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)

National Cancer Institute (NCI)

Funding Opportunity Title
The Blood and Marrow Transplant Clinical Trials Network - Core Clinical Centers (UG1 Clinical Trial Optional)
Activity Code

UG1 Clinical Research Cooperative Agreements - Single Project

Announcement Type
Reissue of RFA-HL-17-018
Related Notices

    See Notices of Special Interest associated with this funding opportunity

  • August 7, 2023 - Notice of Changes to RFA-HL-24-010. See Notice NOT-HL-23-101.
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Notice of Funding Opportunity (NOFO) Number
RFA-HL-24-010
Companion Funding Opportunity
RFA-HL-24-011 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.839, 93.395
Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) issued by the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) invites applications to participate as Core Clinical Centers and Consortia (CCCs) in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN).

Core Clinical Centers and Consortia are expected to support and conduct multi-site trials to compare novel treatment approaches and management strategies for children and adults undergoing hematopoietic stem cell transplantation (HCT) for non-malignant and malignant blood diseases, either alone or in combination with novel adoptive cell-based therapies. The companion NOFO, RFA-HL-24-011, invites applications to participate as the Data Coordinating Center (DCC) for the BMT CTN. The CCCs will collaborate with the DCC, the NHLBI, the NCI, and other stakeholders to facilitate trials for HCT and cell therapies for blood diseases. The overall goals are to identify and address gaps in HCT and adoptive cell therapy outcomes for blood diseases; provide a platform to train emerging clinical trial investigators; build a biorepository for future research that includes specimens linked to clinical data and outcomes from patients with non-malignant blood diseases; rapidly disseminate study results to improve the scientific basis of HCT and adoptive cell therapies; and ultimately improve the life and quality of life for patients who receive HCT or adoptive cell therapies. This is an open competition for new applications and/or the renewal of an existing program.

Key Dates

Posted Date
June 21, 2023
Open Date (Earliest Submission Date)
September 02, 2023
Letter of Intent Due Date(s)

September 02, 2023

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
October 02, 2023 October 02, 2023 Not Applicable March 2024 May 2024 July 2024

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

Expiration Date
October 03, 2023
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 How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Each year in the US, approximately 20,000 patients receive hematopoietic stem cell transplantation (HCT) for rare and various hematological indications. Most HCT centers treat small numbers of patients with this rapidly evolving therapy, despite transplant being the only curative option for larger numbers of patients with acquired and congenital non-malignant blood diseases and for significantly larger numbers of patients with hematological malignancies. Optimizing HCT strategies for patients seeking potentially curative therapies is critical to enabling patients to live longer and with a better quality of life. However, a number of factors make HCT trials challenging, including rare hematologic diseases, small patient populations in need of HCT, the imperative to improve HCT and cell therapy approaches, and the need to engage many centers to obtain sufficient patient numbers. A clinical trials network provides a critical mass of investigators, increases patient availability and opportunity, and provides centralized and efficient approaches to conduct rigorous and well-designed, well-coordinated trials.

The objective of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is to provide the infrastructure for multi-site collaborative clinical trials evaluating HCT and adoptive cell therapy approaches to cure blood diseases. Sponsored since 2001 by the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI), the BMT CTN has conducted more than 50 Phase II and Phase III trials to address key issues for the field, including donor availability, treating or preventing graft versus host disease (GVHD) or infections, disease control, treatment-related toxicity, cost-effectiveness, and quality of life. While many trials were developed from concepts provided by BMT CTN investigators, a large number were guided by the scientific community during State of the Science Symposia conducted in 2007, 2014, and 2021, or in collaboration with other networks and groups, including NCI’s National Clinical Trials Network (NCTN), NCI's AIDS Malignancy Consortium, or implemented with funds provided by other NIH-funded investigator teams or pharmaceutical companies. Six to eight clinical studies are always active. The BMT CTN's past and ongoing activities can be found on the public website for the BMT CTN.

In this next funding cycle, BMT CTN will continue to address the most pressing issues for individuals with non-malignant and malignant blood diseases seeking curative therapies. This Notice of Funding Opportunity (NOFO) and the companion NOFO for the Data Coordinating Center (DCC) (RFA-HL-24-011) will support the BMT CTN infrastructure for seven years. Funds for trials and other studies will be included in the DCC budget, but BMT CTN investigators will also be encouraged to seek funding for additional trials and studies through investigator-initiated grants, industry participation, and foundation grants. Clinical studies that advance HCT approaches for non-malignant blood diseases, where toxicity must be minimized, will be prioritized for BMT CTN funds. Trials evaluating ex vivo manipulated or genetically-modified cells in non-malignant and malignant blood diseases will be encouraged, as will trials evaluating new approaches for stem cell mobilization, less toxic conditioning, reducing regimen-related toxicity and GVHD, and enhanced immune function. As in the past, collaborations with NCTN will be encouraged, often with NCTN leading the trial. Protocol topic areas will be decided cooperatively by the BMT CTN Steering and Executive Committees.

CCCs selected to join the BMT CTN should be prepared to contribute to the development of BMT CTN protocols, to enroll patients on multiple BMT CTN trials simultaneously, and to provide complete data for analysis and dissemination of the findings. Funds available through the DCC will support up to six clinical trials to address the most important HCT problems for non-malignant blood diseases and hematological malignancies. CCCs should have the infrastructure to evaluate ex vivo manipulated and genetically modified cells and have a catchment area or collaborations in place to enroll participants from minority health and health disparity populations, which include patient populations diverse in age, ethnicity, gender, and geographic area. In addition, CCCs should have the ability to contribute to a biorepository for patients with non-malignant blood diseases who receive HCT or cell therapy as part of an observational protocol collecting clinical information and late effects. CCCs must be willing and capable of enrolling patients to BMT CTN protocols with the goal of providing answers through these studies more rapidly than individual centers, and to support the various activities of the BMT CTN.

This NOFO is intended to support CCCs that bring staff with complementary and integrated expertise, where a HCT physician is the Program Director/Principal Investigator (PD/PI), with experts in non-malignant hematology and hematologic malignancies being amongst the team members. This staffing mix is expected to promote cross-fertilization and the optimal expertise needed to cure blood diseases. In addition, each CCC should provide plans to support and mentor an earlier-stage clinical trial investigator for leadership roles in the BMT CTN and a leadership succession plan, should it need to be implemented during the 7-year program.

