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

Background

Sickle Cell Disease (SCD) is a recessively inherited disorder of hemoglobin that is associated with considerable phenotypic heterogeneity. Hallmark complications include hemolytic anemia, acute vaso-occlusive pain and chronic pain syndromes, sepsis, overt and silent stroke, and widespread chronic end organ damage. These complications are associated with premature mortality and ongoing disability.

In the U.S. and other high-income nations, scientific and clinical infrastructures have supported the discovery and implementation research of several preventive and therapeutic strategies. Patients with SCD living in these countries have benefited from newborn screening, penicillin prophylaxis, pneumococcal vaccine, transfusion therapy, stroke prevention, early hydroxyurea therapy, management guidelines, and ongoing comprehensive care. Promising novel treatments that may interrupt vaso-occlusive crises and ameliorate chronic organ damage are under study and curative gene therapies appear to be on a foreseeable horizon.

SCD is one of the most common diseases in the world. Over 300,000 babies are born with SCD annually, and this number is expected to increase to up to 400,000 individuals by 2050. SCD prevalence is exponentially greater in low resource countries, particularly those in sub-Saharan Africa, with more than 75% of global SCD births occurring in the region. Despite the high prevalence of disease, support for effective surveillance, prevention, and therapies is sorely lacking. Without essential programs such as national newborn screening, regionally appropriate management guidelines, and ongoing care, the majority of affected African children die before the age of 5. WHO estimates that SCD accounts for up to 15% of mortality in children under the age of 5 years in Africa. The World Bank has identified SCD as an important cause of disability in sub-Saharan Africa and a leading cause in Nigeria. In all, these statistics constitute a very significant public health problem that has been inadequately addressed.

The first phase of the SCD in Sub-Saharan Africa (SSA) Network was established in 2017 to support capacity building activities and to develop the initial infrastructure for a future regional Network. The Network was envisioned as a sustainable resource that would advance SCD-related epidemiologic, translational, and clinical research studies. In order to achieve these objectives, the Sickle Pan-African Research Consortium (SPARCO), comprised of vanguard sites coordinated by a Clinical Coordinating Center (CCC) and an associated Sickle Africa Data Coordinating Center (SADaCC), were funded in 2017. The CCC is located in Dar es Salaam, Tanzania and collaborating sites are situated in Abuja, Nigeria and Kumasi, Ghana as well as Dar es Salaam, Tanzania. The SADaCC is located in Cape Town, South Africa. The current phase of the Network is aimed at developing: 1) a REDCap SCD registry/database system to include 13,000 subjects of all ages; 2) shared database elements and harmonized phenotype definitions/ontologies; 3) regionally appropriate clinical SCD management guidelines; and 4) associated skills development programs. An additional goal of the Network was to begin planning for the conduct of cohort studies, implementation research studies for newborn screening, infection prevention, and wider hydroxyurea use; and database expansion to include additional sub-Saharan African nations of patients enrolled in the SCD registry in the final funding year.

Purpose

The next phase of the Network, as detailed in this FOA and its companion FOAs, is intended to sustain, enhance and grow the SCD in Sub-Saharan Africa Network and to promote and expand capacity building activities relevant to SCD in sub-Saharan Africa. Enhancement of network infrastructure and the addition of new participating sites will advance SCD-related epidemiologic, translational, and clinical research in the region while concurrently improving SCD care.

This FOA runs in parallel with RFA-HL-21-007, which invites an application from the current awardee institution of the SPARCO CCC, and RFA-HL-21-008, which invites an application from the current awardee institution of the Sickle Africa Data Coordinating Center (SADaCC). The SADaCC, CCC, as well as established and new sites of the Consortium will constitute the SCD in Sub-Saharan Africa (SSA) Network. This Network aims to develop a sustainable resource that will advance SCD-related epidemiologic, translational, and clinical research studies.

Objectives

The expanded program will make it possible to describe (for newly participating countries) or more accurately describe (for already participating countries) the current status of SCD as well as risk modifiers including access to care and clinical management in SSA countries, and provide comparative data to what is observed in the US and other countries.

