Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background 

The National Center for Complementary and Integrative Health (NCCIH) is committed to the rigorous investigation of promising complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions). These mind and body interventions are widely used by the public, and they are increasingly recognized as a nonpharmacologic approach to symptom management (e.g., chronic pain, mild depression, anxiety). These approaches can be used by individuals to help prevent, treat, or self-manage various conditions, and they can be complementary to conventional health care. 

There is a need for research to evaluate mind and body and/or multi-component approaches as they are used and delivered to determine whether they are safe and efficacious or effective for given conditions or disorders. For clinical trials to address this need, they must be well designed and test hypotheses that will guide decisions about the inclusion of these interventions or approaches into the delivery of health care for a given condition or disorder. To accomplish this goal, multisite clinical trials are needed to determine the efficacy or effectiveness in a fully powered clinical trial. NCCIH utilizes the UG3/UH3 funding mechanism to support the U24 funding mechanism to support the independent Data Coordinating Center (DCC) and the companion Clinical Coordinating Center (CCC) for the trial. 

Research Objectives of the Clinical Coordinating Center (CCC; UG3/UH3) and the Data Coordinating Center (DCC; U24) for Multisite Investigator-Initiated Clinical Trials of Mind and Body Interventions 

The National Center of Complementary and Integrative Health (NCCIH) requires companion applications to support a CCC and DCC for multisite investigator-initiated clinical trials to test the efficacy or effectiveness of mind and body or multicomponent interventions. The CCC and DCC will need to collaborate closely to develop the study protocol and select the most rigorous trial design. The CCC has clinical content expertise for the proposed intervention and study population and is responsible for implementing the proposed multisite clinical trial. The DCC has expertise in clinical trial design and conduct and is responsible for overall project coordination, and administrative, data management, and biostatistical support for the proposed clinical trial, including sample size calculations and data analysis plan. NCCIH requires that the DCC be independent from the CCC (e.g., not include overlapping personnel) in order to provide for central coordination of study activities across multiple sites while ensuring the integrity of the intervention delivery, data collection, and study blinding. 

Research Objectives for the DCC (this notice of funding opportunity NOFO) 

This notice of funding opportunity (NOFO) supports applications for a DCC  to support a corresponding investigator-initiated multisite efficacy, effectiveness, or pragmatic clinical trial (Phase III and beyond). The DCC is integral to the proficient operation of a clinical trial. The DCC contributes to the study design, ensures appropriate adverse event monitoring and reporting; manages data, masking of staff to intervention assignment, and randomization; prepares interim data reports for the Data and Safety Monitoring Board (DSMB); conducts statistical analyses; and helps with the dissemination of the results. Clinical trials require the recruitment of human participants, so it is of foremost importance to ensure patient safety; enroll men, women, and children from diverse backgrounds; and retain sufficient numbers for meaningful analysis among subgroups. 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 NOFO, multisite clinical trials are defined as trials that enroll from at least three geographically distinct recruitment sites. Two sites will be permitted if there is a strong justification for how fewer sites can still achieve generalizability and meet the NIH diversity and inclusion requirements for a  Phase III clinical trial. Multiple sites are necessary in efficacy trials to increase generalizability of findings, representativeness of the participants, and the size and diversity of the pool of eligible participants to enhance recruitment efforts. Trials for which this NOFO applies are expected to contribute to the evidence base for important health matters of relevance to the research mission of NCCIH and meet the definition of an 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 NCCIH, applicants are encouraged to consult the NCCIH website (https://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. 

Proposed clinical trials may utilize a design anywhere along the continuum between explanatory and pragmatic. For this NOFO, pragmatic trials are considered those that test an intervention under the usual clinical conditions in which it will be applied, while explanatory trials do so under more idealized circumstances. The trial design should be appropriate for the study question. 

