Part I Overview Information


Department of Health and Human Services

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

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

Title: NINDS PHASE III Investigator-Initiated Multi-Site Clinical Trials (U01)

Announcement Type
New

Update: The following updates relating to this announcement have been issued:

Looking ahead: As part of the Department of Health and Human Services' implementation of e-Government the NIH will gradually transition each research grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. For more information and an initial timeline, seehttp://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-035.html. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html).

Program Announcement (PA) Number: PAR-10-198

Catalog of Federal Domestic Assistance Number(s)
93.853

Key Dates
Release Date: May 14, 2010
Letters of Intent Receipt Date(s): Not Applicable
Application Submission Date(s):July 14, 2010 for the first receipt date; standard U01 dates thereafter.  Please see http://grants1.nih.gov/grants/funding/submissionschedule.htm.
AIDS Application Submission Dates(s): Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date: Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: Changed to March 22, 2011 (Per PAR-11-173); Previously May 8, 2011 (Per NOT-OD-11-048) ; Original Date May 8, 2013

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 of Support
2. Funds Available

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

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

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

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to provide a vehicle for submitting grant applications for investigator initiated multi-site Phase III randomized, controlled clinical trials.  The trials may address any research question related to the mission and goals of NINDS.

NIH defines a Phase III trial as a broadly based prospective Phase III clinical investigation to evaluate an experimental intervention in comparison with a standard or control intervention or to compare two or more existing treatments. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials also are included.

Multi-site clinical trials are trials that recruit study subjects from two or more geographically distinct enrollment sites, or centers.  The sites are usually distinct in other characteristics (e.g. demographic, socioeconomic, or clinical).  Subject enrollment and study protocols are followed at these sites.

Background:

Phase III clinical trials are the most complex and challenging trials to design and implement.  For completion within the funding period and budget awarded clinical trials need extensive planning and proactive oversight.  Prior to beginning patient enrollment several steps need to be completed during a start –up period, including  creating a manual of procedures, finalizing case report forms, building the research database, contracting sites, obtaining IRB approval, training study personnel, etc.  The time and effort required to complete these steps are often underestimated.  In addition to lengthy study start-up, slow participant enrollment can cause trial delays and result in the need of additional funding in order to complete the planned trial.  Preventing trial failure due to poor planning, enrollment and retention requires anticipatory and flexible management to ensure that the completion of the trial is feasible within the award made to the grantee.  The purpose of this FOA is to provide a mechanism suitable for the submission and successful implementation of a large, complex phase III clinical trial, incorporating several stages to allow the investigators and NINDS to assess study progress and feasibility.

Objectives of the Program:

The proposed research must address a scientifically important question, must provide valuable information to the existing knowledge base, and must have public health applicability. Research topics should be based on the NINDS' strategic plan and research interests.

A phase III trial is conducted to provide a definitive answer regarding the safety and efficacy of an intervention.  The main interest resides in falsifying the null hypothesis that the treatment is not effective.  The trial design should therefore primarily ensure that high quality, complete data regarding the primary outcome will be collected in the most efficient manner in terms of time, resources and burden to participants.  Secondary outcomes should be included only when they are anticipated to provide important supportive or explanatory evidence.  This FOA should also be used for the submission of an adaptive trial designed with a seamless phase II/III transition where data from subjects participating in the Phase II portion of the trial are used in the evaluation of Phase III.  If the trial is designed to require more than 5 years to complete (i.e., long-term endpoint, extended follow-up, adaptive design, etc.) the applicant must provide a description of the plans for the entire trial including plans for the submission of a type 2 application for the additional years beyond this 5 yr application and include the total estimated cost and duration of the trial within the research strategy section of this application.  Proposed milestones (described in the next section) should be included for the entire trial.  The inclusion of this information will be used for planning purposes and to support the rationale for the full trial.  The impact/priority score assigned to this proposal will be based on the five year application submitted and will not guarantee the successful funding of the type 2 application.

Biological activity, pharmacodynamic response, or preliminary clinical efficacy should be evaluated in an appropriately designed phase I/II exploratory clinical trial.  Such proposals should refer to the NINDS Exploratory Clinical Trials programs PAR-10-199

Ancillary studies, defined as research activities undertaken to address a scientific question relevant to the parent study and that require access to data or records from the parent study and/or involve collection of additional data, specimens, or records from patients enrolled in the parent study, are not permitted within the phase III clinical trial application.  Ancillary studies to this trial may be submitted separately using the Ancillary Studies in Clinical Trials of CNS/PNS Disorders – NINDS Accelerated Awards Program (http://grants.nih.gov/grants/guide/pa-files/PAR-09-263.html).