This program will support studies that plan to follow-up SCD patients enrolled in the registry (defined as cohort research studies) in the participating countries. These cohort research studies would permit evaluation of: 1) the incidence of clinical events, such as pain crisis and acute chest syndrome (ACS); 2) the possible association with various factors including care and management, such as infection prophylaxis and hydroxyurea use, as well as socio-economic and environmental factors; and 3) the impact on health outcomes of improving the identification and care of patients with SCD that will have occurred during the follow-up period.

This program also anticipates supporting implementation science research studies to evaluate planned intervention(s), such as newborn screening, infection prevention or wider hydroxyurea use, to identify factors that impact uptake across multiple levels, including patient, provider, clinic, facility, organization, and often the broader community and policy environment. In the context of this FOA, implementation science research studies evaluate the impact of planned interventions and provide essential scientific evidence on not only safety and efficacy but also feasibility, efficiency, cost-effectiveness, scalability and sustainability of interventions before wider implementation, while cohort studies are observational in nature and are not interventional.

In the next phase of the Network, NHLBI expects that each already-established Collaborative Consortium site will have responsibility for:

• Following leadership and guidance from the CCC (supported under RFA-HL-21-007) and the SADaCC (supported under RFA-HL-21-008), to perform all activities agreed upon by the Consortium
• Establishing/updating structure, operations, and schedules in con cert with the CCC
• Adding a satellite site(s) to optimize enrollment in the Registry and research studies
• Engaging, as appropriate, with all stakeholders including Consortium participants, committees, regulatory boards, existing skills development programs, Ministries of Health and Education, and NHLBI
• Continuing to implement and improve the sickle hemoglobinopathy registry/database and updating Consortium database elements, phenotype definitions, and ontologies on an ongoing basis, as appropriate
• Maintaining the established registry/database of patients with SCD
• Enrolling new participants with SCD (including those identified via newborn screening) to reach a total of an additional 3,000 participants
• Adopting updated Consortium ELSI (Ethical, Legal and Social Issues) guidelines as needed
• Obtaining all necessary regulatory approvals for the conduct of the registry and the research studies
• Adopting updated Consortium operating manuals (per the CCC and SADaCC)
• Integrating the SCD Management Guidelines (per the CCC and SADaCC)
• Finalizing and obtaining regulatory/ethical approval, and conducting the cohort and implementation research studies at established sites (including satellite sites) starting in Years 1 and 2 of the program
• Instituting newborn screening, penicillin prophylaxis, and wider hydroxyurea use or other implementation research studies as agreed upon by the Consortium in Years 1 and 2 of the program
• Planning and implementing one additional research project appropriate for the local setting, with agreement by the Consortium

In the next phase of the Network, NHLBI expects that each new Collaborative Consortium site will have responsibility for:

• Establishing structure, operations, and schedules in concert with the CCC (supported under RFA-HL-21-007) and with support from the SADaCC) (supported under RFA-HL-21-008) in Year 1 of the program
• Continuing engagement as appropriate with all stakeholders including Consortium participants, committees, regulatory boards, NHLBI, SCD skills development programs, and local Ministries of Health and Education (Years 1-5)
• Adopting and implementing Consortium database elements, phenotype definitions, and ontologies (Years 1-2)
• Working with the SADaCC to establish operations and subsequently enroll and follow 4,000 SCD participants in the sickle hemoglobinopathy registry/database (Years 2-5 of the program)
• Adopting Consortium ELSI (Ethical, Legal and Social Issues) guidelines (Years 1-2)
• Obtaining all necessary regulatory approvals for the conduct of the registry and the research studies (Years 1-2)
• Adopting and implementing Consortium operating manuals (Years 1-2)
• Integrating the SCD Management Guidelines (Years 3-4)
• Helping to finalize the research design, obtain all regulatory/ethical approvals for, and launch approved cohort and implementation research research studies (Years 3-4). No clinical trials other than implementation research clinical trials will be part of the research activities that will be conducted in the SCD in SSA Network.
• Instituting newborn screening, penicillin prophylaxis, and wider hydroxyurea use or other implementation research studies as agreed upon by the Consortium (Years 3-4)
• Planning and implementing one additional research project appropriate for the local setting, with agreement by the Consortium (Years 1-5)

No clinical trials other than implementation research clinical trials will be part of the research activities that will be conducted in the SCD in SSA Network.

