Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title
Limited Competition for the Continuation or Revision of Multisite Clinical Trial Clinical Coordinating Center (Collaborative UH3 Clinical Trial Optional)
Activity Code

UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-117
Companion Funding Opportunity
PAR-21-116 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.213
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) accepts applications for competing renewal of a Clinical Coordinating Center (CCC) for ongoing clinical trials supported by NCCIH or competitive revisions to support ancillary studies to ongoing NCCIH-supported clinical trials. Extension of an ongoing clinical trial will be supported when there is a need for additional time to complete the trial or when an extended period of follow-up is well justified to assess longer term outcomes. Competitive revisions will be supported when there is compelling justification for the addition of an ancillary study to an ongoing clinical trial. The objective of the CCC is to provide the design scientific rationale and a comprehensive scientific and operational plan for the clinical trial. The CCC is expected to be responsible for project management, participant recruitment and retention strategies, performance milestones, scientific conduct, and dissemination of results. Both a Data Coordinating Center (DCC) application and a corresponding CCC application should be submitted simultaneously for consideration by NCCIH if both are needed to complete the ongoing clinical trial.

Applicants are strongly encouraged to contact the appropriate Scientific/Research contact for the ongoing clinical trial for which they are planning a competing renewal application or competitive revision prior to submitting to this FOA.

Key Dates

Posted Date
February 01, 2021
Open Date (Earliest Submission Date)
February 15, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

 

March 15, 2021; May 28, 2021; September 28, 2021; January 28, 2022; May 27, 2022; September 28, 2022; January 27, 2023; May 29, 2023; September 28, 2023

 

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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)

 

March 15, 2021; May 28, 2021; September 28, 2021; January 28, 2022; May 27. 2022; September 28, 2022; January 27, 2023; May 29, 2023; September 28, 2023

 

Scientific Merit Review

June 2021, October 2021, February 2022, June 2022, October 2022, February 2023, June 2023, October 2023, February 2024

Advisory Council Review

 

October 2021, January 2022, May 2022, October 2022, January 2023, May 2023, October 2023, January 2024, May 2024

 

Earliest Start Date

December 2021, April 2022, July 2022, December 2022, April 2023, July 2023, December 2023, April 2024, July 2024

Expiration Date
September 28, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

  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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Research Objectives

This Funding Opportunity Announcement (FOA) accepts applications for competing renewal of Clinical Coordinating Center (CCC) for ongoing clinical trials supported by NCCIH or competitive revisions to support ancillary studies to ongoing NCCIH-supported clinical trials. Extension of an ongoing clinical trial will be supported when there is a need for additional time to complete the trial or when an extended period of follow-up is well justified to assess longer term outcomes. Competitive revisions will be supported when there is compelling justification for the addition of an ancillary study to an ongoing clinical trial. The objective of the CCC is to provide the design scientific rationale and a comprehensive scientific and operational plan for the clinical trial. The CCC is expected to be responsible for project management, participant recruitment and retention strategies, performance milestones, scientific conduct, and dissemination of results. Both a Data Coordination Center (DCC) application and a corresponding CCC application should be submitted simultaneously for consideration by NCCIH if both are needed to complete the ongoing clinical trial. An independent DCC is critical to the integrity of the data collection and intervention delivery because of the need for central coordination of these activities in complex multisite clinical trials.

For this FOA, multisite clinical trials are defined as trials that enroll volunteers from two or more recruitment sites. Multiple sites are necessary for efficacy trials to increase generalizability of findings and enhance recruitment efficiency as well as representativeness of the participants. Multisite clinical trials are expected to be designed with a minimum of 90 percent power for the primary outcome in order to contribute to the evidence base for important health matters of relevance to the research mission of NCCIH and meet the definition of a NIH clinical trial (see NOT-OD-15-015, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html). For additional information about the mission, strategic vision, and research priorities of the NCCIH, applicants are encouraged to consult the NCCIH website (http://www.nccih.nih.gov). In addition to scientific relevance and excellence, these clinical trials are expected to be conducted with a high degree of efficiency, with streamlined administrative procedures wherever possible. Multisite trials will be expected to achieve the required phase III trial requirements of NIH (see: https://humansubjects.nih.gov/glossary and http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm).

