Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Eye Institute (NEI)

Funding Opportunity Title

NEI Collaborative Clinical Vision Research Project :  Chair's Grant (UG1-Clinical Trial Required)

Activity Code

UG1 Clinical Research Cooperative Agreements - Single Project

Announcement Type

Reissue of PAR-14-098

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR 18-523

Companion Funding Opportunity

PAR-18-521 UG1 Clinical Research Cooperative Agreements - Single Project

PAR-18-522 UG1 Clinical Research Cooperative Agreements - Single Project

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.867

Funding Opportunity Purpose

The NEI uses UG1 cooperative agreement awards to support investigator-initiated large-scale clinical trials, human gene-transfer and stem cell therapy trials, and other complex or high resource- or safety-risk clinical trials. These projects are multifaceted and of high public health significance requiring clear delineation of study organization including roles and responsibilities and require careful performance oversight and monitoring. For purposes of this Funding Opportunity Announcement (FOA), the proposed study must be intended to evaluate interventions aimed at screening, diagnosing, preventing, or treating vision disorders, or to compare the effectiveness of two or more established interventions. 

The NEI UG1-supported studies are typically funded as a group of single-component companion grant awards including the Chair’s Grant, the Coordinating Center, and Resource Centers, when appropriate

Specifically, this FOA encourages applications for the Chair's grant, which includes the scientific rationale, study aims and significance of the research project.

Key Dates
Posted Date

December 20, 2017

Open Date (Earliest Submission Date)

December 25, 2017

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Standard AIDS dates apply; by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Scientific Merit Review
Advisory Council Review
Earliest Start Date
Expiration Date

January 8, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    Purpose:

    Purpose:  The purpose of this funding opportunity announcement (FOA) is to provide a framework for applicants seeking a Chair's Grant.

    The Chair's Center provides clinical, scientific and technical leadership in protocol development and implementation for a multicenter or other complex or high resource- or safety-risk clinical trial. The application provides details regarding the protocol, research design, patient population and procedures and methods proposed for accomplishing study goals

    The NEI UG1-supported studies are typically funded as a group of companion grant awards including the Chair’s Grant, the Coordinating Center, and the Resource Centers, as appropriate. 

    Separate applications may be submitted for Coordinating Centers or Resource Centers under the following respective UG1 companion FOAs:

    • PAR-18-521, NEI Collaborative Clinical Vision Research Project: Coordinating Center Grant. (The Coordinating Center proposes a role of statistical and methodologic leadership, logistical coordination and trial support, and safety monitoring including support of the Data and Safety Monitoring Committee)
    • PAR-18-522, NEI Collaborative Clinical Vision Research Project: Resource Center Grant. (The Resource Center provides the expertise and infrastructure for imaging, laboratory or other requisite services)

    Scope of this Funding Opportunity Announcement:

    The scope of this FOA is to encourage grant applications for investigator-initiated clinical trials to establish the efficacy or compare the effectiveness of screening, diagnostic, preventative or therapeutic interventions. The NEI will accept under this FOA vision-related ancillary studies to parent clinical trials supported by the NIH.  Renewal applications that request additional years or funds to complete the original aims of a clinical trial will be accepted under this FOA.  Renewal applications may also be submitted to request support to extend follow-up of clinical trial cohorts after completion of the primary study goals to gather information on longer-term outcomes.  As applicable, this FOA may support laboratory work attending: study product manufacture, repackaging and distribution; quality assurance (i.e. identity, potency, or other aspects of product integrity); and participants safety.

    Applications involving a clinical experiment that are not directly intended to evaluate a screening, diagnostic, preventative or therapeutic intervention, or compare the effectiveness of established interventions, are not suitable for this FOA.  Applications that are not complex or of high resource- or safety-risk are not suitable for this FOA.  Preclinical, developmental, or preparatory studies for gene transfer and stem cell therapy are not supported under this FOA.

