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

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

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

Research Objectives

This FOA supports applications for a collaborating Data Coordinating Center (DCC) for investigator-initiated multi-site clinical trials (Phase II and beyond). The DCC is integral to the proficient operation of a clinical trial. The DCC contributes critically to the study design, ensures appropriate adverse event monitoring and reporting, manages data, conducts statistical analyses, and helps with the dissemination of the results. Often the data are randomized and blinded and the DCC holds the key to the codes. Thus an independent DCC is a necessary component of any multi-site trial in order to ensure integrity of data. Clinical trials require the recruitment of human participants, so it is of foremost importance that patient safety and inclusion of men, women, and children from diverse backgrounds be considered.

Multi-site clinical trials are defined as trials that enroll from two or more recruitment sites. Trials for which this FOA applies are expected to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI and meet the definition of an NIH clinical trial (see NOT-OD-15-015). For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website. 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 FOA, 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 FOA runs in parallel with a companion FOA (PAR-18-407) that encourages applications for a collaborating Clinical Coordinating Center (CCC). Both a DCC application and a collaborating CCC application must be submitted on the same due date for consideration by NHLBI. DCC applications submitted without a collaborative CCC (UG3/UH3) will be deemed incomplete and will not be reviewed. Applicants are encouraged to use the Compendium of Best Practices for Data Coordinating Centers as a reference tool: https://www.nhlbi.nih.gov/research/resources/compendium.

Structure

This FOA will utilize a collaborative resources-related cooperative agreement mechanism and will be milestone-driven and performance-based to achieve completion of the clinical trial on time and on budget. Applicants are strongly encouraged to employ project management principles as appropriate.

Phases of Award

The first year of the DCC will correspond to the UG3 phase of the collaborative CCC application (PAR-18-407) and is intended to support the development of case report forms and other resources necessary to the performance of the clinical trial; further development of study partnerships; finalization and subsequent approval of Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), manual of operations, and project management plans. Applications that address a comprehensive clinical trial project management plan that includes consideration of feasibility of trial launch, conduct, and completion, and also on-time and on-budget performance milestones are strongly encouraged. All necessary regulatory approvals, as well as provision of the necessary drugs, devices or other resources, should be obtained by the end of the UG3 award to allow for the successful launch and execution of the proposed clinical trial in the UH3 phase. In addition, proposed clinical trials are expected to be able to begin enrollment no later than by the end of the first year of the DCC award.

The second year of the DCC award is contingent on the successful completion of the UG3 phase of the collaborative CCC application and corresponds to the first year of the UH3 phase of the CCC. The decision to proceed beyond the first year of the DCC award will be made after administrative reviews of the progress made by both the DCC and the CCC at the end of the first year with particular attention paid to the extent to which agreed-upon milestones have been met and subject to the availability of funds. An additional administrative review will be scheduled for the DCC award within the first two years of the start of the collaborative CCC UH3 (if the UH3 phase is funded). Due to the collaborative and parallel nature of these FOAs, NHLBI will enter into negotiation with the DCC to achieve mutually agreed-upon early phase-out of the award.

Milestones

Delineation of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. It is anticipated that applications will include a description of the milestones that will be reached at the end of the UG3 phase. Milestones are to be performance-based to achieve completion of the trial on time and on budget.

This FOA will support applications that include a series of milestones for synchronized activities designed to support the successful completion of the collaborating CCC activities. NHLBI staff in collaboration with the awardee will closely monitor progress at all stages, milestones, accrual, and safety. It is strongly encouraged that applications include contingency plans to proactively confront potential delays or disturbances in meeting the milestones. If, at any time, CCC recruitment falls significantly below the projected recruitment milestones, the NHLBI will consider ending support and negotiating a phase-out of the award. Continuation of the award is conditional upon satisfactory progress in meeting milestones and subject to the availability of funds.

NHLBI policies regarding milestones and relevant clinical research/studies policies are described in NHLBI Accrual of Human Subjects (Milestones) Policy, NHLBI Policy for Inclusion of Women and Minorities in Clinical Research, and NHLBI Policy for Data and Safety Monitoring of Extramural Clinical Studies).

