Cardiothoracic Surgical Trials Network (CTSN) Linked Clinical Research Centers (LCRCs)

Cardiothoracic Surgical Trials Network (CTSN) Linked Clinical Research Centers (LCRCs) is sponsored by National Heart, Lung, and Blood Institute (NHLBI). This funding opportunity invites applications from qualified institutions to participate in the Cardiothoracic Surgical Trials Network (CTSN) as Linked Clinical Research Centers.

Expired RFA-HL-19-009: Cardiothoracic Surgical Trials Network (CTSN) Linked Clinical Research Centers (UM1 Clinical Trial Not Allowed ) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Heart, Lung, and Blood Institute ( NHLBI ) Funding Opportunity Title Cardiothoracic Surgical Trials Network (CTSN) Linked Clinical Research Centers (UM1 Clinical Trial Not Allowed) UM1 Research Project with Complex Structure Cooperative Agreement June 15, 2018 - Notice of Frequently Asked Questions for RFA-HL-19-009.

See Notice NOT-HL-18-636 . June 01, 2018 - Notice of Change to Application Instructions for RFA-HL-19-009. See Notice NOT-HL-18-634 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-HL-19-010 , U01 Research Project Cooperative Agreements Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) seeks multi-PD/PI applications for Linked Clinical Research Centers (LCRCs) to support the Cardiothoracic Surgical Trials Network (CTSN).

The National Heart, Lung, and Blood Institute (NHLBI) expects applications with highly innovative clinical trial strategies, novel approaches to patient recruitment and retention for challenging cardiothoracic surgical trials, and the ability to build clinical research capacity in areas of need. The LCRCs add a new paradigm to the CTSN model.

Each LCRC will consist of an experienced academic cardiac surgical clinical trial site ("primary site") linked with a less experienced academic cardiac surgical clinical site in a high cardiovascular disease burden area ("affiliate site"), and will also include a Clinical and Implementation Research Skills Program which will be integrated across the two institutions.

It is expected that a single application will be proposed with two PDs/PIs; one PD/PI from the primary site and one PD/PI from An LCRC primary site is expected to demonstrate a strong track record of prior trial performance and clinical research mentoring; the provision of a developmental platform for junior clinical researchers and implementation scientists; and support for novel techniques and strategies to disseminate study results to impact the care of individuals and improve the An LCRC affiliate site must have conducted fewer than three NHLBI-funded randomized controlled trials per year in cardiac surgery and received less than $3 million in NHLBI total grant funding to the institution in 2017.

The affiliate site should be one that would benefit from research mentoring and a collaborative clinical research opportunity, and be located in a high cardiovascular (CV) disease burdened part of the US or Canada to build capacity in these areas.

For the purposes of this FOA, a high CV disease burdened area is broadly defined as an area or region of the US or Canada that has a preponderance of CV disease including hypertension, obesity, diabetes, and stroke, or other unique disease burden characteristic.

These areas might include the geographic regions incorporating the Mississippi Delta, Appalachia, and the Stroke Belt (South East US), Stroke Buckle (coastal plains areas of the Carolinas and Georgia), Newfoundland/Labrador (Canada), rural or inner-city locales, or involve predominantly minority or low socioeconomic status populations.

A separate solicitation seeks applications for a Limited Competition: Data Coordinating Center (DCC) that will support the Network ( RFA-HL-19-010 ). Open Date (Earliest Submission Date) Letter of Intent Due Date(s) August 2, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. AIDS Application Due Date(s) It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of the Announcement I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description According to the American Heart Association’s most recent Disease and Stroke Statistics 2017 Update ), approximately 92. 1 million American adults are living with some form of cardiovascular disease, including the after-effects of stroke. At least half of this population is age 60 years or older.

Total health expenditures and lost productivity costs of cardiovascular diseases and stroke in the US averaged approximately $316. 1 billion annually in 2012 to 2013 and are projected to be approximately $804 billion in 2020.