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)

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

The established Collaborative Consortium sites refer to Non-domestic (non-U.S.) Entities (Foreign Institutions) in African countries that are already part of the Sickle Pan-African Research Consortium, specifically, 1) Ghana (Kwame Nkrumah University of Science and Technology in Kumasi), 2) Nigeria (University of Abuja in Abuja), and 3) Tanzania (Muhimbili University of Health and Allied Science, Dar es Salaam) that have each established a registry/database of at least 2,000 participants with SCD. Each established site needs to have at least one satellite site in the same country.

New Consortium sites need to be located in other Sub-Saharan Africa (SSA) countries; no application for new Consortium sites will be accepted from Ghana, Nigeria or Tanzania. Only one site will be funded for any nation.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

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.

The primary PD/PI shall have an appointment at an institution in a Sub-Saharan African (SSA) country. This affiliation shall constitute at least 75% of full time professional effort of the PD/PI in the past 2 years. For a list of countries in Sub-Saharan Africa, please refer to Sub-Saharan African Region Information provided by the Fogarty International Center of NIH. An investigator from another country cannot serve as a co-PD or co-PI but can serve as a co-investigator or consultant at the invitation of the primary PD/PI although the co-investigator or consultant cannot be compensated (i.e. with 0% effort in the budget) to ensure that all awarded funds will be used at the site and if applicable, the satellite site(s) to carry out the proposed studies.

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
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

Facilities & Other Resources: Applicants must include information regarding the existing facilities and particular expertise. Include a detailed, well-documented description of existing institutional infrastructures and special capabilities. With regard to the institution, describe the current capacity for administration of grants, including information about the placement of the designated administrative infrastructure (e.g., Office of Research, Office of Sponsored Projects) within the institution and its line of authority, the institutional provision of resources such as office space, administrator salary, office equipment, and the applicant institution's plans to support and sustain the proposed research activities. Describe any plans the institution may have for further development of its research administration capabilities.

Other Attachments:

1. Organization Structure: All applicants should include a strategy for organization structure that is no more than two pages. This attachment should be entitled "Org Structure.pdf" and should describe plans for administering, managing, tracking, coordinating, and conducting the research activities at the site.
   
2. Sustainability: All applicants should include a strategy for Sustainability that is no more than two pages. This attachment should be entitled "Sustain.pdf". Discuss the issue of future sustainability beyond the funding period and how the proposed activities will contribute to success in continuing the research efforts of the SCD in SSA. This section of the application should refer to the letters of Institutional and National commitments (see Letters of Support) to provide an overview of the long term prospects for sustained research.
   
3. Performance Capabilities: Applicants should describe the site’s capabilities to enroll patients with SCD in the registry, and should include a description of how they anticipate to address recruitment and retention challenges that they may encounter. This attachment should be entitled "Capabilities.pdf" and must not exceed six pages.
   
4. Skills Development Activities: The applicant is encouraged to take advantage of current programs that are supported by other NIH entities, as well as other agencies and societies. Individuals from the CCC and collaborating sites may participate in the skills development activities. Describe any intent to take advantage of these skills development activities such as the Medical Education Partnership Initiative (MEPI) and and the American Society of Hematology (ASH) Visitor Training Program and identify which programs will be pursued. The document should be attached using the filename "Training Participation.pdf" and may not exceed five pages.