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 area of science of the CCC application for which resource-related research grant is planning to support. Early contact (at least 12 weeks prior to submission) is encouraged. This period of time provides an opportunity for NHLBI staff to discuss the scope and goals, and to provide information and guidance to the applicants.

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

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

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

Applicant Organizations

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

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

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

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

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.

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

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).

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

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

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

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:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Email: [email protected]

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

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.

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

Descriptive Title of Applicant's Project: 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., "1/3", where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.

Cover Letter Attachment: A cover letter is required for each application submitted to this collaborative FOA. The cover letter should include names of the PD/PI(s) for both the collaborating CCC and DCC applications and the names of applicant organizations.

If the direct costs of the combined DCC and CCC budgets equal or exceed $500,000 in any given year, a copy of the NHLBI approval letter must be attached.

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

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

Facilities and Other Resources: 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.

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants must include personnel and corresponding biographical sketches for the DCC only. All Key Personnel who are major contributors to the study must provide an NIH Biosketch whether or not they are budgeted. The PD/PI (or Multi-PDs/PIs) for the DCC cannot be Key Personnel on the CCC application.

The PD/PI (or Multi-PDs/PIs) of the DCC must be experienced in the conduct of multi-center clinical trial coordination and management, including success in meeting milestones and timelines. The experience of each PD/PI and all Key Personnel must be carefully documented and roles and responsibilities must be well-defined. DCCs require a multidisciplinary team and the application should reflect the team's hands-on involvement in DCC functions, including coordination, tracking, logistics and administration, communications, data management (including quality control), data security and IT infrastructure (including development of public and secure study websites), regulatory support, and biostatistical/analytical support.

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

The application must include only its own budget, including any subcontract budgets associated with it. Separate itemized budgets must be prepared for each subcontract. The application must provide detailed annual budgets that will enable the DCC to meet its milestones.

Any cores (e.g., economics/quality of life) must be a subcontract to either the DCC or CCC. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating center or core.

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 costs of the trial are to be provided by sources other than NHLBI, 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 NHLBI.

The DCC should include in their budget all costs associated with DSMB activities. This includes the costs for preparing reports for the DSMB and meeting reimbursement for the DSMB members. The DCC should assess the need for liability insurance for DSMB members and provide a plan commensurate with the risk of the trial. The budget should include provision for executing the plan proposed. The DCC should also include a plan for assessing DSMB member conflict of interest, and put associated costs in the budget. Additionally, if the DSMB is convened by NHLBI, the DCC should include in their budget coordination of support for at least one DSMB meeting per year (by teleconference or videoconference).

Include budget support for personnel to travel to a yearly in-person Steering Committee meeting and/or other meeting of investigators and NHLBI program staff to be held in the Washington, D.C. area.

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

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

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

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

Research Strategy: The Research Strategy must present a discussion of the ways in which the DCC plans to provide expert assistance in protocol design and analysis plans, and feasibility assessments. The following criteria must be addressed:

Significance: Explain why the chosen study design is optimal to answer the scientific questions posed for the trial described in the CCC application.

Innovation: Describe plans to employ unique or novel methodologies that will enhance the clinical trial design, management, or methods of data analysis. Describe how the DCC plans to utilize current best practices to improve the knowledge and/or skills of the multi-site clinical trial it will support.

Approach: Describe how the multi-site clinical trial will be coordinated including plans for providing administrative and operational support. Describe the communications strategy including how the DCC will interact with the CCC and individual sites, how data will be transmitted in an accurate and timely fashion, and how the DCC will establish accessible and secure methods of communication. Describe the DCC contributions to protocol design. Provide plans to assess recruitment feasibility using available data on the target population from registries and prior studies to the extent possible.

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, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Only the following fields are required:
1.1 Study Title
1.2 Is this Study Exempt from Federal Regulations?
1.3 Exemption Number (if applicable)
1.4 Clinical Trials Questionnaire
2.1 Conditions or Focus of Study
2.4 Inclusion of Women, Minorities, and Children
2.7 Study Timeline

3.1 Protection of Human Subjects

3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

3.3 Data and Safety Monitoring Plan

4.2.a. Narrative Study Description

4.4 Statistical Design and Power

4.7 Dissemination Plan

5.1 Other Clinical Trial-related Attachments

Section 2 - Study Population Characteristics

2.1 Conditions or Focus of the Study

The information provided for Conditions or Focus of Study must be the same as that provided in the collaborating CCC application.

