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
NIH Blueprint for Neuroscience Research (http://neuroscienceblueprint.nih.gov/))
National Center for Complementary and Alternative Medicine (NCCAM) (http://nccam.nih.gov/)
National Center for Research Resources (NCRR) (http://www.ncrr.nih.gov/)
National Eye Institute (NEI) (http://www.nei.nih.gov/)
National Institute on Aging (NIA) (http://www.nia.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (http://www.niaaa.nih.gov/)
National Institute of Biomedical Imaging and Bioengineering (NIBIB) (http://www.nibib.nih.gov/)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD) (http://www.nidcd.nih.gov/)
National Institute of Dental and Craniofacial Research (NIDCR) (http://www.nidcr.nih.gov/)
National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS) (http://www.niehs.nih.gov/)
National Institute of General Medical Sciences (NIGMS) (http://www.nigms.nih.gov/)
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov/)
National Institute of Nursing Research (NINR) (http://www.ninr.nih.gov/)
Office of Behavioral and Social Sciences Research (OBSSR) (http://obssr.od.nih.gov/)

Title:  NIH Blueprint for Neuroscience Research Grand Challenge: Developing Novel Drugs for Disorders of the Nervous System (U01)

Announcement Type
New

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

Request For Applications (RFA) Number:  RFA-NS-11-002

Catalog of Federal Domestic Assistance Number(s)
93.213, 93.389, 93.867, 93.866, 93.273, 93.286, 93.865, 93.173, 93.121, 93.279, 93.113, 93.859, 93.242, 93.853, 93.361

Key Dates
Release Date: May 5, 2010
Letters of Intent Receipt Date: July 10, 2010 
Application Receipt Date: August 10, 2010 
Peer Review Date(s): November/December 2010
Council Review Date:  January 2011 
Earliest Anticipated Start Date:  April 2011
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: August 11, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

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, 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

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
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. Dispute Resolution 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

A. Background and Objectives

The NIH Blueprint for Neuroscience Research established the Grand Challenge for Neurotherapeutics in response to the paucity of effective treatments for disorders of the nervous system. This program intends to develop drugs successfully through clinical Phase I and facilitate industry partnerships for their full development. The long-term goal of this grand challenge is to produce at least one novel and effective medication for a disorder of the nervous system that is currently poorly treated or untreatable.

Most promising compounds identified through basic research are not sufficiently drug-like for human testing. Before a new chemical entity can be tested in a clinical setting, it must undergo a process of chemical optimization to improve potency, activity and drug-likeness and pre-clinical safety testing to meet the standards set by the Food and Drug Administration (FDA) for clinical testing. These activities are largely the domain of the pharmaceutical industry and contract research organizations, and the necessary expertise and resources are not commonly available to basic researchers. To address this problem, the NIH Blueprint for Neuroscience Research is establishing a ‘virtual pharma’ network of contract service providers and consultants with extensive industry experience to enable drug development in the NIH neuroscience research community. This Funding Opportunity Announcement (FOA) is soliciting applications for U01 cooperative agreement awards from investigators with small molecule compounds that have potential for development into clinical candidates within this network.

This FOA and the Blueprint Neurotherapeutics ‘virtual pharma’ network is an initiative of the NIH Blueprint for Neuroscience Research, which provides a framework for collaborative activities involving sixteen participating NIH Institutes, Centers, and Offices that support research on the nervous system (http://neuroscienceblueprint.nih.gov/blueprint_basics/about_blueprint.htm). By pooling resources and expertise, the NIH Blueprint for Neuroscience Research takes advantage of economies of scale, confronts challenges too large for any single Institute or Center, and develops research tools and infrastructure that serve the entire neuroscience community.

B. Research Scope

I. Introduction

To be accepted into the network, applicants to this FOA must have in hand the starting compounds for chemical optimization and bioactivity assays for testing new analog compounds generated through the Blueprint Neurotherapeutics drug development network (see Entry Criteria below for more details). Successful applicants under this FOA will receive 1) funding for biological assessment of compounds in their laboratories and 2) no-cost access to drug development resources that typically reside in the pharmaceutical industry, including iterative medicinal chemistry optimization, pharmacokinetics, toxicology, manufacture and formulation, and Phase I clinical safety testing. The budget of the U01 application will support only the work in investigators’ laboratories, which will involve testing of compounds in biological assays and models related to the target disorder.