This DCC NOFO runs in parallel with companion NOFO (PAR-24-090) that encourages applications for a collaborating CCC . Both a DCC application and a collaborating CCC application must be submitted on the same due date for consideration by NCCIH. DCC applications submitted without a collaborative CCC (UG3/UH3) will be deemed incomplete and will not be reviewed. 

Structure 

This NOFO will utilize a collaborative resources-related cooperative agreement (U24) funding mechanism and will be milestone-driven and performance-based to achieve completion of the study on time and on budget. 

Phases of Award 

The first year of the DCC will correspond with the UG3 planning phase of the collaborative CCC application, which is intended to support the development of case report forms, trial database, data quality assurance plan, study partnerships; informed consent(s); institutional review board (IRB) and DSMB approval of the trial protocol; manual of operations, project management plans, and other resources necessary to the performance of the actual clinical trial under the UH3 implementation phase of the CCC. Applications are expected to propose the design of a comprehensive clinical trial project management plan that includes consideration of feasibility of trial launch, conduct, and completion, and on-time and on-budget performance milestones. As appropriate, all necessary regulatory approvals, as well as provision of the necessary natural products, intervention providers, devices, or other necessary resources, should be obtained by the end of the UG3 planning phase to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase. Thus, proposed clinical trials are expected to be able to begin enrollment at the start of the second year of the CCC and DCC award. 

The second-year award and additional outyears of the DCC are contingent on the successful completion of milestones under the first UG3 planning phase of the collaborative CCC  and on approved transition to the second UH3 implementation phase of the CCC. The decision to proceed beyond the first year of the DCC award will be made after an NCCIH administrative review of the progress made by both the DCC and the CCC at the end of their first year. Continued support for both the DCC and CCC will be contingent on the extent to which agreed-upon milestones have been met in the first year  and on the availability of funds and scientific priorities to continue the project. If agreed-upon milestones are not met in either the UG3 or UH3 phases, NCCIH will work with the DCC and CCC to conduct an early and orderly phase-out of the project. 

Milestones 

The use of milestones is a key characteristic of this NOFO. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Applications must be driven by milestones to be reached at the end of the first year of planning and completed prior to implementation of the clinical trial. Milestones are to be objective and performance-based goals to achieve completion of the trial on time and on budget (see example milestones at https://www.nccih.nih.gov/grants/toolbox#milestone). Projects that have met the planning phase milestones will be administratively considered for continuation of the U24 and transition of the CCC from the UG3 planning phase to the UH3 implementation phase.  The DCC application should include key milestones that need to be met during the first phase of the trial (UG3 phase of the CCC) to allow for successful launch of the full trial in the second phase (UH3 phase of the CCC). In addition, the application should describe milestones that will need to be reached in the second phase of the trial to ensure the successful completion of the clinical trial and dissemination of its results.

This NOFO will support applications that utilize a series of milestones that synchronize activities between the DCC and the collaborating CCC activities needed to support the successful completion of the clinical trial. 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, negotiate a phase-out of the award and retain the option of periodic external peer review of progress. NCCIH staff will closely monitor progress at all stages for milestones, accrual, and safety. 

NCCIH policies regarding milestones and relevant clinical research/studies are described in the NCCIH Study Accrual and Retention for Human Subjects Research Policy (https://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 NOFO must adhere to the NIH 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 NOFO, all applicants are strongly encouraged to consult with the Scientific/Research contacts for the area of science of the CCC application for which a resource-related research grant is being submitted. Early contact (at least 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. 

Plan for Enhancing Diverse Perspectives (PEDP)

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV).

Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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. 

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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

This NOFO only accepts applications that are part of a collaborative set of multiple applications. A set must contain one application to this NOFO and one application to PAR-24-090

Applications with Foreign components are encouraged to read NCCIH International Health Research page. Foreign components can include foreign collaborators or consultants, but should not include foreign sites outside of the U.S. or Canada, according to NCCIH’s policy.