    Applicants are strongly encouraged to contact Scientific/Research staff as plans for an application are being developed (see Section VII, Agency Contacts), and no later than 12 weeks prior to the anticipated application submission date.

    See Section VIII. Other Information for award authorities and regulations.

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed

    New
    Renewal of PAR-10-207, PAR-14-096, PAR-14-097, PAR-14-098, PAR-14-099 and PAR 14-100
    Resubmission PAR-10-207, PAR-14-096, PAR-14-097, PAR-14-098, PAR-14-099 and PAR 14-100
    Revision PAR-10-207, PAR-14-096, PAR-14-097, PAR-14-098, PAR-14-099 and PAR 14-100

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Required: Only accepting applications that propose clinical trial(s)

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    Award Project Period

    The scope of the proposed project should determine the project period. The maximum period is five years

    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
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    • Non-domestic (non-U.S.) Entities (Foreign Institutions)
    Foreign Institutions

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are  eligible to apply.
    Foreign components, as defined in the NIH Grants Policy Statement, are  allowed.

    Required Registrations

    Applicant Organizations

    Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

    Program Directors/Principal Investigators (PD(s)/PI(s))

    All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

    Eligible Individuals (Program Director/Principal Investigator)

    Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

    Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

    • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
    • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
    • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide,  except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

    Instructions for Application Submission

    The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Project/Performance Site Locations

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Other Project Information

    All instructions in the SF424 (R&R) Application Guide must be followed.

    The following should be included as an attachment, if applicable

    Other Attachments:

    Clinical Protocol (required) –  a full clinical protocol must be included.  The FDA and NIH developed a Clinical Trial Protocol Template (See http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials) which can be modified for any type of clinical trial.

    The filename "ClinicalProtocol.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. 

    Milestone Plan (required) -  Applicants are required to provide detailed project performance and timeline objectives.  The proposed milestones must include achievable goals for the project as follows:

    • Completion of start-up activities as applicable (finalization of protocol, completion of any final regulatory approvals, contracting of sites, registration in ClinicalTrials.gov, etc.)
    • Enrollment of 25%, 50%, 75% and 100% of the projected recruitment
    • Completion of data collection
    • Completion of primary and major secondary endpoint analyses
    • Publication of primary outcome manuscript(s)
    • Preparation of final dataset for public use
    • Reporting of results in ClinicalTrials.gov

    The filename "MilestonePlan.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. 

    Overall Study Organization, Administration and Procedures (required) -  Without repeating information on the PHS Human Subjects-clinical Trials Information form basic elements regarding study organization, administration, and procedures include but are not limited to:

    Collaborative arrangements, duties and responsibilities of the Study Chair, Coordinating Center, Resource Centers and clinical sites as applicable; Lines of communication among study components; Administrative arrangements for IRB, FDA, and clinicaltrials.gov submissions and adverse event reporting as applicable; Plans and preliminary schedule for preparation, distribution, and review of trial safety monitoring reports; and, provisions for formal documentation of all safety reviews and tracking of safety recommendations and/or action items through implementation.

    The filename "StudyOrganization.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. 

    Manual of Procedures (MOP) (required) –  Basic elements in the MOP may include, but are not limited to: visit schedule; examination and testing procedures; expected adverse events; study publication policies, draft Informed consent forms (ICFs) and, if applicable, assent form(s); sample data collection forms; data capture, management, quality assurance and analytical procedures; and applicable clinical center and resource center information.

    The filename "MOP.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. 

    Interventional Agent(s) or Device(s) Availability (if applicable) - Documentation should be provided on the availability of interventional agent(s) or device(s) as well as plans and support for acquisition and distribution of interventional agent(s) or device(s).

    The filename "InterventionAvailability.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. 

    Applications that lack appropriate attachments are incomplete and will not be reviewed. 

    SF424(R&R) Senior/Key Person Profile

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    R&R Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.

    R&R Subaward Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.

