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
Lung Transplant Consortium - Data Coordinating Center (U24 - Clinical Trial Not Allowed)
Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-HL-22-003
Companion Funding Opportunity
RFA-HL-22-002 , U01 Research Project (Cooperative Agreements)
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.838
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications to serve as the Data Coordinating Center (DCC) that will support the research activities of a cooperative multi-site Lung Transplant Consortium (LTC).

The primary responsibility of the DCC will be to oversee the conduct of multiple observational and complementary mechanistic clinical research studies involving lung transplantation performed under a common research protocol by awarded Clinical Centers (CCs) within the LTC. The NHLBI anticipates that the DCC will collaborate strategically with the CCs to provide support for regulatory and administrative activities, common research protocol development, statistical data analysis, data and biospecimen collection and storage, the reporting of study results through publication in a timely manner, and the dissemination of datasets and biospecimens for secondary analyses by the broader research community at the conclusion of the program. The DCC will promote collaboration and communication among LTC investigators and will coordinate outreach activities including engaging foundations, societies, and other entities with a shared interest in lung transplantation. The DCC will be responsible for integrating the efforts of 8 Clinical Center awards consisting of approximately 24 sites performing local site-specific observational research studies to identify factors that impact donor lung utilization and early post-transplant outcomes such as primary and acute lung allograft dysfunction in lung transplant recipients. In addition, the DCC, in partnership with the LTC Steering Committee, will oversee the creation and implementation of a common research protocol to enroll participants for collection of a core set of data and biospecimens across all participating consortium sites. By leveraging this shared longitudinal resource, LTC investigators will have the tools to identify and answer additional important research questions involving lung transplantation.

This FOA runs in parallel with the LTC Clinical Centers (see RFA-HL-22-002).

Key Dates

Posted Date
February 25, 2021
Open Date (Earliest Submission Date)
May 15, 2021
Letter of Intent Due Date(s)

May 15, 2021

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
June 15, 2021 Not Applicable Not Applicable November 2021 January 2022 April 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
June 16, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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.

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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Lung transplantation serves as end-stage therapy for a number of chronic and potentially fatal lung diseases including idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and pulmonary arterial hypertension (PAH). As such, demand for lung transplantation continues to grow annually, evidenced by a considerable increase in candidates being listed for transplantation and record numbers of lung transplant surgeries being performed with every passing year. However, the demand for donor organs continues to far exceed supply. According to data from the Organ Procurement and Transplantation Network (OPTN) in 2018,more than 1,400 candidates remained on the waiting list for this lifesaving procedure at year’s end; 365 others died or became too sick for transplantation while waiting. Moreover, in adult lung transplant recipients, five-year mortality is 40%, a rate that is approximately two-fold higher than current mortality or graft failure rates among other solid organ transplant recipients. In addition, studies estimate that up to 40% of unused donor lungs may have been suitable for transplantation, suggesting room for and potential benefit derived from increased donor lung utilization.

Lung transplant recipient clinical outcomes are substantially worse than for other solid organs, as median survival following adult lung transplantation stands at 6.2 years and has only marginally improved over the last decade. The reasons for lung transplant failure are many, ranging from primary graft dysfunction (PGD) in the early days post-transplant, to setbacks stemming from acute lung allograft dysfunction (ALAD) over the following weeks and months, to the development of chronic lung allograft dysfunction (CLAD) that becomes clinically apparent years later. PGD is a form of ischemia-reperfusion injury and is the leading cause of death in the first 30 days post-transplant. Beyond 30 days, the majority of deaths in the first year are attributable to ALAD associated most commonly with infection, acute cellular rejection (ACR), or antibody-mediated rejection (AMR). Importantly, PGD and ALAD are also the primary risk factors for the development of CLAD, which in turn leads to lung allograft failure in the majority of patients beyond the first year. However, the basic and clinical mechanisms that give rise to these post-transplant complications remain largely unknown.

The incidence of PGD and ALAD varies widely among lung transplant centers, raising the prospect that site-specific donor and recipient clinical assessment and management practices contribute to this variability. The contribution of particular clinical practices to the incidence and pathogenesis of PGD and ALAD is understudied, which makes it difficult to identify reasons for center variability in outcomes and poses a significant barrier to performing multi-site clinical research studies and interventional trials in lung transplantation.

The goal of this program is to begin to overcome these barriers by creating the Lung Transplant Consortium (LTC) to serve as a research platform for advancing our understanding of how certain site-specific lung transplant selection criteria and clinical management strategies influence donor lung utilization and/or early post-transplant outcomes including PGD and ALAD. In addition, the LTC will build, through consensus, harmonized and standardized observational data and biospecimen collection for a core set of variables across all participating sites. Through this systematic collection of data and biospecimens under a common research protocol, the LTC will provide a basis for performing additional large, unbiased, and well-controlled observational and mechanistic studies investigating factors that influence the incidence and severity of outcomes like PGD and ALAD, and by extension CLAD, across many active lung transplant centers.