2.4 Inclusion of Women, Minorities, and Children

The information provided for Inclusion of Women Minorities and Children must be the same as that provided in the collaborating CCC application.

2.7 Study Timeline

Include estimated time of study duration (in months) including but not limited to when: (a) database will be created; (b) first patient data will be entered; (c) final data analyses will be finished and database locked; and (d) closeout and dissemination are to occur.

Key Milestones. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, measurable, results-focused and time-bound. Milestones must address timing of overall recruitment/enrollment and retention goals. The milestones must address accrual goals for women, minorities and children and any other identified requirements for completion of the approved research.

As is appropriate for the goals of the project, describe the key milestones that need to be met throughout the lifecycle of the clinical trial (UG3 and UH3 phases) 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.

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). It is anticipated that at least one participant must be enrolled by the end of the first phase, as well as about 25% of participating sites activated, so that accrual targets can be met by the end of the second phase. 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 in collaboration with the CCC, it is expected that milestones will be clearly delineated as to which will be performed under the DCC and which will occur under 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 them. However, 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.

During the implementation phase (up to one year) the DCC milestones may include but are not limited to the following:

• Final protocol and informed consent template(s)
• Clinical sites identification, including potential back-up sites
• Final organization/communication plan
• Pharmacy/laboratories identification
• Contracts/third party agreements
• Case Report forms
• Final data management 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, catalogue, 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 including back up plans.
• Regulatory documentation needed before trial enrollment can occur such as, DSMB review, IRB approval(s), or other applicable regulatory agencies' requirements
• Automated 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.
• First phase/second phase (corresponding to the UG3/UH3 transition) meeting

DCC milestones of particular interest during the execution phase of the clinical trial 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
• Update project status in ClinicalTrials.gov
• Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date
• Plans for transfer of data to a clinical trials database through tools provided by the NHLBI at the time of award
• Implementation of data sharing

Section 3 - Protection and Monitoring Plans

3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

If Yes, describe the single IRB Plan

The information provided for the Single IRB Plan must be the same as that provided in the collaborating CCC application.

3.3 Data and Safety Monitoring Plan

Specify criteria for adverse events reporting, intervention discontinuation and stopping guidelines.

Section 4 - Protocol Synopsis

4.2.a Narrative Study Description

Describe the proposed experimental design 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.

4.4 Statistical Design and Power

Provide content requested with respect to each outcome measure listed in Question 4.3 "Outcome Measures" of the collaborating CCC application. Justify the proposed sample size based on appropriate study assumptions, event rates, and power calculations. Justify the event rate and provide contingency plans should the event rate or effect size be underestimated. The calculations must be linked to the study endpoints and to the hypothesis(es) being tested. Explain how the outcome(s) will address the hypothesis(es) being tested. Provide details of the randomization scheme, if applicable. Describe plans for interim and final analyses; methods of bias control; and methods for handling missing data (as applicable). The description should be detailed enough to allow replication of the analysis by an independent statistician.

Adaptive designs should include a pre-specified adaptation plan that allows for clear go/no-go decisions and pre-specified analysis boundaries.

For Phase III clinical trials, include plans for evaluation of the primary outcome(s) by race/ethnicity and gender, and include all relevant data to assess whether or not the trial includes adequate numbers for valid analyses of subgroups. In addition, justify adequacy of power to analyze subgroups of participants.

The approach to data management must include, but is not limited to, a description of:

• Data management systems;
• Methods of data entry and cleaning;
• Event tracking and logistics
• Biospecimen tracking
• Case report forms;
• Methods for quality assurance and quality control;
• Methods for monitoring the quality and consistency of intervention(s);
• Test, validate and optimize data capture systems;
• Policies and methods for ensuring blinding of study results;
• Data confidentiality and subject privacy;
• Plans for data and IT security at each site;
• Disaster recovery plans;
• Adjudication of events (as needed);
• Data analysis reports.