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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

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

To allow NIH to identify a group of applications as a related set of collaborative applications, 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 application 1 for the CCC of the set. The DCC application will be labeled 2/2.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/2, at the beginning of the title. 

Cover Letter Attachment: 

A cover letter is required for each application submitted in response to this collaborative NOFO. The cover letter should include names of the PD/Pl for both the collaborating CCC and DCC applications; the title of the projects (which should be the same in both 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 combined DCC and CCC budgets equal or exceed $500,000 in any given year, a copy of the NCCIH permission to apply letter must be attached (https://www.nccih.nih.gov/grants/policies/nccih-policy-applications-for-large-budget-clinical-trials-over-500000-in-direct-costs-in-any-year). 

SF424(R&R) Project/Performance Site Locations

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

Describe the facilities and resources available for the DCC infrastructure to support and enable the conduct of the research proposed in the multi-site clinical trial. 

SF424(R&R) Other Project Information

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

Other Attachments:

Project Management Plan

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

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 pre-defined 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 CCC, 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. 

The plan should address how enrollment data will be shared on a regular basis with NCCIH, including any proposed use of electronic enrollment data reports sent directly to NCCIH's accrual monitoring system. 

Plan for Enhancing Diverse Perspectives

• "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity
• The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
• Where possible, applicant(s) should align their description with these required elements within the research strategy section
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured
• The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.  

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

All costs requested and all changes in budgets after the first year should be clearly identified and justified. The DCC budget must be synchronized with the CCC budget. 

If parts of the trial costs 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 specific term and condition in the Notice of Award. If the Third Party support ceases and the trial is no longer tenable without the Third Party support, a close-out plan may be requested. 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. 

Specific to this NOFO: 

The application for the DCC must include only the personnel and corresponding biographical sketches for the key personnel for that application. All Key Personnel involved in the data management, analysis, and quality control of the clinical trial must provide an NIH Biosketch regardless of whether they are budgeted. The PD/ Pl (or Multi-PDs/Pls) for the companion CCC cannot be listed as key personnel in the DCC application. 

The DCC should include in their budget all costs associated with preparation of materials for DSMB meetings and travel for key personnel to all in person DSMB meetings. This includes the costs for preparing reports for the DSMB. Budgets should include costs for unmasked biostatistician(s) for generating the randomization scheme and preparing unmasked DSMB reports in addition to the study’s masked biostatistician who will conduct study analyses at the end of the trial and prepare open reports for the DSMB. An independent DSMB will be established to monitor data and oversee participant safety in the clinical trial. NCCIH and the Investigator team will determine if the DSMB will be appointed and established by NCCIH or by the Investigator team, in accordance with NIH and NCCIH policies. Applicants should provide areas of expertise of DSMB members, but not propose DSMB members in the application, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit.. 

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

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

PEDP implementation costs

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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 must present a discussion of the approach to coordination and administration, data management, biostatistical support, and data analysis. 

The following criteria must be addressed: 

Significance: Explain why the chosen study design is optimal to answer the scientific question posed for the trial described in the CCC application. Justify the appropriateness of the study sample size, power, and effect size for the trial. 

Innovation: Describe plans to employ unique or novel methodologies that will enhance the clinical trial design, management, or methods of data analysis. Describe innovation of planned approaches to project coordination and logistical support. Describe plans for utilization of current best practices to improve the knowledge and/or skills of the multi-site clinical trial. 

Approach: Describe the planned approaches to study coordination, data management (including data security procedures), data monitoring and reporting, as well as biostatistical support and include description of how these approaches will contribute to the success of the trial. Describe plans for coordination of the project, study design, data management and quality control, and provide details of the elements of the statistical analysis and milestone plans. 

Coordination: Describe plans for how the multi-site clinical trial will be coordinated including plans for providing administrative and operational support. Describe how the DCC will interact and collaborate with the CCC and individual sites, 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.). Provide details of the randomization scheme, if applicable. 