    PHS 398 Cover Page Supplement

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    PHS 398 Research Plan

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

    Specific Aims: This section should include an overview of the proposed trial highlighting its public health relevance and significance with regard to the ability to move vision science forward, and a plan for how the Chair will provide overall leadership.

    Research Strategy:

    Provide a detailed description of the study including the: scientific background, preliminary data and rationale for the proposed investigation.

    Provide a description of the study administration including, but not limited to:

    • Scientific, clinical and administrative experience and qualifications of the PD(s)/PI(s) and other study personnel; leadership's past track record and/or future performance potential in clinical research (NEI-sponsored or otherwise);
    • Plans for carrying out the leadership's roles and responsibilities on a day-to-day basis, including coordination of and communication amongst multiple research activities and study entities;
    • Plans for identifying and engaging qualified investigators to participate in the study;
    • Plans for assuring study integrity, protocol fidelity and completion;
    • Plans for manuscript preparation and results dissemination;
    • Organization of, and the leadership's involvement in study committees (e.g., Executive, Steering, Operations, Publications, Data and Safety Monitoring).

    Letters of Support: Letters of support from institutions with a key role in the study must be provided.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • All applications must address how datasets will be made available
    • Describe plans for supporting timely publications and dissemination of results

    Appendix:

    Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    PHS Human Subjects and Clinical Trials Information

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Section 4 - Protocol Synopsis

    4.4. Statistical Design

    4.6 Will the study use an FDA-regulated intervention?

    4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:

    Delayed Onset Study

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    PHS Assignment Request Form

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Foreign Institutions

    Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. 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 only as described in the NIH Grants Policy Statement.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

    See more tips for avoiding common errors.

    Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

    To expedite review, applicants are requested to notify the NEI Referral Office by email at {ellenliberman@nei.nih.gov} when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application

    Requests of $500,000 or more for direct costs in any year

    Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

    A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation:

    Overall Impact

    Reviewers will provide an overall impact 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 review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific 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? Is there a strong scientific premise for the project? 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?

    Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?  For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding 

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

    With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center? 

    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?

    Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

    Does the proposed study follow appropriate clinical trial methodologies? .

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

    Does the application adequately address the following, if applicable

    Study Design

    Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

    Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

    Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

    Data Management and Statistical Analysis

    Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

    Is the proposed study organization appropriate to effectively implement the trial?

    For Renewal applications to complete the aims of the original trial or to extend follow-up to gather information on longer-term outcomes, has the progress of the trial to date been appropriate?  Will the proposed extension achieve the stated aims?

    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?  

    If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

    Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

    If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

    If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?  

    Additional Review Criteria

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    Study Timeline

    Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

    Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?  

    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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Children 

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    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.

    Resubmissions

    For Resubmissions, 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.

    Renewals

    For Renewals, the committee will consider the progress made in the last funding period.

    Revisions

    For Revisions, 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 consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact 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 Agent Research

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

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NEI}, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications:

    • Will receive a written critique.

    Applications will be assigned  to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Eye Council. The following will be considered in making funding decisions:

    • Scientific and technical merit of the proposed project as determined by scientific peer review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.See NEI Strategic Plan at https://www.nei.nih.gov/strategicplanning/
    3. Anticipated Announcement and Award Dates

    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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

    A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

    Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

    Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.  ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/ 

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC.

    To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.  Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

    Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE). 

    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  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

    For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    NEI Involvement Statement:

    Applicants must provide a statement acknowledging and agreeing to NEI staff post-award involvement in conducting the aforementioned types of clinical research studies, and should describe plans to accommodate this involvement.