NINDS requires the submission of separate applications for the Clinical Coordinating Center (CCC) and the Data Coordinating Center (DCC).  Separate applications for core functions (e.g., imaging centers, quality of life/economic analyses) may be submitted, but are not required.  For the purposes of peer review all of these applications will be considered as a cluster and will be reviewed together and receive the same impact/priority score and summary statement.  When multiple applications are submitted as part of a cluster, then all the pre-submission requirements for applications requesting direct costs of $500,000 or more in any one year apply when the combined budgets of the clustered applications equal or exceed $500,000 (see section IV.6 for submission instructions).

The NINDS Phase III program is designed to structure the submission and facilitate the execution of a phase III trial.  Applicants are strongly encouraged to consult with NINDS program staff as early as possible prior to the anticipated application submission date (see Agency Contacts, Section VIII).  Applicants requesting direct costs of $500,000 or more for all components of t he trial (e.g., CCC, DCC, etc.) in any one year (excluding consortium F&A costs) should also consult the NINDS Guidelines for submitting large/expensive clinical research projects in order to obtain Institute approval to submit the application http://www.ninds.nih.gov/research/clinical_research/policies/large_projects.htm

Experimental Approach and Implementation:

The proposed experimental approach should include a randomized design and clear description of the study population, subject eligibility and inclusion/exclusion criteria; regulatory status (e.g. open IND or report on pre-IND meetings and IND status); recruitment and retention strategies; methods of randomization; methods of avoiding bias (e.g. blinding); primary and secondary endpoints and outcome measures; treatment and any follow-up procedures; and quality control procedures.  Applicants should provide a plan for using Common Data Elements (CDE; see: http://www.nindscommondataelements.org/) in their study case report forms and include a specific data sharing plan in the application.  Statistical methods should be proposed that are appropriately matched to the study design and include sample size and power calculations, plans for analysis, planned interim analyses, and data management.  Statisticians sometimes use computer simulations to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, taking into account the impact of such factors as noncompliance, dropout, missing data, and subject eligibility criteria (risk profile).  If simulations were performed to aid in the design of this clinical trial, sufficient details about the simulations should be provided (possibly in an appendix to the trial protocol) to assure that the simulations were performed and analyzed in a valid manner.  See the article, “The design of simulation studies in medical statistics”, by Burton et al., Statist. Med. 2006: 25:4279-4292 for guidance on how to document a simulation study.  It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations reveal.  The application must include the status of regulatory approvals as necessary to conduct the proposed research (e.g., open IND/IDE, or report on pre-IND/IDE meetings and IND/IDE status, or exemption letter from FDA if applicable, and/or status of RAC approval, etc).  IRB approval at the coordinating center is strongly preferred but not required at the time of submission.  NINDS requires FDA and IRB approval at the coordinating center prior to award, and encourages investigators to seek regulatory and ethics approvals as early as possible prior to submission.  The implementation of the clinical trial will be divided into three stages and is expected to include the following activities (described as milestones in the application as described above):

1, Planning and Start-up stage:

2. Feasibility stage:

3. Completion stage:

The information provided in the application should be organized in a manner that will facilitate peer review. The body of the application must present an overview of the state of the science, current status of therapeutics for the disease, and relevance of the trial for treatment of the disease.  Also, in the body of the application, the methodological aspects of the protocol, and approach to data collection and analysis should be presented in summary only, with specific references to additional information and details provided in the protocol (submitted as appendix). 

The award and continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies see (NINDS policy for continuation of phase III clinical trials; NOT-NS-10-009).

Institute Staff Involvement

Under this Cooperative Agreement (U01) mechanism, NINDS will have substantial continued staff involvement in the award and execution of this clinical trial award. NINDS staff will closely monitor progress during the award. This monitoring will include oversight of the IRB approved protocol by the NINDS Program Official, documentation of adequate serious adverse event management and reporting, and regular communications with the principal investigator and staff; additional involvement generally includes participation in meetings of the steering committee and other leadership committees.