Competing renewal applications for both a CCC and a corresponding DCC can be submitted simultaneously for consideration by NCCIH if both are needed to complete the ongoing clinical trial (PAR-21-116 ). If clinical trial data collection and follow-up can be completed centrally by the DCC and no study visits at clinical sites are needed, a single application for competing renewal for the DCC can be submitted.

Competitive revision applications will be accepted when there is a compelling rationale to add an ancillary study to an ongoing clinical trial. The ancillary study concept should be reviewed and approved by the ongoing clinical trial's Steering Committee and Data and Safety Monitoring Board (DSMB) to assure that the parent clinical trial will not be adversely impacted. The ancillary study should leverage the infrastructure of the ongoing trial and add new specific aim(s). The new aim(s) should be fully powered to test the hypothesis(es) and may require additional data collection, specimen collection, or procedures. The ancillary study may use some or all of the ongoing clinical trial population.

Milestones

This FOA will utilize a phased award cooperative agreement (UH3) funding mechanism and will be milestone driven and performance based to achieve completion of the study on time and on budget. Delineation of milestones is a key requirement for applications submitted under this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Milestones are to be performance-based goals to achieve completion of the trial on time and on budget.

NCCIH staff in collaboration with the awardee will closely monitor progress, milestones, accrual, and human subject safety at all stages of the project. It is strongly encouraged to develop contingency plans to proactively confront potential delays or disruptions in attaining milestones. If, at any time, recruitment falls significantly below the projected milestones for recruitment, NCCIH will consider ending support and will negotiate a phaseout of the award. Continuation of the award is conditional upon satisfactory progress in meeting milestones and on the availability of funds.

NCCIH policies regarding milestones and relevant clinical research/studies policies are described in NCCIH Accrual of Human Subjects (Milestones) Policy (https://www.nccih.nih.gov/grants/policies/SARP), NCCIH Clinical Terms of Award for Human Subjects Research (https://nccih.nih.gov/research/policies/terms-of-awards.htm), and NCCIH Policy on Data and Safety Monitoring (https://nccih.nih.gov/grants/policies/data-safety-monitoring). Clinical trials supported by this FOA must adhere to the Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-148.html).

Specific Areas of Research Interest

Prior to submitting to this FOA, all applicants are strongly encouraged to consult with the Scientific/Research contacts for the ongoing clinical trial to determine whether a competing renewal application is of interest to NCCIH. Early contact (e.g., 12 weeks prior to submission) is encouraged. This period of time provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance to the applicants.

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

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
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.

Clinical Trial?

Optional: Accepting applications that either propose or do not 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

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

If the budget exceeds direct costs of $500,000 or more in any year, applicants must follow the NCCIH policy for large budget grants to get permission to submit the application (https://nccih.nih.gov/grants/policies/over500k-clinical-trials).

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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)

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)

This FOA is limited to the current awardees of NCCIH funded UH3 Clinical Coordinating Centers for multisite clinical trials.

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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not 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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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.

Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach among groups of experts across sites and possibly collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. If the CCC competing renewal is submitted with a DCC competing renewal, PD(s)/PI(s) from each application should not be designated as multiple PDs/PIs on the other application.

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).

This FOA will accept applications that are part of a collaborative set of multiple applications (DCC competing renewal and CCC competing renewal). If companion applications are submitted, the set should contain 2 applications.

Section IV. Application and Submission Information

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.

Letter of Intent

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

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity.

The letter of intent should be sent to:

Martina Schmidt, Ph.D.

National Center for Complementary and Integrative Health
Telephone: 301-594-3456

Email: schmidma@mail.nih.gov

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.

Descriptive Title of Applicant's Project:

If the CCC renewal application will be submitted in parallel with a competing renewal for the DCC, NIH will need to be able to identify a group of applications as a related set of applications. In this situation, the titles for each application in the set must have the following format: a "1/N" indicator + Identical Title (e.g., "1/2", where the 1/2 means this is site 1 for the competing renewal CCC of the set. The competing renewal DCC site will be labeled 2/2. Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.