Each drug development project will be directed by a collaborative Lead Development Team, co-chaired by the U01 investigator and a consultant with extensive industry expertise identified and supported by the NIH Blueprint for Neuroscience Research. The team will also include consultants with additional expertise, supported by NIH, and NIH staff. Strategic decisions will be made by this team, with oversight from the Blueprint Neurotherapeutics Steering Committee and, ultimately, the NIH Blueprint for Neuroscience Research Institute and Center Directors.

This program is structured to allow U01 awardee institutions to retain ownership of intellectual property for compounds developed within the network.

II. Entry Criteria

To be considered responsive to this announcement, applicants must have in hand at least one small-molecule compound with well-demonstrated bioactivity that can be further developed as a drug for a disease or disorder of the nervous system. Applicants must also be able to conduct bioactivity and efficacy testing to assess compounds synthesized in the development process and provide all pre-clinical validation for the target disorder. Entry criteria for these compounds and assays are detailed below.

1. Entry Criteria for Compounds

To participate in this program, applicants must have in hand well-characterized bioactive small-molecule compounds that can provide a starting point for medicinal chemistry optimization. This program is not designed to support biologics development. Applications may propose development of more than one chemical scaffold showing the desired profile of activity against the target of interest. Although it is desirable to have some knowledge of chemical structure activity relationships (SAR) at the target of interest, individual active compounds that are well-characterized biologically are also appropriate for this program. Compounds proposed for entry into the Blueprint Neurotherapeutics network should possess the following attributes:

Activity in a primary assay. Activity in a primary screening assay should be confirmed by repeat dose-response testing. For biochemical assays, compounds should generally show activity at 1µM or below. For cell-based assays, compounds should ideally show activity at 10µM or below.

Activity in secondary/confirmatory assay(s). Activity must be confirmed in at least one secondary assay relevant to the target disorder.

Cellular activity. Compounds should be active in at least one cell-based assay. An IC50 or EC50 of <10µM is desirable.

In vivo efficacy. Efficacy in an in vivo model of the relevant disorder or disease is desirable but not required.

Determination of identity and purity. The starting compound(s) should have proof of identity and purity (typically >90%, as determined by, e.g., NMR, melting point, or LC/MS) and biological activity should have been demonstrated with more than one batch of compound.

Compound target selectivity. In cases where the molecular target of compound action is known, the applicant should demonstrate the degree of selectivity for the intended target over closely related targets. Counter-screening to determine selectivity across a broad panel of unrelated pharmacological targets (e.g., G protein-coupled receptors, kinases, etc.) is desirable, but not required.

Solubility. Compounds should have reasonable aqueous solubility, typically >1µg/mL at pH7.4.

Structure-activity relationship (SAR). Demonstration that chemical analogs of a proposed compound show similar biological activity is desirable. Limited SAR information may have been derived from activity of analogs in a screening library or from testing of commercially available analogs.

2. Entry Criteria for Bioactivity Assays

This initiative is not intended to support development of new assays, thus the applicant must propose the use of existing, well characterized assays and models. Assays that do not meet all entry criteria may undergo validation as an early stage of the U01, if necessary. However, proposed primary screening assays should be sufficiently well developed and characterized to demonstrate feasibility for validation and use in a medicinal chemistry SAR effort within one year of the start of the award.

Applicants should have three types of assays in hand: 1) a moderate throughput primary screening assay, 2) one or more secondary assays for confirmation of activity and potential efficacy and 3) counter screening assays for target selectivity, where necessary. For each type of assay, the parameters that should be discussed in the application are outlined below.

Primary screening assay. This must be an assay with moderate throughput or better, e.g., a reporter assay, which will be used to perform routine weekly screening of compounds synthesized for iterative medicinal chemistry. To inform the medicinal chemistry design, the assay must be sufficiently robust and reproducible to reliably rank compounds with similar activities. Ultimately, the primary screening assay should meet the following criteria. If these criteria are not already demonstrated for the assay when the application is submitted, the application should include data and discussion to support the feasibility of achieving this level of assay validation within the first year of the award.

Secondary confirmation assays. The applicant must have one or more secondary assays with sufficient biological validation to confirm the activity of compounds identified in the primary assay and demonstrate potential efficacy in the target disorder. These may be low to moderate throughput assays. Ideally, at least one secondary assay would be capable of generating dose-response data for multiple compounds simultaneously. The application should contain the following information about secondary screening assays:

Selectivity and counter-screening assays. Where the molecular target of drug action is known, e.g., a particular kinase, it may bear similarity to other cellular targets.  In these cases, the applicant should describe criteria for compound specificity for these targets and screening assays to determine that specificity. Where aspects of the screening approach are prone to unwanted activities or artifact, counter screens should be available to rule out these unwanted activities. Counter-screening and selectivity assays should have demonstrated reliability and adequate throughput for their proposed use in the development program.