This NOFO seeks applications from Core Clinical Centers/Consortia with expertise in HCT, hematology, and cell therapy that can demonstrate their ability to:

  1. Provide scientific leadership and expertise to work cooperatively to develop and efficiently conduct multi-site HCT trials for children and adults with non-malignant and malignant blood diseases, as well as trials that incorporate adoptive cell therapies such as ex vivo expanded and genetically modified cells.
  2. Conduct trials regulated by the Food and Drug Administration.
  3. Identify, enroll, and retain patients across variousages, races, and ethnic backgrounds with rare blood diseases to facilitate obtaining information across the lifespan and about differences by sex/gender, race and ethnicity (Public Health Service Act sec. 492B, 42 USC. sec 289a-2).
  4. Interface with advocacy groups and patient communities to enhance engagement, recruitment, and retention.
  5. Effectively and efficiently manage administrative duties within the site or consortium and demonstrate that sufficient patients are available for potential enrollment in BMT CTN studies.
  6. Assemble the expertise and resources needed for optimal conduct and support of BMT CTN activities and studies, including an observational study to build a repository containing serial specimens linked to clinical data from patients with non-malignant blood diseases.
  7. Engage an earlier stage investigator to hone the skills necessary to participate and eventually lead multi-site clinical research.

Organization and Governance. The BMT CTN is funded using cooperative agreements. The BMT CTN consists of Core Clinical Centers and Consortia (CCCs), the Data Coordinating Center (DCC), and NHLBI and NCI staff. The organization and governance involve the following components:

1. Core Clinical Centers/Consortia (CCCs)

CCCs are responsible for conducting HCT clinical trial protocols consistent with the mission of the BMT CTN, as described on the public website for BMT CTN. CCCs are responsible for proposing, developing, and refining protocols; identifying, recruiting, and retaining study participants such that the trial will provide information about differences by sex/gender and race and/or ethnicity; entering data promptly and accurately into the electronic data capture system; interpreting the results; contributing to manuscripts and disseminating research findings; and contributing to BMT CTN’s governance through committee participation. The CCCs are expected to participate in a cooperative and interactive manner with staff from the NHLBI and the NCI, the DCC, as well as other collaborators. In addition, the CCCs are expected to enroll participants to multiple BMT CTN trials simultaneously and to contribute high-quality specimens to biorepository from participants with non-malignant blood diseases. These biospecimens will be stored at a central biorepository at the DCC or at a subcontractor to the DCC. Ultimately, the biospecimen collection will be transferred to the NHLBI biorepository and made available to the wider scientific community for cellular and molecular analyses of disease pathogenesis and recovery, disease stratification and mechanistic studies.

Awards to a CCC and to the DCC will not be made to the same principal investigator to ensure that data analyses are conducted independently of data acquisition. However, the same institution may apply for both awards.

2. Data Coordinating Center (DCC)

The DCC will be supported by a separate award, described in RFA-HL-24-011. The DCC is responsible for the overall coordination and administration of the BMT CTN program; maintaining the Manual of Operating Procedures; supporting protocol development, finalization and prioritization; providing sample size calculations, sophisticated statistical advice, and data analyses; developing accrual plans and patient-facing materials; facilitating safety monitoring of BMT CTN trials; providing regulatory support, secure data management systems and systems for quality control; preparing minutes and reports for BMT CTN committees/subcommittees and the NHLBI; identifying, qualifying and subcontracting with Affiliate transplant centers and other collaborators for BMT CTN clinical trials; reimbursing (per-patient) participating centers; subcontracting central laboratories needed for network studies including long-term storage, retrieval, and shipment of biospecimens, and pharmaceutical companies for specific drugs and reagents; preparing data and safety reports for the Data Safety and Monitoring Boards (DSMBs); coordinating the development of manuscripts and presentations; and coordinating meetings and activities of the DSMBs, the BMT CTN Steering Committee, the External Advisory Committee, and other BMT CTN committees and subcommittees.

Funds to support the patient care costs associated with the protocols will be part of the DCC grant award. The DCC will distribute funds on a per-patient basis to the CCCs and other sites (Affiliate Centers) according to the approved protocol budgets.

3. NHLBI & NCI staff

NHLBI and NCI staff are responsible for the strategic direction and support for the BMT CTN. NHLBI staff and Office of Grants Management staff are responsible for the overall management of the grants for the BMT CTN. In addition to regular grant stewardship, NHLBI and NCI staff will be involved with the recipients as partners, consistent with the Cooperative Agreement mechanism.

4. Steering Committee (SC)

The SC will provide overall scientific governance for the BMT CTN and consist of the PD/PI(s) from each CCC, PD/PI(s) of the DCC, and NHLBI and NCI staff. A subcommittee from the SC nominates the Chair, but NHLBI and NCI reserve the right to approve the nomination and may otherwise appoint a Chair for the SC. The Chair rotates every two years. The SC formulates and implements all policy decisions related to the work of the BMT CTN and establishes its scientific agenda. The SC meets in-person up to three times annually and by videoconference on a monthly basis to monitor the progress of the BMT CTN and consider special issues, as needed. Affiliate sites that meet the metrics established by the Steering Committee are invited to serve as voting SC members.

NIH's decision to fund a particular CCC will not commit the BMT CTN to develop a proposed concept into a full protocol. The SC will prioritize concepts and select the protocol(s) to be conducted during the funding period from among those submitted in response to this NOFO. The SC will appoint Protocol Teams, set timelines for protocol development and trial implementation, and ratify changes to the overall BMT CTN Manual of Procedures including updates to procedures and guidelines as appropriate for collaborative trials. The Steering Committee has final responsibility for approving the protocols before review by the Protocol Review Committee (PRC) or DSMB.

5. Executive Committee (EC)

The EC and the DCC provide the day-to-day scientific management of the BMT CTN. The EC is a subset of the SC and will be comprised of the SC Chair, the immediate past Chair, the rising Chair, PD/PI(s) of the DCC, and the NHLBI and NCI Program Directors and Project Scientists. The EC sets the agenda for the SC meetings and makes the necessary day-to-day decisions between SC meetings.