Cover Letter Attachment:

If the CCC renewal application will be submitted in parallel with a competing renewal for the DCC, a cover letter is required for each application submitted to this collaborative FOA. The cover letter should include names of the PD(s)/PI(s) for both the collaborating CCC and DCC applications; the title of the projects (which should be the same in both the CCC and DCC applications); and the names of applicant institutions. If applicable, the letter should indicate the name of the NCCIH program officer with whom the project has been discussed.

If the direct costs of the CCC renewal or revision budget equal or exceed $500,000 in any given year, a copy of the NCCIH permission to apply letter must be attached.

The Cover Letter is one pdf file only.

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.

Facilities and Other Resources:

Describe the facilities and resources available for the CCC infrastructure to support and enable the conduct of the research proposed in the multisite clinical trial.

Other Attachments: The attachment listed below must be completed and attached or the application will not be peer reviewed.

A Project Management Plan must be provided as an "other attachment" called "CCC Project Management Plan.pdf" and must not exceed 3 pages. The Project Management Plan should describe the evidence-based strategy that will be used throughout the project by the CCC to ensure that the unique goals of the clinical trial are met within the constraints of time and funding permitted under this FOA.

Project management planning should directly support the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet predefined study objectives. The Project Management Plan should describe how the planning team will work together and identify control points and processes that are critical for scientific and fiscal performance. This will include a description of the organizational strategy that defines internal control points and business roles. A description of the methodology, standards, and processes governing resource management, study deployment, operations/execution, and study closure should be included. The management plan should also describe how the team, in collaboration with the DCC (if applicable), will proactively evaluate and prioritize issues that could jeopardize study goals and how corrective responses will be developed to resolve fiscal and logistical issues (risk planning) in a timely manner. Describe processes required for orderly project closure. In summary, the Project Management Plan should provide sufficient detail that demonstrates the ability to achieve the goals of the clinical trial on budget and on time. The Project Management Plan should include risk management or contingency plans.

SF424(R&R) Senior/Key Person Profile

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

Biographical Sketches: The application for the CCC must include only the personnel and corresponding biographical sketches for the Key Personnel for that application. All Key Personnel must provide an NIH Biosketch whether or not they are budgeted. If the CCC application will be submitted in parallel with a renewal for the DCC, the PD/PI (or Multi-PDs/PIs) for the DCC cannot be listed as key personnel in the CCC application.

The PD(s)/PI(s) of the clinical trial must be experienced in the conduct of clinical trials and have expertise in the content area of the trial, as well as experience conducting trials under a Food and Drug Administration (FDA) Investigational New Drug (IND) application (if applicable). If a revision application is submitted, additional expertise in the area of the new scope of research should be described. The experience of all key personnel must be carefully documented. Most clinical trials will require a multidisciplinary team (clinician, statistician, data manager, study coordinator(s), etc.), and the application should reflect their roles and responsibilities in the design and implementation of the study protocol.

R&R Budget

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

If the CCC renewal application will be submitted in parallel with a competing renewal for the DCC, the CCC budget must be synchronized with the DCC budget to avoid overlap.

If parts of the costs of the trial are to be provided by sources other than NCCIH, these contributions must be presented in detail in the budget justification. Third party support of the proposed research activity (if approved) will be incorporated as a Special Award Condition. Applicants are reminded that although Cost Share is not required, if these types of costs are included in the research application and peer reviewed, it is expected that these costs will not be covered by NCCIH.

The CCC should include in their budget all costs associated with travel for key personnel to all in-person DSMB meetings. Other DSMB expenses and activities such as DSMB member travel costs, liability insurance, and conflict of interest assessment will be provided by NCCIH if the DSMB was convened by NCCIH.

The CCC should budget for the attendance of their key personnel at all in-person steering committee meetings in collaboration with the DCC.

Include budget support for publication, data sharing, and dissemination of results.

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:

Research Strategy

Note: Discuss the following without duplicating information collected in the PHS Human Subjects and Clinical Trials Information Form.

The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application shouldpresent a discussion of the approach to coordination and administration, data management, biostatistical support, and data analysis.

The application from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration. If the CCC application will be submitted in parallel with a renewal for the DCC, all variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site." In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration for trial completion.