Purpose and Objectives

This Funding Opportunity Announcement (FOA) is intended to support the Data Coordinating Center (DCC) that will facilitate the organization and conduct of all shared research activities within the Lung Transplant Consortium (LTC). The LTC will bring together approximately 24 lung transplant sites (funded through up to 8 collaborative multi-site Clinical Center awards under the companion RFA-HL-22-002) and the DCC to form a cooperative research platform for performing observational and complementary mechanistic studies involving lung transplantation. The LTC will also be supported by project scientists from the NHLBI and the Human Resources and Services Administration (HRSA), as well as an NHLBI-appointed Protocol Review Committee, Observational Study Monitoring Board (OSMB), and External Advisory Board (EAB).

The Clinical Centers (CCs) will be tasked with the local conduct of observational and related mechanistic studies evaluating site-specific lung transplant selection criteria and clinical management strategies as they relate to donor lung utilization and/or post-transplant outcomes such as the development of primary graft dysfunction (PGD) and acute lung allograft dysfunction (ALAD) in recipients as proposed in their respective applications. The DCC will serve to facilitate the standardized collection of a core set of data variables and biospecimens from lung transplant donors, candidates, and/or recipients across all participating CCs that can be used to perform studies that inform lung transplant donor/candidate selection criteria and/or treatment approaches to the development of PGD and ALAD in recipients. Beyond improving our understanding of factors that influence the incidence of these important post-transplant complications through local studies performed at the CCs, the harmonization of a subset of clinical data and biospecimen collection by the DCC across all participating lung transplant centers will serve as a critical first step towards standardizing early clinical management and assessment practices in lung transplantation and facilitating future clinical trials to optimize donor lung utilization and improve short- and long-term outcomes for lung transplant recipients.

Each CC application funded under the companion RFA-HL-22-002  will involve hypothesis-driven scientific questions assessing donor, candidate, and/or recipient clinical practices and their impact on donor utilization or short-term post-transplant outcomes such as PGD and ALAD that can be addressed through observational data collection and analysis at the sites included in their application. These studies may also be complemented by proposed mechanistic analyses of biological data to connect these practice patterns with biomarkers and/or biological or behavioral changes associated with early lung transplant outcomes. Participation in the LTC is also contingent upon the CCs agreeing to the standardized and cooperative collection of a core set of clinical data elements and biospecimens through a common protocol shared across all participating sites. Development of the common protocol will be facilitated by the DCC and several meetings of the LTC Steering Committee to select the core data variables and biospecimens. Once a common protocol governing the set of core data variables and biospecimens is established, the Steering Committee in conjunction with the DCC will iteratively consider adding variables or biospecimens to the core dataset based on results from the hypothesis-based longitudinal studies running in parallel at the individual CCs. In addition, LTC investigators will have the opportunity to propose studies that leverage the common protocol data and biospecimens by identifying important research questions involving lung transplantation that require use of this unique shared longitudinal resource to adequately answer.

Responsibilities of the Data Coordinating Center (DCC)

It is expected that the DCC will utilize the cooperative U24 resource infrastructure to strategically collaborate with the CCs to provide support for regulatory and administrative activities, common protocol development and related aspects of studies conducted under this protocol including data/biospecimen collection, storage, and analysis, the reporting of study results through publication in a timely manner, and the dissemination of datasets and biospecimens for secondary analyses by the broader research community at the conclusion of the program. The DCC will promote collaboration and communication among LTC investigators and will coordinate outreach activities including engaging foundations, societies, and other entities with a shared interest in lung transplantation. The DCC will also facilitate development and review of the common protocol through the SC, PRC, and OSMB processes after CC cooperative agreement awards are made. Protocol funds (approximately $1,309,000 total costs per year) to support execution of consortium-wide studies (i.e. data and biospecimen collection and analysis that occurs under the common protocol) at the CCs will be a part of the DCC cooperative agreement award and will be distributed back to the approximately 24 individual CC sites via subcontract from the DCC on a per-enrollee basis and according to Steering Committee- and NHLBI-approved common protocol budgets. Additional details regarding these areas of responsibility are described below:

Overall Management and Coordination

Management of overall funding of the DCC grant award, project timelines, and establishment of an LTC website that is updated at regular intervals.

Administrative Management

Administrative support to the LTC Chair and Co-Chair, the SC, and other stakeholders as needed, including but not limited to drafting meeting or teleconference agendas and minutes, manuscripts, and presentations; Coordination and facilitation of meetings, teleconferences, and training among study personnel, committees, subcommittees, oversight bodies such as the PRC, OSMB, EAB, and other collaborators.