III. Timeline of Drug Development in the Network and the U01 Investigator’s Role

Directing compounds through the drug development pipeline will be a collaborative effort. After award, each successful applicant will work closely with NIH staff and drug development consultants to finalize a drug development plan involving the Blueprint Neurotherapeutics Network contractors. This plan will define activities and advancement criteria for a series of stages through which compounds will progress during development. This section outlines the stages and timeline of work that will be conducted throughout the development pipeline, beginning with the entry of a well-characterized hit compound and ending with a novel candidate drug with demonstrated safety in humans. This section also outlines the roles of the NIH Blueprint Neurotherapeutics Network and the U01 investigator in each stage of the pipeline. In conjunction with the Generic Project Timeline at: http://neuroscienceblueprint.nih.gov/bpdrugs/apply.htm, this section can be used as a guide to develop the budget for the U01 application, which should include only the activities that will be conducted in the investigator’s laboratory. Activities supported by Blueprint Neurotherapeutics contracts, such as chemistry, pharmacology, toxicology, regulatory activities and clinical testing, should not be included in the U01 application budget.

1. Exploratory chemisty/feasibility (for budget purposes, assume 6 months). Each project will undergo a feasibility phase in which investigators will validate their primary screening assays for SAR studies and test a collection of approximately 50-100 chemical compound analogs. These will be primarily identified from commercial sources and supplied to the investigator by NIH Blueprint Neurotherapeutics contractors. Work in this phase will be directed toward determining whether the compounds and assays are amenable to medicinal chemistry optimization.

2. Medicinal chemistry optimization (for budget purposes, assume 2 years). If the outcomes of the feasibility studies are successful, compounds will enter a full-scale, iterative medicinal chemistry optimization phase to improve bioactivity, potency and pharmacological properties. This process of understanding the structure activity relationship (SAR) between the compounds and the desired drug properties typically requires dozens of rounds of compound synthesis and testing. The ultimate goal of the SAR effort is selection of a pre-clinical candidate compound with sufficient bioactivity and drug-likeness to proceed to IND-directed pre-clinical safety assessment.

During this stage, a Lead Development Team will be formed to collaboratively manage and coordinate the progress of compounds through the development pipeline. The team will be co-chaired by the U01 investigator and a drug development consultant identified and supported by the Blueprint Neurotherapeutics program. The team will include other consultants as needed at each stage of the project to advise on chemistry, biology and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) study design and interpretation.

The major role of the U01-funded investigator in this process is to conduct primary biological assessment of compounds on a regular, one-to-two week schedule to inform the design of subsequent iterations of compound synthesis. In addition to a regular testing schedule in the primary assay, the PI will provide confirmation of the activity of select compounds in secondary assays and possibly animal models relevant to the drug target.

NIH Blueprint Neurotherapeutics contractors will produce compound analogs for SAR testing and provide standard screening services to assess in vitro and in vivo ADMET characteristics of the compounds.

In the first year, medicinal chemistry will be in a ‘hit-to-lead’ phase, focusing heavily on optimizing activity and potency of compounds in the primary and secondary disease assays. In the subsequent ‘lead optimization’ phase, SAR will increase emphasis on ADMET properties of the compounds, with continued monitoring and optimization of bioactivity. If compound testing in in vivo animal models is proposed, this should be limited to testing a small number of selected advanced compound analogs (e.g., 3) in year 3.

3. IND-enabling studies (for budget purposes, assume 1.5 years). If a therapeutic candidate is identified which meets the target criteria for activity, efficacy, and favorable physicochemical and ADMET properties, it will move into IND-directed pharmacology and toxicology studies. Blueprint Neurotherapeutics contractors, with direction from the Lead Development Team, will conduct the preclinical safety studies, GMP synthesis, formulation and other activities required to ready a compound for human testing.  Blueprint Neurotherapeutics contractors will provide data and reports in a format suitable for inclusion in an IND application and will assist in the development of the application. The U01 investigator will be responsible for the submission of the IND application and scheduling meetings with the FDA.   

