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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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.

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The Cardiothoracic Surgical Trials Network (CTSN) has been a successful and impactful clinical research enterprise since 2007, building a cadre of cardiac surgical trial investigators and a platform for broad collaboration among allied specialties, foundations, professional societies and industry. The CTSN includes cardiac surgical academic centers across the U.S., Canada, Germany, the United Kingdom (UK), and Spain. Over the last 18 years, the CTSN has become a critical resource to the cardiac surgery, cardiology, and neurology communities. Studies that promote the dissemination and re-use of implementation strategies of evidence-based interventions among relevant communities are encouraged. During this funding cycle, the CTSN will expand the scope of an international cardiac surgery research platform with the intention of being more accessible to the heart, lung, blood, and sleep research community, small businesses, foundations, professional societies, and international research entities. In this new iteration, funding of the enterprise will be shared by government and other sources wanting to leverage the infrastructure and collaborate on important scientific research questions. Additional CTSN trial information can be found at ctsurgerynet.org (http://ctsurgerynet.org/).

Purpose and Objectives

This is a Notice of Funding Opportunity (NOFO) for a Single Source that will invite an application from the eligible organization to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application will be peer-reviewed, and only meritorious applications will be considered. This is a non-competitive funding opportunity intended to fund a single award. The NHLBI is announcing its intent to issue a single source cooperative agreement award to the Icahn School of Medicine at Mount Sinai to support a Data Coordinating Center (DCC) to conduct the activities of the Cardiothoracic Surgical Trials Network (CTSN). This single source cooperative agreement award to the current DCC will enable this highly productive coordinating center to continue analysis and publication of secondary and exploratory projects/studies without interruption utilizing their state-of-the art electronic data capture system, which contains rigorously collected data from the 10 completed and 3 ongoing Network clinical trials.  The DCC will consist of two collaborating components including a Data Management and Analytics Center (DMAC) and a Clinical Coordination Center (CCC). NHLBI strongly encourages multi-PD/PI applications with two PDs/PIs; one PD/PI for the DMAC and one PD/PI for the CCC.

Network Organization and Governance

In this funding cycle, the CTSN will be a single data management and clinical coordinating center with clinical trial agreements in place for collaboration with clinical sites. International clinical site collaborations are facilitated through country-side agreements with the Global Cardiovascular Research Funders Forum (GCRFF). The Network will consist of a rotating Network Chair (cardiothoracic surgeon) and rotating Vice Chairs for Cardiology, for Strategic Development and for other areas as needed, and the NHLBI.

The Data Coordinating Center coordinates, administers, and supports all Network clinical research, operational, and administrative and statistical activities. Briefly, these activities include but are not limited to supporting protocol development; developing manuals of procedures and electronic case report forms; providing sample size calculations, statistical advice, common questionnaires, and data analysis; supporting manuscript preparation; and providing overall study coordination and quality assurance, including support for the Data and Safety Monitoring Board (DSMB), the Protocol Review Committee (PRC), the Steering Committee, and other standing committees meetings/conference calls. Funds to support execution of the protocols at the clinical centers are part of the DCC cooperative agreement (hereafter referred to as award) and are distributed to the sites by the DCC on a per-patient basis and according to the approved protocol budgets. For some protocols the DCC conducts long-term patient follow-up. Additionally, the DCC will centrally manage the CIRSP.

Clinical Centers (CCs) The DCC will execute clinical trial agreements with clinical centers to enroll trial participants, develop protocols, prepare manuscripts, and perform other key Network activities. All domestic sites are reimbursed on a per-capita basis and do not receive infrastructure funding. It is anticipated that up to 150 CCs in the US, Canada, and Europe will participate.

The Steering Committee (SC) is the main governing body of the CTSN. The SC comprises the Principal Investigators (PIs) from the NHLBI-selected, high performing CCs and the DCC, the Network Chair, Vice Chairs, and NHLBI staff. Voting members of the SC include the Chair (a cardiothoracic surgeon), PIs from the NHLBI-selected CCs, one DCC MPI, and the NHLBI Program Scientist. The Chair and Vice Chair positions may be rotated among the CC Investigators. The SC has primary responsibility for the general organization of the CTSN, the approval of clinical protocols and protocol changes, the conduct and monitoring of studies, and the expeditious reporting of study results. All major scientific and administrative decisions are determined by majority vote of the SC, which meets in-person annually and by teleconference on a monthly basis. This Committee ensures that all decisions are reported to the Investigators Committee.

Committees and Subcommittees of the SC, such as the Operations Committee and subcommittees for Protocol Development, Protocol Operations, Publications and Biorepository have been established and may be continued or added to at the discretion of the SC.

