research Centers (GRC) and one Data Coordinating Center (DCC) to continue the efforts of the NIH in the field of Ischemic Stroke Genetics and Genome Wide association studies (GWAS).  The application may include previously collected samples with matching, high quality clinical data, as well as methods for enriching phenotypes of collections including those banked at the NINDS repository or other similar repositories.  Each application should propose a method for rapid investigation and dissemination of genetic association findings in a cohort study or clinical trial, or consortium of cohorts or trials, involving large numbers (6,000 or more as a rough estimate) of well-characterized participants in whom extensive phenotype, covariate, and exposure data are available and high-quality DNA is isolated and accessible, or could be isolated from stored specimens.  Application should also include the replication studies and plans for follow up studies: e.g., replication studies using other large gene databases, additional genotyping and/or DNA sequencing, functional testing of variants.  Investigators may propose to work within a single population study or in multiple population studies to cover the full range of putative causal variants for stroke or variants affecting the after-stroke recovery.  Applicants are encouraged to include a broad range of participants approximating the diversity of the U.S. population on factors such as age, sex, race/ethnicity, socioeconomic status, U.S. geographic region, and urban/rural residence.  Studies involving racial or ethnic minorities, particularly those experiencing disproportionate burdens of disease, would particularly be sought.

Consortium structure, organization and specific requirements

The consortium will include a single Data Coordinating Center and multiple Genetic Centers and is welcome to use the multiple Principal Investigator (PI) option.  One PI should be designated as the director of the DCC (see below).  Other PIs may be designated as appropriate (e.g. as leaders of GRCs).  The DCC director may also serve as GRC PI.

Data Coordinating Center (DCC)

This center will be responsible for management and integration of the genetic data, the clinical data, and the endophenotype assignments from all GRC sites as well as coordination of public sharing of genotyping and associated phenotypic data.  The DCC will coordinate its activities as directed by a steering committee representing the GRCs and the NINDS representatives.  The DCC alone, or together with specifically designated GRCs, will take responsibility for the logistics involved in the planning, development and analysis stages of the project.  The DCC working with the steering committee will establish the data acquisition, transfer, and management system, develop procedures for ensuring subject and control confidentiality, unified phenotyping and supervise the orderly centralized collection and transmission of data.

Specifically the DCC will be responsible for a number of critical activities, but may execute these responsibilities through subcontracts with specifically designated GRCs:

• develop transparent rules used throughout the consortium to assign stroke subtype and other endophenotypes;
• minimize and measure the inter-site variability in assigning stroke subtype and other endophenotypes;
• the collation, management and support of analysis of both the genetic and clinical data;
• coordination of communication and research with the GRCs;
• developing data dictionaries to integrate the clinical data;
• coordination of data submission to the DbGaP;
• assisting the GRCs in developing study protocols;
• coordination of genotyping services by the Genotyping Center (GC) (see below);
• organizing DNA preparation, QC, and delivery of specimens from the GRCs to the GC;
• quality control to assure that all specimens delivered to the GC are accompanied by the established clinical data set, including the clinical data supporting the assigned stroke subtype.
• reviewing consent documents and assuring that all sharing requirements and restrictions are met and noted for sharing within the consortium and publicly via DbGaP (see http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap).

Genetic Research Centers

The GRCs will have accumulated or have access to a set of well-characterized subjects and control individuals for this work, which when utilized by this consortium, will allow power for gene discovery in ischemic stroke.  The GRCs will coordinate sharing of data and DNA not only from their own private archival collections but also from collections banked in public repositories (such as but not limited to the NINDS repository).  They will transmit genetic, familial and clinical data to be shared within the consortium, and to be made public in a de-identified manner, per consortium steering committee recommendations and as decided by the NINDS Program Staff.  The GRC will assure that the stroke-subtype assignment and endophenotypic data accompanying each of the DNA samples they submit are in compliance with the standards established by the consortium.  It is expected that most of the funds to the GRC will support this activity.  The GRCs will have full responsibility for identifying and providing the necessary number of study samples to meet the study goals and bring the study to completion.  The GRCs must participate in a consortium effort to harmonize the clinical data to be submitted, especially the subtype and endophenotype data.  While additional sample acquisition by a GRC is allowed under this RFA, it will require the recruitment of sufficient numbers of members of minority populations (e.g., including but not limited to American Indian, African American, Hispanics) to permit statistically meaningful analyses of these subsets of subjects.