4. Phase I clinical trial (for budget purposes, assume 1 year). Once an IND has been submitted successfully to the FDA, a Phase I clinical trial, typically in healthy volunteer subjects, will be conducted by a Blueprint Neurotherapeutics contractor. The development of the protocol and conduct of the trial will involve input from a Clinical Development Team, which will include the U01 investigator, clinical consultants identified by the NIH, and Blueprint Neurotherapeutics staff. Costs associated with the conduct of clinical trials will be supported outside the U01 and should not be included in the requested budget. In most cases, Phase I human studies will be conducted under a contract in the NIH Blueprint Neurotherapeutics Network.

IV. Milestones

Because drug development is an inherently high-risk process, it is anticipated that there will be a significant attrition rate as projects move through the pipeline. Go/No-Go milestones will be agreed upon at the start of each project and, in consultation with the Lead Development Team, investigators will produce milestone progress reports for independent evaluation by the Blueprint Neurotherapeutics Steering Committee.

If a funded project does not make sufficient progress toward the agreed upon milestones at any stage, funding for the project and access to Blueprint Neurotherapeutics contract resources may be discontinued unless an additional source of funding is identified.

V. Projects Not Responsive to this Announcement:

C. Instructions to Applicants

An application to this FOA should address the points raised below.

Significance:

Disease of interest: Describe the current state of knowledge of the disease etiology, clinical characteristics, and current and projected disease prevelance. Briefly discuss available treatments and their limitations. Provide a brief overview of the state of clinical trials research in this disease area, including relevant clinical outcome measures and biomarkers. Describe the clinical feasibility of the target disorder, for example, the availability of clinical trials networks and sites for later-phase clinical trials, and identify any clinical collaborators for this project.

Drug Target: Describe the intended molecular or cellular drug target. Provide evidence for a role of the target in disease pathophysiology, target validation, druggability, and novelty of the target with respect to ongoing biopharma development programs or existing drugs. Describe the expected clinical impact that a drug directed against this target might have on the features of disease and disease progression, e.g., whether the intervention is expected to be palliative or disease-modifying. Indicate whether there are reliable biomarker(s) available to monitor effects on the target in a clinical or pre-clinical setting. Indicate whether a drug must cross the blood brain barrier to successfully impact this target.

Summary of Key Drug Characteristics: Include a table of key properties for the intended drug (see guidance and table template at: http://neuroscienceblueprint.nih.gov/bpdrugs/apply.htm, including the intended disorder, patient population, mode, duration and frequency of delivery, and standards for efficacy.

Approach:

In addition to at least one small molecule compound proposed for development, the applicant must provide data demonstrating the suitability of the intended primary and confirmatory assays and models for drug development. 

Small molecule compounds proposed for development: Applicants should address the compound entry criteria outlined in the Research Scope section of the FOA. Applicants may propose the development of more than one chemical scaffold showing the desired profile of activity against the target of interest. Describe the evidence for activity of the compounds(s) on the target and disease of interest. Describe the level of activity and potency (EC50 or IC50) of the compounds in biochemical and cellular bioassays and the in vitro toxicity (LD50). In addition to chemical structures, information should be provided on known chemical and physical characteristics of the compound(s), e.g., drug-like properties, solubility, chemical liabilities, etc. Present the results of testing any chemical analogs and inferences about structure activity relationships (SAR). 

Proposed primary and secondary assays: Describe the primary assay that will be used to inform chemical SAR studies. Provide justification for the relationship of the primary assay to the disease target. Present data to support validation of the assay for reproducible ranking of similarly active compounds based on activity and potency, addressing the assay entry criteria outlined in section B.II of the Funding Opportunity Description above. If the primary assay is not fully validated when the application is submitted, discuss the feasibility of achieving these entry criteria within the first year of the award.

Identify secondary and confirmatory assays and models (in vitro and in vivo) for preclinical bioactivity validation of optimized compounds.   Describe the degree of pre-clinical or clinical validation of each assay and model for the disease of interest and the relevance of each to the proposed target of drug action. Provide data to demonstrate the correspondence between results of the primary and secondary assays.

Approach for use of primary and secondary assays: Summarize methods for the primary and secondary assays proposed for compound optimization, including methods for ongoing internal quality control, data analysis and plans for routine submission of data to a centralized Blueprint Neurotherapeutics database. The application should include a Summary Table of Bioactivity Assays (see table template at: http://neuroscienceblueprint.nih.gov/bpdrugs/apply.htm) proposed for evaluating the clinical promise of compounds, indicating the throughput for each assay and advancement criteria for progressing compounds from one assay to the next. Describe any potential pitfalls associated with the use of the primary and secondary assays and approaches to their resolution. 