6. External Advisory Committee (EAC)

NHLBI will appoint an independent EAC to review the BMT CTN portfolio and to make recommendations to the Institute regarding the progress and scope of the BMT CTN program. The EAC will convene at least once during the 7-year project period and upon NHLBI request. The BMT CTN will have an opportunity to provide input on potential EAC members, and the DCC will support the activities of the EAC.

7. Protocol Review Committee (PRC)

An independent NHLBI-appointed PRC, comprised of experts in HCT, hematology, cell therapy, statistics, and ethics, is charged with the scientific review of BMT CTN protocols. The PRC may require protocol modification, or may recommend or not recommend to NHLBI that the protocol be implemented.

8. Data and Safety Monitoring Board (DSMB)

An NHLBI-appointed DSMB(s) will review and recommend BMT CTN protocols for implementation and monitor patient safety and the study performance for the implemented trials. As a part of their monitoring responsibility, the DSMB(s) will submit recommendations to the NHLBI regarding the conduct and continuation of each clinical study.

9. Single Institutional Review Board of Record (sIRB)

The BMT CTN will utilize a single Institutional Review Board of Record (sIRB), per NIH policy for multi-site research (NOT-OD-16-094). The DCC will select and administer an sIRB to streamline IRB approvals, provide ethical review, and maintain patient safety. The sIRB will reduce the inefficiencies and burden of each clinical site conducting a duplicative IRB review. All CCCs must provide an institutional letter and agree to utilize the sIRB engaged and implemented on the BMT CTN's behalf by the DCC.

10. Administrative & Technical Committees

The BMT CTN's administrative and scientific work is assisted by staff drawn from the CCCs, the DCC, the NHLBI, the NCI, Affiliate Centers, and additional experts as needed. Committees may include protocol development, publications, finance, patient advocacy, biospecimen and core lab, clinical research associate, pharmacy, ancillary studies, implementation, and training. Other committees will be constituted as needed. The PI/PDs of each CCC will nominate members to serve on various committees; selected investigators are expected to participate actively in committee activities.

11. Identification and Selection of new BMT CTN Trials

Once convened in the new funding cycle, the BMT CTN Executive and Steering Committees will review and prioritize the concepts proposed for new studies. Four to six new trials will be funded by the NHLBI and the NCI, depending on the nature and extent of the investigations proposed, as well as a protocol for a biospecimen collection for patients with non-malignant blood diseases. Clinical protocols need to be reviewed by the NHLBI PRC and DSMB, approved by the Director of NHLBI (or his/her designee), and approved by the sIRB prior to initiation of trials. It is expected that clinical trial protocols will be launched and completed within the timeframe of the program. The program funded by this NOFO is of seven-year duration.

The CCCs will be proposing concepts for clinical trials that address a significant gap in the clinical practice of HCT. The specific topics are anticipated to address the significance of the research, the need for a multi-site approach, and feasibility considerations. Potential topics should address significant barriers and knowledge gaps in HCT therapy including, but not limited to, testing new treatment approaches and management strategies to:

  • Improve engraftment.
  • Improve immune reconstitution.
  • Prevent or reduce regimen related toxicities.
  • Prevent or treat GVHD.
  • Cure non-malignant blood diseases.
  • Cure hematologic malignancies or prevent disease relapse.
  • Evaluate emerging adoptive cellular therapies or engineered grafts designed to address specific blood diseases or complications of HCT.

While these topics are very important, they are provided only as examples of areas that the applicants may address. Applicants are also encouraged to consider other topics that are responsive to the objectives of the NOFO. NHLBI is encouraging trials for non-malignant blood diseases that include ancillary studies.

For studies conducted in collaboration with and led by the NCTN, NCI processes will be used for the scientific review of the protocol and conduct of the trial. Collaborations with other clinical trial groups, networks, R01-funded investigators, or pharmaceutical companies, will be considered on a case-by-case basis. For these trials, the DCC will negotiate support and per-patient reimbursement, and most protocols and trials will be reviewed and monitored per NHLBI processes.

12. Participation in BMT CTN Trials

NHLBI and NCI expect that each CCC will participate in multiple BMT CTN-led protocols each year and that each CCC will participate in most protocols selected during the project period by the SC. Protocol budgets and the per-patient reimbursement will be set by the DCC at the time the trial is launched. Each CCC must be willing to pursue this funding arrangement with the DCC.

In addition, several BMT CTN clinical trials from the existing network may still be enrolling participants when awards are made for this NOFO. Recipients of the new BMT CTN program will be encouraged to enroll subjects to these trials. Recruitment status and details on each trial can be found on the BMT CTN website.

Plan for Enhancing Diverse Perspectives (PEDP)

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

Notice of NIH's Interest in Diversity

Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Despite tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences, such as:

A. Individuals from racial and ethnic groups that have been shown by the National Science Foundation to be underrepresented in health-related sciences on a national basis (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27) and the report Women, Minorities, and Persons with Disabilities in Science and Engineering). The following racial and ethnic groups have been shown to be underrepresented in biomedical research: Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians and other Pacific Islanders. In addition, it is recognized that underrepresentation can vary from setting to setting; individuals from racial or ethnic groups that can be demonstrated convincingly to be underrepresented by the grantee institution should be encouraged to participate in NIH programs to enhance diversity. For more information on racial and ethnic categories and definitions, see the OMB Revisions to the Standards for Classification of Federal Data on Race and Ethnicity (https://www.govinfo.gov/content/pkg/FR-1997-10-30/html/97-28653.htm).

B. Individuals with disabilities, who are defined as those with a physical or mental impairment that substantially limits one or more major life activities, as described in the Americans with Disabilities Act of 1990, as amended. See NSF data at, https://www.nsf.gov/statistics/2017/nsf17310/static/data/tab7-5.pdf.