4.7 Dissemination Plan

The information provided for Dissemination Plan must be the same as that provided in the collaborating CCC application.

The dataset should be prepared in accordance with requirements for NHLBI data repository datasets and associated documentation for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) and the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, and in accordance with the Guidelines for NHLBI Data Set Preparation.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Research Experience: Applicants must provide a detailed table listing the characteristics of trials that demonstrate experience in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Research Experience.pdf" and may not exceed 3 pages.

The table columns must include:

Column A: clinical trial title

Column B: applicant's role in the trial

Column C: a brief description of the trial design

Column D: planned enrollment

Column E: actual enrollment

Column F: number of sites

Column G: whether the trial(s) were completed on schedule or not

Column H: publication reference(s)

2. Project Management Plan: A Project Management Plan must be provided as an attachment called "Project Management Plan.pdf" and may not exceed 3 pages. The Project Management Plan should describe the strategy that will be used throughout the project by the DCC to ensure that the unique goals of the clinical trial are met.

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:

• The role of the project manager;
• The project's critical path to meet scientific objectives within budgetary limits;
• Business roles, executive decision-making, and accountability standards;
• The contingency plans in the event that there is inadequate progress toward achieving the milestones of the DCC or CCC application;
• Key methodology and standard operating procedures governing resource management, study deployment, operations/execution, and study closure;
• How the project management team, in collaboration with the CCC, will resolve fiscal and logistical issues in a timely manner including plans to pro-actively evaluate and prioritize study risks and issue corrective responses;
• Processes required for orderly project closure including how data and specimens will be handled.

In summary, the project management plan must provide sufficient detail to demonstrate the ability to achieve the goals of the clinical trial on-budget and on-time and to successfully manage and mitigate risks.

Delayed Onset Study

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

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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.

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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 year.

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

Important Update: See NOT-OD-18-228 for updated inclusion and human subjects review language for due dates on or after January 25, 2019.

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

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

For this particular announcement, note the following:

Reviewers will consider the overall feasibility of the project and whether the clinical trial will answer a key scientific question and be completed on time and within the proposed budget.

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.

How strongly does the proposed DCC address the needs of the research program that it will support? Is the scope of activities proposed for the DCC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program?

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

Are the PD(s)/PI(s), collaborators, and other researchers well suited to their roles in the DCC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing DCCs? Do the investigators demonstrate significant experience with coordinating collaborative research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

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?

Specific to this FOA

How strong is the Clinical Trial Experience attachment in demonstrating the expertise of the personnel to conduct the proposed trial? How strong are PDs/PIs and Key Personnel experience and capability to manage the DCC of a multi-center trial and meet milestones and timelines? How well defined are their roles and responsibilities? How strong is the project management expertise represented among the key personnel? Do the PDs/PIs and Key Personnel have the experience and capability in multidisciplinary DCC functions including coordination, tracking, logistics and administration, communications, data management (including quality control), data security and IT infrastructure (including development of public and secure study websites), regulatory support, and biostatistical/analytical support?

Does the application propose novel organizational concepts, management strategies, or electronic and information technologies to support multi-site clinical trial conduct? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

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

Specific to this FOA

Does the application propose innovative and useful approaches to clinical trial design, management, or methods of data analysis? Where appropriate, does the proposed DCC utilize current best practices to improve the knowledge and/or skills of the multi-site clinical trial it will support?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the multi-site clinical trial the DCC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the clinical trial, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the DCC is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the research program? Is an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of human subjects?

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?

Specific to this FOA

How strong are the plans to monitor accrual? What is the quality of the Project Management Plan?

How well does the Project Management Plan address the critical parameters for the launch, conduct, and completion of the study? How effectively does the Project Management Plan identify and describe risks to implementation and how well are contingency plans described? Since this is a multi-site application, how strong is the evidence of the ability of the DCC to operate within the proposed organizational structure, communicate with the individual sites, and collect and transmit data in an accurate and timely fashion?