Management plan: Describe the roles and extent of participation of key personnel over the course of the small molecule development process, from compound optimization through Phase I clinical trials. Indicate the willingness of the Principal Investigator and key personnel to operate under the cooperative agreement terms and conditions outlined in section VI.2.A of the FOA. If needed, describe the availability of a clinical consultant with expertise in the target disorder. Clinical experts should be sought as needed to develop the application (e.g., to determine the Summary of Key Drug Characteristics: http://neuroscienceblueprint.nih.gov/bpdrugs/apply.htm), and available after award to aid in determining the goals of the drug development program and to consult on the design of the clinical trial.

Resources: (Note that this is a separate section of the application from the Research Strategy section).

Intellectual property considerations for small molecule compounds proposed for development: Applicants should describe any constraints that they are or may be aware of that would impede use or development of the compound(s) in achieving the program goals (e.g., certain restrictions under transfer or sharing agreements, applicant’s previous or present intellectual property filings and publications).

Intellectual property considerations for primary and secondary assays: Applicants should describe any constraints that they are or may be aware of that would impede use of the assays and models for research purposes and/or commercial development.

Intellectual property management and commercialization: Applicants should describe their institutions’ existing or planned infrastructure for bringing the compounds to practical application (e.g., licensing for further drug development, managing intellectual property, commercializing discoveries) consistent with achieving the program goals  For a multiple-PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing intellectual property) among the institutions consistent with achieving the goals of the program.

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the U01 award mechanism(s).
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 http://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".

2. Funds Available

The participating ICs intend to commit up to $1,750,000 in FY 11 to fund up to 10 awards in response to this FOA.  It is anticipated that applications will carry direct costs of up to $125,000 per year for in vitro and/or in vivo screening of targets.

The estimated amount of funds available for support of up to 10 projects awarded as a result of this announcement is $1,750,000 for fiscal year 2011. 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://grants.nih.gov/grants/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. 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 http://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


1. Address to Request Application Information

The current 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) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Prepare all applications using the PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

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: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

In addition, for applications from foreign organizations:

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.

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.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the 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
Letter of Intent Receipt Date(s): July 10, 2010
Application Receipt Date(s): August 10, 2010
Peer Review Date(s):  November/December 2010
Council Review Date(s): January 2011
Earliest Anticipated Start Date(s): April 2011

3.A.1. Letter of Intent

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

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

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Jill Heemskerk, PhD
Office of Translational Research
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard
Neuroscience Center/Room 2229
Bethesda, MD 20892
Telephone: (301) 496-1779
FAX: 301-402-1501
Email: jill.heemskerk@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 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix 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 http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements

For cooperative agreements, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

PHS398 Research Plan Sections

All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements:

Budget

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

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.

Appendix Materials

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

Do not use the Appendix to circumvent the page limitations.  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 and further the advancement of the 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 the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

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.

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

Review 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 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:

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

Overall Impact

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

Scored Review Criteria

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

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

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Recognizing that the NIH does not require the applicant to have drug development expertise, is the experience with biological testing sufficient to support and inform a drug development effort? Is there access to clinical expertise necessary to define the goals of a drug development effort in the target disorder? 

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Is the drug target novel among ongoing drug development programs in industry and academia, regardless of perceived market value?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Is the target disorder at an appropriate stage of translational readiness for a drug development effort? Is there a compelling biological rationale for the role of the proposed drug target in the disorder of interest? Has the target been properly and appropriately validated, at least at a pre-clinical stage? Is the Summary of Key Drug Characteristics appropriate to the disorder? Is there clinical feasibility for testing a compound that would emerge from the proposed effort? Recoginzing that NIH does not require a proposal for an overall drug development strategy, is the proposed approach for a biological testing scheme sufficient to provide complete pre-clinical assessment of a candidate compound in the target disorder? Is the biological testing strategy maximally efficient and feasible for a five-year development program? Is the proposed primary screening assay suitable for a rapidly iterative medicinal chemistry program? Do the starting compound(s) constitute a tractable starting point for medicinal chemistry optimization? Are intellectual property or patent issues explained in the application and approaches for navigating these satisfactorily described?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

Additional Review Criteria

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

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

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

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

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

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

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

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

Revision Applications.  Revision applications are not permitted in response to this FOA.

Additional Review Considerations

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

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

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

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms ((Not Applicable) and 3) Genome Wide Association Studies (GWAS) (Not applicable).

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

Selection Process

The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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

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

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.

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/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 (http://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 will have the primary responsibility for:

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.