The following criteria must be addressed:

Significance: The significance of the proposed clinical trial and importance of the question must be clearly stated. It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and why there is clinical equipoise. The application should make clear the need for and timeliness of the study with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area. A discussion of the costs and benefits of the study should be included for evaluation of the trial's significance. For renewal applications, describe the reasons for why additional time is needed to complete the trial or why extended follow-up for longer term outcomes is important. For revision applications, provide a description of what additional knowledge will be gained in the ancillary study.

Innovation: Explain how the application challenges and seeks to shift current research or clinical practice paradigms.

Approach: The research approach section should include a description of the supporting data (including strengths and weaknesses of the published literature), clinical trial experience, the experimental approach, and a milestone plan.

Coordination: Describe plans for how the multisite clinical trial will be coordinated including plans for providing administrative and operational support. Describe how the CCC will interact and collaborate with the DCC and individual sites (if applicable for the competing renewal), including transmission of data in an accurate and timely fashion.

Study Design: Describe the proposed experimental approach including a discussion of the clinical trial design and the rationale for the particular design chosen (pragmatic, explanatory, cluster-randomized, adaptive, etc.).

Progress of Ongoing Clinical Trial: Provide a summary of the ongoing clinical trial's progress including recruitment, retention, and timeline for study completion. Describe any changes that have been made to the study design, sample size, or power calculations during the course of the prior funding period. Provide a description of any recommendations from the trial's DSMB, such as need for extended follow-up or longer term outcome assessments.

Letters of Support:

Letters of support from institutions with a key role in the study must be provided. Include copies of letters from the latest DSMB meeting, such as recommendation for the continuation of the trial or any recommended changes in study duration of period of follow-up.

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.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.

  • 2.5 Recruitment and Retention Plan
  • 3.3 Data and Safety Monitoring Plan
  • 3.5 Overall Structure of the Study Team
  • 4.7 Dissemination Plan
  • 5.1 Other Clinical Trial-related Attachments

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe the following: 1) the planned recruitment methods including use of contact lists, databases or other prescreening resources, advertisements, outreach, media / social media, and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants. Investigators are encouraged to review the NCCIH Study Accrual and Retention Plan policy (https://nccih.nih.gov/grants/policies/SARP).

Applicants must provide strong evidence of the availability of appropriate institutional resources and suitable patient populations. Documentation of availability of eligible subjects at clinic sites, presented in tabular format, must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the clinical study or trial. Specifically, applicants must provide evidence that each recruiting center in the study or trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multisite applications, information must be provided for each participating site.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

In addition to the NIH application requirements for a data and safety monitoring plan for clinical trials, NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to NIH's policy on data and safety monitoring (https://grants.nih.gov/policy/humansubjects/policies-and-regulations/data-safety.htm), as well as the NCCIH Guidelines for Data and Safety Monitoring (https://nccih.nih.gov/grants/policies/data-safety-monitoring). The independent DSMB will continue to monitor data and oversee participant safety in the clinical trial. The DSMB has the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early. Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to NCCIH. The DSMB will meet in person or by phone at least twice a year.

3.5 Overall Structure of the Study Team

The Overall Structure of the Study Team attachment should describe the study organization and administration and include a communication plan. The attachment can include but is not necessarily limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any subcontractors or providers of services, personnel, or facilities. The plan should explain how these will integrate with the organizational framework described in the DCC application and should address how the CCC and DCC will coordinate leadership for clinical trial implementation. The communication plan should include a description of the coordination between the separate components including NCCIH and identify the key channels used to reach and inform each stakeholder group and receive feedback. The organization plan should also describe how disputes will be resolved between the CCC, DCC, and all stakeholders.

Section 4 - Study Design

4.7 Dissemination Plan

Describe how the CCC will facilitate and support timely publication and dissemination of results as appropriate and consistent with achieving the goals of the program.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

The following attachments must be included as a part of the collaborative application. Attachments permit expansion but not duplication of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Experience

Applicants must provide a detailed table listing the characteristics of trials that demonstrates experience of the study Key Personnel in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf" and must not exceed 3 pages. If more than one study record is submitted the files should be named "Clinical Trial Experience 1.pdf"; "Clinical Trial Experience 2.pdf"; etc.