While the goal of this FOA is a single, large, definitive Genome-Wide association study in ischemic stroke, this FOA will also support the following types of projects at the individual GRCs and the DCC:

• Genetic studies of subsets of subjects defined by their specific clinical presentation, ethnicity, genetic constitution, or environmental exposure
• Study designs and analyses based on genetic linkage, association, linkage-disequilibrium, or resequencing of alleles of candidate genes
• Statistical analysis tool development
• Analyses of pleiotropy, epistasis, and gene-by-environment interaction.

Genotyping

Genotyping Center.  Unless a special exception is granted by the NINDS, genotyping funded by this award is required to be performed using high-throughput genotyping facilities at the Center for Inherited Disease Research (CIDR, http://www.cidr.jhmi.edu/).  After formation, the Consortium will apply and receive approval to use CIDR facilities for genotyping. Cost of the genotyping will be covered by CIDR and is therefore should not be included in the budget for this study.

The GRCs, the DCC and the NINDS Staff will form a steering committee after award is made.  A scientific steering committee, consisting of the consortium director, the PIs from each collaborating site in the consortium, NIH staff and external advisors (identified by the NIH staff) will be a component of the consortium organized by the NINDS. The purpose of the scientific steering committee where decisions are made regarding the assignment of function within the consortium including publications policy, collaborations within and outside of the consortium, data analysis plans, quality control plans, phenotyping, and other activities.  At the meetings, participants will also discuss quality assurance, data collection, project coordination, protocol consistency and training. The committee will meet twice per year to discuss progress, coordinate activities and at one meeting each year, exchange information. The role of the NIH Project Scientist is described under COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF THE AWARD, Section VI 2.A.2. The Project Official is responsible for reviewing annual progress of the consortium and signing-off on the Grant Progress Reports.

Specific benchmarks

The specific milestones for the Consortium are listed below.  These benchmarks will be evaluated annually by the NINDS to determine whether the Consortium is on course to fulfill the goals and purpose of the program.  The timeline and benchmarks listed can be adjusted depending on the specific circumstances.  The NINDS will adjust or discontinue funding in response to lack of progress in achieving milestones, or in the case that new data significantly diminishes the relevance of the research to the NINDS mission.

1. In Years 1 and 2 the Consortium will

• develop standardized unified phenotyping;
• set up standards and procedures for collection of standardized phenotypic data;
• estimate the overall number of available usable samples with standardized phenotypic data, which should be no less than 6,000 prior to genotyping;
• initiate  phenotypic data collection;
• determine the need for the potential collection of additional samples;
• Develop collaborative agreements for replication studies to follow GWAS analysis;
• submit a proposal to CIDR.

2. In Year  3

• Sample processing and  genotyping will be performed;

3. During Years 3 and 4

• GWAS data will be analyzed and reported ;
• replication studies will be performed;
• genetic substudies will be performed. 

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the NIH cooperative agreement research grant (U01) award mechanism.  The Project Director/Principal Investigator (PD/PI) 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 https://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

At this time, it is not known if this FOA will be reissued.

2. Funds Available

• The NINDS intends to commit approximately $3.6 million (total costs) to fund one award in response to this FOA. 
• The expected direct cost amount for the entire project period is up to $1.8 million.  Direct costs are limited to $450,000/year.
• The total project period for an application submitted in response to this funding opportunity may not exceed four years.

The estimated amount of funds available for support of one project awarded as a result of this announcement is $900,000 in total costs for fiscal year 2009.  Future year amounts will depend on annual appropriations.