C. Individuals from disadvantaged backgrounds, defined as those who meet two or more of the following criteria:

1. Were or currently are homeless, as defined by the McKinney-Vento Homeless Assistance Act (Definition: https://nche.ed.gov/mckinney-vento/);
2. Were or currently are in the foster care system, as defined by the Administration for Children and Families (Definition: https://www.acf.hhs.gov/cb/focus-areas/foster-care);
3. Were eligible for the Federal Free and Reduced Lunch Program for two or more years (Definition: https://www.fns.usda.gov/school-meals/income-eligibility-guidelines);
4. Have/had no parents or legal guardians who completed a bachelor’s degree (see https://nces.ed.gov/pubs2018/2018009.pdf);
5. Were or currently are eligible for Federal Pell grants (Definition: https://www2.ed.gov/programs/fpg/eligibility.html);
6. Received support from the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) as a parent or child (Definition: https://www.fns.usda.gov/wic/wic-eligibility-requirements).
7. Grew up in one of the following areas: a) a U.S. rural area, as designated by the Health Resources and Services Administration (HRSA) Rural Health Grants Eligibility Analyzer (https://data.hrsa.gov/tools/rural-health), or b) a Centers for Medicare and Medicaid Services-designated Low-Income and Health Professional Shortage Areas (qualifying zipcodes are included in the file). Only one of the two possibilities in #7 can be used as a criterion for the disadvantaged background definition.

Students from low socioeconomic (SES) status backgrounds have been shown to obtain bachelor’s and advanced degrees at significantly lower rates than students from middle and high SES groups (see https://nces.ed.gov/programs/coe/indicator_tva.asp), and are subsequently less likely to be represented in biomedical research. For background see Department of Education data at, https://nces.ed.gov/; https://nces.ed.gov/programs/coe/indicator_tva.asp; https://www2.ed.gov/rschstat/research/pubs/advancing-diversity-inclusion.pdf.

D. Literature shows that women from the above backgrounds (categories A, B, and C) face particular challenges at the graduate level and beyond in scientific fields. (See, e.g., From the NIH: A Systems Approach to Increasing the Diversity of Biomedical Research Workforce https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008902/ ).

See NOT-OD-20-031 and NOT-OD-22-019 for details.

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

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

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 NOFO.

Application Types Allowed
New
Renewal

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 NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Funds Available and Anticipated Number of Awards

NHLBI and NCI intend to commit total costs of up to $4.32M in Fiscal Year 2024 to fund approximately 18 awards.

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

Award Budget

Application budgets may request up to $150,000 direct costs per year in FY24 through FY30. Investigators are encouraged to request what is well-justified for their research program.

Award Project Period

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

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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 not 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • 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.
    • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

Early Stage Investigator (ESI) applicants can be the PI/PD of an application, providing they can show support of investigators with appropriate clinical trials experience (as part of a multiple PI team). ESIs are encouraged to be part of the?study?team?and?they should be?budgeted for?support?at a level appropriate for the role on the project.?

2. Cost Sharing

This NOFO 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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. 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
Division of Extramural Research Activities
National Heart, Lung and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
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 NOFO.

SF424(R&R) Cover

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

Descriptive Title of the Applicant’s Project: Applicants must use the naming convention BMT Core - [insert name of Site or Consortium] replacing the words in italics with the name of the applicant site. If application is a consortium, the word Consortium must be in the application title.

SF424(R&R) Project/Performance Site Locations

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

Enter primary site and other sites included in the consortium, if applicable.

SF424(R&R) Other Project Information

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

Facilities and Other Resources: Include the following information:

Describe the facilities and resources available to facilitate trials evaluating HCT and cell therapies for nonmalignant blood diseases and hematologic malignancies. Document the availability and capacity of an institutional pharmacy capable of supporting clinical research, and the capacity of cell processing laboratories that could be available to support the proposed CCC.

Other Attachments: Attachments marked as Required must be provided or the application will not be peer reviewed. The Attachments will be assessed during the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions. Upload each attachment as a separate pdf file with the names specified below.

1. Protocol Synopsis (Synopsis) Required

In this attachment, provide a protocol synopsis. The filename Synopsis.pdf must be used and reflected in the final image bookmarking for easy access for reviewers. This attachment cannot exceed 1 page.

The synopsis must identify a key study to improve the health and quality of life for children and adults receiving HCT or adoptive cell therapy that requires the BMT CTN’s infrastructure for multi-site collaborative research. Approaches to address concerns for non-malignant blood diseases will be considered a strength. The synopsis must be formatted using the headings: Population, Intervention, Comparator, Outcome and Time. Additional details on the background, rationale, preliminary data, feasibility, etc. should be included in the PHS 398 Research Plan, Sub-Section B (Scientific Direction).

2. Transplant Activity (Transplant Activity) Required

In this attachment, provide a summary of patient demographics and types of HCT and adoptive cell therapies at the CCC for the 5-year period spanning 2018-2022. The filename of this attachment, "Transplant Activity.pdf", must be reflected in the final image bookmarking for easy access for reviewers. If the application is for a single site, this attachment cannot exceed 2 pages. For applicants proposing a consortium, the attachment must include separate Tables for each site's information (not exceeding 2 pages per site). For a consortium with 5 or more sites, this attachment cannot exceed 10 pages.

To summarize the information requested, provide a table that includes the items (1-7) listed below as rows, with 3 separate columns tabulating the number of patients who received HCT or cell therapy at the CCC (column 1), the number of those in the first column who were either Enrolled in Single Site Clinical Trials (column 2) or who were Enrolled in Multi-site Trials (where a multi-site trial utilized 5 or more centers) (column 3). Each of the 3 columns must include the total number and the percent of the total for the 5-year period spanning 2018-2022, except when medians are requested.

1) Recipients Age
a. Median Age
b. <18 years old
c. > 18 years old
2) Recipients Disease
a. Hematologic malignancy
b. Non-malignant blood diseases*. Include a footnote to the Table listing the diseases included*
3) Racial Categories, below
a. Non-White
b. White
c. Multiracial, Unknown or Not Reported4) Graft/Donor Source
a. Autologous
b. HLA-identical siblings
c. Haplo-identical donors (and mismatched related)
d. Unrelated donors
5) Unmanipulated Grafts
a. Peripheral Blood Stem Cells
b. Bone Marrow
c. Umbilical Cord Blood
6) Ex vivo Manipulated (selected or expanded) Grafts
a. Recipients with non-malignant blood diseases
b. Recipients with hematologic malignancies
7) Genetically-modified Cells
a. Recipients with non-malignant blood diseases
b. Recipients with hematologic malignancies

3. Clinical Trial Experience (CT Experience) Required

An attachment with the filename "CT Experience.pdf" is meant to provide the clinical trial experience of key personnel in the CCC. The filename, CT Experience.pdf , must be reflected in the final image bookmarking for easy access for reviewers. For a single-site application, this attachment cannot exceed 5 pages. For applicants proposing a consortium, include separate Tables with each site's information. For applications with 3 or more sites in a consortium, this attachment cannot exceed 15 pages.