Common Protocol Development, Study Design, and Analysis

Lending study design, statistical and biomedical scientific writing expertise to the Common Protocol Committee, including defining sample size requirements, assisting in the determination of study endpoints and analytical approaches for CC proposals to leverage the common protocol data/biospecimen resources. Facilitation of Common Protocol Committee meetings/teleconferences to ensure that the protocol is developed and executed within specified LTC timelines, and review of the common protocol through the SC, PRC, and OSMB processes. The DCC will also oversee data and biospecimen-related document development and finalization for each common protocol study. Once the common protocol has been established, each CC will be expected to enroll a minimum of 75 lung transplant recipients (or approximately 75% of the CC's cumulative lung transplant volume) per year for data and biospecimen collection into the common protocol. CC applicants are required to demonstrate the feasibility of meeting that enrollment requirement among the collaborating lung transplant centers in their application. In addition, if the local CC study involves lung transplant donors or candidates, the CC will be expected to enroll 75% of those participants into the common protocol as well. It is anticipated that the biospecimens collected under the common protocol may include, but are not limited to, blood, urine, bronchoalveolar lavage fluid, lung biopsy tissues, and radiographic or other medical images. LTC investigators will also have the opportunity to design, propose, and if approved by the LTC governance apparatus as outlined below, perform studies that leverage the common data and biospecimens to answer important questions involving lung transplantation made possible by the existence of this unique resource. Based on these expectations, DCC applicants should plan for coordinating the prospective enrollment of 800 participants per year from the CCs into the common protocol from Q4 in Year 1 through Q3 of Year 5 (i.e. 3200 total prospective common protocol enrollees over a 4 year period). This timeline is intended to provide adequate time for common protocol development in the Year 1, enrollment and follow-up halfway through Year 5, and the completion of data analysis, manuscripts, and study closeout by the end of Year 5.

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 studies conducted by the LTC, assuring high data quality through edit/validation checks; Serving as a central repository for study data and a central biorepository for biospecimens pertinent to the common protocol studies. Additional DCC responsibilities are expected to include overseeing secure data and biospecimen collection, storage, and, when appropriate, transfer of study-generated data; preparing confidential data analyses and reports as requested by the NHLBI, the SC, the OSMB, and regulatory agencies; and coordinating data analysis, reporting, and publishing of LTC research in high-quality peer-reviewed journals, as they relate to the common protocol. A required function of the DCC is to make common protocol data available to the LTC investigators during the project period, and to the public after study completion, consistent with the NIH Policy for Data Management and Sharing (NOT-OD-21-013). The DCC is expected to facilitate the sharing of common protocol data and biospecimens to the broader research community upon study completion via deposition into publicly available resources including the NHLBI Biorepository (BioLINCChttps://biolincc.nhlbi.nih.gov/home).

Clinical Center Reimbursement

Administration of approximately 24 individual CC site subcontracts and other agreements as necessary to facilitate reimbursement for enrollment, biospecimen collection (including associated procurement, storage, and shipping costs), and biospecimen/data analysis (at the CCs or other contract facilities as needed) under the common protocol after they have been approved by the PRC and OSMB and the NHLBI has approved the funds for distribution; Integration of common protocol activities of all awarded CCs and CC subaward sites to minimize duplication of effort and to maximize resources by utilizing existing resources whenever possible; Establishment and tracking of site enrollment targets. Additionally, the NHLBI anticipates the DCC will prepare, distribute for review, finalize, and then disseminate the approved common protocol, protocol amendments, manual of procedures (MOP), and other materials necessary for consortium-wide study conduct. The DCC will provide common protocol training upon initial approval, following significant amendments, and otherwise as needed. Applicants should note that only research-related costs above those incurred as part of usual clinical care are eligible to be covered by grant funds and/or reimbursement via protocol costs from the DCC.

Biorepository Establishment and Management

Establishment of a centralized Biorepository with necessary personnel, equipment, and protocols. Administration of subcontracts to the approximately 24 CC sites including providing reimbursement to these facilities for associated procurement, storage, and shipping costs related to the collection and transfer of biospecimens collected under the common protocol into the centralized biorepository, and subsequently out to core facilities/laboratories (at the CCs or otherwise) as needed for analysis in a timely manner. The DCC will also develop standardized protocols for the collection, storage, and shipment of biospecimens (e.g. blood, urine, BAL fluid, lung tissue) into and out of the Biorepository, provide training of Clinical Center personnel on the proper collection and storage of biospecimens as needed, and will maintain accurate inventories of what is available in the Biorepository.

Human Subjects Protection

Overseeing the preparation of informed consent templates, recruitment brochures, and other common protocol study-related patient materials; Ensuring that all DCC and CC personnel are trained on common protocol human subjects procedures including the informed consent process, LTC policies, applicable regulations, and Good Clinical Practice (GCP). Additional DCC responsibilities in this area include routine tracking and reporting of adverse events and unanticipated problems to NHLBI, the OSMB, and other regulatory agencies as appropriate. Monitoring study execution at Clinical Centers to assure compliance with the common protocol, manual of procedures, LTC policies, applicable regulations and guidelines throughout the duration of the program. The DCC will be expected to identify any study-related issues at the CCs 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 plans.