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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

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

    The PD/PI will have the primary responsibility for:

    Defining objectives and approaches, and planning, conducting, analyzing, interpreting, drawing conclusions from and publishing trial results.  The design, methods, and procedures of the clinical trial will be detailed in an awardee-prepared and maintained, study-adopted Manual(s) of Procedures and the awardees will have the responsibility for following the protocol

    Retaining custody of and have primary rights to the data developed under these awards, subject to Government rights of access, consistent with current DHHS, PHS, and NIH policies.  Ensuring that study progress, quality and safety reports are prepared and distributed as requested by the medical monitor or Data and Safety Monitoring Committee (DSMC).  Ensuring that there is formal documentation of all medical monitor safety reviews, or DSMC deliberations, as applicable. This documentation will clearly list all recommendations and explicit action items and will be reviewed and approved by the medical monitor or quorum of DSMC members as applicable. It is the responsibility of the PD/PI to ensure that their responses to safety or oversight monitoring recommendations or action items are formally reviewed and approved by the medical monitor or quorum of the DSMC. The PD/PI is responsible for ensuring that there is proper administration of applicable medical monitoring and/or management of the Committee. The PD/PI must give all medical monitors or DSMC members the name and contact information of the responsible NEI program director and advise them to contact the NEI program director directly with any concerns about the adequacy of trial safety or study implementation, as applicable. In addition, the trial PD/PI must officially notify the NEI program director within 24 hours whenever the medical monitor or DSMC makes a recommendation to substantively modify or stop the study.

    Ensuring that the NEI and the medical monitor or DSMC receives study progress and safety reports as requested.

    Ensuring that the DSMC receives a copy of the study’s primary manuscript(s) for review and approval in advance of journal submission.

    Implementing DSMC recommendations -Timely implementation of substantive DSMC recommendations is expected. If the study leadership and/or NEI do not concur with the DSMC recommendation, it will be the responsibility of the NEI Director or designee, study leadership, and DSMC Chair to reach a mutually acceptable decision.

    Notifying the NEI program director within 24 hours of any FDA regulatory actions including: clinical hold; requests for modification; or, termination for trials requiring regulatory approval

    Reporting details of the safety monitoring process in the grant’s annual non-competing renewal (also called RPPR). Specifically, the renewal must note: 1) actual dates for all medical monitor or DSMC meetings as applicable; 2) verification that monitoring minutes have been reviewed and approved by the medical monitor, or quorum of DSMC and, 3) an update on the status of monitoring and general medical monitor or DSMC action items. Note: status reports must not contain any confidential study data or patient information.

    NEI guidelines for Data and Safety Monitoring of Clinical Trials can be found at: https://nei.nih.gov/funding/policy/policy6

    Data and Safety Monitoring Committee training is available at: https://dsmblearningcenter.niaid.nih.gov/Pages/default.aspx

    Documenting progress toward the stated study timeline and milestones as specified in the in the grant application and/or as modified during pre- or post-award negotiations. Specifically, the annual non-competing renewal must include but not be limited to: 1) actual dates of regulatory approvals if applicable; 2) date of enrollment of 1st study participant; 3) date of ClinicalTrials.gov registration, if applicable; 4) enrollment completion date; 5) date of completion of participant follow-up; 6) date of ClinicalTrials.gov results reporting, and, 7) date of initiation of data sharing.

    Reporting on compliance with NIH policies related to the study. Specifically, for clinical trials, the RPPR must note the status of or compliance with: 1) registration on ClinicalTrials.gov (i.e. by providing the clinicaltrials.gov identifier); 2) submission of summary results information on clinicaltrials.gov; 3) Relevant NIH trainings (e.g. GCP, human protection etc.) for applicable study personnel; 4) data sharing; and, 5) public access.

    The Chairperson is responsible for the overall conduct of the clinical trial and for providing scientific, technical, and administrative leadership to the study. He/She will have lead responsibility for planning and directing all phases of the study and for using the study's resources. In carrying out these responsibilities, the Study Chairperson will actively seek advice from all the study's components, including the representative of the NEI. The Chairperson is usually the individual who developed the idea for the clinical trial and is the leader in preparing the Manual of Procedures and organizing the study components.