Data Management and Quality Control: Describe the approach to data management including data management systems, methods of data entry, case report forms, methods for assessing the quality and consistency of the intervention(s) and data collection; policies and methods for ensuring blinding of study results; data confidentiality and subject privacy. 

Letters of Support: 

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

Letters of support from department chairs whose support are necessary for the functions of the DCC should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating organization. 

For renewal applications, a summary of progress made during the initial funding period must be included.

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.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 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/grants/guide/notice-files/NOT-OD-00-038.html), as well as the NCCIH Guidelines for Data and Safety Monitoring (https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research). An independent DSMB will be established to monitor data and oversee participant safety in the clinical trial. NCCIH will determine if the DSMB will be appointed and established by NCCIH or by the Investigator team, in accordance with NIH and NCCIH policies.  The initial DSMB or Protocol Review Committee meeting is during the UG3 phase, and the DSMB will review the awardee’s protocol and potentially recommend modifications. The DSMB should approve the protocol prior to submitting it to the single IRB. Subsequently, the DSMB will monitor and review study recruitment and retention as well as other study information including adverse events, unanticipated problems, demographic trends, data quality, outcome data, and overall awardee performance. 

The DSMB has the responsibility to review interim 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, the DSMB's 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, generating a recommendation for study continuance, alteration or stopping. Applicants should not propose DSMB members in the application, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit. For revision and renewal applications, applicants should provide a list of the DSMB members in the application. 

Section 4 - Protocol Synopsis 

4.3 Statistical Design and Power 

Applicants must describe the Statistical Analysis Plan (SAP). If the SAP is not a part of the DCC application, both the CCC and the DCC applications will be deemed incomplete and will not proceed to peer review. The SAP should correspond to major aims of the study, and include plans for randomization, final statistical analyses; and methods for handling missing data. The power calculations must be linked to the study endpoints and to the hypothesis(es) being tested. The power calculation description should be detailed enough to allow replication of the analysis by an independent statistician. NCCIH requires a minimum of 90% power for the primary outcome. Multiplicity adjustment should be made if there are multiple primary outcomes. The effect size used in power calculations should be clinically meaningful. Plans for interim analyses should be described in detail and include plans to assess futility based on the inability of successfully completing the trial, due to poor enrollment or poor adherence to the intervention; conditions for early stopping due to such futility  or early achievement of primary clinical outcomes; plans to assess safety; and while not common, any plans to reassess or recalculate power, or modify sample size (e.g., confirm expected event rate during the trial or confirm expected Intra-class Correlation (ICC) for cluster-randomized trials). If the application is not proposing interim analyses, the application should justify why they are not planned.

For phase III clinical trials, the SAP must address plans for the analysis of intervention effect differences required by the policy unless there is clear evidence that such differences are unlikely to be seen (https://grants.nih.gov/policy/inclusion/women-and-minorities.htm).  

Studies with adaptive designs should include a pre-specified adaptation plan that specifies design type, adaptable element(s), clear decision rules and pre-specified statistical analysis boundaries. 

4.7 Dissemination Plan 

Describe how the DCC 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 demonstrate 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 three pages. 

The table columns 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 "DCC Milestone Plan.pdf' and must not exceed five pages. 

The plan should describe the key milestones that need to be met throughout the lifecycle of the clinical trial to ensure its success; the processes that will be used to reach the milestones; and a timetable identifying when each of these key milestones will be met. 

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 action strategies. Milestones should address accrual goals for individuals across the lifespan per https://grants.nih.gov/policy/inclusion/lifespan.html , and any other identified requirements for completion of the approved research. The Terms and Conditions for an award under this NOFO will include a Milestone Plan that is mutually agreed upon by the investigators and NCCIH. 