If the clinical trial is Phase III, does the application include all relevant data to assess whether or not the trial should include adequate numbers of subgroups of participants to allow for valid and/or adequately powered analyses? If applicable, do the plans for adaptive designs include a pre-specified adaptation plan that allows for clear go/no-go decisions and pre-specified analysis boundaries?

Does the statistical approach justify the proposed sample size based on appropriate study assumptions; provide for plans for interim and final analyses; methods of bias control; and methods for handling missing data (as applicable)? Is the statistical methodology detailed enough to allow replication of the analyses by an independent statistician?

How strong is the plan for data management and validation, including data management systems, methods of data entry and cleaning, event tracking and logistics, case report forms, and methods for monitoring 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; adjudication of events (as needed); and data reports?

Is there a plan for the proposed dataset to be prepared in accordance with requirements for NHLBI data repository datasets and associated documentation for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) and the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, and in accordance with the Guidelines for NHLBI Data Set Preparation?

Will the institutional environment in which the DCC will operate contribute to the probability of success in facilitating the research it supports? Are the institutional support, equipment and other physical resources available to the investigators adequate for the DCC proposed? Will the DCC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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?

Specific to this FOA

How strong is the evidence that the facilities and resources available for the DCC infrastructure will support and enable the conduct of the research proposed in the multi-site clinical trial?

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

Study Timeline

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

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

Specific to this FOA

Are the listed milestones appropriate for the DCC? To what extent are the milestones relevant, measurable, achievable, result-focused and time-bound? Does the DCC application explain contingency plans in the event the CCC application is not achieving its milestones?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

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

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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

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

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, 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:

• 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.
• Will receive a written critique.

Keep the appeals sentence for RFAs only; otherwise delete for all PA, PAR, PAS.

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 Heart, Lung, and Blood Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

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

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

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

If progress is deemed satisfactory in the first phase, milestones and timelines for the second phase (execution of the trial) may stay the same as originally agreed upon. In certain cases the milestones and timelines may need to be revised and finalized prior to transitioning into the second phase of the award. If revision of the milestone plan is needed, investigators and NHLBI staff will review and mutually agree upon a revised milestone plan for the second phase of the trial.

If the CCC is terminated early for cause (i.e., failure to comply with terms and conditions of their award) it would leave the DCC unable to complete the objectives of its grant, but not because of any fault on the part of the DCC. In such a case, NHLBI will enter into negotiation with the DCC awardee to achieve mutually agreed-upon early phase-out of the award per 45 CFR 75.372.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The awardee PD/PI will have primary and lead responsibilities for the project as a whole, including research design and protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, as well as collaborations with other awardees.

Upon completion of the project, awardees are expected to put their data into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community (see section 3 below "Collaborative Responsibilities").

Third Party support of the proposed research activity (if proposed, accepted and approved) will be incorporated as a Special Award Condition in the Notice of Award (NoA). Awardees will be responsible for ensuring third party compliance and if the 3rd party support is no longer available, and not replaceable in a timely fashion negotiated phase-out of the award may occur.

Cost Share is not a requirement for this program; however, if cost share is proposed, peer reviewed

and accepted by NHLBI it will become a Special Award Condition in the NoA.

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

The NHLBI Project Scientist will assist with development of research protocols, monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. NHLBI will appoint the Data and Safety Monitoring Board (DSMB).

The NHLBI Project Scientist will serve on the Steering Committee and other study committees, when appropriate, as a non-voting member. The NHLBI Project Scientists may work with awardees on issues coming before the Steering Committee such as recruitment, protocol development, follow-up, quality control, adherence to protocol, possible changes to the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.

In addition to the Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as both the NHLBI Project Scientist and Program Official. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Program Official will participate in activities that rise to a level of involvement (i.e., additional role as Project Scientist) that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, etc., other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

The NHLBI policy on authorship and manuscript review of NHLBI sponsored extramural research protects against conflicts of interest with the Program Officer.