• MEPI: Where possible, applicants are encouraged to collaborate with MEPI grantees in order to take advantage of the training infrastructure and opportunities available through MEPI.
• ASH Visitor Training Program (VTP): The purpose of the VTP is to help build hematology capacity in low income countries, ultimately improving patient care. It provides funding for hematologists or hematology-related healthcare professionals in low income countries to receive training on a specific topic or technique for up to 12 weeks. Training is carried out in the clinic or laboratory of an ASH member under their supervision and mentorship. Upon completion of the training, participants return to their home institution to implement the skills and knowledge that they have acquired.

Applicants are expected to assemble a research team whose members demonstrate experience and expertise in relevant areas including the diagnosis and care of individuals with SCD, administration and coordination of clinical study research, database development, clinical and research skills instruction, as well as research planning, implementation, and monitoring.

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

The budget should include, but not be limited to, the following items:

• PDs/PIs supervision of day to day operation and oversight of the professional activities of the collaborative site
• Staff training and certification in core operations and procedures
• Reasonable administrative costs
• Development of a Manual of Operating Procedures (MOP) for the SCD in SSA Network, which will be coordinated by the Consortium CCC and will be done in concert with the DCC
• Budgeting for registry/database of participants with SCD
• Maintaining and expanding the existing registry/database (applicable to existing/established sites only)
• ?Developing registry/database (applicable to new sites only)
• Budgeting for satellite site subcontract(s) (applicable to existing/established sites)

Include travel costs for the PI and Co-PI to attend Steering Committee (SC) and SCD in SSA Network Committee meetings (held simultaneously), two times a year, in an African location. Include travel costs for an additional one to two people to attend the Network Committee meetings. SC meetings are attended by the PI and Co-PI of each Consortium site as well as the PIs and Co-PIs/Coordinators of the CCC and SADaCC. Network Committee meetings are attended by two to four people from the CCC, two to four people from the SADaCC and two to four people from each of the Consortium sites, including those who also attend the Steering Committee meetings. The budget should also include support for other travel related to anticipated Collaborative Consortium operations.

NOTE: Costs for meeting planning, coordination, space, equipment etc. will be covered by the separate SADaCC (RFA -HL-21-008) application budget and are not part of this application.

Specific Aims: Describe a concise set of specific aims that explain the overall goals of the site and expected outcomes through potential participation in the Collaborative Consortium.

Research Strategy: include detailed plans for consortium development (including milestones and timelines) as follows:

1. Operations and Governance:
Briefly outline the planned infrastructure logistics for communications as well as interactions with the CCC, SADaCC, local Ministries of Health and Education, NHLBI, the Steering Committee , and potential partnering programs. Communication and interaction with the CCC and SADaCC will include regular progress updates and comprehensive reports for the CCC and SADaCC to update the Observational Study Monitoring Board about progress as well as adverse issues and unanticipated problems at a minimum of every six months, or more often as appropriate. Additional details will have been provided in the "Facilities and Other Resources" section of the application.

2. Registry Development:
Describe plans (with the help of the CCC and SADaCC) to continue to build (for established sites) or develop (for new sites) a centralized, electronic, patient consented, sickle hemoglobinopathy registry that will facilitate registration and follow-up of SCD patients. The following information should be included:

• Anticipated roles (distinct and shared) to be played within the Collaborative Consortium
• Steps that will be pursued to incrementally expand or develop the registry
• Methods that will be used to create shared data elements as well as harmonized phenotype definitions and ontologies
• How the diagnosis of SCD will be defined
• Patient recruitment and enrollment strategies
• Plans to collaborate with the CCC to ensure adherence to unique regional consent regulations relevant to the protection of human subjects/informed consent procedures
• Feasibility of enrolling the total number of participants (for new sites)
• Feasibility of continuing to follow-up currently enrolled participants (for established sites) as required and how to leverage/build-upon the existing registry that has been developed in the first funding period of the program
• Additional ethical, legal and social issues (ELSI) relevant to the conduct of regional SCD data acquisition and research, and how these will be addressed
• Unique responsibilities of the CCC, SADaCC and Consortium sites, including how the SADaCC will provide a data management system, training, and technical support to the sites; how the sites will provide data to the CCC for compilation and quality control; how the CCC will provide compiled data to the SADaCC for additional/final quality check and clean-up, storage and analysis; how the SADaCC will be responsible for developing the public-use datasets at completion of the program per the data sharing plan.

