Part 1. Overview Information

Key Dates

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This funding opportunity announcement will support a Data Coordinating Center (DCC) to conduct the activities of the BLOODSAFE program to enhance the availability and delivery of safe blood for transfusion for patients in low or lower-middle income countries in Sub-Saharan Africa. Refer to RFA-HL-20-009 for detailed information on the BLOODSAFE program FOA. The primary responsibilities of the DCC are to coordinate the activities of the research consortium, assist with program oversight by NHLBI, provide expertise in study design and management as well as data management and analysis, develop common measures and outcomes, ensure data quality, and facilitate collaboration and mutual learning among all research teams.

Background and Objectives

Inadequate blood collection and donation screening are associated with significantly reduced blood transfusion availability and safety in many LLMICs. Key vulnerable populations, particularly women and children, are most impacted by transfusion inadequacies. Inadequacies in blood supply have significant impact on population health in LLMIC contexts across much of Sub-Saharan Africa (SSA). Malaria-associated anemia is a common indication for transfusion therapy in the region. Malaria is the most common cause of severe anemia in childhood and many affected children are known to die of otherwise preventable death due to blood shortage. Obstetric hemorrhage, one of the most significant causes of maternal mortality worldwide, constitutes another important indication for transfusion in SSA. A reduction in maternal mortality is one of the United Nations Millennium Development Goals. Many of these women are not transfused due to a limited blood supply, a situation that likely exacerbates the already high maternal death rates seen in SSA. Patients with sickle cell disease (SCD) and other hemoglobinopathies also often require transfusion. The majority of the world's SCD occurs in SSA. Many SCD patients require acute transfusion therapies for complications such as stroke, and severe anemia secondary to splenic sequestration and aplastic crises. Lack or delay of such therapies is associated with high morbidity and mortality. Improvement in blood supply availability and quality as well as access to transfusion could significantly impact SCD clinical outcomes and quality of life.

BLOODSAFE Program Structure

The BLOODSAFE program will consist of two functional units including 1) a Data Coordinating Center (DCC) and 2) up to three UG3/UH3 Research Teams (RFA-HL-20-009), and will be governed by a Steering Committee (SC).

The Data Coordinating Center (DCC) will coordinate the activities of the research consortium, support the Steering Committee of the research consortium, and provide study design and statistical support for the needs assessment of core problems associated with poor transfusion services in an SSA LMIV local area or region (UG3 phase of RFA-HL-20-009) and the implementation science or hybrid projects (i.e., mixed effectiveness and implementation science) to test the strategies (UH3 phase of RFA-HL-20-009). The DCC will provide expertise in project management and ensure that all regulations and policies have been adhered to (e.g., keeping track of all ethical review board approvals). The DCC will provide data management expertise, contribute to harmonization and interoperability for common measures and outcomes, ensure data quality in collaboration with the Research Teams, and facilitate collaboration, cross-fertilization as well as skills development and capacity building. The DCC will be responsible for providing data management systems to the research teams, receiving and managing datasets from all research teams, and executing certain data analyses such as those evaluating common data elements across teams (e.g., core data elements of the Needs Assessment) or those involving more complex statistical methodologies. Research teams will also be able to conduct their own analyses in collaboration with the DCC as long as they have appropriate data programming and statistical expertise, as evaluated by the DCC and NHLBI.

The NHLBI will be responsible for providing program oversight through an NHLBI Observational Study Monitoring Board (OSMB) or Data and Safety Monitoring Board (DSMB); overall monitoring of interim data and safety issues; providing representation on the Steering Committee; and collaborating with the DCC and all investigators in the development and implementation of the research program. The OSMB/DSMB will review progress related to the various approved study protocols. The OSMB/DSMB will make recommendations to the NHLBI Director regarding protocol continuation and potential modifications. The OSMB/DSMB will consist of five members with expertise in blood supply availability and safety, implementation science, statistics and ethics.

The Steering Committee (SC) for the program will be composed of each the PD/PI from each Research Team and one additional investigator, the PD/PI of the DCC and one additional team member, NHLBI scientific staff, and an independent chairperson appointed by the NHLBI. The DCC and each Research Team will have one vote on the SC. The SC will identify issues that have broad applicability across the program. Initial recommendations regarding program level organization (overall program procedures), and an evaluation of where studies can achieve consistencies (e.g., common data elements) will be made by the SC. It is expected that the SC will review the protocols developed by the Research Teams and provide comments to optimize the protocol designs. Such recommendations might involve areas such as study design, standardized aspects of informed consent, sharing of expertise in implementation science research, optimizing stakeholder involvement, data collection, data sharing, data quality control plans and data analysis. Protocols that have been reviewed and approved by the SC will then undergo review by the NHLBI Protocol Review Committee before they can be implemented. In addition, all information and documents developed for the public website must be reviewed and approved by the SC and NHLBI prior to posting on the public website.