    The principal investigator of each resource core center (e.g., data coordinating center, image reading center, laboratory center) will play an important role in the design, implementation, and execution of the clinical trial. Each PD/PI is responsible for all aspects of the operations of his/her resource center and for the local implementation of the study protocol. The resource core centers are involved in performing specified support functions such as training and certification of clinical center staff, designing and maintaining quality assurance programs, data management, data analysis, and preparing publications.

    The principal investigator of each participating clinical center has the primary responsibility of identifying and recruiting eligible patients at his/her center. He/She will be responsible for the follow-up, as specified in the study protocol, of each patient enrolled in the clinical study and for submitting required data to the resource center(s). The PD/PI is also responsible for ensuring that his/her clinic personnel are trained and certified to carry out study procedures.

    PD/PI are expected to publish and publicly disseminate results, data and other products of the study, concordant with governance policies and protocols and according to NIH Policies (https://grants.nih.gov/grants/policy/data_sharing/).

    Publications and oral presentations of work performed under this agreement will require appropriate acknowledgement of support by the NEI/NIH. The PD/PI must ensure that trial publications are entered in Clinicaltrials.gov by including the registered CT.gov “NCT number” to all trial publications.

    Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources, citing the name of the study or NEI support, or special access to study results, data, findings or resources requires notification and concurrence by the NEI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NEI.

    The grantee institution 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.

    NIH Responsibilities:

    An NIH Program Director, serving as Project Coordinator, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    The appropriate NEI extramural Program Director from the Division of Extramural Science Programs whose name appears on the Notice of Grant Award (NoA) will:

    Nominate members of an independent Data and Safety Monitoring Committee (DSMC). The DSMC membership will be based on recommendations from the Study Leadership and NEI program staff. Assist the Study Chairperson, Coordinating Center Director, and, when appropriate, the Executive Committee, in assuring that patient information handbooks, recruitment information, press releases, and publicity exhibits are properly prepared, approved and disseminated.

    Assist the Study Chairperson and Coordinating Center Director in the identification of additional participating clinics, if necessary, to enhance patient recruitment.

    Assist the Study Leadership Committee in site visits and routine performance monitoring of the entire study including matters of quality control within and among various components, and in the determination of inadequate patient recruitment or failure to comply with the protocol on the part of individual clinics or study core centers.  The NEI Program Director will attend and participate in study meetings as appropriate.

    Assist the Editorial/Writing Committee in the preparation and review of study results for publication.

    Assist the DSMC as an expert resource in their evaluation of safety, efficacy, quality and progress on an ongoing basis, as applicable.  Serving as a steward of federal funds, the NEI Program Official will assist but not direct deliberations and decisions of the Committee, e.g., proceeding from one phase of the study to the next; implementing protocol changes, evaluating study progress and quality including patient recruitment, overall clinical and resource center performance; monitoring study timeliness and progress toward meeting milestones, approving ancillary studies, planning data analysis; releasing unmasked data; announcing study findings; determining the timing of release of any interim or final reports; and, reviewing primary outcome manuscript(s) prior to journal submission.

    The NEI reserves the right to curtail, withhold, or terminate support for the study, for an individual award, or support for a participating consortium, in situations involving: inadequate progress toward meeting study milestones including those related to: availability and regulatory approval of study product as applicable, patient recruitment, follow-up, data reporting, or quality control; a major breach of the study protocol or NEI/NIH policy; a substantive change in the agreed-upon protocol to which the NEI does not agree; statistical evidence that the major study endpoint has been reached ahead of schedule; or, human subject ethical issues that dictate a premature termination. Prior to taking such actions, NEI will consult with and receive recommendations from the DSMC.  Additionally, the NEI Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

    Areas of Joint Responsibility Include:

    Data and Safety Monitoring Committee (DSMC)