3. Consistent Standards of Care:
The applicant should describe the methods they would use to establish or update regional SCD standards of care (appropriate to current resource availability and medical needs). The following information should be included:

• Three priority areas in which care standards are needed and feasible in the regions where the new Consortium sites will be located
• Updating of standards of care by building on what has been achieved in phase 1 of the program for the established Consortium sites
• How the Collaborative Consortium will establish consensus regarding standards of care and how it will allow for Collaborating Site-specific modifications based upon regional feasibility/resources

4. Research Activities:
For established sites, an applicant is expected to build on what has been achieved in the first phase of the program (i.e., finalize research design, obtain all necessary regulatory/ethical approvals, and launch cohort and implementation research projects that have been planned in the first phase of the program). The applicant can include other cohort studies or implementation research projects but needs to specify which ones have already been planned for and, if applicable, why a planned cohort study or implementation research developed in the first phase should not proceed to execution in the second phase as supported by this FOA.

4A. Cohort research studies:
Describe three feasible cohort studies, their general study design, and why these would represent consortium priorities. The following list provides some examples and is meant only to provide guidance; it is not exhaustive and appropriate topics are not limited to the examples provided below: given here:

• Estimate the hereditability of particular SCD clinical or laboratory phenotype(s) by examining incidence in multiply affected families
• Investigate the relationship between selected SCD patient characteristics (such as gender, hemoglobin, infection history, TCD velocities, etc.) and stroke, pain, acute chest syndrome, or other phenotype
• Perform prospective epidemiological studies to assess the natural history of SCD clinical phenotypes in SCD, assessing regional differences and/or the impact of newly implemented therapeutic or preventive strategies
• Evaluate the efficacy of different approaches to the institution of evidence based clinical interventions (such as penicillin prophylaxis, newborn screening, hydroxyurea, etc.)
• Investigate the ethical and legal ramifications of newborn screening, genetic counseling, and trait identification

4B. Implementation research of new preventive/therapeutic practices:
Identify three new clinical practices and broadly describe them and their study design. Explain why these practices would represent Collaborative Consortium priorities, what implementation barriers are foreseen, and what additional resources would be needed. The following list provides some examples of SCD-related preventive/therapeutic practices and is meant only to provide guidance; it is in no way exhaustive and appropriate topics are not limited to the examples provided below:

• Newborn screening procedures
• Genetic counseling
• Pneumococcal vaccines
• Penicillin prophylaxis
• Transcranial Doppler screening
• Hydroxyurea use

4C. Management of Biospecimens
The applicant should describe plans for management of biospecimens (including their aliquots). Unique responsibilities of the CCC, SADaCC and Consortium sites are as follows:

• The SADaCC will provide a repository management system for biospecimens and training and technical support to the sites, including specimen tracking
• The sites will provide data on specimens, including real-time updates following addition of new specimens or use/disposal of existing specimens to the CCC for compilation and quality control
• The CCC will provide compiled repository data to the SADaCC for additional/final quality check, clean-up, and storage, and for further updates
• The sites will also be responsible for delivering repository specimens to the NHLBI repository or another agreed-upon repository for long-term storage and further research, provided that the site PI(s) agree to such centralized long-term storage and management following the completion of this program.

5. Milestones and Metrics:

Discuss how progress will be assessed and how success and impact will be defined and determined. To facilitate monitoring and evaluation, include a well-defined set of yearly milestones for the proposed activities. Milestones should conform to the timeline described below, as continued support during Years 2-5 will be provided only while timely achievement of milestones can be demonstrated. Adjusted milestones will be considered a Prior Approval action and must be submitted in writing from the grantee AOR (Authorized Organizational Representative) to the NHLBI Grants Office. Agreement shall be evidenced by a revised Notice of Award including adjusted milestones. Milestones will be reconsidered on an annual basis to account for the Collaborative Consortium's experience and progress.