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 NOT-OD-05-004.

NIH grants policies as described in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see https://grants.nih.gov/grants/multi_pi.

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 they are scientifically distinct.

Resubmissions.  Resubmission applications are not permitted in response to this FOA. 

Renewals.  Renewal applications are not permitted in response to this FOA.  

Section IV. Application and Submission Information

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1. Address to Request Application Information

The PHS 398 application instructions are available at https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

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

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

Applications from foreign organizations must:

• Request budgets in U.S. dollars.
• Contain detailed budgets. See NOT-OD-06-096.

In addition, for components, which include foreign organizations:

• Charge back of customs and import fees is not allowed.
• Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF.
• Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested.  See NOT-OD-01-028, March 29, 2001.                        
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., “Administrative and National Policy Requirements”

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

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs 

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

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

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

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Letters of Intent Receipt Date: April 15, 2009
Application Receipt Date: May 15, 2009
Peer Review Date: July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 30, 2009

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.

The letter of intent should be sent to:

Eugene Golanov, M.D., Ph.D.
Program Director
NINDS, NIH
NSC, Room 2118
6001 Executive Blvd.
Bethesda, MD  20892-9521
(FED EX or courier shipments use Rockville, MD 20852)
Phone: (301) 496-1431
FAX : (301) 402-2060
E-mail: golanove@ninds.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the 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 https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

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

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.).  If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application.  However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at 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 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 award.

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

6. Other Submission Requirements and Information

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Plan Page Limitations

Applications submitted in response to this FOA are limited to 25 pages for sections 2-5 of PHS 398.

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 https://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 https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators 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 Data-Sharing Policy or https://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 https://grants.nih.gov/grants/gwas/.

The consortium and its participants are expected to outline their ability to share de-identified samples and data for ultimate use via a public database (DbGaP).  Each applicant should specify how their particular sample and data set not only contribute to a consortium scientifically, but also, how their samples in particular will contribute significantly to a national public genotype-phenotype resource.  They should also clarify any restrictions in their consent forms for sharing (limited to disease only studies, limited to academic only, any other restrictions) and if needed, specify in the plan any intent to re-consent individuals.  If consent form documents contain restrictions that the IRB has over-ridden to allow sharing via DbGaP and with the consortium, that should be included in Appendix materials.  The availability of data for sharing will be considered.  If samples have been banked in the NINDS or another repository, that information should also be included, and any costs associated with withdrawal of samples from such a repository should be included in the application.  All applications must specify their intent to comply with NIH GWAS Policy specifically (see https://grants.nih.gov/grants/gwas/), and their plans to deposit all raw genotyping and all associated phenotyping data and documents in DbGaP.

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

Section V. Application Review Information

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1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the 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 a priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Neurological Disorders and Stroke Council

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• All applications must specify their intent to comply with the NIH GWAS Policy specifically (see https://grants.nih.gov/grants/gwas/), and their plans to deposit all raw genotyping and all associated phenotyping data and documents in DbGaP.

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 meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Innovation:  Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?   

Investigators: Are the PD/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? 

Environment:  Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? 