The Investigators Committee (IC) consists of all clinical site investigators and study coordinators from the CCs, staff members from the DCC and NIH, and the CTSN Chair and Vice Chairs. The Network Chair Vice-Chairs are named by NHLBI to oversee and guide SC and IC activities. The IC meets in-person annually and by teleconference on a monthly basis. Subcommittees are established as necessary, and membership includes physician and nurse investigators from the CCs, representatives from the DCC, and members from NIH.

The NHLBI is responsible for organizing and providing overall support for the CTSN. The NHLBI Program Office and Office of Grants Management are responsible for the federal stewardship of the award (scientific management, financial and administrative oversight). In addition to regular award oversight, the NHLBI Program staff, i.e., project scientists, including biostatisticians, and Program Officer, will be involved substantially with the awardees as a partner, consistent with the Cooperative Agreement mechanism. The NHLBI will appoint the Protocol Review Committee, the Data Safety and Monitoring Board, and the Network Chair and Vice Chairs. The Study Chairs are independent of the DCC and are responsible for ensuring that there are well-documented policies and procedures in place to guide all aspects of Network activities and operation. In collaboration with NHLBI staff, the Chairs facilitate Network activities, oversee its functions, and conduct SC and IC meetings.

An independent Protocol Review Committee (PRC) is appointed by and advisory to the NHLBI. It consists of a chairperson, clinicians, and scientists with expertise in basic and clinical cardiothoracic surgery research, bioethics, cardiology, neurology, clinical trial design, biostatistics, enabling technologies, outcome measures, and other areas of expertise as needed. The PRC will evaluate protocols approved by the SC based on the following criteria: importance of the question to be addressed, the scientific merit of the experimental design and approach, feasibility, appropriateness for the Network, and consistency with NHLBI mission and policies. All new study protocols performed by the CTSN that have not previously been peer reviewed must be approved by the PRC before referral to the Data and Safety Monitoring Board.

An independent Data and Safety Monitoring Board (DSMB) is appointed by and advisory to the NHLBI, in accordance with established policies to ensure data quality and participant safety. The DSMB consists of a chairperson and clinicians and scientists with expertise in cardiothoracic surgery research, bioethics, cardiology, neurology, clinical trial design, biostatistics, enabling technologies, outcome measures, and other areas of expertise as needed. All CTSN protocols must be approved and monitored by the DSMB, generally after their approval by the PRC, or peer review. The DSMB will be responsible for providing independent advice to the NHLBI regarding the progress of each trial and the appropriateness of continuing each study. The DSMB will meet approximately every six months, with interim meetings as necessary.

An independent External Expert Panel with expertise in areas such as cardiothoracic surgery, cardiology, neurology, as well as clinical trial management and regulatory oversight will review the CTSN during the fourth or fifth year of the Network and advise the NHLBI (and Steering Committee) on opportunities to improve operations and future scientific directions.

Requirements for the CTSN Data and Clinical Coordinating Center

The DCC will coordinate all trials to be run in the Network facilitating use of the collaborative infrastructure. DCC planning should consider protocols to be completed in a two-to five-year time frame (recipients shall not assume that follow-up will occur outside of the lifetime of the award with Federal support). The DCC will facilitate protocols and new concepts being reviewed and prioritized through the CTSN SC process. Protocols that are voted by the SC to be developed will be supported by protocol development committees coordinated by the DCC and comprised of membership from CCs, the DCC, and NIH. The DCC will coordinate CTSN conducted peer review of protocols through the PRC in collaboration with the NHLBI.

The DCC will centrally manage the Clinical and Implementation Research Skills Program (CIRSP) through one or both of its two collaborating components, i.e., a data management and analytics center (DMAC) and clinical coordination center (CCC). It is anticipated that the CIRSP will be integrated across clinical sites to provide skills development opportunities to early-stage investigators in the conduct of cardiothoracic surgical trials and dissemination and implementation science research. Research capacity-building/skills development elements are expected to be suited to the needs of the geographic region, with the goal of significantly enhancing the future capacity for implementation science researchers for cardiovascular surgery by the end of the project period. These efforts will be aligned throughout the Network.

The DCC will consist of two collaborating components including:

1. Data Management and Analytics Center (DMAC)
2. Clinical Coordination Center (CCC)

Data Management and Analytics Center (DMAC)

NHLBI expects that the DMAC component will work in close collaboration with the CCC and that the DMAC will have primary responsibility for:

• Overall management and coordination of the Network

Management of overall funding of the DCC award, Network project timelines, and the CTSN website to ensure that it is updated at regular intervals; overall coordination of Network activities across all components (i.e., the CCC, CCs, core laboratories, Network leadership, small business partners, and NIH); and provide coordination and leadership in the early identification and resolution of issues arising within the Network. 