    The DSMC is an independent group composed of individuals not directly involved in patient care or data collection for the study who are responsible for safeguarding the interests of all trial participants, assessing the safety and efficacy of the treatment during the trial, and for monitoring the overall conduct of the trial.  The DMSC receives and reviews the accruing data from the trial and provides recommendations about stopping or continuing the trial. The DSMC may also formulate recommendations to enhance the trial’s scientific integrity and timeliness including recommendations relating to the selection/ recruitment/ retention of participants, their management, improving adherence to protocol-specified treatments, and procedures for data management and quality control. The DSMC operates under the guidance of an approved Charter

    Key responsibilities of the DSMC include but are not limited to:

    • Reviewing and approving: the DSMC charter, the trial protocol, informed consent documents, methods for bias control, statistical analysis plan including methods for handling missing data and final analyses, data and safety monitoring plan including interim monitoring for safety, efficacy, and futility, data table shells, study organizational and operational procedures, study timeline and milestone plan and assessing data quality, including completeness
    • Monitoring recruitment and losses to follow-up
    • Monitoring compliance with the treatment protocol by participants and investigators
    • Evaluating study timeliness and progress toward meeting milestones, and recommending modifications as appropriate
    • Monitoring evidence for treatment differences in the main efficacy outcomes
    • Monitoring the safety of treatment (e.g. toxicity, adverse events)
    • Deciding whether to recommend that the trial continues as planned or whether recruitment or treatment should be terminated in some treatment groups
    • Reviewing proposed major modifications to the study prior to their implementation (e.g., increasing target sample size, dropping an arm based on other trial outcomes or toxicity results).
    • Suggesting additional data analyses
    • Assessing the relevance and impact of external evidence including published reports of related studies submitted by NEI, the study leadership, or DSMC members to determine whether the study needs to be changed or terminated
    • Reviewing proposals for sub- or ancillary studies for scientific merit and potential impact on the trial.
    • Ensuring the timely and accurate reporting of main results from the trial
    • Reviewing and approving the primary trial manuscript(s) with regard to determining that the results are fairly presented and the conclusions appropriate, prior to submission for publication(s) or presentation(s).

    Study Leadership Committee:

    Comprised of the Study Chairperson, PD/PIs of the Coordinating Center (s) and Resource Center(s) as applicable and the NEI representative. This committee acts as the administrative and executive arm of the study. It makes decisions on operational issues; schedules study meetings and conference calls; considers and adopts changes in study procedures as necessary; reviews and implements recommendations from the DSMC; reviews progress of the study in achieving its main goal and takes steps required to enhance likelihood of success; and, reviews data collection practices and procedures as summarized in performance monitoring reports for individual resource centers and clinical centers to identify and correct remediable deficiencies.

    Editorial Committee/Writing Committee:

    This committee has the responsibility for reviewing all study presentations, publications and for assisting in the interpretation and preparation of the main study results. Its members are the study chair, coordinating center director, the NEI representative, and several clinical center investigators, as applicable.

    Dispute Resolution:

    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 regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

    Section VII. Agency Contacts

    We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Scientific/Research Contact(s)

    Sangeeta Bhargava , PhD,
    National Eye Institute (NEI)
    Telephone: 301-451-2020 
    Email: bhargavas@mail.nih.gov

    Donald Everett, MA 
    National Eye Institute (NEI) 
    Telephone: 301-451-2020 
    Email: everettd@mail.nih.gov

    Maryann Redford, DDS, MPH 
    National Eye Institute (NEI)
    Telephone: 301-451-2020 
    Email: redfordm@mail.nih.gov

    Peer Review Contact(s)

    Anne Schaffner, PhD (NEI)
    National Eye Institute 
    Telephone: 301-451-2020 
    Email: 
    aes@nei.nih.gov

    Financial/Grants Management Contact(s)

    Karen Robinson-Smith 
    National Eye Institute (NEI)
    Telephone 301-451-2020
    Email: 
    Karen.Robinson.Smith@nei.nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    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 Part 52 and 45 CFR Part 75.

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