National Institutes of Health (NIH)
National Eye Institute (NEI)
U01 Research Project Cooperative Agreements
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
The NEI uses U01 cooperative agreement awards to support investigator-initiated early-stage clinical trials that are greater than minimal risk and typically are Phase I or II trials. The risk level of the U01 trial requires appropriate performance oversight and safety monitoring. For purposes of this FOA, the proposed study must be intended to evaluate interventions aimed at screening, diagnosing, preventing, or treating vision disorders.
Applicants are strongly advised to consult with NEI program staff prior to submitting an application with human subjects to determine the appropriate funding opportunity.
Not Applicable
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| May 24, 2022 | May 24, 2022 | September 07, 2022 * | November 2022 | January 2023 | April 2023 |
| September 23, 2022 | September 23, 2022 | January 07, 2023 * | March 2023 | May 2023 | July 2023 |
| January 24, 2023 | January 24, 2023 | May 07, 2023 * | June 2023 | October 2023 | December 2023 |
| May 24, 2023 | May 24, 2023 | September 07, 2023 * | November 2023 | January 2024 | April 2024 |
| September 22, 2023 | September 22, 2023 | January 07, 2024 * | March 2024 | May 2024 | July 2024 |
| January 24, 2024 | January 24, 2024 | May 07, 2024 * | June 2024 | October 2024 | December 2024 |
| May 24, 2024 | May 24, 2024 | September 07, 2024 * | November 2024 | January 2025 | April 2025 |
| September 23, 2024 | September 23, 2024 | January 07, 2025 * | March 2025 | May 2025 | July 2025 |
| January 24, 2025 | January 24, 2025 | May 07, 2025 * | June 2025 | October 2025 | December 2025 |
All applications are due by 5:00 PM local time of applicant organization.
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.
Not Applicable
It is critical that applicants follow the instructions in 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 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.
- Use the NIH ASSIST system to prepare, submit and track your application online.
- 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.
- Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
Purpose:
The purpose of this Funding Opportunity Announcement (FOA) is to invite cooperative agreement (U01) applications to the National Eye Institute (NEI) for early-stage clinical trials that are greater than minimal risk but are not administratively complex. Projects that are administratively complex often involve several recruiting clinical centers, an independent data coordinating center and often include resource centers. The proposed trials using this U01 mechanism typically are Phase I or II trials with strong scientific rationale and must evaluate interventions aimed at screening, diagnosing, preventing, or treating vision disorders.
Applications supported by this FOA must meet the NIH definition of a clinical trial (see NOT-OD-15-015) and must be greater than minimal risk trials. As defined in 45 CFR 46.102, a minimal risk trial is one in which the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
Background
Currently, the NEI supports mechanistic or minimal risk trials using the R01, R21, R15, and SBIR/STTR (R43/R44 and R41/R42) grant mechanisms and supports large-scale, multi-center clinical trials, human gene-transfer and stem cell therapy trials, and other complex or high resource- or safety-risk clinical trials using the UG1 cooperative agreement mechanism. UG1 clinical trials are multifaceted and typically funded as a group of single-component companion grant awards including the Chair’s Grant, the Coordinating Center, and Resource Centers, when appropriate.
This NEI Cooperative Agreement (U01) for Clinical Trials is designed to support early-stage clinical trials that are greater than minimal risk but are not suitable under NEI Collaborative Clinical Vision Research: Chair's Grant (UG1) https://grants.nih.gov/grants/guide/pa-files/PAR-21-041.html.
Scope of this Funding Opportunity Announcement:
The scope of this FOA is to support U01 applications for clinical trials to investigate the safety and/or efficacy of screening, diagnostic, preventative, or therapeutic interventions. This FOA is specifically intended for early-stage clinical trials with greater than minimal risk that meet all of the following criteria:
- Include strong preliminary and/or pre-clinical data
- Are early-stage clinical trials (generally Phase I or II trials)
Examples of appropriate studies include, but are not limited to, those designed to:
- Evaluate and optimize the dose, formulation, safety, tolerability, or pharmacokinetics of an intervention in healthy volunteers or the target population.
- Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, target engagement, dose-response trends, pharmacodynamic response) in a human proof of concept trial.
- Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, biological activity, or preliminary clinical efficacy.
- Determining the optimal outcome measure (endpoint), its variability, and/or the optimal timing of outcome evaluations in the context of the intervention.
- Establish proof-of-principle and optimize techniques, operation, and usability of a device, inform the final device design decisions, and estimate the magnitude of treatment effects.
- Collecting information on the utility of questionnaires, rating scales, or biomarkers.
Milestones
Delineation of milestones is a key characteristic of the NEI Cooperative Agreement (U01) for Early-Stage Clinical Trials with Greater than Minimal Risk. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.
Applications Not Responsive to this FOA:
The following types of activities remain outside of the scope of this FOA, and applications proposing such activities will be considered non-responsive to this FOA and will be withdrawn without review:
- Applications involving a clinical experiment that is not directly intended to evaluate a screening, diagnostic, preventative, or therapeutic intervention
- NIH-defined clinical trial applications proposing mechanistic and/or minimal risk studies
- Applications that are Phase III, large-scale, multi-center clinical trials, human gene-transfer and stem cell therapy trials, and other complex or high resource clinical trials
- Applications that propose animal studies
- Applications that lack appropriate attachments (See Other Attachments in Section IV. Application and Submission Information)
Data Monitoring and Safety Committee (DSMC):
A DSMC is required for this mechanism. 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 DSMC operates under the guidance of an approved Charter.
Programmatic Oversight:
NEI program staff will closely monitor progress in meeting the milestones of all projects funded by cooperative agreements under this FOA and will also oversee the management and reporting of adverse events and have regular communications with the PD(s)/PI(s). The NEI Program Official will participate in the DSMC meetings and will serve as a technical representative to the DSMC.
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.
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.
Renewal
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s).
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
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 from this FOA.
1. Eligible Applicants
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)
Local 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)
Federal Governments
- 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)
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.
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.
- System for Award Management (SAM) 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.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. 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 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.
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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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 instructions in 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.Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Instructions for Application Submission
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
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) that can be modified for any type of clinical trial.
The filename "ClinicalProtocol.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers.
Manual of Procedures (MOP) (optional)
A MOP may be submitted to include basic elements including, 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 information.
The filename "MOP.pdf" must 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)
In addition to the information requested in the PHS Human Subjects and Clinical Trials Information Instructions, if the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following scenarios:
(a) The protocol has been submitted under an open IND and the IND is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.
(b) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement. Under this scenario, applicants must provide documentation of an IDE or IDE supplement full approval letter from the FDA. The IDE or IDE supplement is required to be specific for the clinical trial protocol proposed (e.g., design, sample size, population, device model, etc.) and correspond with the FDA approval. Collation of multiple IDE supplement approvals for different components of the protocol is not adequate.
(c) The protocol has been submitted under an IND and is on full or partial hold. Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations. Applicants must discuss how they intend to address the hold issues and when they believe they will have FDA approval to proceed with trial implementation.
(d) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has conditionally approved the IDE or IDE supplement. Under this scenario applicants must provide full documentation from the FDA on the conditions of approval. Applicants must discuss how they intend to address these conditions and when they believe they will have FDA approval to proceed with trial implementation.
(e) A pre-submission has been submitted for FDA advice on the protocol design and intervention. Under this scenario, applications must provide the FDA response and discuss how they intend to address issues identified related to the safety, design, and implementation of the protocol.
(f) The protocol is exempt from an IND. Under this scenario applicants must provide a copy of the exemption letter from the FDA.
(g) The protocol is either exempt from the IDE regulations or does not require IDE approval because it is determined to be nonsignificant risk. Under this scenario applicants must provide either an IDE exemption letter or a copy of the risk determination letter from the FDA or IRB.
Note: Do not include the IND/IDE application, manufacturer’s product specifications, study protocol, or protocol amendments in this attachment
The filename "FDADocumentation.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers.
Data Management, Quality Assurance and Monitoring Plans (required)
This document must provide details of data management, quality assurance and monitoring plans. The description must include but is not limited to the following: methods of data entry, management procedures and systems; data coordination; data storage and security; personnel training and certification procedures; plans for handling deficiencies; participant safety monitoring including activities of the data and safety monitoring committee; appropriate oversight over the conduct of the trial including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring, regulatory submissions and compliance and quality management; policies and methods for ensuring masking of study results; data confidentiality and participant privacy; preparation of study reports and meeting minutes; other data quality control and monitoring; and, the process for locking the final dataset and sharing.