Administrative Management: Administrative support to the Network Chairs, scientific leadership, and other stakeholders as needed, including but not limited to drafting Network meeting/teleconference agendas and minutes, manuscripts, and presentations, as well as publicizing ongoing clinical trials via appropriate advertising venues; Coordination and facilitation of meetings, teleconferences, and training among study personnel, committees, subcommittees, oversight bodies such as the DSMB, small business partners and other collaborators.

Additional responsibilities of the DMAC include developing, negotiating, and executing agreements such as investigator agreements, agreements with core laboratories identified by the CCC, materials transfer agreements, agreements with small business partners and other collaborators.

• Trial/Study Design and Protocol Development

Trial/study design, statistical and biomedical/scientific writing expertise to Protocol Development Committees (PDCs), including defining sample size requirements and randomization schemes, assisting in the determination of trial endpoints and analytical approaches, as well as developing trial stopping rules, as appropriate, for NHLBI review and DSMB approval. It is also expected that the DMAC will facilitate PDC meetings/teleconferences to ensure that protocols are developed within Network timelines and coordinate protocol review by the NHLBI-appointed PRC and DSMB in collaboration with the Executive Secretaries of each. The DMAC will also oversee data management-related document development and finalization for each trial/study in collaboration with the CCC.

• Data Management and Analysis

Development, maintenance, and/or refinement of data dictionaries and a 21CRF Part 11-compliant electronic data capture system (EDC) for clinical research trials and studies conducted by the Network; assuring high data quality through edit/validation checks; and serving as a central repository for trial/study data and acquired large data sets (e.g., CMS and other relevant data sets) pertinent to Network trials and studies. Additional DMAC responsibilities are expected to include overseeing secure data collection, storage, and, when appropriate, transfer of CC- core laboratory and ancillary study-generated data; preparing confidential data analyses and reports as requested by the NHLBI, Network leadership, SC, the DSMB, and regulatory agencies in collaboration with the CCC; and coordinating data analysis, reporting, and publishing of Network research, the latter in high quality peer-reviewed journals.

Clinical Coordination Center (CCC)

NHLBI expects that the CCC, working in close collaboration with the DMAC, will have responsibility for:

• Enrolling Clinical Centers

Identification of CCs and administration of their corresponding investigator agreements; providing reimbursement for patient care costs for all domestic sites as a fee for service arrangement after a protocol has been approved and the NHLBI has approved the funds for distribution; integration of activities of all CCs to minimize duplication of effort and to maximize resources by utilizing existing resources whenever possible; and establishment and tracking of site enrollment targets, encouraging recruitment, and developing strategies to encourage referrals from other specialty areas. Additionally, the NHLBI anticipates the CCC will prepare, distribute for review, finalize, and then distribute protocols, protocol amendments, manuals of policies and procedures (MOPPs), and other materials necessary for study implementation. In collaboration with the DMAC, the CCC will provide protocol training as an integral part of site initiation activities and as needed throughout the trial.

• Biorepositories, Core and Collaborating Laboratories

Identification and administration of agreements with biorepositories and core laboratories and investigators as needed; administration of agreement including providing reimbursement to these facilities as applicable and/or ensuring transfer of biospecimens to collaborating laboratories in a timely manner; training of clinical center personnel; as well as distribution of materials and supplies furnished by core laboratories. Within the scope of these, the CCC will also coordinate with biorepositories to ensure accurate inventories of fluid and tissue specimens for laboratory studies and their transfer to collaborating laboratories. The CCC is expected to assist biorepositories and core laboratories as needed with the preparation of procedures manuals and their distribution to clinical centers and to facilitate efforts by investigators to obtain funding for secondary analysis of specimens.

• Study Products

Administration of agreements with manufacturers and arrangement and tracking of the supply of study products, including drugs, biologics, devices and/or combination products, to clinical centers, and coordinate study product training of clinical center personnel, as needed.

• Clinical Research Activities

Long-term follow-up of trial participants through centralized remote visits at key time points. Activities may include obtaining vital status, the occurrence of protocol-specified adverse events (e.g., major adverse cardiovascular and cerebrovascular events, other cardiovascular and neurological events), hospitalizations, and quality of life; entering data obtained into the electronic data capture system and maintaining GCP-compliant records of all telephone visits; collection of source documentation pertaining to serious adverse events as defined by the protocol and uploading the documents into the EDC for review by the Events Adjudication Committee.