The table should include:

  • clinical trial title
  • applicant's role in the trial
  • a brief description of the trial design
  • planned enrollment
  • actual enrollment
  • number of sites
  • whether the trial(s) were completed on schedule or not
  • publication reference(s)

.

2. Milestone Plan

A Milestone Plan must be provided as an attachment called "CCC Milestone Plan.pdf" and must not exceed 5 pages.

The plan should describe the key milestones that need to be met throughout the lifecycle of the clinical trial to ensure its success, describe the processes that will be used to reach the milestones, and provide a timetable identifying when each of these key milestones will be met (this can be provided as a table or a graph).

All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable. The Milestone Plan should include anticipated challenges to meeting milestones and propose potential mitigation or corrective actions strategies. Milestones should address accrual goals for women, minorities, and children and any other identified requirements for completion of the approved research. The Terms and Conditions for an award under this FOA will include a Milestone Plan that is mutually agreed upon by the investigators and NCCIH.

The aim of the CCC Milestone Plan is to describe the milestones that need to be met by the CCC in coordination with the activities of the DCC, if applicable, for the completion of the ongoing clinical trial. The Milestone Plan needs to describe the milestones that need to be reached to ensure the successful completion of the clinical trial and dissemination of its results, or for the completion of the proposed ancillary study in a revision application.

If the CCC renewal application will be submitted in parallel with a renewal for the DCC, it is expected that milestones will be clearly delineated as to which will be met by the CCC and which will be the responsibility of the DCC.

CCC milestones of particular interest during the conduct of the clinical trial and follow-up that should be described in the application may include but are not limited to:

  • Target dates for enrollment of 10, 25, 50, 75, and 100 percent of the projected recruitment for all study participants, including women, minorities, and children (as appropriate)
  • Assessment of site(s) protocol implementation performance
  • Collection of data related to primary and secondary endpoints and database lock
  • Collection of data for ancillary studies
  • Submission of primary manuscript to peer-reviewed scientific journal
  • Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date
  • Data sharing plan for study data and biospecimens (if applicable).

During the award, achievement of each milestone for the UH3 will need to be communicated to the NCCIH Program Officer listed on the Notice of Award. Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. If, at any time, recruitment, as defined in the NCCIH Study Accrual and Retention Plan (https://nccih.nih.gov/grants/policies/SARP), falls significantly below projections, or core milestones mutually agreed upon by the PD(s)/PI(s) and NCCIH are not met, the Center may consider ending support and negotiating an orderly phaseout of the award. NCCIH retains, as an option, periodic external peer review of progress. NCCIH staff will closely monitor progress at all trial stages including milestones, accrual, and safety.

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.

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. If the UH3 renewal is submitted with a companion U24 application, each application of a collaborative set must be on-time. Considerations for late applications that are based on the institution or PD/PI apply only to his/her individual application.

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 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or noncompliant, will not be reviewed. Each application of a collaborative set must be complete and compliant.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at schmidma@mail.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.

If the application is submitted with a companion U24 renewal application, the combined budgets of the UH3 and U24 will be used to determine whether the policy regarding direct costs of $500,000 or more in any year will be applied. Applicants requesting $500,000 or more in direct costs need to follow the NCCIH process for large budget grants to get permission to submit the application (https://nccih.nih.gov/grants/policies/over500k-clinical-trials).

Applicants requesting $500,000 or more in direct costs need to follow the NCCIH process for large budget grants to get permission to submit the application (https://nccih.nih.gov/grants/policies/over500k-clinical-trials).

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.

In addition to the NIH policy-allowed post-submission materials in NOT-OD-19-083, the following post-submission materials are allowed:

  • Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials
  • CCC Milestone Plan (e.g., due to new recommendations from the DSMB; the hiring, replacement, or loss of an investigator; change to health care systems participating in the trial; or change in electronic health record or IT infrastructure).

Section V. Application Review Information

1. Criteria

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 a study design, methods, and an 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.

For this particular announcement, note the following:

If the DCC application will be submitted in parallel with a competing renewal for the CCC, the applications will be reviewed together. Reviewers will emphasize the overall feasibility of the project and whether the competing renewal of the clinical trial will answer a key scientific question. Each application will be scored separately.

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 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?