Regulatory Affairs and Compliance

Assuring compliance with the Health Insurance Portability and Accountability Act (HIPAA) within the LTC in accordance with 45 CFR Parts 160, 162, and 164 or corresponding regulations for any participating international Clinical Centers; Implementation and supervision of the revised Common Rule (45 Part 46) within the LTC, including the use of a single-IRB review for federally-funded, multi-institutional studies conducted in the United States. In addition, the DCC will be expected to register and report results of common protocol clinical studies in ClinicalTrials.gov as required by 42 CFR Part 11. Establishing and maintaining written procedures for all internal processes within the DCC.

Given these numerous duties, the NHLBI strongly encourages multi-PD/PI applications with at least two PDs/PIs; one a senior statistician with demonstrated experience in coordinating large multi-site clinical research studies and another senior investigator with extensive clinical research experience and expertise in the areas of lung transplant pulmonology and/or lung transplant surgery.

LTC Consortium Organization and Governance

It is anticipated that the LTC will be a cooperative consortium comprised of approximately 24 lung transplant sites (funded collectively through up to 8 collaborative CC awards funded via the companion FOA, RFA-HL-22-002), a DCC (funded via this FOA), a Steering Committee Chair and Co-Chair, and program staff from the NHLBI and the Health Resources and Services Administration (HRSA). The NHLBI will also appoint an independent Protocol Review Committee (PRC), an Observational Study Monitoring Board (OSMB), and an External Advisory Board (EAB).

The LTC Data Coordinating Center (DCC) will coordinate, administer, and support all LTC clinical research, operational, administrative, and statistical activities related to the common protocol. These activities may include but are not limited to supporting the development of a standardized common protocol to guide core data and biospecimen collection across participating sites; developing a manual of procedures and electronic case report forms; providing sample size calculations, statistical advice, patient questionnaires, and data analysis; supporting manuscript preparation; and providing overall study coordination and quality assurance, including support for the Steering Committee (SC), the Protocol Review Committee (PRC), the Observational Study Monitoring Board (OSMB), and the External Advisory Board (EAB). Protocol funds (approximately $1,309,000 total costs per year) to support execution of consortium-wide studies (i.e. data and biospecimen collection and analysis that occurs under the common protocol) at the CCs will be a part of the DCC cooperative agreement award and will be distributed to the CCs by the DCC on a per-enrollee basis and according to Steering Committee- and NHLBI-approved common protocol budgets.

A Steering Committee (SC) will be the main governing body of the LTC. Voting members of the SC will include two representatives (one a lung transplant pulmonologist and one a lung transplant surgeon) from each CC award, two representatives from the DCC award, the SC Chair, the SC co-Chair, and one NHLBI Project Scientist. Additional Project Scientists/Program Staff from NHLBI and the Health Resources and Services Administration (HRSA) may participate on the SC as non-voting members. NHLBI will appoint the SC Chair and Co-Chair who are independent of the CC and DCC. The SC Chair and Co-Chair will be compensated for their effort and travel by subcontract from the DCC, and will be responsible for ensuring that there are well-documented policies and procedures in place to guide all aspects of LTC-associated activities and operation. In collaboration with NHLBI staff, the Chairs will facilitate LTC activities, oversee its functions, and conduct SC meetings. The SC has primary responsibility for the general organization of the LTC, approval of the common protocol and any subsequent protocol changes, the conduct and monitoring of LTC studies, and the expeditious reporting of study results. All major scientific and administrative decisions are determined by majority vote of the SC, which will meet in-person, when possible, at least once per year and by teleconference on at least a monthly basis. The SC will also contain a number of subcommittees, including those to oversee the Biorepository, Common Protocol Studies, and Data Dissemination.

During the first award year, the SC in conjunction with the DCC will be responsible for developing the common protocol for use across all participating centers that outlines standardized procedures for the collection of a subset of core clinical data and biospecimens across all participating CC sites within the LTC. It is expected that the common protocol may be refined iteratively over the course of the project period as new data become available. The common protocol, and any subsequent changes to that protocol, will be voted on and must be approved by majority vote of the SC in order to be implemented. The SC will also be responsible for reviewing and approving proposed studies from LTC investigators that seek to utilize the data or biospecimens collected under the common protocol to answer critical scientific questions involving lung transplantation. SC-approved common protocol studies that have not previously been peer reviewed will be referred to an independent Protocol Review Committee (PRC) and an Observational Study Monitoring Board (OSMB) for review and approval.

An independent Protocol Review Committee (PRC) will be appointed by and advisory to the NHLBI. It will consist of a chairperson, clinicians and scientists with expertise in clinical pulmonology and thoracic surgery research, observational study design, outcome measures, biostatistics, ethics, and other areas of expertise as needed. The PRC will review and, if deemed appropriate, approve common protocol-related studies put forth by the Steering Committee. The PRC will evaluate proposed common protocol studies on the basis of the significance of the questions to be addressed, scientific merit, innovation of the experimental design and approach, feasibility, appropriateness in the context of the LTC program goals, and consistency with NHLBI's mission and policies.