• Network Activities

Participation in Network activities to provide clinical trial operational guidance including SC, IC, and coordinator meetings and teleconferences, trial-specific operations teleconferences, and trial-specific training workshops.

• Human Subjects Protection

Overseeing Human Subjects Protection within the Network by preparation of informed consent templates and patient-centered materials (e.g., brochures and letters) for review by the trial/study sponsor(s); and ensuring that all DCC, CC, and core laboratory personnel are properly trained on protocol-specific procedures (including the informed consent process), CTSN policies, applicable regulations, and Good Clinical Practice (GCP), in collaboration with the DMAC. Additional CCC responsibilities include evaluating screening logs and patient eligibility, as well as triaging unexpected adverse events regardless of the clinical center investigator's determination for further assessment by independent Medical Monitors.

• Regulatory Affairs

Facilitation of interactions with regulatory authorities such as the Food and Drug Administration (FDA), Centers for Medicare and Medicaid (CMS), and other relevant regulatory agencies; appointment of a qualified staff member to serve as the ClinicalTrials.Gov (https://clinicaltrials.gov/) Responsible Party and Sponsor of Investigational New Drug applications (INDs) and Investigational Device Exemptions (IDEs); and reporting and tracking of unexpected adverse events and unanticipated problems to NHLBI, other study sponsors, oversight bodies, and regulatory agencies. Moreover, after triage, CCC staff will coordinate adverse event review by Network Medical Monitors, the Events Adjudication Committee, and IND/IDE safety monitors (the latter for IND/IDE trials). Additional CCC responsibilities are expected to include preparing and submitting all regulatory documents (e.g., briefing packages, initial regulatory applications, amendments to regulatory applications, responses to regulatory authority inquiries, etc.) to regulatory agencies, as well as CMS applications for coverage of IND/IDE trials to CMS.

• Regulatory Compliance

Assuring compliance with the Health Insurance Portability and Accountability Act (HIPAA) within the CTSN in accordance with 45 CFR Parts 160, 162, and 164 or corresponding regulations for all other international clinical centers as noted above; Implementation and supervision of the revised Common Rule (45 Part 46) within the CTSN, including the use of a single-IRB review for federally-funded, multi-institutional studies conducted in the United States. In addition, the CCC will be expected to register and report results of clinical studies and trials in ClinicalTrial.Gov as required by 42 CFR Part 11. In collaboration with the DMAC, the CCC will be expected to establish and maintain written procedures for all internal processes within the DCC. To supplement the monitoring program discussed below, the CCC will have independent auditing to assure regulatory compliance within the Network, as needed.

• Monitoring Program

Developing, organizing and conducting a monitoring program for all enrolling clinical centers, core laboratories, biorepositories, and other collaborators participating in CTSN research to ensure high quality clinical research. The monitoring program will include preparing and providing trial-specific monitoring plans to the trial sponsor(s) and monitoring study execution at clinical centers, core laboratories, and biorepositories to assure compliance with the protocol, procedures manuals, CTSN policies, applicable regulations and guidelines throughout the duration of the trial. Additionally, the CCC will be responsible for conducting site initiation, interim and close-out visits (central/remote) in accordance with the monitoring plan; preparing monitoring reports for the trial sponsor (e.g., the NHLBI) and monitoring letters for enrolling clinical centers, core laboratories, and biorepositories after completion of monitoring visits and in accordance with required timelines; and providing monthly monitoring schedule updates/trackers to the trial sponsor (e.g., the NHLBI). The CCC will be expected to identify underperforming centers and laboratories as early as possible, develop corrective and preventative action plans in consultation with the NHLBI, and oversee the implementation of the corrective and preventative action plan.

DCC key personnel will be expected to conduct remote site visits as needed to ensure the rigorous standards required by the CTSN. The entire CTSN program will be reviewed by an External Expert Panel during Year 4 or 5, and the DCC in collaboration with NHLBI staff will be responsible for developing and providing relevant materials to the External Expert Panel for this review.

Applications submitted in response to this NOFO must propose one or more delayed onset clinical trial studies. The delayed onset clinical trial studies represent future proof-of-concept/early feasibility/early translation area, RCTs in the comparative effectiveness realm, and innovative trials leveraging registry data and electronic medical records, among others approaches to be conducted by the CTSN and should not provide specific details about the proposed clinical studies.

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

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

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

Only the following applicant is eligible to apply for this single source funding: Icahn School of Medicine at Mount Sinai. Please refer to Section I. Notice of Funding Opportunity Information for more details.

Foreign Organizations/International Collaborations

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.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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 the 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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.

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 How to Apply-Application Guide.

