RFA-HL-27-002-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Single Source: Cardiothoracic Surgical Trials Network (CTSN) Data Coordinating Center (U01 Clinical Trial Required)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of

RFA-HL-19-010

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-HL-27-002

Companion Funding Opportunity

None

Number of Applications

Only 1 application per institution is allowed. See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.837, 93.838, 93.233, 93.839, 93.840

Funding Opportunity Purpose

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 if it is not a meritorious application, it will not be funded. This single source NOFO is intended to support a Data Coordinating Center (DCC) to conduct the activities of the Cardiothoracic Surgical Trials Network (CTSN). 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. 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 will coordinate outreach activities including engaging foundations, research entities, and small businesses in trials of mutual interest and public health importance. The DCC is responsible for integrating the efforts of 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 manage a Clinical and Implementation Research Skills Program centrally. The clinical and implementation research scholars program will support the expanded integration of clinical skills with dissemination and implementation science scholarship to enhance implementation research capacity. The scholars program would be designed to foster additional research questions within CTSN as well as generate a cohort of researchers who would transport their scholarship as they transition to leadership positions in academic and clinical programs.

Funding Opportunity Goal(s)

The National Heart, Lung, and Blood Institute (NHLBI) provides global leadership for a research, training, and education program to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives.

Key Dates

Posted Date

May 27, 2026

Open Date (Earliest Submission Date)

June 05, 2026

Not Applicable

July 07, 2026

Not Applicable

April 2027

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).

Due Dates for E.O. 12372

Not Applicable

Expiration Date

July 08, 2026

Required Application Instructions

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.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of 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

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:

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

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

Renewal

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NHLBI intends to commit up to $8M in total costs for a new award in Fiscal Year 2027; $8.1M in total costs for fiscal years, 2028, 2029, 2030, and 2031; and $8.0M in total costs for fiscal years 2032, and 2033. This is a total of $56.4M over seven years of funding. The NHLBI intends to fund up to 1 new award in Fiscal Year 2027.

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Total application budgets for non-protocol costs must not exceed $6,161,728 in direct costs in Fiscal Year 2027, $6,261,728 in direct costs per year in Fiscal Years 2028-2031, and $6,161,789 in direct costs per year in Fiscal Year 2032 -2033.

Total application budgets for protocol costs must not exceed $1,838,272 per year in Fiscal Years 2027-2033.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is up to 7 years.

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

Eligible Organizations

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.

Required Registrations

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.

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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.

Instructions for Application Submission

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

SF424(R&R) Senior/Key Person Profile

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

Application budgets must plan for the following:

For all non-protocol costs:

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

PHS 398 Cover Page Supplement

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.