An Observational Study Monitoring Board (OSMB) will be appointed by and advisory to the NHLBI. The OSMB will be responsible for providing independent advice to the NHLBI regarding study safety and related ethical considerations, the progress of each study, and the appropriateness of continuing each study performed by the LTC. The OSMB will also review and, if deemed appropriate, concur with the implementation of the common protocol and associated studies approved by the Protocol Review Committee. The OSMB will meet approximately every six months, with interim meetings as necessary.

An independent External Advisory Board (EAB) with regulatory and scientific expertise in areas including but not limited to transplant pulmonology, thoracic surgery, ethical issues in organ transplantation, and organ procurement and allocation policies will be appointed by NHLBI and advisory to the NHLBI and the Steering Committee on opportunities to improve operations, facilitate data dissemination and review by interested parties, and future scientific directions.

The NHLBI is responsible for organizing and providing overall support for the LTC. NHLBI Program Officers and the Office of Grants Management are responsible for the federal stewardship of the grant awards (management, financial, and administrative oversight). In addition to regular award oversight, NHLBI Project Scientists will be involved substantially with the awardees as a partner, consistent with the Cooperative Agreement mechanism.

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

Section II. Award Information

Funding Instrument

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
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need 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 $2,387,000 per year in fiscal years 2022-2026 to support up to 1 award.

Award Budget

Application budgets are limited to $700,000 direct costs in each year of the project period, but should reflect the actual needs of the proposed project.

In addition, protocol funds ($1,309,000 in patient care costs per year) will be included in the Data Coordinating Center award and will be distributed to the Clinical Centers in accordance with Steering Committee- and NHLBI-approved budgets for the enrollment and execution of studies under a common protocol that governs the collection of a core set of data and biospecimens across all participating sites.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

The NHLBI strongly encourages multi-PD/PI applications with at least two PDs/PIs; one a senior statistician with demonstrated experience in coordinating large multi-site clinical research studies and another senior investigator with extensive clinical research experience and expertise in the areas of transplant pulmonary and/or thoracic surgery.

2. Cost Sharing

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

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.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

In addition, the PDs/PIs should describe any prior experience working productively in collaborative programs.

The NHLBI strongly recommends that the Key Personnel include:

  • A senior PD/PI with biostatistical expertise and a demonstrated experience in coordinating large multi-site clinical research studies.
  • A senior PD/PI with extensive clinical research experience and expertise in the areas of transplant pulmonology and/or thoracic surgery.
  • A co-investigator with experience in the establishment/day-to-day management of a human tissue biorepository.
  • An information technology professional with a degree 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 study data (to include medical imaging data) management systems and support systems (e.g., web-based document management and tracking systems), data systems validation, and website design and management.

R&R Budget

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

Application budgets should plan for the following:

  • A suggested cumulative 4.8 person-months among the PD(s)/PI(s) to cover expenses related to supervision of the day to day operation of the DCC, and contribution and oversight of DCC professional activities.
  • For other Investigators/Staff, the person-months should be commensurate with the effort required for the proposed personnel activities. This should include biostatistical support staff with demonstrated experience in the oversight of large clinical research studies and datasets to manage the DCC's day-to-day activities involving data management and statistical analysis and clinical research support staff with demonstrated clinical research experience to facilitate the day-to-day clinical study operations of the DCC including: managing collaborations with other clinical research coordinators; receipt, processing, and storage of human biospecimens; a comprehensive knowledge of GCP study conduct; development of study enrollment accrual benchmarks; generation of case report forms; administration of agreements with clinical centers and other research collaborators.
  • Expenses related to the development and implementation of the common protocol, including designing case report forms, informed consent documents, a manual of procedures, methods for timely safety monitoring and reporting of adverse events to the appropriate entities, study monitoring reports to track patient accrual, follow-up rates, adherence to protocol, and data quality. Applicants should assume that each awarded Clinical Center has the capacity to enroll on average up to 100 study participants (i.e. 800 prospective annual enrollees) for multiple data collection points per year into the common protocol beginning in Q4 in Year 1 through Q3 in Year 5 of the project period (i.e. 3200 total prospective enrollees).
  • Support for the Steering Committee Chair and Co-Chair at 1.0 person-month each.
  • Expenses related to managing the Steering Committee to include travel expenses for two DCC representatives to attend at least one meeting occurring annually in-person in Bethesda, Maryland, and other meetings occurring at least monthly by conference call.
  • Expenses related to managing the Observational Study Monitoring Board to include remuneration for services provided and travel expenses for approximately 5 members to attend a one-day meeting occurring in-person in Bethesda, Maryland, during the first year and additional meetings by conference call on an as-needed basis but no less frequently than every 6 months thereafter.
  • Expenses related to managing the Protocol Review Committee to include remuneration for services provided and travel expenses for approximately 5 members to attend one meeting occurring in-person in Bethesda, Maryland, during the first year and additional meetings on an as-needed basis by conference call.
  • Expenses related to managing the External Advisory Board to include travel expenses for approximately ten members to attend one in-person meeting occurring in conjunction with the Steering Committee meeting in-person in Bethesda, Maryland, during the first year and by teleconference during the annual Steering Committee meetings in subsequent years.
  • Site monitoring activities that will be conducted via centralized monitoring to the extent possible, but provisions for site visits to improve training and site performance as needed.
  • Expenses associated with contracting and the day to day oversight and operational management of approximately 24 individual CC sites for training on GCP, the implementation of the common protocol and related data and biospecimen collection.
  • Expenses associated with the day to day operations of a centralized biorepository: to include the expenses associated with procurement, storage, and shipping of common protocol biospecimens from the CC sites to the DCC, training site coordinators and other study personnel to obtain the data and biospecimens for shared protocols in a uniform manner, and instituting quality control measures. It is anticipated that the biospecimens collected under the common protocol may include, but are not limited to, blood, urine, bronchoalveolar lavage fluid, and lung biopsy tissues. Expenses associated with obtaining the data and biospecimens for local site protocols will not come from the DCC, but rather the individual CC budgets as proposed in their respective applications. The biorepository budget should include sufficient labor to establish procedures that meet quality standards of the NHLBI Biorepository (BioLINCC). Expenses should include plans for facilitating data and biospecimen analyses on common protocol biospecimens at the direction of the Steering Committee a proposed by CC investigators, (e.g. sample collection kits assuming several types of biospecimens that would be useful for molecular phenotyping of inflammatory and other biomarkers, expression analysis, and tissue analysis), shipping containers and shipping costs for the CCs, costs for storage at the DCC biorepository during the project period, and costs for final shipping to the NHLBI Biorepository upon study completion. Costs for biospecimen quality assurance should be described. The biospecimen collection plan will be finalized by the SC, but the DCC should present a vision and budget for the biospecimen collection. A subcontract may be proposed for the Biorepository.
  • Expenses associated with providing statistical support to the CCs and analysis of aggregate common protocol data, including the development and maintenance of systems for data entry, transmission, quality control, and analysis.
  • Expenses associated with the creation and maintenance of a secure data access portal with project management dashboards to coordinate efficient workflow, assessment of progress, and enable open access of study data to LTC investigators, as well as related costs to ensure compliance with the NIH Data Management and Sharing Policy.
  • Costs related to the design and maintenance of an LTC website.
  • Costs to engage a single IRB (sIRB) for all LTC-supported studies.
  • Other expenses related to DCC core activities as appropriate.
  • Protocol funds (approximately $1,309,000 total costs per year) to develop and execute consortium-wide common protocol studies will be part of the Data Coordinating Center award and will be distributed by the DCC to the approximately 24 individual CC sites in accordance with budgets approved by the Steering Committee and NHLBI. As such, the DCC should request a line item for Protocol Costs in total cost amounts of $1,309,000 for each year of the project period, money which will be restricted for this use only. Only research-related costs above those incurred as part of usual clinical care are eligible to be covered by reimbursement via protocol costs from the DCC.
R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The research strategy must describe the following:

Plans for leading and coordinating complex multi-center observational studies evaluating lung transplant selection criteria and clinical management strategies as they relate to donor lung utilization and/or post-transplant outcomes such as PGD and ALAD:

  • Discuss experience with prior relevant studies as a means of justifying the proposed approach to overseeing the design and conduct of a common protocol for data and biospecimen collection, ways to maximize recruitment and retention, and minimize logistical, operational, and regulatory issues, in the context of multiple clinical studies running simultaneously. Include a description of novel clinical research approaches to enhance data and biospecimen collection, analysis, and dissemination in order to maximize scientific output from the consortium.
  • Discuss the approach to operations management by providing evidence of data management and program support capabilities and describing the plan for data collection, management, analysis, data security and backup, privacy protections, and quality control. The plan should include an approach to monitoring common protocol patient safety, protocol execution quality, data entry quality, and participant accrual into shared protocols; providing relevant reports to NHLBI, the Steering Committee (SC) and the Observational Study Monitoring Board (OSMB); and training and competence certification of research staff conducting the common protocol at the participating Clinical Centers.
  • Discuss the timeline and plans for how the DCC will cooperate and interact within the DCC and across the CCs to achieve coordination of all LTC activities during the project period: include strategies to manage and support electronic and other communications; support regulatory affairs and compliance, human subjects protections, data monitoring, clinical operations and administrative activities; inform study design; provide support for data collection, management, and statistical analysis for common protocol studies; and reporting of results in a timely manner.
  • Provisions for logistical and communications support to the Clinical Centers within the LTC, and to the broader research and patient communities. Web resources and data management systems should provide secure distribution of study documents, forms, and metrics of study progress and performance. Plans should also include an open-access web site that communicates information about the LTC to the public and prospective research participants.
  • Plans for developing and managing, as well as distributing protocol funds to the individual CC sites, for conducting consortium-wide studies under the common protocol for data and biospecimen collection. This should include a vision for how the Common Protocol Committee will function, as well as plans for facilitating efficient review and approval of proposed common protocol studies by the SC, independent Protocol Review Committee (PRC), and OSMB. Applicants should assume that each awarded Clinical Center has the capacity to enroll on average up to 100 study participants (i.e. 800 total prospective annual enrollees) for multiple data collection points per year into the common protocol beginning in Q4 of Year 1 through Q3 of Year 5 of the project period (i.e. 3200 total enrollees over a 4-year period). It is anticipated that the biospecimens collected under the common protocol may include, but are not limited to, blood, urine, bronchoalveolar lavage fluid, lung biopsy tissues, and radiographic or other medical images, and the applicant should discuss special considerations for the collection and storage of these samples types. These plans should also include how the DCC plans to facilitate a timeline that includes common protocol development in Year 1, enrollment and follow-up halfway through Year 5, and the completion of data analysis, manuscripts, and study closeout by the end of Year 5.
  • Plans for conducting outreach activities including engaging foundations and other entities with a shared interest in lung transplantation.
  • Plans for engaging a centralized single institutional review board (sIRB) to oversee the LTC studies.