Only the PI/PDs associated with the award issued under RFA-HL19-010 are eligible to apply for this single source funding. Please refer to Section I. Notice of Funding Opportunity Information for more details 

2. Cost Sharing

This NOFO does not require cost sharing as defined in the 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).

Only a single award will be issued to Icahn School of Medicine at Mount Sinai under this single source funding opportunity. Please refer to Section I. Notice of Funding Opportunity Information for more details.

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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 How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

Key personnel should include:

• The PD/PI of the DMAC, with responsibility over the entire DCC (signified below by DMAC/DCC), and the PD/PI of the CCC are both required to have doctoral degrees in a field relevant to biomedical research; expertise in the evaluation of surgical, biologic and device trials; and leadership expertise in NIH Network or Cooperative Group-based clinical trials to seamlessly orchestrate DCC activities involved in conducting the multiple, multi-center clinical trials and studies performed within the Network.
   
• The PD/PI of the DMAC/DCC must have a comprehensive understanding of the measurement of the long-term clinical outcomes and economic impact of clinical interventions; patient safety and quality of care research; policy analysis; innovative trial design, methodology and conduct of complex surgical and device trials; the assessment of quality of life and economic analysis of clinical procedures, and volume-outcome studies; and policy studies on technological change; as well as an understanding of translational research and implementation science.
   
• The PD/PI of the CCC must be certified as a clinical research professional (CCRP), or have equivalent experience with a comprehensive understanding of human subjects protection; safety and pharmacovigilance in drugs, biologics, devices and combination products to ensure timely, complete, and accurate reporting to oversight bodies and regulatory agencies; applicable regulatory requirements; electronic data capture and database development; as well as the technical background to review comprehensive IND and IDE risk assessments and safety reports.
   
• Medical Officer/Senior Cardiologist (i.e., MD, DO or equivalent doctoral degree) specializing in adult cardiology with expertise in heart failure, electrophysiology, and/or interventional cardiology. The Medical Officer should be experienced in the area of safety and pharmacovigilance in drugs, biologics, devices, and combination products to review and evaluate information relevant to the safety of these products.
   
• Senior Regulatory Professional to organize and manage all regulatory affairs and compliance activities. This individual must have a Masters or higher degree with Regulatory Affairs Certification (RAC) or equivalent experience and comprehensive experience supervising other regulatory professionals, medical writers, clinical trial monitors and clinical trial auditors/auditing consultants.
   
• Senior Regulatory/Medical Writer with a Master's degree and more than 5 years of medical writing or doctoral degree with more than 2 years of medical writing experience to conduct thorough literature searches, prepare complete and accurate regulatory documents (e.g., briefing packets, initial INDs/IDEs, IND/IDE amendments, responses to regulatory authorities, reports to oversight bodies and regulatory authorities, formal meeting minutes, clinical study reports, and other types of regulatory documents).
   
• Senior Clinical Research Professional with an RN, BSN, or higher degree in a relevant field and certification as a clinical research professional or equivalent experience to manage the day-to-day activities of clinical operations. This individual must have at least 10 years of clinical research experience and at least 5 years of supervisory experience managing other clinical research professionals (e.g., clinical trial project managers and supporting staff), as well as substantial experience working with clinical center research coordinators and other clinical center staff. Comprehensive knowledge of GCP, data-driven development of trial accrual benchmarks, arranging the supply of study products, development of case report forms, and administration of agreements with clinical centers, core laboratories, small business partners and other collaborators is also required.
   
• Senior Biostatistician with a doctoral degree in biostatistics and at least 5 years of experience supervising data management and statistical analysis staff to manage the day-to-day activities of data management and analysis, ensuring all timelines are met. This individual should have at least 10 years of experience in multisite clinical trial design and analysis, expertise in project management, the ability to work collaboratively as part of a multidisciplinary team as well as to meet timelines.
   
• Information Technology Professional with a Bachelor's degree or higher in computer science, informatics, or other relevant field to manage research informatics activities. This individual should have in-depth experience developing large-scale, web-based, clinical trial data management systems and support systems (e.g., web-based document management and tracking systems), data systems validation, as well as experience supervising research informatics staff including website designers.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

Application budgets must plan for the following:

For all non-protocol costs:

• Limits for budget amounts that applicants may request for all non-protocol costs are listed in Section II Award Information, Award Budget
• A suggested 9 person-months for the PDs/PIs for the DMAC/DCC and the CCC
• Medical Officer/Senior Cardiologist at suggested 3 person-months 
• Senior Regulatory Professional at suggested 9 person-months
• Senior Regulatory/Medical Writer at suggested 4 person-months
• Senior Clinical Research Professional at suggested 9 person-months 
• Senior Biostatistician at suggested 5 person-months
• Information technology professional at suggested 3 person-months
• For other Investigators/staff, the effort should be commensurate with the oversight required
• Expenses related to managing the DSMB will include approximately eight and up to ten members with regularly scheduled meetings occurring virtually via videoconference twice yearly and an additional one to two virtual ad hoc meetings annually
• Expenses related to managing the Protocol Review Committee will include approximately five to seven members with all meetings occurring on an as needed basis by videoconference
• Steering Committee and All Investigators Committee expenses will include an average of annual in-person meetings and monthly conference calls and monthly subcommittee calls for each active protocol subcommittee; DCC staff travel to Steering Committee and All Investigators Committee meetings should be included in the DCC budget
• Coordinators Group expenses include an average of one in-person meeting per year and video conferences up to three times per month., DCC staff travel to Coordinators Group meetings should be included in the DCC budget
• Site monitoring visit expenses include costs for site initiation, interim monitoring, and close-out monitoring activities that will be conducted via centralized and remote monitoring; the DCC will remotely visit each actively accruing clinical site in accordance with the trial monitoring plan, which takes into account the level of risk and established policies and regulations; these monitoring visits will be dependent on the number of ongoing CTSN trials, trial accrual rate(s), applicable regulations, and findings from centralized monitoring and previous remote site visits
• Site evaluation and video conference expenses for one or two videoconferences per enrolling clinical center to follow up on any recruitment issues
• Expenses associated with identifying, negotiating agreements and overseeing up to 150 CCs
• Costs associated with training to include costs related to the design and implementation of web-based training and assessment for protocols and annual Good Clinical Practice training for all investigators and study coordinators. NOTE: In-person training for coordinators and investigators should be addressed above in the annual and bi-annual in-person committee meetings, respectively
• Support for the Network Chair and Vice Chairs as well as the Publications Committee Chair and NHLBI-selected SC members at 1.2 person-months (10% effort) each, including travel to the annual investigator and the annual steering committees and modest administrative expenses
• Support for consultants needed for the centralized Clinical and Implementation Research Skills Program at suggested 2.4 person-months (20% effort) each 
• Support for patient and caregiver representatives needed for the development of research protocols at suggested 1.2 person-months (10% effort) each
• Costs related to the design and implementation and maintenance of the CTSN public and private websites and development of web-based programs for financial management of the Network
• Support for independent medical monitors experienced in cardiothoracic surgery, as well as an independent Events Adjudication Committee with expertise in cardiothoracic surgery and cardiology
• Center costs also should include the costs of updating the Network Administrative Manual of Policies and Procedures, trial-specific manuals of procedures and of developing questionnaires, forms, and marketing activities and materials (brochures, videos, seminars)
• Other expenses as appropriate

Protocol associated funds will be awarded to the DCC for subsequent distribution to the domestic clinical centers and core labs on the following schedule: Year 1 - $1,838,272; Year 2- $1,838,272; Year 3 - $1,838,272; Year 4 - $1,838,272; Year 5 - $1,838,272; Year 6 - $1,838,272; Year 7 - $1,838,272. Future year amounts will depend on annual appropriations. The budget justification for protocol associated costs for each year should include a table that apportions the direct costs among the following categories: patient care costs, core lab costs, biorepository costs, and CC agreements. The DCC applicant should assume that two to three protocols will be active in the first year and seven to ten total protocols will be developed and begin active recruitment during the award period covered by this NOFO. The budget should include, but is not limited to:

• Protocol associated costs (e.g. clinical costs that are not part of routine clinical care such as laboratory tests, sample and data collection, supplies)
   
• Expenses associated with drug or device acquisition and distribution when required, and application to the Food and Drug Administration (FDA) for Investigational New Drugs (INDs) and Investigational Device Exemptions (IDEs), as well as the Centers for Medicare and Medicaid (CMS)
   
• Expenses associated with procuring and operating centralized laboratories will include the expense of transferring the data or specimens to the central lab(s), training technicians to obtain the data in a uniform manner, and instituting quality control measures (e.g., provision for re-reading a proportion of the studies to determine accuracy of interpretation) will be included in the DCC budget
   
• Costs to engage a single IRB (https://grants.nih.gov/grants/policy /faq_single_IRB_policy _research.htm#I?) (sIRB ( https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-004.html)) for up to 10 CTSN-led trials

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

The primary responsibility of the DCC is to oversee the conduct of multiple randomized clinical trials in the CTSN. The DCC will support regulatory and administrative activities, data collection and management, and statistical analysis and reporting of trial results in a timely manner. The DCC will promote collaboration and communication among CTSN investigators and the broader research community and coordinate outreach activities including engaging foundations, research entities, and small business in trials of mutual interest and public health importance. The DCC is responsible for integrating the efforts of individual clinical sites, core laboratories, and other collaborators, and conducting long-term follow-up centrally via telephone follow-up at the DCC. The NHLBI anticipates that the DCC will strategically manage the Clinical and Implementation Research Skills Program (CIRSP) component to enhance the development of junior investigators by facilitating their involvement in protocol development (including clinical trial design and statistical approaches), publication committees, and by providing datasets for secondary analyses.