A Protocol Review Committee (PRC) will be appointed by NHLBI. The membership of this committee will consist of members with expertise in transfusion medicine, epidemiology, implementation science research, biostatistics, and ethics. The PRC will review protocols after they have been reviewed by the SC. Recommendations from the PRC will be given to NHLBI for approval, before a study can be launched by a Research Team.

An independent program-wide Observational Study Monitoring Board (OSMB) or Data and Safety Monitoring Board (DSMB) will be appointed by the Director of NHLBI. Members of the OSMB or DSMB will advise the Institute regarding study feasibility, participant safety and burden, data monitoring, and successful achievement of milestones for each project. The OSMB/DSMB will consist of five members with expertise in blood supply availability and safety, implementation science, statistics and ethics. Meetings will be held via conference calls and will use web-based systems. The DCC will budget honoraria for the OSMB or DSMB. The DSMB or OSMB may also serve as the Protocol Review Committee (PRC) for this program.

A sub-Committee of the SC will serve as the Publications Committee. The Publications Committee will follow a publications policy approved by the SC at the beginning of the program period and will be responsible for review of all abstracts, presentations, and manuscript submissions by all BLOODSAFE investigators. The DCC will coordinate and support meetings and calls of all subcommittees including the Publications Committee.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

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)

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)
• U.S. Territory or Possession

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

Applicant organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

Letter of Intent

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review

National Heart, Lung, and Blood Institute

Telephone: 301-435-0270
?Email: nhlbichiefreviewbranch@nhlbi.nih.gov

The team must include investigators who have the following knowledge, experience and skills: 1) Experience in coordinating and supporting multi-center international research programs, particularly programs that include key components in low or middle income settings preferably in Sub-Saharan Africa. 2) ?Expertise in data coordination and statistical support. 3) Expertise in epidemiologic and implementation science research, including expertise in study design, as well as the ability to conduct simple as well as complex, and sometimes novel analyses. 4) For optimal functioning, the DCC should also have one to two staff members with expertise relevant to availability and delivery of safe blood for transfusion, including transfusion medicine, epidemiology, and implementation science, which could be provided by consultants.

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

Include a budget for coordinating approximately three, 3-hour conference calls of the OSMB/DSMB using web-based systems, and for providing support for each Board member.

Include costs for two, 2-day Steering Committee meetings to be held in Bethesda, Maryland in each year of the program. The Steering Committee will otherwise meet by teleconferences. The DCC will be responsible for reimbursing the Steering Committee Chair at 20% full time professional effort and supporting the Chair's travel and administrative expenses.

Budget for ?two site visits (five days each, including trave l) for each of up to three sub-Saharan Research Teams during the first year of the grant period and one to two site visits in each subsequent year . The applicant should plan to have two DCC participants per site visit .

Research Strategy

Include detailed plans for DCC development and management.

1. Overall Program Coordination and Administrative Support

Facilitation of interactions and functions
Describe plans for coordinating interactions between the consortium Research Teams; the consortium and the DCC; and the consortium/DCC and the Steering Committee (SC), NHLBI, and partners. Specifically address the following activities:

• Scheduling meetings and calls, including those of the consortium Research Teams, SC and its subcommittees
• Preparing and distributing agendas
• Compiling and distributing review materials
• Preparing and distributing a list of action items within five working days of a meeting/call
• Preparing and distributing minutes for review and approval by associated PDs/ PIs, chairpersons, and NHLBI scientists within ten working days of a meeting/call
• Tracking and maintaining a central repository of minutes and materials relating to the functioning of the various Research Teams and committees on the consortium website
• Informing consortium participants when minutes and materials are posted
• Reproducing, distributing, and posting Manuals of Procedures (MOP), including updates
• Preparing and submitting reports regarding database development, subject privacy, data capture/quality, data and performance of collaborative consortium Research Teams to the SC and OSMB/DSMB

Development and maintenance of Manuals of Procedures (MOP)

Describe plans to help the consortium develop protocols, including associated Manuals of Procedures. Content of the Manuals of Procedures should include the following:

• Governance, coordination, communication, and the development and approval of database elements, definitions, and development of a common dictionary
• Plans for data collection, management, security, and sharing
• Human subject considerations, if applicable
• Statistical and analytical requests; publication policy; processes to obtain all necessary approvals and administrative/regulatory clearances; and performance metrics for both the collaborative consortium and the DCC

Creation and management of private website

Describe plans for the development and maintenance of a private interactive, secure, scalable, flexible, and robust web-based consortium platform that will contain all information pertaining to program activities and serve as a communication and administrative portal.