For this attachment, provide an introduction to the table requested below that highlights the significance of key studies and illustrates the potential ability of the CCC to contribute meaningfully to the BMT CTN.

Include a table listing the characteristics of trials conducted during the 5-year period including 2018-2022 and information on the CCC leadership or role for each study. The table must include the following information for each trial:

A: Brief name of the study/trial; ClinicalTrials.gov number
B: Trial design: Phase I, II, III; single or multi-site; Single Arm, Parallel Arms, or Randomized
C: Applicant’s Role on Study: Protocol PI/co-PI, Site PI, Site investigator, or Other (applicant must specify)
D: IND or IDE: yes/no
E: Funding source(s): NIH, industry, foundation, or other
F: Site enrollment: number planned/month, number actual/month, and total enrolled on the trial
G: Publication references
H: Impact (or potential future impact) to the field

4. Plan for Enhancing Diverse Perspectives (PEPD) Required

A summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity must be provided as an attachment using the file name PEDP.pdf . The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP cannot exceed 1 page. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

  • Plans to establish an interdisciplinary clinical team that include experts in blood and marrow transplantation, hematology (non-malignant blood diseases), cell therapies and genetically-modified cells, or to develop transdisciplinary collaboration(s) and/or solicit diverse perspectives to address research question(s).
  • Plan to support career-enhancing research opportunities for early- and mid-career researchers and women and individuals from groups traditionally under-represented in the biomedical research workforce through the BMT CTN activities.
  • Participation of investigators from diverse backgrounds, including groups historically underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
  • Plans for partnerships that may enhance geographic and regional diversity and monitoring activities to measure PEDP progress benchmarks.
  • Plans for outreach or engagement activities to enhance recruitment of individuals as research participants from underserved racial and ethnic groups.

5. Consortium Plan (CP) Required for Applications Proposing a Consortium

For applicants designating a Consortium as part of their application, a consortium plan is required. The filename "Consortium Plan.pdf" must be used and will be reflected in the final image bookmarking for easy access for reviewers. This attachment cannot exceed 2 pages.

  • Describe the rationale for and benefits of including the specific sites that comprise the proposed Consortium, including the aspects of the combined sites that will contribute significantly to scientific leadership of the BMT CTN (e.g., potential contributions to the BMT CTN administrative or technical committees). Describe the communication plan and interactions among Consortium sites, the process for making decisions on scientific direction, the process to ensure operational continuity at consortium sites (timely submission of regulatory documents and contracts; staff training) and procedures for resolving conflicts. Describe any project management tools that will be used. An NIH biosketch for the PI at each site must be included in the application (see Key Personnel).

SF424(R&R) Senior/Key Person Profile

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

The PD/PI submitting this application must be a transplant physician experienced in the conduct of multi-site HCT trials for either adult or pediatric patients. The application should propose a multidisciplinary team, with at least one team member who is a hematologist (an individual experienced in the care of patients with non-malignant blood diseases is preferred); other team members may include additional physicians, a cell therapist, data managers, study coordinator(s), and other individuals required to facilitate the implementation of all aspects of BMT CTN trials, including recruitment and retention of subjects. Applicants proposing a Consortium must identify a site investigator to oversee activities at their respective site. All Key Personnel who are major contributors to the CCC must provide an NIH Biosketch, whether budgeted or not.

Applications with Multiple PDs/PIs:

When multiple PD/PIs are proposed, one PD/PI must be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system. Follow all instructions in the SF424 (R&R) Application Guide.

Multiple PD/PI Leadership Plan: For applications designating multiple PD/PIs, all such individuals must be assigned the PD/PI role on the G.240 - R&R Senior/Key Profile (Expanded) Form, even those at organizations other than the applicant organization.

For applications designating multiple PDs/PIs, the section of the Research Plan, Sub-Section C, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach must be described. The governance and organizational structure of the leadership team and the research project must be described and include communication plans, the process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Whether the application is single-PD/PI or multi-PD/PI, a Leadership Succession Strategy should be provided in the application in the Research Strategy, Sub-Section C. The Leadership Succession Strategy should describe the procedure for selecting a proposed replacement for the PD/PI, should the needs arise. The NHLBI must approve any request to replace the PD/PI.

R&R Budget

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

CCC awards will be for core infrastructure costs only (see section II: Award Information).

Personnel:

  • PD/PI or Multiple PD/PI(s): at least 1.2 person-months (10 percent) effort, which may be split between multiple PIs.
  • Hematologist and early stage investigator(s): at least 1.2 person-months (10 percent) effort, which may be split between multiple PIs.
  • Additional members of the Team, including a coordinator and administrative support, as needed.

The budget must include the effort required for Network participation, including regular video or teleconferences for discussion of protocols and other Network committees, regular SC conferences and technical committees, activities related to IRB approval and updates, and manuscript preparation.

Travel costs for the PI/PD to attend three in-person SC meetings per year, two of which will be held in Washington, D.C., and the third likely to be held in conjunction with the annual CIBMTR/ASTCT meeting.

Patient-related costs (e.g., clinical costs that are not part of routine clinical care such as laboratory tests, sample and data collection, supplies, drugs) are not part of the budget, but will be distributed from the DCC budget in proportion to recruitment.

NHLBI and NCI may adjust a CCC’s core budget based on accrual and the performance of that CCC, using input from the Executive Committee and/or External Advisory Committee.

For PEDP implementation, applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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:

The Research Strategy should contain the three sub-sections (A-C) described below. The Research Strategy should include clear plans for participation as a Core Clinical Center in the BMT CTN.

NOTE: All applications in response to this specific NOFO will use the Delayed Onset record designation as described in the section PHS Human Subjects and Clinical Trials Information, Delayed Onset Study. Applicants must check the Delayed Onset box on the application form. This is inherent in the BMT CTN, as sites will be submitting protocol concepts, but these concepts, if approved by the BMT CTN, will be delayed since they are concepts only, and will not be fully defined.