Applicants will be expected to conform to the following timeline:

Development Phase: Year 1

• Update or establish structure, operations, and meeting schedule for consortium site
• Update or establish working relationships and operating procedures with the CCC and SADaCC, Ministries of Health and Education, the NHLBI, review/monitoring bodies, and other partners
• Update or develop (with guidance from the CCC and assistance from SADaCC) agreed upon database elements, phenotype definitions, and ontologies
• Work with the CCC and SADaCC to maintain (including follow-up) and expand or develop a centralized, electronic, patient consented, sickle hemoglobinopathy registry
• Update or establish ethical, legal and social issue (ELSI) guidelines
• Compile and update locally feasible and consistent SCD standards of care
• Obtain necessary regulatory approvals
• Work with the CCC and SADaCC to prepare or update Collaborative Consortium registry- and research study- specific protocols as well as Collaborative Consortium operating manuals
• Participate in training programs of the Collaborative Consortium
• Where applicable, begin participation in independently-funded training programs

For established sites:

• Begin introduction of feasible practices, based upon Collaborative Consortium priorities and with guidance and support from the CCC and SADaCC
• Finalize Collaborative Consortium- approved study protocols, obtain regulatory/ethical approvals, and if possible, initiate some of the SCD cohort and/or implementation research studies, guided by Collaborative Consortium priorities and with guidance and support from the CCC and SADaCC

For new sites:

• Plan for introduction of feasible practices, based upon Collaborative Consortium priorities and with guidance and support from the CCC and SADaCC
• Help develop and finalize study protocols with established sites and their satellites, the CCC, and SADaCC, and plan for the implementation and conduct of the Collaborative Consortium-approved cohort and implementation research studies, guided by Collaborative Consortium priorities and with guidance and support from the CCC and SADaCC

Implementation Phase: Years 2 to 5

• Expand and enhance the registry in collaboration with the CCC and SADaCC
• Complete full registration and data entry
• Continue training activities
• Participation and conduct of the Collaborative Consortium-approved cohort research studies
• Participation and conduct of the Collaborative Consortium-approved implementation research of feasible practices, based upon Collaborative Consortium priorities
• Participation in other research activities as approved by the Collaborative Consortium and NHLBI, including analyses of data and publication of research finding

Letters of Support: Applications should include Letters of Support from the appropriate institutional official (University or Medical School President, Dean or Director, or the head research administrator or equivalent) from all collaborating institutions to substantiate the institutions commitment to the proposed plan. Each institution should also state its commitment to overcoming any administrative obstacles to the implementation of the application. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and resources needed for the success of the planned activities. Where applicable, the letter should address institutional commitment to any faculty who participate in associated skill building programs. It should also address commitment to collaborating and sharing data as appropriate. The letter should also briefly discuss the institution's plans for sustaining an active program of SCD related research subsequent to the end of the funding period. Applications should also include letters of support from Ministries of Health and/or Education and any other national entities that can further endorse the project.

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. In addition, applicants must:

• Include an initial plan for sharing data and resources generated. For the purposes of this initiative, data and resource sharing will be limited exclusively to participating African Collaborative Sites, the CCC and the DCC during the years (five) of grant support. In addition, this limitation will continue for at least one year after the funding period or, in the event of termination, at least one year after the date of termination. (Subsequent plans and timing for wider data and resource sharing will be developed during year five, or at any time there is reason to terminate funding. These plans will be subject to the same approvals and processes applied to the initial plan as discussed below.)
• Describe overall plans for data monitoring and evaluation.

The applicant is only required to provide the initial local sharing plan in this application. This plan should be consistent with achieving the goals of the SCD in SSA Network. The initial plan must be approved by NHLBI program staff before the application can be funded. Notably, after the Collaborative Consortium CCC and DCC awards have been made, these two entities and the NHLBI will develop a unified initial policy for data and resource release. Final, uniform policies will ultimately be determined by the Steering Committee. This application must include a statement that the Collaborating Site will abide by all agreed upon data and resource policies, consistent with the relevant NIH policies, laws and regulations once the awards have been made.