• Provide plans for a secure environment and the necessary data management system(s) and informatics support to acquire, store, catalogue, query, and distribute documents and materials required for the successful performance of the program.
• Include plans for posting consortium documents including, but not limited to, protocols, Manuals of Procedures, minutes of the SC and its subcommittees, presentations, and manuscripts.

Creation and management of public website

Describe plans for the development and maintenance of a public website with content that will include a description of the program and its objectives, a list of participants, a list of publications, contact information, and other information of interest to the general public.

Committee management and coordination

Describe plans for coordination of the OSMB/DSMB/PRC and the SC and its subcommittees for accomplishing the review of study protocols and database materials. Include the planned approach for preparing and presenting data reports to the OSMB/DSMB.

2. Data Coordination and Statistical Support

• Describe plans for project management including ensuring adherence to all regulations and policies
• Describe plans for harmonization and interoperability, management of common measures and outcomes, ensuring data quality in collaboration with the Research Teams, and facilitating collaboration, cross-fertilization as well as training and capacity building
• Describe plans to develop and implement secure and robust data collection, tracking, management, and storage procedures for all data compiled by the program. and to provide necessary data management systems to the Research Teams. Include plans for implementing innovative, cost effective procedures that take advantage, whenever possible, of the Research Teams existing data platforms. Plans should also include new approaches to database support and management that will mitigate increases in the cost of software
• Describe the planned approach to collecting, organizing, and storing data that will be transmitted to the DCC by the individual Research Teams, and for assuring the quality of the study data submitted and stored. Provide the planned approach for developing a Data Management Plan, a Data Quality Control/Quality Assurance Plan, and a Data Security Plan to be included in the Manuals of Procedures
• Describe plans for ensuring that the computer programs, data management systems, databases, and other resources developed through this cooperative agreement will be compliant with terminology and data standards established by the NIH. Include plans for ensuring that the computer hardware and software procedures comply with all relevant regulations of the countries in which Research Teams are located as well as those of the United States
• Detail the expected process for routine web-based data entry by Research Teams and management. Include plans for instructing users web-based data entry; monitoring and evaluating database enrollment; and for developing site performance metrics and corrective actions for under-performance
• Detail plans for delivering innovative and flexible biomedical informatics that can specifically support the creation of database elements, harmonized definitions, and dictionary; facilitate operations, administration, and research activities. Describe how the proposed approaches and technologies will be suited to regional resources. Provide a detailed strategy for continual assessment of informatics performance
• Describe plans to manage review of all protocols in this program by the institutional review board (IRB) at the DCC institution or a single IRB as required. Include a plan to monitor the status of IRB review and approval as well as timeline for review of all studies in the program Describe how the DCC will instruct staff within each individual consortium Research Team in procedures delineated in the MOP including consultation regarding data collection, entry, storage, and transmission procedures. Describe the planned approach for establishing procedures for quality control/improvement and certification of data management for consortium Research Teams and for conducting site visits to address and remedy issues in the conduct of database-related activities.
• Describe how the DCC will transform the centralized database and datasets into public-use datasets that will be delivered,at a time specified by the NHLBI, with associated detailed documentation to NHLBI and be made available to the scientific community. Describe how these datasets will be de-identified and placed in a format that will be appropriate for independent use by an investigator external to the study.

3. Epidemiologic and Implementation Science Research

• Describe plans for project management including ensuring adherence to all regulations and policies
• Detail statistical and analytical plans to assist the collaborative consortium Research Teams develop epidemiologic and implementation science studies and data analyses
• Describe how the DCC will assist with the preparation of scientific reports and publications, including development of scientific abstracts, presentations and publications; coordination of Publications Committee activities and meetings/calls and other relevant subcommittees calls; checking data accuracy; and posting presentations and publications on the website
• Outline plans for submitting manuscripts accepted for publication to PubMed Central according to Federal and NIH policy (http://publicaccess.nih.gov/); tracking progress of publications, including PubMed Central reference number, and presentation of findings

4. Milestones and metrics

Provide a well-defined set of yearly milestones for proposed activities related to monitoring and evaluating the administrative performance of both the collaborative consortium and the DCC. These should conform to the timeline described below. Continued support during years 2-6 will be provided only if timely achievement of milestones can be demonstrated. Milestones will be reconsidered on an annual basis to account for the DCC's experience and progress.