Cardiothoracic surgical treatments have been instrumental in addressing many of the most prominent cardiovascular conditions, including coronary artery disease, congestive heart failure, atrial fibrillation (AF) and valvular disease, among others.

Coronary artery bypass grafting (CABG), cardiac valve repairs, mechanical circulatory support devices, and arrhythmia surgery have extended survival and improved quality of life for many patients.

However, the accelerating pace of innovation in surgical practice, including the utilization of new approaches and technologies and the extension of surgical approaches to older patients with greater co-morbidities, continues to outpace the ability of randomized controlled trials (RCTs) to provide an evidence base for establishing improved outcomes and benefit.

Additionally, the advances made in interventional cardiology (e.g., transcatheter-based interventions), particularly over the last decade, compound this issue.

The primary goal of the Cardiothoracic Surgical Trials Network (CTSN) is to design, conduct, and analyze multiple, collaborative clinical trials and studies that evaluate novel products, surgical interventions, and related management approaches, for the treatment of cardiovascular disease in adult patients.

An important objective of the CTSN is to continue to increase the efficiency of clinical research by providing a clinical laboratory in which multiple clinical trials can be conducted without having to create a new infrastructure for each one.

This initiative proposes a transition from a traditional research network model to a flexible clinical trials platform accessible to the research community, industry, foundations, professional societies, and international research entities.

The CTSN has been a successful and impactful clinical research enterprise since 2007, building a cadre of cardiac surgical trials investigators, and a platform for broad collaboration among allied specialties, foundations, professional societies, and industry. Currently the CTSN includes cardiac surgical academic centers across the US, Canada, and Germany.

The CTSN has been instrumental in addressing scientific and public health questions in cardiothoracic surgery, and has proven to be an ideal interdisciplinary infrastructure to link cardiothoracic surgeons with other medical research specialties, including neurology, anesthesiology, and all areas of cardiology.

Moreover, the CTSN is moving into the new area of implementation research, to go beyond adding to scientific knowledge to translate and sustain benefits to populations. The inclusion of implementation research is needed to determine optimal strategies for delivering RCT-proven effective therapies and cardiac surgical approaches to populations, in order to improve CV outcomes in communities.

The key achievements that speak to the importance of this Network include completion and reporting of six RCTs and three large observational studies and multiple ancillary and sub studies, with over 2,000 randomized patients and more than 14,000 observed patients participating.

These trials have been conducted efficiently and at considerable cost savings to the government, as compared to individual investigator-initiated or industry-sponsored trials. The Network has a broad research agenda that includes valvular heart disease, arrhythmias, heart failure, coronary artery disease, and reducing complications of surgery.

The trials have spanned early translation, RCTs in the comparative effectiveness realm to large observational studie s. The Network has produced numerous high impact publications. Findings from the CTSN trials have advanced knowledge and influenced professional society guidelines in the US, Canada and Europe.

Previous Network studies have fallen into three domains: (1) randomized clinical trials in the comparative effectiveness arena; (2) exploratory and proof of concept trials; and (3) observational studies directed at quality improvement. Three trials are currently ongoing as are several ancillary studies.

There is ongoing consideration of new trial concepts from both inside and outside the CTSN as well as efforts to develop new protocols of clinically meaningful questions that address important public health issues. Additional CTSN trial information can be found at http://www. ctsurgerynet.

org/ . This Funding Opportunity Announcement (FOA) seeks multi-PD/PI applications for Linked Clinical Research Centers (LCRCs) to support the CTSN.

The National Heart, Lung, and Blood Institute (NHLBI) expects applications with highly innovative clinical trial strategies, novel approaches to patient recruitment and retention for challenging cardiothoracic surgical trials, and the ability to build clinical research capacity in areas of need. The LCRCs add a new paradigm to the CTSN model.

Each LCRC will consists of an experienced academic cardiac surgical clinical trial site ("primary site") linked with a less experienced academic cardiac surgical clinical site in a high cardiovascular disease burden area ("affiliate site"), and will also include a Clinical and Implementation Research Skills Program which will be integrated across the two sites.