For this specific FOA:

If the primary outcomes of the trial are achieved, how critical will the information be to addressing the evidence gap and advancing knowledge of theory and practice? Could results of the trial have a significant influence on clinical care and improve health? Is there sufficient demonstration for the presence of equipoise? Is there a sufficient and consistent body of relevant preclinical or clinical research of high scientific rigor to support the study rationale? For renewal applications, how well have the investigators justified the need for additional time to complete the trial or extend follow-up of participants for longer term outcomes?

In addition, for applications involving clinical trials

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?

For this specific FOA:

How well defined are their roles and responsibilities? Have the investigators provided sufficient evidence to ensure that the clinical centers will employ the appropriate personnel to recruit subjects and implement the clinical protocol? How strong is the plan for leadership and coordination of roles/responsibilities for CCC leadership? How well does the application provide evidence of necessary experience and expertise of the investigators with the intervention, the study population, and the research methods to be employed? How strong is the evidence to ensure that the clinical centers will employ the appropriate personnel to recruit subjects and design/implement the clinical protocol? Does the investigative team have a track record of publishing the results of clinical trials previously completed?

In addition, for applications involving clinical trials

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?

Specific to this FOA:

For Phase III clinical trials, has the investigator sufficiently described how the proposed clinical trial will change clinical practice or practice guidelines? Does the proposed research have the potential to advance the field even if the proposed study design, methods, and intervention are not innovative?

In addition, for applications involving clinical trials

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?

Approach

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?

In addition, for applications involving clinical trials

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?

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?

Specific to this FOA:

How strong are the facilities and resources and does the investigator sufficiently justify they are available to adequately coordinate multisite clinical trials? Is there strong evidence that the institutions have the available resources needed to conduct a multisite trial at the CCC and the performance sites? How well does the application document the availability of the requisite eligible subject pool at proposed clinical site(s)? Is there sufficient documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

In addition, for applications involving clinical trials

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.

Milestones

Are the specific milestones proposed measurable, achievable, and reasonable, so that the milestones will be achieved in the time frame proposed? Does the CCC application adequately address contingency plans? How well do the contingency plans proposed support the overall program if problems are encountered? Are the listed milestones appropriate for the CCC?

Organization

Is the proposed organizational structure appropriate? Does the applicant adequately address the integration of the CCC in the organizational structure and the impact it will have on the scientific goals of the project? What is the quality of the Project Management Plan? How well does the application provide details to facilitate clear communication and coordination between the CCC and DCC (if applicable)?

Study Timeline

Specific to applications involving clinical trials
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 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

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

Not Applicable

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 NCCIH, 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.

Applications will be assigned on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. 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.

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 recipient'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 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 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, Recipients, 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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.

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 “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

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 reside with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • Research design and protocol development, including definition of objectives and approaches, planning, implementation, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.
  • Continuing the activities of the Steering Committee to coordinate and manage the project. The PD(s)/PI(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Study investigators will be required to accept and implement the common protocol and procedures approved by the Steering Committee.
  • Working with the DCC to implement the core data collection method and strategy collectively decided upon by the Steering Committee. It is the responsibility of each clinical site to ensure that data will be submitted in a timely way to the study's data entry system according to the study protocol. Additionally, sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.
  • Working with the DCC to maintain mechanisms for quality control and monitoring. The recipients are responsible for ensuring accurate and timely assessment of the progress of the study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis, (2) as simple as appropriate in order to encourage maximum participation of physicians and patients and to avoid unnecessary expense, and (3) sufficiently staffed across the participating institutions.
  • Continuing procedures, where applicable, for all participating institutions to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects and the NIH policy requirements for the inclusion of women, minorities, and children.
  • Cooperating in the reporting of the study findings. NIH will have access to and may periodically review all data generated under an award. Where warranted by appropriate participation, plans for joint publication with NIH of pooled data and conclusions are to be developed by the Principal Investigator or Steering Committee, as applicable. NIH policies governing possible coauthorship of publications with NIH staff will apply in all cases. In general, to warrant coauthorship, NIH staff must have contributed to the following areas: (a) design of the concepts or experiments being tested, (b) performance of significant portions of the activity, and (c) preparation and authorship of pertinent manuscripts.
  • Overseeing the overall budget, activities, and performance of the cooperative agreement. Accepting the participatory and cooperative nature of the collaborative research process and complying with policies and practices of NCCIH.
  • Sharing data, resources, and software as appropriate and consistent with achieving the goals of the program and the approved sharing policies for NIH.
  • Cooperating with the NIH staff and contracted on-site monitors in the design and conduct of protocols, analysis of data, and reporting of results of research.
  • Agreeing to accept close coordination, cooperation, and management of the project with NIH, including those outlined below under "NIH Responsibilities."
  • Support or other involvement of industry or any other third party in the study—e.g., participation by the third party; involvement of study resources or citing the name of the study or NCCIH or other NIH Institute or Center support; or special access to study results, data, findings, or resources—may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
  • Any of the above functions may be performed by the applicant organization or by subcontract to the applicant organization.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