The filename "DataManagement.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers. This attachment must not duplicate information already addressed in MOP.pdf attachment.
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 must describe plans to accommodate this involvement.
Applications that lack appropriate attachments are incomplete, will not be reviewed, and will be withdrawn.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must also be included. In addition to funds required to support clinical trial conduct, the budget must reflect sufficient funds to support independent study monitoring, regulatory submissions, quality management, safety oversight activities. Costs of study drug/product, labeling, distribution must also be delineated, if applicable. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and must not be presented either as part of the requested budget or as Estimated Project Funding. NEI reserves the right to independently procure drug for the study if that offers cost or other advantages to the clinical trial.
Further information concerning budget preparation may be obtained from the Financial/Grants Management Contact(s) listed in Section VII. Agency Contacts.
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
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims:
This section must include an overview of the proposed trial highlighting its public health relevance and significance with regard to the ability to move vision science forward. State the goals of the clinical trial and the expected outcome(s). Clearly and concisely present the specific objectives of the trial, as well as a specification of the primary and/or major secondary endpoints to be measured. Provide a clear explanation of the importance of various endpoints.
Research Strategy:
Provide a detailed description of the study including the: scientific background, preliminary data and rationale for the proposed investigation.
- An overview of the state of the science, a discussion of the significance of the clinical problem(s) being studied, the need for the trial, and the potential impact of the results of the trial, discussion of how the trial will test the hypothesis(es) proposed.
- A discussion of studies that led to the proposed clinical trial and information or data from preliminary studies which address the need for and the feasibility of the trial.
- A discussion of potential biases or challenges in the protocol and how they will be addressed.
- A description of the plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.
- The appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring; regulatory submissions and compliance and quality management (this is in addition to what is in the Data Safety Monitoring Plan);
- Plans for acquisition and handling of study agent(s), if applicable.
- Demonstrated consideration of ethical issues involving the disease/condition under study.
- A discussion of activities related to the conduct, completion, and analysis of the clinical trial.
- Any anticipated impediments that could require a revision in the timeline must be identified and accompanied by a discussion of alternative approaches.
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, if applicable.
- 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.
The following modifications also apply:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
- All applications should address how datasets will be made available.
- Describe plans for supporting timely publications and dissemination of results.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
- No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 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.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 form. 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 unique entity identifier (DUNS number or UEI as required) provided 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.
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. Please see specific NEI submission information for applications requesting $500,000 or more in direct costs.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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).
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.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?
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?
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?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), 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?
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?
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.
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)?
Milestones
Are the proposed milestones feasible and well justified?
For research that involves human subjects but does not involve one of the 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 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.
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 individuals of all ages (including children and older adults) 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.
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.
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.
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.
For Renewals, the committee will consider the progress made in the last funding period.
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.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
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.
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).
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).
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.
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 may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- 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.
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.
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 recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
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 and 2 CFR Part 200.206 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 ofAward:
Thefollowing special terms ofaward are in addition to, and not in lieu of, otherwise applicable U.S. Office ofManagement and Budget (OMB) administrative guidelines, U.S. Department ofHealth and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative andfunding instrument usedfor this program will be the cooperative agreement, an"assistance"mechanism (rather than an"acquisition"mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance ofthe 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 recipientsfor theproject as a whole, althoughspecific tasks and activities may be shared among the recipients and the NIH as defined below.