The DCC, together with the clinical site investigators, will be responsible for proposing and developing protocols, recruiting participants, entering data into the web-based data entry system, assuring good clinical practice, mentoring junior investigators in both clinical research and implementation science, and disseminating research findings. The DCC will also develop and implement a standardized pathway for investigators from outside the network, including small businesses and other organizations, to bring trial concepts to the Network for consideration. 

The research strategy must describe the following:

• Plans for leading and coordinating complex multi-center clinical cardiothoracic surgical studies and trials.
   
• Experience with representative studies from CTSN as a means of discussing the proposed approach to the design and conduct of cardiothoracic and/or cardiovascular surgical protocols, maximize recruitment and retention, and minimize logistical, operational, and regulatory issues, all in the context of multiple trials running simultaneously. Include a description of novel clinical research approaches and innovative technologies that can be applied to the clinical trial enterprise.
   
• Proposed strategy to conduct long-term follow-up of trial participants at the DCC.
   
• Plans for how the DCC will cooperate and interact with all CTSN components to achieve coordination of all Network activities. Include strategies to manage and support electronic and other communications; support regulatory affairs and compliance, human subjects protections, site/core lab and data monitoring, clinical operations and administrative activities; conduct data collection, management, statistical analysis and reporting of clinical trial results in a timely manner.
   
• The DCC's proposed model for the development of clinical and implementation research junior investigators in collaboration with the sites CCs. The applicant is encouraged to propose a model of mentoring, skills development, and career development for early-stage investigators. Skills development activities, in turn, may focus on the development of independent researchers by providing mentorship and supporting research development projects for early fellows, early career faculty, and investigators who may wish to refocus their careers on dissemination and implementation science. While applications should not propose to support an academic degree program, leveraging existing educational infrastructure at the DCC or CCs and aligning appropriate areas of emphasis to drive sustained implementation research efforts is encouraged. Additionally, validated skills development materials and resources is encouraged. Where appropriate, discussion of developed and implemented best practices may be included.Research skills development activities may include, but are not limited to:
  • Short courses on implementation science methodology, dissemination and implementation research designs, and/or mixed methods research
  • Summer research institutes to enhance scientific writing skills and increase publication rates
  • Establishment of distance learning and research mentoring networks
     
• Plans for conducting outreach activities including engaging foundations, international research entities and small business partners in trials of mutual interest and public health importance.

Research Team

Provide an overview of the overall organization of personnel in the Research Team of the DCC and describe the ability and commitment of the investigators to function as a coordinated research team, to work efficiently and expeditiously with, and to enhance the research goals of, the CTSN.

A sound rationale should be provided as to why the research team is the most appropriate and likely to generate an exceptionally high impact if successful. Provide an overview of the DCC team member roles and responsibilities in light of the requirements of concurrently managing multiple studies at various stages of study design, conduct, and closeout.

Clinical and Translational (CTSA) Organizations

The NHLBI encourages academic centers participating in the CTSN to partner with the CTSA, if one exists at the applicant institution, to enhance the scientific and operational aspects of the Network.

If applicable, describe how the CTSN DCC will interface with a CTSA structure including plans for leveraging bioinformatic, clinical trial design and biostatistics expertise. Describe how the CTSA network may be leveraged to establish strong and interactive relationships with local communities and clinics, and to enhance recruitment of various patient populations. If appropriate, describe how the CTSN DCC might partner with translational investigators in the CTSA to create state-of-the art mechanistic and translational sub-studies that could be conducted within the Network's clinical protocols.

Multiple PD/PI Leadership Plan

Describe plans for how the DMAC/DCC PD/PI and the CCC PD/PI will work collaboratively together to lead the identified multidisciplinary team. Include a description of planned strategies for effective communications between and within the DMAC and CCC.