Milestones, (UG3 phase of the BLOODSAFE program)

Describe the key milestones that must be met in years 1-2 to ensure the success of the BLOODSAFE program and the processes that will be used to reach the key milestones, and a timetable identifying when each of these key milestones will be met.. The DCC milestone plan should include key milestones that need to be met during the first phase of the award (UG3 phase) to allow for successful transition to the second phase (UH3 phase). UG3 milestones must include, but are not limited to the following:

• Establishment of working relationships and manuals of procedures within the BLOODSAFE program, with the NHLBI, with review/monitoring bodies, and other partners
• Completion of the database elements, definitions and dictionary
• Creation of secure electronic databases
• Provision of biostatistical and analytic support
• Assisting in the preparation of ethical, legal and social issues (ELSI) guidelines for the BLOODSAFE program
• Provision of assistance to Research Teams with regulatory reviews
• Design of skills development programs and educational materials appropriate to each Research Team
• Assisting Research Teams with needs assessments, including study design, data collection, data transmission to the DCC, data analysis, report preparation, and review by the SC, OSMB/DSMB, and the NHLBI
• Assist Research Teams with identification and prioritization of strategies for improving availability and delivery of safe blood for transfusion

?Milestones, (UH3 phase of the BLOODSAFE program)

Provision of coordination and administrative support
Assisting Research Teams with preparation of Manuals of Procedures for research protocols
Assisting Research Teams with execution of implementation science research protocols, including all necessary regulatory review and approval, instruction, data collection, quality assurance and quality control, data analysis and reporting
Coordinating each Research Team's project progress and review by the SC, OSMB/DSMB, and the NHLBI

Letters of Support
Each DCC applicant must provide a statement that addresses how institutional commitment will be established and sustained, and how the DCC efforts will be given a high priority within the institution. The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the DCC Director, assignment of space, and/or other ways proposed by the applicant institution. Letters from a high-level institution official(s) (e.g., Dean of the School of Medicine, President, or Vice President for Research) should be attached confirming this commitment. Applications that do not include these letters of support will be considered incomplete and will not be peer reviewed.

Provide letters of support from collaborators, including consultants and advisors, whose supports are necessary to the successful conduct of the research.
If additional funding is to be provided by sources other than NHLBI, provide Letter(s) of Support signed by an authorized organization representative (AOR).

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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.

Significance

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

Investigator(s)

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

Specific to this FOA

?Has the applicant assembled a team with demonstrated expertise in biomedical informatics, data management, biostatistics, epidemiology, implementation science, clinical study design, and/or other relevant areas? Does at least one investigator have substantial expertise in availability and delivery of safe blood for transfusion? How adequate is the experience of the proposed project team in coordinating multi-center, interdisciplinary international research programs, especially such programs in low or middle- income countries, preferably including SSA countries? How effective will the proposed project team's assistance be in helping to design and implement observational studies and clinical trials (if appropriate) including effectiveness or hybrid effectiveness-implementation studies? Does the proposed team of investigators have sufficient experience in data coordination and statistical support? Does the applicant provide evidence of sufficient experience in epidemiology and implementation science to successfully execute proposed plans? How strong is the leadership to coordinate the multicenter research consortium?

Innovation

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

Specific to this FOA

Within the constraints of available regional resources, how innovative and flexible are the proposed approaches to ensure that the DCC infrastructure will be capably established and able to support the activities outlined in the Research Plan?

Approach

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

Specific to this FOA

How reasonable is the plan to facilitate interactions among the Research Teams, the NHLBI, the SC? How likely are the planned activities to result in a clear and useful Manual of Procedures? How appropriate is the plan for developing the private and public websites? How well-defined, feasible, and comprehensive is the plan for supporting, monitoring, and evaluating the administrative performance of the collaborative consortium and the DCC during each phase of BLOODSAFE? Are milestones clearly delineated, feasible, and sufficiently comprehensive? How effective is the proposed approach for monitoring program performance?

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

Environment

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

Specific to this FOA

Are the institutional environment (resources, space, personnel) and organizational structure (management, coordination, tracking) appropriate for implementing the proposed DCC plan? Is the grants administration capacity adequate? Are there sufficient clinical data management resources to support the development of a secure system for collection, storage, and analysis of data from up to 3 Research Teams? Does the application demonstrate the ability to develop private and public web-based systems? Does the application adequately address privacy and confidentiality issues related to database management, distributed computing, and multiple levels of data sharing as appropriate and consistent with achieving the goals of the program? Does the application describe a proactive plan to incorporate existing data platforms and take advantage of existing resources within Research Teams?