Sub-Section A. CCC Capabilities for BMT CTN

Describe the plans to leverage the CCC’s capabilities to address the scientific goals of the BMT CTN, including how the CCC plans to be a contributing member of the BMT CTN. This Sub-Section cannot exceed 3 pages.

Expand and reference the information in the Other Attachments while describing:

  • Scientific leadership and expertise available for optimal conduct of multi-site trials, HCT trials for children and adults with non-malignant and malignant blood diseases, as well as trials that incorporate adoptive cell therapies such as ex vivo expanded and genetically modified cells.
  • Plans to facilitate and enroll participants to trials conducted by the BMT CTN, including BMT CTN trials regulated by the FDA.
  • Communication plans between clinical services, including HCT, oncology, hematology, and cell therapy/manufacturing, and how clinical activities and responsibilities will be coordinated.
  • Special or unique strengths that may be relevant for the BMT CTN. This can include state-of-the art scientific capabilities available that may develop and expand the scientific productivity of the BMT CTN, such as experience in cell manufacturing, care for patients with non-malignant blood diseases, including HCT for these disorders, or unique personnel resources to enhance the scientific productivity of the BMT CTN.
  • Plans to include all genders, and approaches to enhance the numbers of racial and ethnic minorities recruited to trials, as appropriate for the scientific goals of the research within the BMT CTN. Also, describe any relationships with advocacy groups pertinent to the mission of the BMT CTN.
  • Plans for provision of mentorship and opportunities to benefit the next-generation of clinician-scientists (early- and mid-career investigators) and to hone the skills necessary to conduct multi-site trials in HCT and adoptive cell therapy for non-malignant and malignant blood diseases.
  • Describe the CCC’s referral base for patients with non-malignant blood diseases and plans to contribute to the observational study to build a repository containing serial specimens linked to clinical data from patients with non-malignant blood diseases.

Sub-Section B. Scientific Direction

Propose a new scientific direction to be considered by the BMT CTN. Using the information in the Other Attachment 1: Protocol Synopsis (file name Synopsis.pdf ) develop a protocol concept for consideration by the Steering Committee. This sub-section cannot exceed 5 pages and must include a timeline for completing the study. BMT CTN studies may be selected by the Steering Committee from the proposed protocol concepts provided by the successful applicants, but a decision to fund particular CCCs will not commit the BMT CTN to developing proposed protocol concepts by recipientsinto clinical protocols.

The proposed protocol concept must address a significant unmet need in HCT that requires multic-site implementation; be consistent with the goals of this NOFO; illustrate the applicant’s knowledge of, and vision for, HCT research in the United States; and define the importance of the protocol to the science of transplantation, the evolution of clinical HCT standards, or the improvement in the management of HCT recipients, as appropriate. The protocol concept should not describe or replicate a study being planned, conducted, or undertaken by the current BMT CTN program or by NCI’s NCTN. Although the application is not requesting a full protocol, the concept should include the background, rationale and strength of available pilot or preliminary data, and the study hypothesis (hypotheses); further describe key inclusion and exclusion criteria for the patient population; address the appropriate inclusion of individuals across the lifespan, including children per NOT-OD-18-116, and minorities; describe the rationale for the treatment plan (type of HCT, conditioning, etc.) and the primary and key secondary endpoints; estimate the sample size and number of sites and or site locations (domestic, international) required for success of the trial given the project period; and provide a projected timeline for completing accrual and achieving the study endpoints. Accrual to the proposed study should take four years or less.

The proposed protocol concept should also describe feasibility issues, including potential challenges for recruitment and retention of the trial participants. If the study design includes randomization, assess how burdensome it might be to screen/enroll/randomize participants (e.g., screen failure rate). Describe also the potential ethical issues and benefit(s) to human subjects, and the impact of the proposed protocol concept on clinical care and public health. The protocol concept should describe how the study proposed would improve outcomes. Appropriate mechanistic/correlative studies linked to the application should be described, although funding for these studies should be sought through other mechanisms.

Describe the attributes of the CCC which are important for the success of the proposed protocol concept, referencing each of the attachments, as appropriate.

Sub-Section C. Operational and Scientific Approach to HCT Trials

Describe operational and scientific approaches to conducting HCT trials, and provide a Leadership Succession Strategy. This sub-section cannot exceed 4 pages.

Provide a detailed description of the transplant program at the CCC to illustrate the operational approach to contribute to the BMT CTN. Describe approaches and institutional resources or approaches to ensure:

  • Compliance with applicable laws, regulations, and legal requirements, including but not limited to those governing privacy, security, data, research, and human subjects; and studies under IND.
  • Quality assurance and complete and accurate transmission of data to the DCC, as well as processes for responses to data entry edits and audits, including suggested timelines for responses.
  • Biospecimens are collected as required by the protocol, appropriately processed and stored, and linked to the clinical data.
  • Follow-up assessments for transplant patients enrolled on clinical trials.
  • The sIRB-reliance agreement facilitates participation in network trials.
  • The technical and personnel capabilities at the site that facilitate data integration efforts with the CIBMTR, including patient reported outcomes.
  • Opportunities and mentorship increase the role of earlier-stage investigators in the BMT CTN and help advance their careers as well as their expertise as a clinical trialist.

For applications proposing a Consortium, address the above points from that perspective.

Using the studies presented in the attachment called "CT Experience", describe how the CCC has helped to advance the field of HCT and adoptive cell therapy, and how these experiences will benefit the BMT CTN. Describe challenges, successes and lessons learned from up to three HCT trials/studies in each of the 4 categories in the bullets below:

  • Trials that struggled with recruitment or retention of subjects, and how challenges were addressed.
  • Trials that engaged a team having a diverse background or expertise, the degree to which this impacted the trial.
  • Early phase HCT trials from the prior 6 years that led to a multi-site trial.
  • FDA-regulated clinical trials for recipients of HCT or adoptive cell therapy.

Describe considerations for selecting and prioritizing BMT CTN clinical trials. All CCCs are encouraged to contribute patients to most of the trials launched by the BMT CTN, including the BMT CTN trials enrolling participants, as listed on the BMT CTN website. Describe strategies for allocating patients between these studies and competing studies.

Whether the application is single-PD/PI or multi-PD/PI, provide a Leadership Succession Strategy that describes the procedure for selecting a proposed replacement for the PD/PI, should the need arise. The NHLBI must approve any request to replace the PD/PI.