Research Team

  • Provide an overview of the overall organization of personnel in the proposed DCC's research team 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 LTC.
  • A sound rationale should be provided as to why the research team is the most appropriate, and likely to generate an exceptionally highimpact common protocol and maximize scientific output/study results from the consortium 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.
  • Describe how the research team is poised to provide scientific leadership and scholarship to the LTC through collaboration with the CCs, the SC, and NHLBI.
  • Comment on how the research team plans to provide performance leadership by identifying, leveraging, and capitalizing on other federally sponsored projects and resources to address scientific objectives within the LTC with greater efficiency and success.

Multiple PD/PI Leadership Plan:
For applications with multiple PD/PIs, describe with the Multi-PD/PI Leadership Plan how the PDs/PIs will work collaboratively together to lead the identified multidisciplinary team. Include a description of planned strategies for effective communications within the DCC and to the CCs.

Letters of Support:
Provide documentation of institutional commitment to supporting lung transplant research and to prioritization of LTC-associated activities. This can be in the form of letters or memoranda provided to the Program Directors/Principal Investigators. These assurances to provide support should address areas such as fiscal administration, personnel management, space allocation, procurement, planning, equipment, and budgeting.

A letter of support is required from the submitting organization that indicates institutional willingness to participate in all aspects of the LTC studies and related activities, including engaging a single IRB (sIRB) to oversee the LTC studies.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Plans to make common protocol data available to the LTC investigators during the project period, and to the public after study completion should be described. The DCC is expected to facilitate the sharing of common protocol data and biospecimens to the broader research community upon study completion via deposition into publicly available resources including the NHLBI Biorepository (BioLINCC).
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

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

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

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

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

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.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

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.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:
How compelling are the experiences from presented representative research studies and related support activities, and how well do these experiences predict the ability of the proposed DCC to successfully coordinate high-impact collaborative observational studies involving lung transplantation? To what extent does the proposed project consider unique challenges to conducting large multi-center clinical research studies involving lung transplant donors and/or recipients, and how likely are the proposed plans to address these challenges to yield impactful results and achieve the stated public health goals of the LTC?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:
How likely is it that the investigators have sufficient expertise to manage and operate the DCC as proposed, notably in the oversight of the development and execution of a standardized common research protocol and related data and biospecimen acquisition and storage across many lung transplant sites? To what extent are the PD/PIs and any key personnel likely to be able to accomplish all the objectives in a highly collaborative, fair, and flexible manner, appropriate to the roles and responsibilities of the DCC?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:
To what degree are novel organizational concepts and analytical approaches, including innovative statistical methodologies, data management strategies, and/or electronic and information technologies, proposed to support rapid and efficient integration of disparate data types derived from lung transplant clinical research, and how likely are these to succeed? To what extent are innovative and useful approaches to project coordination and logistical support that are likely to work in the setting of lung transplantation research proposed? How innovative and cost-effective are the proposed approaches to common protocol study design, data and biospecimen collection, staff training, CC oversight, and information sharing?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA:
To what extent does the approach engender the DCC will be successful in the administrative oversight and management of scientific activities across a large multi-site lung transplant consortium conducting a common clinical research protocol, while adequately addressing human subjects protections, providing regulatory affairs and compliance support, and facilitating dissemination of results? How efficient are the proposed means of communication within the DCC and among CCs, namely for facilitating the development and execution of a common clinical research protocol? How sufficient are the plans for establishing dedicated data and biospecimen repositories for samples derived from the performance of a common research protocol across many sites, and how likely are they to result in high-quality data and biospecimen acquisition, storage, and dissemination? How feasible are the suggested recruitment timelines, and are plans to monitor, evaluate, and enhance this accrual appropriate and likely to ensure robust data collection across all participating CC sites? How adequate are the proposed statistical support and data management plans, including the development and maintenance of a secure website?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:
How adequate are the currently available or proposed novel resources for secure data and biospecimen storage on the scale appropriate for the common protocol activities? Does the required letter of support indicate a sufficient level of institutional support and commitment to participation in all activities expected of the LTC DCC?