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?

Specific to this FOA:
If successful, how will the proposed activities help establish the necessary infrastructure to develop a SCD in SSA Research Network?

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?

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:
Do the investigators have expertise in relevant areas including the diagnosis and care of individuals with SCD, administration and coordination of research, database development, skills instruction, research planning, implementation, and monitoring? Are the proposed collaborators likely to work together synergistically?

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? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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:
Keeping in mind regional resources and existing constraints, are the proposed activities sufficiently innovative to ensure that the Collaborative Consortium infrastructure will be capably established, able to promote planned operations, and sufficiently flexible to support future efforts? How innovative are the proposed approaches to the development of regional skills?How innovative are proposed approaches to SCD cohort study design, new practice implementation research, and methods to engage new sub-Saharan African sites?

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?

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 will the proposed organizational structure and Data Sharing/Release Strategies achieve the goals of the program? How will the proposed inter-site and inter-group interactions promote communication and synergy? Does the application provide approaches to registry maintenance and expansion (for established sites) or establishment (for new sites) as well as the update of phenotype/ontology definitions? Does the application describe recruitment, enrollment and consent strategies? Is the estimated number of enrollees sufficient? Are approaches to regulatory approvals, regional consents, and a data sharing plan, as appropriate, described? Are plans to establish and update regional SCD standards of care adequately explained and are they feasible? Are proposed plans for skill development activities appropriate and compelling? Are plans for developing protocols, implementing procedures for the corresponding Manual of Procedures, conducting, compiling and providing all data to the DCC, and disseminating results well described? Are plans to assess the progress of the Collaborative site reasonable and feasible?

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?

Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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

Environment

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

Specific to this FOA:
How strong are the plans to identify and leverage unique resources and expertise at the Collaborative site?

In addition, for applications involving clinical trials:
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? 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?

The Collaborative Consortium as an Integrated Effort:
How will the proposed Collaborative site structure and communication/coordination plan achieve program goals?

Performance Capabilities:
How adequate are the site's capabilities to enroll patients with SCD in the registry? How adequate are the site's plans to address recruitment and retention challenges that they may encounter?

Sustainability:
How well do the Letters of Support demonstrate institutional and national commitment? How likely will the proposed collaborations with the Consortium CCC, the DCC and other Collaborative Sites sustain viable long-term partnerships?

In addition, for applications involving clinical trials:

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories 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, 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.

• 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 appropriate national Advisory Council or Board. 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.

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

2. Administrative and National Policy Requirements

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.htmlor 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 following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 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 recipient’s activities by involvement in and otherwise working jointly with the award recipient 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 awardee(s) for the project as a whole, although specific tasks and activities may be shared among the awardee(s) and the NIH as defined below.

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

The awardee will have the primary responsibility for the conduct of Collaborative Consortium activities, modifications of project design, quality control, data compilation, biospecimen collection, processing and storage, analytical output interpretation, preparation of publications, and collaborations with other partners, unless otherwise provided for in these terms or by action of the Steering Committee, or NHLBI-approved recommendations from the OSMB.