Project Director/Principal Investigator (PD/PI) Rights and Responsibilities:
The PD/PI will have the primary responsibilityfor:
Defining objectives and approaches, and planning, conducting, analyzing, interpreting, drawing conclusionsfrom and publishing trial results. The design, methods, and procedures ofthe clinical trial will be detailed in a recipient-prepared and maintained, study-adopted Manual(s) ofProcedures and the recipients will have the responsibilityforfollowing the protocol
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 isformal documentation ofall 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 ofDSMC members as applicable. It is the responsibility ofthe PD/PI to ensure that their responses to safety or oversight monitoring recommendations or action items areformally reviewed and approved by the medical monitor or quorum ofthe DSMC. The PD/PI is responsiblefor ensuring that there is proper administration ofapplicable medical monitoring and/or management ofthe Committee. The PD/PI must give all medical monitors or DSMC members the name and contact information ofthe responsible NEI program director and advise them to contact the NEI program director directly with any concerns about the adequacy oftrial 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 ofthe study’s primary manuscript(s)for review and approval in advance ofjournal submission.
Implementing DSMC recommendations -Timely implementation ofsubstantive DSMC recommendations is expected.
Notifying the NEI program director within 24 hours ofanyFDA regulatory actions including: clinical hold; requestsfor modification;orterminationfor trials requiring regulatory approval.
Reporting details ofthe safety monitoring process in the grant’s annual non-competing renewal (also called RPPR). Specifically, the renewal must note: 1) actual datesfor all medical monitor or DSMC meetings as applicable; 2) verification that monitoring minutes have been reviewed and approved by the medical monitor, or quorum ofDSMC and, 3) an update on the status ofmonitoring and general medical monitor or DSMC action items.?Note: status reports must not contain any confidential study data or patient information.
NEI guidelinesfor Data and Safety Monitoring ofClinical Trials can befoundat:https://www.nei.nih.gov/grants-and-training/policies-and-procedures/guidelines-data-and-safety-monitoring-clinical-trials
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 limitedto:1) actual dates ofregulatory approvals ifapplicable; 2) date ofenrollment of1st study participant; 3) date ofClinicalTrials.gov registration, ifapplicable; 4) enrollment completion date; 5) date ofcompletion ofparticipantfollow-up; 6) date ofClinicalTrials.gov results reporting,and,7) date ofinitiation ofdata sharing.
Reporting on compliance with NIH policies related to the study. Specifically,for clinical trials, the RPPR must note the status ofor compliancewith:1) registration on ClinicalTrials.gov (i.e.by providing the clinicaltrials.gov identifier); 2) submission ofsummary 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.
ThePD/PIis responsiblefor the overall conduct ofthe clinical trial andfor providing scientific, technical, and administrative leadership to the study.He/Shewill have lead responsibilityfor planning and directing all phases ofthe study andfor using the study's resources. ThePD/PIis usually the individual who developed the ideafor the clinical trial and is the leader in preparing the Manual ofProcedures and organizing the study components.
PD/PI are expected to publish and publicly disseminate results,dataand other products ofthe study, concordant with governance policies and protocols and according to NIH Policies (https://grants.nih.gov/grants/policy/data_sharing/).
Publications and oral presentations ofwork performed under this agreement will require appropriate acknowledgement ofsupport 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 ofindustry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement ofstudy resources, citing the name ofthe study or NEI support, or special access to study results, data,findingsor resources requires notification and concurrence by the NEI. Exceptfor licensing ofpatents or copyrights,supportor involvement ofany third party will occur onlyfollowing notification ofand concurrence by the NEI.
As applicable, any therapeutic agent manufactured using NEI grant support is reservedfor either 1) the sole use oftreating participants enrolled in the NEI supported trial or 2) laboratory work attending: study product manufacture, repackaging and distribution; quality assurance (i.e.identity, potency, or other aspects ofproduct integrity); and participant safety. Any alternative use ofstudy product requires the express approval ofthe NEI.
The grantee institution will retain custody ofand have primary rights to the data and software developed under these awards, subject to Government rights ofaccess 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 Directorfrom the Division ofExtramural Science Programs whose name appears on the Notice ofGrant Award (NoA) will:
Nominate members ofan independent Data and Safety Monitoring Committee (DSMC). The DSMC membership will be based on recommendationsfrom the Study Leadership and NEI program staff. Assist thePI/PD, in assuring that participant information handbooks, recruitment information, press releases, and publicity exhibits are properly prepared, approved and disseminated.
Assist thePI/PDin the identification ofadditional participating clinics, ifnecessary, to enhance patient recruitment.