The Terms and Conditions for an award for a clinical trial will include recruitment milestones expected to be met by the study as a whole at specific time periods, accrual goals for women and minorities (as appropriate), and any other identified requirements for completion of the approved research.

As with any award, continuation, even during the period recommended for support, is conditional upon satisfactory progress. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NINDS will consider ending support and negotiating a phase-out of the award. The NINDS retains the option to obtain periodic external peer review of progress.

Due to the unique requirements of the NINDS Phase III Clinical Trials Program, applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application.  This early contact will provide an opportunity to clarify the applicant's understanding of NINDS’ policies and guidelines, including the scope of projects within the NINDS and the requirement that trial objectives be milestone-driven.  These discussions also provide important information and guidance on how to develop an appropriate timeline and milestone plan, which are subject to peer review under this program.  Pre-application consultation includes an introductory call to discuss the scope and goals of the program (at least 3 months prior to submission), followed by a conference call or in-person meeting with NINDS staff. 

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 announcement (FOA) will use the U01 Cooperative Agreement award mechanism. The applicant will be solely responsible for planning, directing, and executing the proposed project.  

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

This is 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, plans beyond the current funding opportunity are indefinite

2. Funds Available

The total amount awarded and the number of awards will depend upon the impact, quality, number, duration, and cost of the applications received. The maximum request cannot exceed 5 years but the actual funded project period is dependent on reaching specific milestones as described in this FOA.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

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

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

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see 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 that each application is scientifically distinct.

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

Renewals. Applicants may submit a renewal application.  See also NINDS policy for continuation of phase III clinical trials (NOT-NS-10-009). 

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 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/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

In addition, for applications from foreign organizations:

·         Charge back of customs and import fees is not allowed.

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 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

See Section IV.3.A. for details.

3.A. Submission, Review and Anticipated Start Dates
Letter of Intent Receipt Date(s):  Not Applicable   
Application Receipt Date(s):  July 14, 2010 for the first receipt date; standard U01 dates thereafter. Please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

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

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

3.C. Application Processing

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

Upon receipt applications will be evaluated for completeness by CSR. Incomplete 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 merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

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

All NINDS multi-center phase III clinical trials awarded under this FOA will be given an initial award for 2 to 3 years (of the 5 year approved for funding by NINDS) in order to start-up the trial and establish performance feasibility.  Continuation of the award and restoration of the remaining budget and years of the five year application approved by NINDS past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned.  Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed Data and Safety Monitoring Board (DSMB) and NINDS program officer. A decision to either continue with the completion of the trial or to discontinue enrollment of subjects in the trial will be based on some or all of the following factors: (1) implementation feasibility (i.e., ability to start the trial as planned; (2) enrollment feasibility (i.e., establishing an acceptable enrollment rate to at least 80% of projected rate), (3) no safety concerns (i.e., recommendation from the Data and Safety Monitoring Committee to continue the trial), (4) if applicable, interim analysis evaluating the probability that the trial will be futile or inconclusive; (5) other criteria as appropriate to the individual trial. (see NOT-NS-10-009).    

6. Other Submission Requirements

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

Overall Plan for Study Milestones:

Applications must include proposed yearly milestones, which will be subject to peer review. The milestones must include achievable goals for the study start-up stage, enrollment feasibility stage, and completion stage as described below. Investigators should strongly consider including an interim analysis for futility in their milestone plan.   Adaptive designs, allowed under this mechanism, should include a pre-specified adaptation plan and allow for clear go/no-go decisions.  During the execution of the project, NINDS staff will assess progress toward and achievement of milestones. Achievement of these milestones will be evaluated by NINDS prior to releasing funding for each year of the award and failure to achieve these milestones may lead to study termination.

PHS398 Research Plan Sections

All application instructions outlined in the PHS 398 Application Instructions are to be followed, with the following additional requirements:

The Manual of Study Procedures (MOP) is not required under this program announcement and should not be included in the application.

The following sections must be included in the application:

Specific Aims:  The hypotheses and specific aims of the trial must be clearly and concisely stated. The primary and secondary endpoints to be measured must be clearly defined.  The inclusion of secondary endpoints should be justified by stating the need for the supportive or explanatory data they are likely to yield.   