It is expected that a single application will be proposed with two PDs/PIs; one PD/PI from the primary site and one PD/PI from the An LCRC primary site is expected to demonstrate a strong track record of prior trial performance and clinical research mentoring; the provision of a developmental platform for junior clinical researchers and implementation scientists; and support for novel techniques and strategies to disseminate study results to impact the care of individuals and improve the An LCRC affiliate site must have conducted fewer than three NHLBI-funded randomized controlled trials per year in cardiac surgery and received less than $3 million in NHLBI total grant funding to the institution in 2017.

The affiliate site should be one that would benefit from research mentoring and a collaborative clinical research opportunity, and be located in a high cardiovascular (CV) disease burdened part of the US or Canada to build capacity in these areas.

For the purposes of this FOA, a high CV disease burdened area is broadly defined as an area or region of the US or Canada that has a preponderance of CV disease including hypertension, obesity, diabetes, and stroke, or other unique disease burden characteristic.

These areas might include the geographic regions incorporating the Mississippi Delta, Appalachia, and the Stroke Belt (South East US), Stroke Buckle (coastal plains areas of the Carolinas and Georgia), Newfoundland/Labrador (Canada), rural or inner-city locales, or involve predominantly minority or low socioeconomic status A separate solicitation seeks applications for a Limited Competition: Data Coordinating Center (DCC) that will support the Network ( RFA-HL-19-010 ).

To achieve budget efficiencies, while at the same time enhancing the output and scope of the enterprise, the CTSN infrastructure will be modified to include a new clinical research paradigm that will be comprised of an experienced academic cardiac surgical clinical trial site ("primary site") linked with a less experienced academic cardiac surgical clinical site ("affiliate site") in a high cardiovascular disease burden area as a multi-PD/PI application.

The intent is for the experienced primary site to mentor the new, less experienced affiliate site in the conduct of RCTs, including but not limited to: screening, enrolling, randomizing and retaining participants, as well as obtaining informed consent, capturing timely and complete data and maintaining complete, current auditable records.

This will provide an opportunity for the affiliate site to collaborate on impactful cardiac surgical trials and thereby expand clinical research capacity in areas where it is most needed. Funds to support protocol costs associated with the RCTs will be provided through the CTSN DCC award ( RFA-HL-19-010 ), outside investigator-initiated grants, industry and foundations.

An important component of the new CTSN paradigm is that it will establish a develomental platform for the next generation of clinical and implementation researchers. The NHLBI expects that LCRC applications will propose a plan for a Clinical and Implementation Research Skills Program (CIRSP) to expand the skills and knowledge of junior investigators who have the potential to transition into research leadership roles.

It is anticipated that the CIRSP will be integrated across both the primary site and the affiliate site. Applications that propose to address needed diversity within the cardiac surgical clinical research workforce by proposing to include underrepresented minorities are of high programmatic interest.

This FOA seeks applications for LCRCs with the ability to: Work cooperatively within CTSN to design impactful cardiothoracic surgical trials and to conduct the trials with rigorous good clinical practice Identify, enroll and retain participants in sufficient number to complete trials in a timely and efficient manner Interface with a variety of cardiovascular databases and registries and incorporate these resources into innovative trial designs Assemble the resources necessary for optimal conduct and support of CTSN activities and studies Integrate questions and endpoints into the design of RCTs that can inform subsequent implementation activities to enhance adoption by the surgical community post study and bolster translation of findings Provide skills development opportunities in the conduct of cardiothoracic surgical trials and clinical research and implementation science, contributing to the development of the next generation of clinical and implementation researchers Organization and Governance In this funding cycle, the CTSN will be a cooperative Network of up to five academic LCRCs, a DCC, a rotating Network Chair (cardiothoracic surgeon) and rotating Co-Chair (cardiologist), a Vice Chair for Strategic Development, a Vice Chair for International Collaboration, and NHLBI.