Consortium/Contractual Arrangements: Applicants can propose consortia of two or more sites. For an application proposing a consortium, collaboration and interaction among institutions should be clearly documented in the application, including the investigator responsible at the collaborating site(s). Management plans including supervision, training, certification, data handling, quality assurance, and communication should be documented in the required Other Attachment 5: Consortium Plan. The required Other Attachment 2: Transplant Activity must include the racial demographics of patients who have participated in Single Site Clinical Trials or Multi-site Trialsat each site and collectively. Information on attachments can be found in the section titled SF424(R&R) Other Project Information.

Letters of Support: Letters of institutional and departmental support for participation in the BMT CTN are required. Specifically, the letters affirm the reliance of institutional review board (IRB) review for BMT CTN protocols and trials to a single IRB (sIRB) selected by the DCC for the BMT CTN. The letters of support should also include assurances that in the case of studies competing for the same patient population, BMT CTN studies will be prioritized. Applications proposing a consortium should include a letter of support with these assurances from the PI of each site in the proposed consortium.

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.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in the 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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the 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 NHLBI, NIH. Applications that are incomplete or non-compliant will not be reviewed.

This NOFO requires a plan for Enhancing Diverse Perspectives (PEDP) as part of the application.

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.

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

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.


Does the Core Clinical Center or Conorations 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 Core Clinical Center or Consortium rigorous? If the aims of the Core Clinical Center or Consortium 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?

In addition, for applications involving clinical trials

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

Specific to this NOFO:

How well does the application align with the priorities of this NOFO for HCT or cell therapy to cure non-malignant blood diseases or hematologic malignancies, or to improve the quality of life for those who might receive the proposed therapy? To what degree does the protocol concept contribute important knowledge that could be used to substantially promote health for patients with blood disease, advance health equity, address a significant unmet need, or challenge an existing paradigm in blood and marrow transplantation for either malignant or non-malignant blood diseases?

If ex vivo manipulated cells or genetically-modified cells were proposed, how likely is it that the treatment will contribute to improved outcomes, advanced equity, or change clinical practice?

How strongly do the efforts described in the Plan for Enhancing Diverse Perspectives (PEPD) contribute to the significance of the proposal?


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 Early-Stage Investigators or those in the early stages of independent careers are proposed, do they have appropriate experience and training? 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?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines?

Specific to this NOFO:

How strong are the scientific, administrative, clinical and academic qualifications of the PD/PI(s) for leading the proposed CCC?

How diverse is the CCC’s expertise across the clinical areas to be addressed by the BMT CTN, including HCT to treat non-malignant and malignant blood diseases, and trials using either adoptive cell therapy including genetically modified cells during transplant therapy?


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?

In addition, for applications involving clinical trials

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

Specific to this NOFO:

How likely will the proposed protocol concept challenge and shift current research or clinical practice paradigms? To what extent is the proposed protocol concept an innovative approach to HCT and or cell therapy?

To what extent are the efforts described in the Plan for Enhancing Diverse Perspectives (PEPD) innovative?


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?

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?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Specific to this NOFO:

How strong are the clinical trials capabilities of the applicant in support of the scientific goals and mission of the BMT CTN, including leadership, expertise, plans to facilitate and enroll participants, communication, relevant strengths, and plans to include diverse patient populations? How strong is the provision of mentorship and opportunities for the next generation of clinician scientists? How strong is the approach to recruit patients with rare non-malignant blood diseases to clinical trials, as appropriate, and to contribute to the observational study to build a repository containing serial specimens linked to clinical data from patients with non-malignant blood diseases?

How strongly does the proposed concept address an unmet need in HCT that requires multi-site implementation and illustrate the applicant’s knowledge of, and vision for, HCT research in the United States? How strongly does the proposed concept contribute to the evolution of clinical HCT standards, or the improvement in the management of HCT recipients? How appropriate are the proposed design, methods, and intervention and plans to include minorities and people across all ages and genders?

What is the likelihood of success for the proposed CCC research team(s) for conducting HCT trials in diverse clinical areas (i.e., non-malignant blood diseases, using novel cell products such as ex vivo expanded or genetically-modified cells, and using approaches to cure hematological malignancies)?

How strong is the communication and management plan for the CCC?


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?

In addition, for applications involving clinical trials

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this NOFO:

Does the application demonstrate adequate prior experience with multi-site collaborative HCT clinical research in adult and pediatric patients? Does the application bring experience in HCT for patients with non-malignant blood diseases or using adoptive cell therapies or genetically modified cells? Do the number of transplants and types of transplant recipients listed in the Transplant Activity attachment support the ability to contribute to contribute to multiple BMT CTN clinical trials and to the biorepository protocol simultaneously? How experienced is the team in conducting clinical trials regulated by the FDA?

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.


Not applicable


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.


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.


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 Animals Section.


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


Not Applicable


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


Not Applicable


If applicable, how strong are the plans for communication, decision making and conflict resolution between the core and collaborating sites as detailed in the Consortium Plan attachment?

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.


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


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


Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.


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


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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI Office of Scientific Review, 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 NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Advisory Council. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

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

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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 NOFO.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the purpose of the 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, although specific tasks and activities may be shared amongst the recipients and the NIH as defined below.

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

The BMT CTN program includes the CCCs, a DCC, and staff from the NHLBI and the NCI. All CCCs will be required to participate in a cooperative and interactive manner with one another and with the DCC. Recipients agree to the governance of the BMT CTN through a Steering Committee, and agree to work with the DCC, NHLBI, and NCI Staff to achieve the BMT CTN’s objectives.

The Principal Investigators are responsible for the following: accepting the coordinating role of the DCC and the participatory and cooperative nature of the BMT CTN process; identifying new priority areas of research; developing and implementing network clinical trials; accurately projecting patient enrollment for each protocol during a specified timeframe; collecting and submitting protocol-specific data to the DCC accurately and in a timely manner; participating in data analysis and interpretation; interpreting data and disseminating results through publications and presentations in a timely manner; complying with the BMT CTN’s Manuals of Operations and all federally mandated regulatory requirements.