  • The NIH will assign a Project Scientist as the point of contact to work with the PD(s)/PI(s) and participate in the Steering Committee to ensure the objectives of the program are being met. The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the NIH Project Scientist. With the agreement of the Principal Investigator, the NCCIH Project Scientist or designee may assist in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data, in the preparation of questionnaires and other data recording forms, and/or in the publication of results.
  • The NIH will assign a Program Officer who will be responsible for retaining overall programmatic responsibility for the award, and will clearly specify to the recipient the name(s) and role(s) of any additional individuals with substantial involvement in the project and the lines of reporting authority.
  • NCCIH may designate additional staff to provide advice to the recipient on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the recipients to optimize the conduct and/or analysis of the study or who may assist in the coordination of activities across multiple sites.
  • NIH will monitor protocol progress and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete the study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. NIH will not permit further expenditures of NIH funds for a study after requesting closure (except for patients already on study).
  • Serve as a resource with respect to other ongoing NIH activities that may be relevant to the protocol to facilitate compatibility and avoid unnecessary duplication of effort.
  • NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(s) and his/her staff, periodic site visits for discussion with the awardees' research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship activities. NCCIH may designate NIH staff or contractors to conduct site initiation, interim, and closeout site visits
  • NIH reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting.
  • NIH staff will provide input, expert advice, and suggestions in the design, development, and coordination and implementation of the study objectives.
  • NCCIH staff will make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

  • A Steering Committee organized by the Principal Investigator will be the main oversight body of the study.
  • The Steering Committee has primary responsibility to design and conduct research activities; establish priorities; develop common protocols and manuals, questionnaires, and other data recording forms; establish and maintain quality control among recipients; review progress; monitor patient accrual; coordinate and standardize data management; and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NCCIH Program Officer and will provide periodic supplementary reports upon request.
  • The Steering Committee will be composed of the PI(s)/PD(s) and coinvestigators as deemed necessary, such as the study biostatistician and trial manager, the NCCIH Project Scientist, and additional designees of NIH. The NCCIH Project Scientist or designee will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NCCIH Program Officer will serve as an "ex officio" member of the Steering Committee. The Steering Committee will typically meet in person twice in the first year of the award and then at least yearly thereafter. More frequent phone meetings will occur as required during the award period. The first in-person meeting will occur before clinical activities begin.
  • Ensuring that sites and investigators as well as NIH and other research partners fully comply with federal regulatory requirements. This includes but is not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
  • Jointly developing appropriate confidentiality procedures for data collection, processing, storage, and analysis to ensure the confidentiality of data on individual health.
  • A Data and Safety Monitoring Plan will be required for the project. An independent DSMB may be appointed and established by NCCIH for the clinical trial, in accordance with NIH and NCCIH policies for monitoring (https://nccih.nih.gov/grants/policies/data-safety-monitoring). The DSMB will play a crucial role in ensuring safety and welfare of patients enrolled in the trial, will regularly review study progress and some interim data, and will provide recommendations to NIH. During the award the recipient will provide interim data and reporting, as requested, to the Board as outlined in NCCIH Guidelines (https://nccih.nih.gov/research/policies/datasafety).

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and 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, 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Wendy Weber, N.D., Ph.D., M.P.H.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-402-1272
Email: weberwj@mail.nih.gov

Peer Review Contact(s)

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: schmidma@mail.nih.gov

Financial/Grants Management Contact(s)

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: carows@mail.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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