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

Project Lead Development Team (LDT): The LDT will be co-chaired by the PI and an NIH-contracted drug development consultant and will include additional members from the PI’s group, consultants and NIH staff. This team will collaboratively set strategic direction and guide the work flow for the project on an ongoing basis. The LDT will meet every two weeks via teleconference to analyze and interpret data from the PI and contracted laboratories and to formulate the subsequent experimental plan. The team will produce progress reports for evaluation by the BPN Steering Committee and BPN Project Team as needed.    

 BPN Steering Committee:  The Steering Committee will be responsible for reviewing and evaluating the progress of the BPN projects in meeting their milestones and goals, and making recommendations about the progress and directions of the BPN and individual projects to the BPN Project Team. The Steering Committee will be composed of 6-8 senior non-federal scientists who are not directly involved in the activities of the BPN. The BPN Project Team will appoint members to the Steering Committee. The BPN Program Officers, Project Scientists and BPN Project Team members may attend the Steering Committee meetings as non-voting participants.

The BPN Steering Committee will have the following involvement:

2.A.4. Dispute Resolution 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 Dispute Resolution. A Dispute Resolution 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 dispute resolution procedure does not alter 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


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:

Primary Contacts:

Jill Heemskerk, PhD
Office of Translational Research
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard
Neuroscience Center/Room 2229
Bethesda, MD 20892
Telephone: (301) 496-1779
FAX: 301-402-1501
Email: jill.heemskerk@nih.gov

Rebecca Farkas, PhD
Office of Translational Research
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard
Neuroscience Center/Room 2109
Bethesda, MD 20892
Telephone: (301) 496-1779
FAX: 301-402-1501
Email: farkasr@ninds.nih.gov  

NIH Blueprint for Neuroscience Research Institute and Center Contacts:

Rosemarie Filart, MD, MPH, MBA
Division for Clinical Research Resources
National Center for Research Resources
6701 Democracy Blvd
Bethesda, MD 20892-4874
Telephone: (301) 435-0178/(301)-642-5421
FAX: 301-480-3661
Email: Rosemarie.Filart@nih.gov

Tom Greenwell, PhD
Retinal Neuroscience
Division of Extramural Research
National Eye Institute
Suite 1300 / MSC 9300
5635 Fishers Lane
Bethesda, MD 20892

Telephone: (301) 451-2020
FAX: 301-402-0528
Email: greenwellt@mail.nih.gov  

Lorenzo M. Refolo, PhD
National Institute on Aging
Division of Neuroscience
Dementias of Aging Branch
7201 Wisconsin Ave
Gateway Bldg, Suite 350
Bethesda, MD 20892
Telephone: (301) 594-7576
Email: refolol@mail.nih.gov  

Qi-Ying Liu, MD, MSci
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2053
Bethesda, MD 20892
Telephone: (301) 443-2678
FAX: 301-443-1650
Email: liuqiy@mail.nih.gov

Zhaoxia Ren, PhD
National Institute of Child Health and Human Development
6100 Executive Blvd; MSC 7510
Bethesda, MD 20892
Telephone: (301) 402-9340
FAX: 301-480-2897
Email: zren@mail.nih.gov

Nancy L. Freeman, PhD
Division of Scientific Programs
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd; MSC 7180
Bethesda, MD 20892
Telephone: (301) 402-3458
FAX: 301-402-6251
Email: FreemanN@mail.nih.gov

John Kusiak, PhD
National Institute of Dental and Craniofacial Research
6701 Democracy Blvd; MSC 4878
Bethesda, MD 20892
Telephone: (301) 594-7984
FAX: 301-480-8319
Email: kusiakj@nidcr.nih.gov  

Elena Koustova, PhD, MBA
Genetics and Molecular Neurobiology Research Branch
Division of Basic Neuroscience and Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard; Room 4292
Bethesda, MD 20892
Telephone: (301) 496-8768
FAX: 301-594-6043
Email: koustovae@mail.nih.gov  

Cindy Lawler, PhD
National Institute of Environmental Health Sciences
530 Davis Dr; MSC K3-15
Durham, NC 27713
Telephone: (919) 316-4671
FAX: 919-541-5064
Email: lawler@niehs.nih.gov  

Jamie Driscoll
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard; Room 7194
Bethesda, MD 20892
Telephone: (301) 443-5288
FAX: 301-451-5615
Email: jdrisco1@mail.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


Required Federal Citations

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

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

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

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

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

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

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

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

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

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

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

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

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

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

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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