An independent Data and Safety Monitoring Board (DSMB) may be appointed by the Director, NHLBI will be established to oversee participant safety in the clinical trial and provide overall monitoring of interim data and safety issues. Meetings of the DSMB will ordinarily be held in Bethesda, MD. As part of the collaborative activities under this cooperative agreement, the NHLBI will collaborate with the awardees to appoint and/or agree upon a single DSMB for monitoring the clinical trial. The DSMB may be appointed by the NHLBI, or with the approval of NHLBI, the DSMB could be an institutional DSMB. At the first meeting in the UG3 phase, the DSMB will review the awardee's protocol and potentially recommend modifications. Subsequently, the DSMB will monitor and review recruitment, adverse events, data quality, outcome data, and overall awardee performance. 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. An NHLBI scientist other than the NHLBI Program Official or Project Scientist will serve as Executive Secretary to the Board. Because the DSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with DSMB members regarding study issues, except as authorized by the Board's Executive Secretary.

NHLBI will conduct at least two administrative reviews to determine progress toward achievement of milestones included in the mutually-agreed upon milestone plan, one towards the end of the UG3 phase, and one within the first two years of the CCC UH3 phase. If either the DCC or the CCC milestones have not been satisfactorily met, subsequent funding years may not be approved.

The NHLBI reserves the right to phase-out or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable protocol, (b) substantial shortfall in subject recruitment milestones, core milestones mutually agreed upon by the recipient organization and PD/PI and the NHLBI, consortium participation and collaboration with other awardees, (c) substantive changes in the agreed-upon methodologies and tools with which NIH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.

Areas of Joint Responsibility include:

The Authorized Organizational Representative (AOR) is responsible for communicating progress on achievement of each milestone for the collaborative project to the NHLBI Grants and Program Officers 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 NHLBI Accrual of Human Subjects (Milestones) Policy, falls significantly below projections, or core milestones mutually agreed upon by the recipient organization and PD/PI and the NHLBI are not met, the NHLBI may consider ending support and negotiating an orderly phase-out of the award. NHLBI Grants Management and Program Officers will closely monitor progress at all trial stages including milestones, accrual, and safety.

Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The Principal Investigator of this award will be required to participate in periodic meetings and telephone conference calls with other investigators performing large-scale genome wide association studies supported by the NHLBI. These meetings and calls will be arranged by NHLBI staff to promote sharing of information among investigators regarding state of science technologies, data management techniques, analytical strategies and tools, and data sharing. 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 NHLBI support; or special access to study results, data, findings or resource) 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 NHLBI.

NHLBI Program Official will partner with the PD/PI to ensure that the dataset preparation is congruent with requirements for NHLBI data repository datasets and associated documentation for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) and the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, and is in accordance with the Guidelines for NHLBI Data Set Preparation.

Study investigators are encouraged to publish and to release publicly and disseminate results, tools, resources and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely matter to the scientific community. A plan for dissemination of study results will be developed by the awardee PD/PI in collaboration with the NIH Project Scientist and incorporated as a Special Term and Condition in the NoA. Within 3 years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed are expected to be made available to individuals who are not study investigators in accordance with the NHLBI Data Sharing Policy available at http://www.nhlbi.nih.gov/funding/datasharing.htm.

Dispute Resolution:

Any disagreement that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed will be convened. It will have three members: a designee selected by the Executive Committee (with the NHLBI member absent from the discussion) or by the individual awardee in the event of an individual disagreement, a second member selected by NIH, and the third designee with expertise in the relevant area selected by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution does not alter the awardees' right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16.

Multiple PD/PI Dispute Resolution

If a conflict develops between PD(s)/PI(s) in a multiple PD/PI application, the following procedures will apply:

The Departmental administrators representing the PD(s)/PI(s) shall meet and attempt in good faith to settle any dispute, claim or controversy arising out of or relating to the interpretation, performance or breach of this disagreement. However, if the Departmental administrators fail to reach resolution in 30 days then NIH may invoke dispute resolution procedures as described in the above paragraph.

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.

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Division of Blood Diseases and Resources

Nancy DiFronzo, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: [email protected]

Division of Cardiovascular Sciences

Yves Rosenberg, MD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0550
Email: [email protected]

Division of Lung Diseases

Gail Weinmann, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0233
Email: [email protected]

Keary A. Cope, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0287
Email: [email protected]

Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8014
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.