The aim of the DCC Milestone Plan is to describe the milestones that need to be met by the DCC in coordination with the UG3/UH3 activities of the CCC. The DCC Milestone Plan should include key milestones that need to be met during the first phase of the trial (UG3 phase of the CCC) to allow for successful launch of the full trial in the second phase (UH3 phase of the CCC). The Milestone Plan also needs to describe the milestones that need to be reached in the second phase of the trial to ensure the successful completion of the clinical trial and dissemination of its results. 

Since the DCC functions are developed and carried out in collaboration with the CCC, it is expected that milestones will be clearly delineated as to which will be met by the DCC and which will be the responsibility of the CCC. For those activities (e.g., protocol development) that require involvement of both the CCC and the DCC, the DCC Milestone Plan should address the aspect of the milestone that is relevant to the DCC. Synchronicity with the CCC Milestone Plan is expected (e.g., the timeline for finalization of the protocol should be the same in both the DCC and CCC milestone plans). 

The application should describe DCC milestones for the planning phase (phase 1, up to one year) which may include but are not limited to the following: 

• Final protocol and informed consent(s) 
• Clinical sites identification, including potential back-up sites 
• Final organization/communication plan 
• Pharmacy/laboratories identification (as appropriate) 
• Contracts/third-party agreements 
• Case report forms 
• Data management and sharing (DMS) plan 
• Final data and safety monitoring plan 
• Site training plan 
• Private website that provides a secure environment and the necessary data management system(s) and informatics support to acquire, store, catalog, query, and distribute documents and materials required for the successful performance of the clinical trial. 
• Final Manual of Procedures (MOP) 
• Agreements in place for product supply or provider availability including back up plans (depending on the needs of the trial). 
• Regulatory documentation needed before trial enrollment can occur, such as DSMB review, IRB approval(s), or other applicable regulatory agencies' requirements (e.g., FDA) 
• Tracking of biological samples in place including metrics and quality control 
• Listing with regular updates of clinical trial information on ClinicalTrials.gov, as per NIH policy. 

DCC milestones of particular interest during the implementation phase that should be described in the application may include but are not limited to: 

• Data safety and monitoring reports to the DSMB 
• Completion of subject assessments and data collection 
• Completion of data cleaning 
• Completion of primary data analyses 
• Completion of secondary data analyses 
• Completion and submission of primary manuscript 
• Updated project status in ClinicalTrials.gov 
• Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date 
• Implementation of Data Management and Sharing (DMS) Plan 

The aims of the DCC Milestone Plan are to describe the goals that need to be met by the DCC in coordination with the UG3/UH3 activities of the CCC. 

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications. 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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

Specific to this NOFO:

• Awards issued under this NOFO will be incrementally funded for up to 7 years. These will not be Multi-Year Funded. 
• Awards issued under this NOFO will be excluded from automatic carryover. All carryover actions will require NCCIH prior approval. 
• Awards issued under this NOFO will not be provided the authority to automatically extend the final budget period. All extensions, including the first, will require NCCIH prior approval. 
• Awards issued under this NOFO will be excluded from SNAP. 

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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 [email protected] when the application has been submitted. Please include the NOFO 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. 

This policy applies when the combined budget for the collaborative DCC and CCC applications exceeds $500,000 in direct costs in any given year. 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://www.nccih.nih.gov/grants/policies/nccih-policy-applications-for-large-budget-clinical-trials-over-500000-in-direct-costs-in-any-year). 

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: 

• Revised Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials). 
• Revised DCC 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). 
• Revised DCC Project Management Plan (e.g., due to 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). 

Applications must include annual milestones and a project management plan. Applications that fail to include annual milestones and a project management plan will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.Applications must incude a clinical trial experience table as an attachement. Applications that fail to include a clinical trial experience table will be considered incomplete and will be withdrawn before review.

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

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

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

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.

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.

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  National Advisory Council for Complementary and Integrative Health . 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 2.4.4 Disposition of Applications.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.

HHS recognizes that NIH 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 NOFO.

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 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2CFR Part 200, 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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below. 

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

Working with the CCC to finalize 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. 