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

• Population.  Applicants should provide strong justification for the choice of population and describe all relevant phenotypic and environmental exposure measures from the study.  Each application should clearly define the source population, eligibility criteria, informed consent and consultation process, recruitment methods, percent participation, losses to follow-up, and numbers and demographics of participants currently in the population study or proposed for inclusion, and inclusion of minorities.  It will be important to justify to peer reviewers the merits of each of the particular cohort studies that were chosen to be included in the consortium and plans to harmonize the combined studies. 
• Sampling.  Applicants should provide strong justification for the choice of sampling design and sizes of the studies proposed for inclusion.  Studies should be of sufficient size and breadth to permit examination of a wide range of variants and traits, and to identify associations and interactions with sufficient power.  Applicants should describe any previous genotyping carried out on the specimens to be submitted, particularly whether any genome-wide linkage or association studies have been carried out and how those data will be incorporated into the analyses proposed in this application. 
• Specimen access.  Applicants are expected to document access to existing DNA specimens and phenotypic data from an existing human population-, clinic-, or family-based study. 
• Informed consent.  Adequacy of current informed consent and IRB approvals for genotyping and other assays proposed for inclusion, and for investigation and dissemination of grouped descriptive and association data, should be clearly described along with any restrictions on research use of the data.
• Data sharing.  Consistent with the data sharing plan, specimens should be available for sharing with the NINDS Genotyping Facilities (CIDR) and DbGaP.
• Management plan.  In forming a consortium, applicants proposing to combine multiple studies might consider including a management plan that explains to peer reviewers how funds would be distributed among the various participating institutions and what the PI's role will be in leading this collaborative group.

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 rating:

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 on Human Subjects in the PHS 398 instructions).

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 on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

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

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed. 

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

• Data Sharing Plan. [https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm] 
• Sharing Model Organisms. [https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

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1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator(s) will have the primary responsibility for planning, organizing and administering Ischemic Stroke Genetic Consortium. He/She will participate as a member of the Scientific Steering Committee with the PIs from the other sites within the consortium, external advisors and NIH staff. This includes defining and planning objectives and approaches; planning, conducting, analyzing, and publishing results, interpretations, and conclusions of the studies; and organizing and carrying-out administrative and research activities to serve the consortium. The PI agrees to comply with any consortia-wide policies established by the Scientific Steering Committee.

Awardees are responsible together with the NINDS staff for establishing a Scientific Steering Committee.

The PI agrees to comply with any consortia-wide policies established by The Scientific Steering Committee.

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

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

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

The Consortium will have the support of one or more Project Scientists from NIH program staff who are assigned an administrative role.

The NIH Project Scientists will have substantial scientific-programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.

NIH Project Scientists will be responsible for assessing the progress of the projects toward the accomplishment of specified milestones, and for recommending if further funds should be released to the project. The Project Official is responsible for reviewing annual progress of the consortium and signing-off on the Grant Progress Reports

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

2.A.3. Collaborative Responsibilities (optional)

A Scientific Steering committee will serve as the governing board for the award. The Scientific Steering Committee will make strategic decisions regarding collaborations within and outside of the consortium, phenotyping, meeting the milestones, data analysis and quality control plans, and other activities.

Membership will include: the consortium director, the PIs from each collaborating site in the consortium, NIH staff and external advisors (identified by the NIH staff). The project PI and the PI from collaborating sites of the consortium will each have one vote, and the NIH Project Scientists will have a single NIH vote. The project PI will serve as chairperson of the Steering Committee. Consortium members will be required to accept and implement policies approved by the Steering Committee.

The committee will meet twice per year to coordinate activities, progress toward the milestones, and at one meeting each year, exchange information.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

1. Scientific/Research Contacts:

Eugene Golanov, M.D., Ph.D.
Program Director
NINDS, NIH
NSC, Room 2118
6001 Executive Blvd.
Bethesda, MD  20892-9521
(FED EX or courier shipments use Rockville, MD 20852)
Phone: (301) 496-1431
FAX : (301) 402-2060
E-mail: golanove@ninds.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:

Tijuanna E. DeCoster, MPA
Chief Grants Management Officer
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Suite 3290, MSC 9537
Bethesda, Maryland 20892-9537
(Rockville, MD 20852 for express/courier service)
Telephone: 301-496-9231
Fax: 301-402-0219
Email: decostert@mail.nih.gov

Section VIII. Other Information

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Required Federal Citations

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

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, https://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 (https://grants.nih.gov/grants/policy/data_sharing).

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

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 https://grants.nih.gov/grants/gwas/.

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

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

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 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at https://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 (https://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 https://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 https://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 (https://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 https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This 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 https://grants.nih.gov/grants/policy/policy.htm.

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

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