Research Strategy:

Significance and Biological Relevance: The significance and biological relevance of the proposed clinical trial must be clearly stated. It is particularly important that there be a discussion of how the trial will test the hypothesis proposed and how results of the trial (positive or negative) may be explained based on the biological action of the proposed intervention. The application should state why the proposed study is necessary with an emphasis on the public health relevance or significance of the question and how the results will advance our knowledge or clinical practice in this disease area. A discussion of the costs and benefits of the study should be included for evaluation of the trial's significance.

Preliminary Studies:  The major findings of the pre-clinical and clinical studies that led to the proposed clinical trial should be presented. Data from pre-clinical and pilot studies demonstrating the need for and the feasibility of the trial should also be presented. Additional supporting data from other research should be included so that the approach chosen is clearly justified. Conceptualization and planning must have progressed to a stage sufficient to allow for an overall assessment of the likelihood of the completion of the trial and the potential impact of the results.

Approach: A concise summary of the proposed research plan should include-

Study Organization and Administration:

Investigators:

The overall clinical trial must be directed by an investigator with experience in the conduct of clinical trials and expertise in the content area of the trial. Such experience must be documented. Biographical sketches for all key investigators must be provided. Most clinical trial designs will require a multidisciplinary team.

Human Subjects:

NIH policy require education on the protection of human research participants for all key personnel submitting applications for grants or proposals for contracts or receiving new or non-competing awards for projects involving human research participants.  Certification of this requirement will be requested on during the Just-in-Time process.

Applicants should refer to Part II of the PHS398 Application Instructions “Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan.”

Assurances of the protection of human participants and the biohazard safety of employees (if applicable) must be provided both for the overall study and for individual clinical sites. The applicant must discuss any issues which might lead to concern for the welfare of participants.  Master templates of the forms to be used to obtain informed consent at each site must be included in an appendix. At a minimum, the human subjects sections of data coordinating center applications must address data security measures and confidentiality.

Data and Safety Monitoring Plan

Applicants must include a Data and Safety Monitoring (DSM) Plan for all clinical trials that is commensurate with the risk level of the proposed clinical research. All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the NINDS/NIH, the Office of Biotechnology Activities, Office of Human Research Protections, the Food and Drug Administration, and the Data and Safety Monitoring Board (if one is used)  Therefore, the DSM Plan must address the following areas:

NIH requires the establishment of Data and Safety Monitoring Boards (DSMBs) for multi-site clinical trials involving interventions that entail potential risk to participants (http://grants.nih.gov/grants/guide/notice-files/not98-084.html). The purpose of this board is to provide independent advice to NINDS concerning scientific issues pertaining to subject safety, data quality, study conduct and study continuation. In monitoring safety in the trial, the board also may recommend termination in the event of early significance of findings or futility, or the determination of unacceptable adverse effects. The DSMB is appointed by the NINDS and consists of individuals who are not associated with the institutions participating in the trial (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm).  Potential members of this board should NOT be named in the application, although the areas of expertise needed for the board should be indicated.

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). 

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year

Applicants requesting $500,000 or more in direct costs for the entire cluster of components for the trial (e.g., CCC, DCC, etc.) for any year (excluding consortium F&A costs) must carry out the following steps:

1) Consult the NINDS Guidelines for submitting large/expensive clinical research projects in order to obtain Institute approval to submit the application http://www.ninds.nih.gov/research/clinical_research/policies/large_projects.htm

2) Obtain agreement from the IC staff that the IC will accept the application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004.

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.

The study protocol (required and formatted using the NINDS protocol template: http://www.ninds.nih.gov/research/clinical_research/toolkit/protocol.htm)., Clinical Investigator’s Brochure or equivalent, as well as any of the other items relevant to the protocol (e.g., the consent form, documentation to access the study population, etc.), are to be submitted as appendices.  The study protocol should be inserted as the first item in the appendix. 

Special Instructions for Submitting Applications as Part of a Cluster

Title

Cover Letter     

Budget

Information Required for the Enrollment of Subjects into the Clinical Trial

As required by the NINDS Guidelines for the enrollment of subjects into trial submitted to Institute (see http://grants.nih.gov/grants/guide/notice-files/NOT-NS-05-010.html), the clinical trial application must include relevant information that addresses the feasibility of recruiting subjects who are eligible for the clinical trial. Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of study participants who meet the eligibility criteria as defined in the submitted protocol. For multi-site applications, information must be provided for each site participating in the trial.  This information should only be included in the research plan of the primary application for the Clinical Coordinating Center.