Assist thePD/PIStudy Leadership Committeein site visits and routine performance monitoring ofthe entire study including matters ofquality control,within and among various components,and in the determination ofinadequate patient recruitment orfailure to comply with the protocol.on the part ofindividual clinics or study core centers.The NEI Program Director will attend and participate in study meetings as appropriate.
Assist thePI/PDin the preparation and review ofstudy resultsfor publication.
Assist the DSMC as an expert resource in their evaluation ofsafety, efficacy, quality, and progress on an ongoing basis, as applicable. Serving as a steward offederalfunds, the NEI Program Official will assist but not direct deliberations and decisions ofthe Committee, e.g., proceedingfrom one phase ofthe 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 studyfindings; determining the timing ofrelease ofany interim orfinal reports; and, reviewing primary outcome manuscript(s) prior to journal submission.
The NEI reserves the right to curtail, withhold, or terminate supportfor the study,for an individual award, or supportfor a participating consortium, in situations involving: inadequate progress toward meeting study milestones including those related to: availability and regulatory approval ofstudy product asapplicable, patient recruitment,follow-up, data reporting, or quality control; a major breach ofthe 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 ofschedule; or, human subject ethical issues that dictate a premature termination. Prior to taking such actions, NEI will consult with and receive recommendationsfrom the DSMC. Additionally, the NEI Program Director will be responsiblefor the normal scientific and programmatic stewardship ofthe award and will be named in the award notice.
Areas ofJoint Responsibility Include:
Data and Safety Monitoring Committee (DSMC)
The DSMC is an independent group composed ofindividuals not directly involved in patient care or data collectionfor the study who are responsiblefor safeguarding the interests ofall trial participants, assessing the safety and efficacy ofthe treatment during the trial, andfor monitoring the overall conduct ofthe trial. The DMSC receives and reviews the accruing datafrom the trial and provides recommendations about stopping or continuing the trial. The DSMC may alsoformulate recommendations to enhance the trial’s scientific integrity and timeliness including recommendations relating to the selection/ recruitment/ retention ofparticipants, their management, improving adherence to protocol-specified treatments, and proceduresfor data management and quality control. The DSMC operates under the guidance ofan approved Charter
Key responsibilities ofthe DSMC include but are not limited to:
- Reviewing and approving: the DSMC charter, the trial protocol, informed consent documents, methodsfor bias control, statistical analysis plan including methodsfor handling missing data andfinal analyses, data and safety monitoring plan including interim monitoringfor safety, efficacy, andfutility, data table shells, study organizational and operational procedures, study timeline and milestone plan and assessing data quality, including completeness
- Monitoring recruitment and losses tofollow-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 evidencefor treatment differences in the main efficacy outcomes
- Monitoring the safety oftreatment (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 ofexternal evidence including published reports ofrelated studies submitted by NEI, the study leadership, or DSMC members to determine whether the study needs to be changed or terminated
- Reviewing proposalsfor sub- or ancillary studiesfor scientific merit and potential impact on the trial.
- Ensuring the timely and accurate reporting ofmain resultsfrom the trial
- Reviewing and approving the primary trial manuscript(s)with regard todetermining that the results arefairly presented and the conclusions appropriate, prior to submissionfor publication(s) or presentation(s).
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope ofthe award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed ofthree members will be convened. It will have three members: a designee ofthe Steering Committee chosen without NIH staffvoting, one NIH designee, and a third designee with expertise in therelevant area who is chosen by the other two; in the case ofindividual disagreement, thefirst member may be chosen by the recipients. This special dispute resolution procedure does not alter the recipients' 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.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
3. Reporting
When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Sangeeta Bhargava, PhD
National Eye Institute (NEI)
Telephone:301-435-8175
Email: [email protected]
Donald Everett, MA
National Eye Institute (NEI)
Telephone:301-435-8181
Email: [email protected]
Jimmy Le, ScD
National Eye Institute (NEI)
Telephone: 301-435-8160
Email: [email protected]
Brian Hoshaw, PhD
National Eye Institute (NEI)
Telephone: 301-402-0566
Email: [email protected]
Karen Robinson-Smith
National Eye Institute (NEI)
Telephone: 301-435-8178
Email: [email protected]
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.
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 and 2 CFR Part 200.
and Human Services (HHS)