• The awardee will agree to the governance of the Collaborative Consortium through the Steering Committee and NHLBI-approved recommendations from the OSMB.
  The awardee 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 "NIH Program Staff Responsibilities."
• The awardee will provide information regarding Collaborative Consortium goals and progress toward those goals to NHLBI staff annually and will ensure that the data produced meet the quality standards agreed upon at the beginning of the project.
• The awardee will ensure that Consortium site activities are well integrated and coordinated with those of the Consortium, the CCC and the DCC.
• The awardee(s) will retain custody of, and have primary rights to, the data and biospecimens developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• One NHLBI Program Officer/Project Scientist will serve on the Steering Committee. The NHLBI Program Officer/Project Scientist may also serve on sub-committees or working groups, e.g., data sharing, data release, quality control etc., as appropriate. The NHLBI member may work with the CCC, Consortium sites and the DCC on issues coming before the Steering Committee and other sub-committees and working groups.
• The NHLBI Program Officer/Project Scientist will help the Steering Committee coordinate the group process of exchanging information about the Collaborative Consortium activities and the development of policies.
• The NHLBI Project Officer/Project Scientist will serve as liaison between the Awardee, Collaborative Consortium Sites as well as the DCC, the OSMB, other Councils, and the larger international scientific community; will attend all Steering Committee meetings as voting members as described above; and will assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• The NHLBI Project Officer/Project Scientist will periodically report progress about the Collaborative Consortium to the Director of the NHLBI (or his/her designee).
  The NIH reserves the right to withhold funding or curtail the study (or an individual award) in the event of a substantive change in, or failure to make sufficient progress, toward the agreed-upon work scope with which the NIH cannot concur or human subject ethical issues that may dictate a premature termination.
• Involvement of industry or other third party with the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

In addition, an NHLBI Program Officer will be assigned and will be responsible for normal scientific and programmatic stewardship and guidance.

Steering Committee (SC) Responsibilities:

The Steering Committee (SC) will consist of the PI and Co-PI of each Consortium site as well as the PI, Co-PI and if there is no Co-PI, the Coordinator of CCC and the same from SADaCC, as well as one representative from NHLBI. The Chair for the Steering Committee will be appointed by NHLBI.
The Steering Committee will monitor progress; facilitate coordination and synergy across the entire program; develop recommendations for uniform procedures and policies
The Steering committee will meet twice a year with intermittent conference calls; ensure that awardees accept and implement policies approved by the Steering Committee.

Observational Study Monitoring Committee (OSMB) Responsibilities:

The NHLBI OSMB will be responsible for safeguarding the interests of study participants, ensuring data quality, and monitoring the overall conduct of the Consortium and DCC Programs.
The OSMB will be asked to make recommendations to the Office of the Director, NHLBI about: Review of protocols and informed consent/assent forms; selection, recruitment and retention of registry and study enrollees; adherence to established procedures for all program activities; completeness and quality of all data collected; the data and biospecimen plan; statistical analytic plans; amendments to the data and specimen acquisition protocols and consent forms; performance of the CCC, SADaCC and individual sites; participant safety, including review of consent/assent forms; notification of, and review of, unexpected findings and severe adverse events; the SCD in SSA Network's progress toward SCD in SSA program goals, and necessary program changes.

Each NHLBI OSMB is assigned an NHLBI Executive Secretary to provide unbiased staff interface between the OSMB members and other meeting participants, especially during closed and executive sessions. The executive secretary is responsible for assuring the accuracy and timely transmission of the final recommendations and OSMB minutes.
OSMB meetings will be held via conference calls using web-based processes

Areas of Joint Responsibility include:

The awardee will retain custody of and have primary rights to data and biospecimens developed under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The Principal Investigator of this award will be required to participate in periodic meetings and telephone conference calls with the Consortium CCC, SADaCC (DCC) staff and other Consortium sites supported by the NHLBI.

Support or other involvement of industry or any other third party in the Sickle Cell Disease in Sub-Saharan Africa project- e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, biospecimens, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

The PD/PI is encouraged to publish and release publicly and disseminate results, tools, resources and other products, in accordance with Program’s procedures (Program’s operational and publication procedures and manuals of procedures) and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely matter to the scientific community.

Dispute Resolution:

Any disagreement that may arise in scientific/programmatic matters (within the scope of the award); between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the Steering Committee (with the NHLBI member absent from the discussion) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardees' right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, Subpart D and DHHS regulation at 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 agreementsare 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
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8301
Email: shimian.zou@nih.gov

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

Taryn Cobb
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-827-8025
Email: taryn.cobb@nih.gov

Section VIII. Other Information