CCCs are responsible for maintaining a high level of performance in the BMT CTN. Performance will be evaluated using the BMT CTN Center Performance Report as well as the following criteria: participation in BMT CTN clinical trials and meeting projected enrollment targets; participation in research design and clinical trial protocol development, including serving as Chair of a clinical trial protocol or as a member of a protocol study team; participation in the scientific and administrative committees needed to support the BMT CTN’s research objectives; compliance with all applicable DHHS regulations concerning protection of human subject; timely reporting of all serious and/or unexpected adverse events and all relevant medical information; collection, processing, storage, and shipping of biospecimens per protocol specifications; providing biospecimen-associated clinical data per protocol specifications; serving as a resource for conduct of protocol-specified laboratory assays and ancillary studies, mechanistic, and biomarker studies; and other scientific contributions such as developing presentations and publications following the BMT CTN publication procedures.

Awardees will retain 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. Study PDs/PIs are encouraged to publish and disseminate results and other products of the study in accordance with study protocols and governance. Data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance and according to NHLBI Policy (http://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing and https://sharing.nih.gov/data-management-and-sharing-policy).

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party through involvement of study resources, citing the name of the study or NHLBI support, or special access to study results, data, findings, or resources requires notification and concurrence by NHLBI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Study PDs/PIs are required to provide updates at least annually on the implementation of the PEDP.

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

NIH Project Scientists will have substantial programmatic involvement above and beyond the normal stewardship role in awards and will monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. NHLBI will appoint an independent Protocol Review Committee and independent Data and Safety Monitoring Boards (DSMBs). The Steering Committee Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of BMT CTN activities and operations.

NHLBI will appoint an NHLBI Program Official who will be responsible for the normal program stewardship of the cooperative agreement, and will be identified in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as the NHLBI Project Scientist and Project Officer. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist/Program Official will participate 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 will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

The NHLBI reserves the right to phase-out or curtail trials (or an individual award) in the event of (a) failure to develop or implement mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocols or substantive changes in the agreed-upon protocols with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

BMT CTN Steering Committee:

Recipient(s) agree to the governance of the study through a Steering Committee. The Steering Committee will have primary responsibility for identification of priority areas for research, the conduct of protocols, data analysis and the preparation of publications and dissemination of products. The Steering Committee will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of BMT CTN activities and operations.

Steering Committee voting membership shall consist of all Principal Investigators (i.e., cooperative agreement recipients), one NHLBI Project Scientist, and one NCI Project Scientist. Each Award is limited to one vote. The NIH members of the committee will share one vote in support of the project, with the administering/lead IC having the final say. Recipient members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. All major scientific decisions will be determined by majority vote of the Steering Committee. The Steering Committee has final responsibility for approving the protocol before review by the DSMB. Technical Committees (i.e., Pharmacy, Publication) and subcommittees of the Steering Committee will be established as necessary. A protocol is the detailed written plan of a clinical experiment; DSMB reviews, NHLBI approval (with NCI consultation), FDA approval of IND or IDE (as appropriate), and IRB approvals are required prior to activating a clinical trial. All study protocols must adhere to current NIH policies for human subjects research. NHLBI must approve each protocol prior to implementation. The PD/PI(s) will establish mutually agreed upon milestones with the steering committee for the development of each clinical research protocol and trial implementation; milestones may include such things as time to DSMB approval, time to a signed institutional contract for per-patient reimbursement, first patient enrolled, etc. Trial performance should be consistent with NIH and NHLBI policies, including the Milestone Accrual Policy.

In-person meetings of the Steering Committee will be convened three times a year, typically held in June and October in the metropolitan Washington, D.C. area, and in conjunction with the annual Tandem Meeting that is typically held in February. In the other months of each year, the Steering Committee will meet by videoconference. Steering Committee members must make every effort to attend Steering Committee meetings and participate in the monthly meetings. Should the Lead PD/PI(s) find it impossible to attend a Steering Committee meeting or videoconference, they are required to notify the NHLBI Program Officer and/or Steering Committee Chair of the expected absence and ensure attendance by their designated alternate.

The Steering Committee and the DCC will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of BMT CTN activities and operations.

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

NHLBI-appointed DSMB:

The NHLBI Director appoints an independent DSMB(s) to provide overall monitoring of interim data and safety issues, and to recommend to the NHLBI whether trials may continue. Meetings of the DSMB are ordinarily held by videoconference or in the metropolitan Washington, D.C. area. An Executive Secretary to the Board, other than the NHLBI Program Official, will be appointed by NHLBI to support the DSMB. Because the DSMB serves as an independent advisory group, study investigators should not communicate with the DSMB members regarding study issues, except as authorized by the DSMB’s Executive Secretary. The DSMB will consist of a chairperson and scientists with expertise in hematopoietic stem cell transplantation, bioethics, clinical research, clinical trial design, biostatistics, and other areas of expertise as needed. The DSMB will provide a written critique of each protocol and a final recommendation to the NHLBI. All study protocols must be reviewed and recommended by the DSMB and approved by the NHLBI before IRB submissions occur. The DSMB is also responsible for monitoring clinical trials with particular attention to safety issues.

Single Institutional Review Board of Record (sIRB):

The BMT CTN will utilize a single Institutional Review Board of Record (sIRB) for BMT CTN-led trials, per NIH policy for multi-site research (NOT-OD-16-094). A sIRB is expected to eliminate duplicative IRB review, reduce unnecessary administrative burdens and systemic inefficiencies, and shift workload away from conducting redundant reviews to allow institutional IRBs to concentrate more time and attention on the review of single site protocols. The DCC will engage and implement this board on the BMT CTN's behalf. The sIRB will carry out the functions required for institutional compliance with IRB review set forth in the HHS regulations at 45 CFR 46 and allow research to proceed as expeditiously as possible without sacrificing ethical principles and protections for participants enrolled in BMT CTN studies. Reliance agreements will delineate the respective authorities, roles, responsibilities, and communication between the sIRB and the U.S. sites participating in BMT CTN-led trials. All BMT CTN CCC members must agree to participate in the registered sIRB engaged and implemented on the BMT CTN's behalf by the DCC.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient'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. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition 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: https://www.era.nih.gov/need-help (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: 301-637-3015

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)

Nancy L. DiFronzo, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: nancy.difronzo@nih.gov

Lori A. Henderson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5930
Email: hendersonlori@mail.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)

Tanya Smith
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-7072
Email: tanya.smith@nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.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 and 2 CFR Part 200.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.