Letters of Support

Provide documentation of departmental and institutional commitment to supporting cardiothoracic surgery research and to prioritization of Network research. This can be in the form of letters or memoranda provided to the Program Directors/Principal Investigators, and by citing evidence of past support. These assurances to provide support should address areas such as fiscal administration, personnel management, space allocation, procurement, planning, equipment, and budgeting.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of large-scale human genomic data are expected to outline in the budget section of their funding application the resources they will need to prepare the data for submission to appropriate repositories. The policy clarifies that only a basic genomic data sharing plan, in the Resource Sharing Plan section of grant applications, needs to be submitted with the funding application and that a more detailed plan should be provided prior to award. 

 Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - 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 How to Apply- 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

Applications must include one or more delayed onset Studies.

Justification Attachment. Provide a brief description (must be no more than one page) of potential delayed onset study(ies) to be conducted by the CTSN that represent future proof-of-concept/early feasibility/early translation studies, RCTs in the comparative effectiveness realm, and/or innovative trials leveraging registry data and electronic medical records.

The CTSN has established data and safety monitoring principles and processes for all studies conducted within the Network and according to Good Clinical Practices. Applicants are only required to provide a statement that the Data and Safety Monitoring Plan for the CTSN trials is to adhere to the standard CTSN policies and procedures for data and safety monitoring.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. 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. 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.

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 NHLBI 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 NHLBI prior approval.
• Awards issued under this NOFO will be excluded from SNAP.

Applications must be submitted electronically following the instructions described in the  How to Apply – 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  How to Apply – Application Guide.

See more tips for avoiding common errors.

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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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 CSR, in accordance with NIH peer review policies and practices, 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.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 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.

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

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 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 resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The DCC PDs/PIs play an important role in all aspects of CTSN studies, including participating in protocol development, preparing protocol budgets in collaboration with the Clinical Research Centers, modifying proposals if indicated, monitoring recruitment of study participants, assuring the quality of study participant protocol adherence, assuring the accurate and timely transmission of data, analyzing and interpreting data, preparing publications, and enrolling CCs and NHLBI to disseminate research findings. The DCC will also be responsible for working with the CCs and Study Chairs to develop common definitions and standardization across protocols wherever appropriate. Recipients must agree to the governance of the study through a Steering Committee. Investigators will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment and the DCC will monitor this in collaboration with the NHLBI.

Support or other involvement of small business 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 resources may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

PIs are encouraged to publish and disseminate results and other products of the study in accordance with study protocols and governance. For applicable studies, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance. Recipients will retain in custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

The NHLBI project scientists will assist with development of research protocols, monitor patient recruitment and study progress, disclosure of conflicts of interest, and adherence to NHLBI policies. NHLBI will appoint the Study Chairs, Protocol Review Committee (PRC) and the Data and Safety Monitoring Board (DSMB).

The NHLBI-designated lead Project Scientist will serve on the Steering Committee and other study committees, when appropriate, and will have one vote. NHLBI project scientists in collaboration with the lead Project Scientist may work with recipients on issues coming before the SC and as appropriate, other committees, such as: recruitment intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in 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 lead 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. 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. It is not anticipated that the lead Project Scientist will participate in activities that rise to a level of involvement that results in conflicts of interest.  Rather, the Program Official will handle those activities.

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 mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocols or substantive changes in the agreed-upon protocols with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Recipient(s) agree to the governance of the study through a Steering Committee. The Steering Committee will have primary responsibility for identification of priority areas for research, the conduct of protocols, data analysis and the preparation of publications and dissemination products. Steering Committee voting membership shall consist of NHLBI-selected Principal Investigators from high performance CCs, one NHLBI Project Scientist, and Network Chair(s), and one DCC MPI. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
   
• Recipient(s) agree to collaboratively develop achievable/feasible agreed-upon metrics to evaluate the overall success of the CTSN during review by the NHLBI appointed External Expert Panel during years 4 or 5. Metrics should include stakeholder feedback and modifications to enhance the efficiency and scientific rigor of the program.
   
• Recipient(s) agree to negotiate mutually agreed upon milestones during the development of each clinical research protocol and may include such things as time to IRB approval, time to subcontract finalization, first patient screened, first patient enrolled, etc.
   
• A Data and Safety Monitoring Board will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues. An NHLBI scientist, other than the NHLBI Project Scientist, shall serve as Executive Secretary to the Boards. Because the Boards serve as independent groups advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board's Executive Secretary.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. 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.

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.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

Cardiothoracic Surgical Trials Network
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0513 
Email: NHLBI_CTSN@nhlbi.nih.gov 

Center for Scientific Review (CSR) 
Email: NOFOReviewContact@csr.nih.gov
 

Office of Grants Management
National Heart, Lung, and Blood Institute (NHLBI) 
Email: NHLBIOGMInbox@nhlbi.nih.gov
Subject: RFA-HL-27-002

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.