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Heart, Lung, and Blood Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 FOA. 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.

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 VI. Award Administration Information

1. Award Notices

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

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

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

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

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

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the 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 the LTC, including participating in common protocol development, monitoring recruitment of common protocol study participants, assuring the quality of study participant common protocol adherence, assuring the accurate and timely transmission of data, analyzing and interpreting data, preparing publications, and working with the CCs and NHLBI to disseminate research findings related to common protocol studies. The DCC will also be responsible for working with the CC PDs/PIs and Steering Committee Chair and Co-Chair to develop common definitions and standardized procedures for the common protocol. Awardees must agree to the governance of the study through a Steering Committee. CC investigators will be required to project patient enrollment for the agreed upon common protocol during the project period; continuation and level of funding will in part be based on actual recruitment and the DCC will monitor this in collaboration with the NHLBI.

Support or other involvement of any other third party in the study,--e.g. participation by the third party 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 the common protocol and governance. Consistent with the current NIH Data Management and Sharing Policy (NOT-OD-21-013), shared scientific data should be made accessible as soon as possible, and no later than the time of an associated publication, or the end of the award/support period, whichever comes first. The DCC, in concert with the CCs, is expected to facilitate the sharing of data and biospecimens among the LTC participants during the project period and to the broader research community upon study completion via deposition into publicly available resources including the NHLBI Biorepository (BioLINCC) and in accordance with the NHLBI Data Sharing Policy. 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:

NHLBI will appoint the Steering Committee Chair and Co-Chair, the Protocol Review Committee (PRC), the Observational Study Monitoring Board (OSMB), and the External Advisory Board (EAB).

NHLBI Project Scientists will assist with development of the common protocol, monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. NHLBI Project Scientists will serve on the Steering Committee and other study committees, when appropriate, and will have a single vote between them. The NHLBI Project Scientists 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 Project Scientist, an NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement and will be named in the Notice of Award. NHLBI may elect to have a dual-role approach where a single individual may act as an NHLBI Project Scientist and the Program Official. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist/Program Official. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. In the event that a Project Scientist/Program Official participates in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff who are also not a named Project Scientist will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award for a period of no less than three years from the time of co-publication.

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) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

Awardee(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 and the conduct of studies related to the common protocol, data analysis and the preparation of publications and dissemination products. Steering Committee voting membership shall consist of exactly two representatives (one who must be a lung transplant pulmonologist and the other who must be a lung transplant surgeon) from each Clinical Center award, two representatives from the Data Coordinating Center award, one NHLBI-appointed independent Steering Committee Chair, one NHLBI-appointed independent Steering Committee Co-Chair, and one NHLBI Project Scientist. Each of these full members of the Steering Committee will have one vote.  Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

An independent Protocol Review Committee (PRC) will provide peer review for the common protocol and proposed studies that utilize the common protocol within the LTC. The PRC may be involved in reviewing and prioritizing protocol ideas for significance. The PRC will be appointed by and be advisory to the NHLBI. It will consist of a chairperson, and Executive Secretary who is an NHLBI scientist other than the NHLBI Program Scientist or Program Official, and scientists with expertise in clinical study design, transplant pulmonology, thoracic surgery, biostatistics, ethics, and other areas of expertise as needed. Because the PRC serves as an independent group advisory to the NHLBI, study investigators will not communicate with PRC members regarding study issues, except as authorized by the PRC Executive Secretary. The PRC will evaluate common protocol studies put forth by the SC based on the significance of the questions to be addressed, scientific merit and innovation of the experimental design and approach, feasibility, appropriateness for the LTC and consistency with NHLBI missions and policies. The PRC will provide a written critique of each proposal and a final recommendation to the NHLBI. All common protocol studies performed by the LTC will be recommended by the PRC and approved by the NHLBI before initiation.

An Observational Safety Monitoring Board (OSMB) 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 or Program Official, shall serve as Executive Secretary to the OSMB. Because the OSMB serves as an independent group advisory to the NHLBI, study investigators will not communicate with OSMB members regarding study issues, except as authorized by the Board’s Executive Secretary. All local CC site-specific and common protocol performed within the LTC will be recommended by the OSMB and approved by the NHLBI before initiation.

An External Advisory Board (EAB) will be appointed by the NHLBI and advisory to the NHLBI and the Steering Committee by providing feedback on LTC-associated activities. This EAB will consist of non-consortium-affiliated scientists and other experts to provide feedback to the SC and NHLBI on progress, scientific direction, and ways to enhance data dissemination to groups with an interest in lung transplantation research.

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 awardee. 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.

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Matt Craig, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-7841
Email: matt.craig@nih.gov

Neil Aggarwal, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-7820
Email: neil.aggarwal@nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Nina Hall
Office of Grants Management
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-2393
Email: nina.hall@nih.gov

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.

Authority and Regulations

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


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