Information for the Use of NINDS Common Data Elements

The NINDS expects that applications submitted as an Investigator Initiated Phase III trial will use the NINDS Common Data Elements resource when constructing data collection forms.  The Common Data Element website (see: http://www.nindscommondataelements.org/) serves as a repository and dissemination tool for all NINDS CDEs for Investigators to utilize.

Resource Sharing Plan(s)

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

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

NINDS expects the primary outcome paper of the trial to be submitted for publication within 1 year of the completion of the trial (i.e., when the last participant completes follow-up of the primary outcome.  The complete dataset should be made available for sharing within 2 years of the publication of the primary outcome paper. 

The following resource sharing policies do not apply to this FOA:

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 will be evaluated for scientific and technical merit by  the NINDS 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?  Does the preliminary data or the literature support the need for a clinical trial to test the proposed hypothesis or intervention? Is there adequate biologic and/or public health rationale for the study? Is the study ethically justified?  

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? 

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

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?  Are there appropriate plans for the rigorous management and quality control of research data or materials?

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? Are NINDS common data elements used?

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?  Does the information provided support achievement of the goal that the study population can be enrolled in the time-frame of the proposed trial? Have necessary agreements with participating industry partners, if any, been established?  Is there documentation of the commitment of any subcontractor and consultants, and of service agreements for personnel and facilities? Is there evidence that the study drug or device will be available in sufficient quantities? 

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.

Clinical Trial Documentation (Study protocol, Clinical Investigator's Brochure or equivalent, etc):

Plans for Patient Recruitment/Retention: Does the application document the following:

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

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

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

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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

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

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

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.

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Milestones will be established by the NINDS prior to the award of the grant based on recommendations from the primary review group.  NINDs will make an award for 2 to 3 years in order to start-up the trial and establish performance feasibility.  Continuation of the award past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned.  Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed Data and Safety Monitoring Board (DSMB) and NINDS program officer.  Achievement of these milestones will be evaluated by NINDS prior to releasing funding for each year of the award and failure to achieve these milestones may lead to study termination.   

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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. Project Director/Principal Investigator (PD/PI) Rights and Responsibilities

The Principal Investigator will have the primary responsibility to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.

The PI will oversee all aspects of the organization and execution of the studies outlined in the application and approved by NINDS after peer review.

Awardees have primary and lead responsibilities for the project as a whole, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the primary leadership 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 during conduct of the phase III clinical trial, through technical assistance, advice, and/or other coordination that is above and beyond the normal stewardship role in awards, as described below.

The Project Scientific Officer will function as one of several co-investigators, collaborating and interacting as necessary with the Principal Investigators in accomplishing the overall goals of the Research Program.

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.  This individual will provide normal program stewardship as carried out for grants and she will serve on the clinical trial committees as deemed appropriate. 

A third NINDS Program Official, from the Office of Clinical Research, will serve as the NINDS liaison to the Data and Safety Monitoring Board.

2.A.3. Collaborative Responsibilities

The NINDS Project Scientific Officer will serve on the primary leadership committee.  In addition, the Program Scientific Officer, or other NINDS Program Officials, may serve on other study committees regarding recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.  The NINDS Project Scientific Officer will have voting membership on the primary leadership committee and its subcommittees.

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

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 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

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.  A report of the milestones, as described in section VI.1, achieved during the prior project period must be included in the non-competing application.   

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 Contact(s):

Scott Janis, PhD
Office of Clinical Research
National Institute of Neurological Disorders & Stroke
Neuroscience Center, Room 2191
6001 Executive Blvd.
Bethesda, MD 20892

Telephone: (301) 496-9135
Fax: (301) 480-1080
Email: janiss@ninds.nih.gov

2. Peer Review Contact(s):

Chief, Scientific Review Branch
National Institute of Neurological Disorders & Stroke
Neuroscience Center, Room 3201
6001 Executive Blvd.
Bethesda, MD 20892-9529

Telephone: (301) 496-9223
Fax: (301) 402-0182
Email: nindsreview.nih.gov@mail.nih.gov

3. Financial/Grants Management Contact(s):

Ms. Tijunna DeCoster, MPA
Grants Management Officer
National Institute of Neurological Disorders & Stroke
Neuroscience Center, Room 3528
6001 Executive Blvd.
Bethesda, MD 20892

Telephone: (301) 496-9531
Fax: (301) 402-0219
Email: decostert@ninds.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/.

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

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

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

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-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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