The Program as an Integrated Effort

How conducive is the proposed structure of the DCC to achieving early program goals? Are adequate mechanisms proposed for regular communication and coordination among investigators within the DCC and with those in the Research Teams? Are adequate administrative structures in place for the day-to day management of the DCC and its communication with the consortium?

Sustainability

Do the letters of Institutional and National commitment suggest that the overall environment is conducive to a sustained DCC enterprise that will be able to support this multi-center, interdisciplinary international program for the entire duration?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Applications from Foreign Organizations

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.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI. Assignment to a Scientific Review Group will be shown in the eRA Commons.

• 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.
• Will receive a written critique.

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 FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Advisory Council.

The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

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

2. Administrative and National Policy Requirements

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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.

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

Awardee and PI(s)/PD(s) Rights and Responsibilities

The PI(s)/PD(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PI(s)/PD(s) assume responsibility and accountability to the applicant organization officials and to the NHLBI for the performance and proper conduct of the research supported by the award. All awardees proposing clinical research must comply with federal, state, and local regulations regarding clinical research and monitoring of clinical trials and oversee that all training requirements for the protection of human subject are in compliance.

The PI(s)/PD(s) or their delegates will participate in all annual meetings, workshops, and working groups. The PI(s)/PD(s) will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under the NIH Program Staff: Program Official (PO) and Project Scientist (PS) Roles. The PI(s)/PD(s) will agree to the governance of the program through the Steering Committee (SC).

The PI(s)/PD(s) will be responsible for the timely submission to the Publication Committee for review and approval of all abstracts, manuscripts and reviews (co)authored by members of the grant and supported in part or in total under this cooperative agreement before submission for presentation or publication. Manuscripts shall be submitted to the NIH Program Official within two weeks of acceptance for publication and must comply with the NIH Public Access Policy. Publications or oral presentations of work performed under this cooperative agreement will require appropriate acknowledgement of NHLBI support. Timely publication of major findings is encouraged. The awardee will retain custody of and have primary rights to the documents, publications and other items developed under the award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH Responsibilities

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

The NIH Project Scientists will coordinate and facilitate interactions and collaborations among the awardees of this research consortium and provide technical assistance and advice to the awardees as appropriate. The NIH Project Scientists will serve as the liaison between individual projects and NHLBI. The NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned NIH Program Official may also serve as an NIH Project Scientist. The NIH Program Official will periodically report progress about the program to NHLBI leadership including the Director of the NHLBI; PI(s)/PD(s) will provide timely assistance in providing relevant updates, documents, and other materials for the annual progress reports to the NHLBI.

Collaborative Responsibilities

A Steering Committee (SC) will serve as the main governing board and monitor progress; facilitate coordination and synergy across the entire program; and develop recommendations for uniform procedures and policies.

The Steering Committee membership will include the NIH Project Scientist(s) and the PI(s)/PD(s) of each award. The Steering Committee Chair will not be an NIH staff member but will be appointed by NHLBI staff. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. As necessary, the Steering Committee will create appropriate subcommittees to handle interests that may be specific to a set of awardees funded by this FOA.

SC Responsibilities:

SC will discuss progress in meeting the goals of various research projects; facilitate coordination and synergy across the entire program; and develop recommendations for uniform procedures and policies necessary to meet the goals of the program. For example, SC will determine research collaborations such as methodology, data, and core measures and assessment available.

SC will lead organizational management including the schedule and concise summaries of the Steering Committee meetings. The SC will meet at least once a year in person and hold regular conference call meetings. The SC will seek to operate by consensus, but in the event that a vote is needed, the PI(s)/PD(s) of each award and NIH will have one vote. In the case of multiple PD/PI awards, the awardee will identify one PD/PI who will vote on behalf of the awardee's team.

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. The three members will be: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

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

Section VII. Agency Contacts

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

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

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

Shimian Zou, PhD

Division of Blood Diseases and Resources

National Heart, Lung, and Blood Institute (NHLBI)

Telephone: 301-435-0065
Email: shimian.zou@nih.gov

LeShawndra Price, PhD

Center for Translation Research and Implementation Science
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8166
Email:leshawndra.price@nih.gov

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

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Laurel Kennedy
Division of Extramural Research Activities
The National Heart, Lung, and Blood Institute
Telephone: 301-827-4777
Email: laurel.kennedy@nih.gov

Section VIII. Other Information