Working with the CCC to establish a Trial Management Committee to coordinate and manage the project. The PD(s)/PI(s) will name investigators and staff to serve as members on a Trial Management Committee (and other subcommittees as needed). Study investigators will be required to accept and implement the common protocol and procedures approved by the Trial Management Committee. 

Implementing the core data collection method and strategy collectively decided upon by the Trial Management 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. 

Establishing 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 health professionals and patients and to avoid unnecessary expense, and (3) sufficiently staffed across the participating institutions. 

Establishing 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 PD(s)/PI(s), as applicable. NIH policies governing possible co-authorship of publications with NIH staff will apply in all cases. In general, to warrant co-authorship, 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 according to the approved sharing policies for NIH. 

Cooperating with 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." 

Submitting a detailed summary of milestones completed in the planning phase that corresponds with the UG3 phase of the CCC application. This summary should be submitted 2 months before the end of the end of the CCC UG3 phase. The submission should also include detailed plans, budget and annual milestones for the conduct of the trial for the DCC award. Note that funding of the planning phase activities of the cooperative agreement does not guarantee support of the study conduct phase of the DCC. 

Managing 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 – which 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 recipient organization or by subrecipient organization. 

Recipients 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: 

NIH will assign a Project Scientist as the point of contact to work with the PD(s)/PI(s) and participate in the Trial Management Committee to ensure the objectives of the program are being met. The primary responsibility for the program resides with the recipient, although specific tasks and activities will be shared among the recipient and the NIH Project Scientist. With the agreement of the PD(s)/PI(s), 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. 

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. 

Prior to the start of clinical activities, NIH staff will review and approve study protocols to ensure they are within the scope of peer review and for safety considerations, as required by Federal regulations. 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 participants already on-study). 

NIH will 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 their staff, periodic site visits for discussion with the recipients’ 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 Study Team/NIH 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. 

NIH staff will conduct an administrative review of the summary of milestone completion from the DCC and the CCC UH3 transition request to determine whether the project will transition to conducting the clinical trial with continued DCC funding and CCC UH3 funding. Criteria for transition to the clinical trial conductphase used in the NIH administrative review include successful achievement of the DCC and CCC UG3 milestones, potential for successfully meeting the study conduct phase plans and milestones, demonstrated ability of the team to work within the consortium arrangement, and the availability of funds. 

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. 

Areas of Joint Responsibility include: 

Close interaction between the participating grantee(s) and the PO/PS team will be required, to manage, assess, and implement the activities of the UG3 and UH3 phases. 

A Trial Management Committee organized by the PD(s)/PI(s) will be the main oversight body of the study. 

The Trial Management Committee has primary responsibility to design 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 Trial Management Committee. The Trial Management Committee will document progress in written reports to the NCCIH Program Officer and will provide periodic supplementary reports upon request. 

The Trial Management Committee will be composed of the PD(s)/PI(s), co-investigators, or staff 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 Trial Management Committee. 

The Trial Management Committee will ensure 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. 

The Trial Management Committee will develop appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health. 

A detailed data and safety monitoring plan (DSMP) will be required for the clinical trial(s) supported by the award.  

An independent data and safety monitoring board (DSMB) will be required for the  clinical trial. NCCIH and the Investigator team will determine if the DSMB will be appointed and established by NCCIH or by the Investigator team, in accordance with NIH and NCCIH policies for monitoring (https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research). 

The DSMB will play a crucial role in ensuring safety and welfare of patients enrolled in the trial. The DSMB is expected to regularly review study progress, participant safty, the quality of accumulating data, and  interim data.The study team will provide periodicdata reports, as requested, to the DSMB. 

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 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR. 

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

Recipients will provide updates at least annually on implementation of the PEDP.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition 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.

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: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Elizabeth Ginexi, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-827-0160
Email: [email protected]

Jessica McKlveen, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: [email protected]  

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected] 

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.

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 2 CFR Part 200.