Clinical Research Centers (LCRCs) are responsible for proposing and developing protocols, recruiting participants, entering data into the web-based data entry system, assuring good clinical practice, developing skills of junior investigators in both clinical research and implementation science, and disseminating research findings.

All LCRCs are required to participate in a cooperative and interactive manner with one another and with the Data Coordinating Coordinating Center, described in more detail in RFA-HL-19-010 , 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 clinical centers (both LCRCs and Consortium Centers) 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.

Center (CC) sites are subcontracted through the DCC to enhance trial enrollment, protocol development, manuscript preparation, and other key Network activities. These sites are reimbursed on a per-capita basis and do not receive infrastructure funding. It is anticipated that up to 40 CCs in the US, Canada, and Europe will participate.

Steering Committee (SC) is the main governing body of the CTSN. The SC comprises the Principal Investigators (PDs/PIs) from the LCRCs and the DCC, the Network Chair, co-Chair, Vice Chairs, and NHLBI staff. Voting members of the SC include the Chair (a cardiothoracic surgeon) and Co-Chair (a cardiologist), the Vice Chairs and the remaining PD/PIs of the LCRCs and DCC, and the NHLBI Program Official.

The Chair and Co-Chair positions may be rotated among the LCRC Investigators and others as appropriate. 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 an average of twice a year and by teleconference on a monthly basis. This Committee ensures that all decisions are reported to the Investigators Committee.

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 Investigators Committee (IC) consists of all CTSN investigators and study coordinators from the LCRCs and Consortium Centers, staff members from the DCC and NIH, and the CTSN Chair, co-Chair and Vice Chairs.

The Network Chair, Co-Chair and Vice-Chairs are named by NHLBI to oversee and guide SC and IC activities. The IC meets in-person an average of twice a year and by teleconference on a monthly basis. Subcommittees are established as necessary and membership includes physician and nurse investigators from the LCRCs and 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 (management, financial and administrative oversight). In addition to regular award oversight, the NHLBI Project Scientists 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, Co-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. Review Committee (PRC) is appointed by and advisory to the NHLBI.

It consists of a chairperson and clinicians and scientists with expertise in basic and clinical cardiothoracic surgery research, 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 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. 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 Review Committee with expertise in areas such as cardiothoracic surgery, cardiology, cellular therapy, 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.

Areas of Research Interest and Experimental Approaches Being Sought This FOA focuses on clinical studies in the 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.

The Network has identified a range of timely and clinically important questions in cardiac surgery, which will require further development. Clinical trial/study protocols being contemplated and/or developed in the Network fall into two categories: 1) actively underway and 2) ready for implementation.

The following three high-priority research questions are actively underway by the Network at the current time : 1) long-term neurological and cognitive outcomes following AVR; 2) bundled payment and 90-day readmissions after CABG surgery; and 3) patient-centered outcomes and the creation of a patient alliance.

The Network has identified four high-priority research areas to develop trial protocols that may be ready for implementation after the start of the funding period : 1.

Preventing and Managing Thrombo-Embolic Risk: In follow-up of the CTSN Neuroprotection Trial ( NCT02389894) , the Network investigators in conjunction with Industry (should there be funding interest) are considering developing cerebral embolic protection trial protocols for novel interventions, such as second-generation embolic protection devices, new drugs and/or biologicals, such as nitric oxide. 2.

Anticoagulation Management Strategies for Bioprosthetic Valves and AF: Many questions remain regarding the post-operative management of several cardiac surgical patient subsets, particularly those with AF and/or valve repairs or replacements.

A future CTSN trial may evaluate when it is safe to start an alternative direct oral anticoagulant (e.g., apixaban) in non-mechanical heart valve patients with an indication for anticoagulation after CT surgery. Patient groups could include those with post-operative AF and/or bioprosthetic heart valve replacements or annuloplasty repairs.

A particular area of intense interest involves the recent recognition of bioprosthetic leaflet thrombosis and the comparative efficacy of antiplatelet versus anticoagulant agents for its prevention and treatment. 3. Valvular Heart Disease: Several important trials can be developed in the valvular heart disease realm.

A trial focused on relative merits and long-term outcomes of SAVR versus TAVR in bicuspid aortic valve disease is under consideration. Bicuspid aortic valve disease has been excluded from TAVR pivotal trials, but TAVR is increasingly used in this population, despite a relatively weak evidence base. Another potential study in collaboration with TVT investigators might seek to evaluate QOL after SAVR versus TAVR, leveraging registry data.

4. Circulatory Assist Devices and Cardiac Regeneration: The Network has built expertise in conducting stem cell trials in LVAD patients, and could conduct a follow-up trial of the nearly-completed LVAD MPC II Trial ( NCT02362646 ), or expand our portfolio by evaluating new biologicals, such as cardiosphere-derived cells, exosomes, or human embryonic stem cells derived from cardiomyocytes.

Optimizing outcomes in patients receiving circulatory support alone remains an important goal. A randomized trial of a constellation ( bundle ) of management strategies versus standard therapy to reduce complications in LVAD patients is under consideration.

Finally, cardiogenic shock remains a high-mortality condition, and the Network investigators are exploring trials of both ECMO and percutaneous VADs to improve the fate of this Multiple trials will be conducted during the project period. Trial protocols that are under development in the CTSN will be considered for Network funding by the CTSN Steering Committee once the funding period for this FOA has commenced.

It is anticipated that each protocol will be implemented in all of the LCRCs and in the Consortium Centers that have the appropriate patient populations. Specific protocol reimbursement will be determined for each protocol and negotiated with the participating centers. During this award cycle, trials will be supported with CTSN funds, individual investigator-initiated grant awards and through industry and foundation collaborations.

While a finite number of trials will be supported directly through CTSN funding, the Network expects to complete between 7-10 trials due to the utilization of new revenue streams.

Outside independent investigators and small businesses wishing to collaborate with the CTSN will have the opportunity to submit grant applications through the NHLBI multi-center clinical trial FOAs ( PAR-18-407 and PAR-18-410 ) which will in turn support CTSN infrastructure and provide protocol reimbursement costs.

Other entities, such as industry, foundations and international research entities who share scientific research priorities, similarly will be encouraged to approach the CTSN Leadership to sponsor/fund and conduct collaborative trials and studies.

Collaborations with the Patient Centered Outcomes Research Institute (PCORI) and the Centers for Medicare and Medicaid Services (CMS) addressing patient-centered outcomes, patient advocacy, and cost effectiveness will be strongly encouraged. Cardiovascular device trials in collaboration with the FDA Center for Devices and Radiological Health utilizing innovative approaches and statistical designs will also be strongly VIII.

Other Information for award authorities and regulations. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this FOA. Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Not Allowed: Only accepting applications that do not help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. NHLBI intends to commit total costs of up to $3,200,00 in FY2019 to fund up to 5 Application budgets must not exceed $400,000 direct costs per year in Fiscal Years 2019 through 2025. The scope of the proposed project should determine the project period.

The maximum project period is up to 7 years. Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Foreign Institutions and foreign components based only in Canada Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply but only if they are based in Canada.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply except for Canadian components. Foreign components, as defined in the NIH Grants Policy Statement , are not allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually .

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to must have an active DUNS number and SAM registration in order to complete the Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

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

Eligible Individuals (Program Director/Principal Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 Multi-PD/PI applications are required in response to this FOA.

It is expected that a single application will be proposed with two PDs/PIs; one PD/PI from the primary site and one PD/PI from the affiliate site. Applications that do not use a Multi-PD/PI application will be considered non-compliant and will not proceed to peer review . This FOA does not require cost sharing as defined in the NIH Grants Policy Statement .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ). Section IV. Application and Submission Information Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA.

See your administrative office for