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 limited competition Funding Opportunity Announcement (FOA) invites an application from the current awardee of the Sickle Africa Data Coordinating Center (SADaCC) to continue support of the activities of the expanded Sickle Pan-African Research Consortium (SPARCO), including the Clinical Coordinating Center (CCC) in Tanzania, the three established sites in Ghana, Nigeria and Tanzania (and additional satellite sites), as well as up to three new sites located in additional sub-Saharan African nations.

The SADaCC is expected to propose a feasible and meritorious plan to provide overall project coordination, administration, data management, and biostatistical support of the SCD in Sub-Saharan Africa Network. A key responsibility of the SADaCC includes effective integration of SADaCC activities with those of SPARCO, Consortium sites, NHLBI, and review/monitoring bodies.

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-21-009, which invites applications for Consortium sites. 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 the SADaCC will have primary responsibility for:

• Providing overall coordination and administrative support for the already established sites in Ghana, Nigeria and Tanzania (and their satellite sites) as well as up to three new sites located in additional sub-Saharan African nations (these sites and satellite sites will be funded separately through RFA-HL-21-009). This includes, but is not limited to facilitating interactions and functions among Network participants; developing and maintaining operating procedures for the Network; expanding and maintaining an internal and external website; coordinating meetings/calls of the Network and Steering Committees and associated Subcommittees and/or Working Groups, and providing resulting minutes and action items.
• Closely collaborating ?with the SPARCO CCC, which provides clinical research expertise to oversee and coordinate research activities at the Consortium sites.
• 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.
• Maintaining (and expanding) a robust, high-quality, and secure centralized, electronic sickle hemoglobinopathy registry database which was developed in the first funding period of the Network. This includes developing and maintaining protocols and procedures, materials, and services; developing and maintaining data management and tracking systems; ensuring implementation of data quality control (QC) procedures to ensure accuracy and completeness; supporting and documenting appropriate procedures related to informed consent; providing database training and site visits; and creating public use datasets according to NIH and NHLBI data sharing policies.
• Providing biostatistical, study development, data management, data QC, analytic, and scientific and/or medical expertise in SCD to assist with Registry, cohort, and implementation research studies' planning, design, implementation, and conduct. 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.
• Assisting with planning for African-based biorepository activities, including providing all necessary tracking systems to allow for tracking of biospecimens and providing the Network with the procedures for specimen collection, processing, storage, and training, as appropriate.
• Assisting with data analysis and publication preparation.

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)

Eligibility is limited to current PD(s)/PI(s) of the NHLBI-funded Sickle Cell Disease in Sub-Saharan Africa: Data Coordinating Center (RFA-HL-17-007).

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.

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: [email protected]

Facilities & Other Resources: The applicant must include a brief description of the features of the institutional environment that are relevant to the effective implementation of the proposed SADaCC. As appropriate, describe the available resources, geographic distribution of space and personnel, and consultative resources. The applicant must also provide a description of the current capacity for the administration of grants, including information about the placement of the designated administrative infrastructure within the institution and its line of authority, the institutional provision of resources such as office space, administrator salary, and office equipment.

Clinical Data Management: The applicant must specifically address the resources currently available to leverage, further develop, and maintain secure, customizable coordinated clinical data management systems, which build, as appropriate, on what was established in the first phase of the Network for collection, QC, data storage (including back-up of data), and analysis of all Network data. The applicant must also address the resources currently available to: 1) update and continue to provide a user-friendly private web-based system for subject enrollment and inter-site communication, as well as a public website to communicate information about Network activities; 2) have the computational sophistication for scaling the systems and tools to allow incorporation of these systems in a SCD in SSA research Network that will include no fewer than seven institutions (up to three established sites and their satellites, up to three new sites, and the SPARCO CCC); 3) address privacy and confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing as appropriate.

Biospecimen Management: Biospecimens similar to data may be collected as part of specific Network studies or as part of the Registry per the Network Steering Committee. The applicant must therefore specifically address the resources currently available to manage biospecimen collections for the Network, as appropriate. This includes providing the necessary biospecimen tracking tools and procedures, including end of program disposition, to ensure consistency in collection, processing, storage, and the ability to retrieve biospecimens for testing, as appropriate; as well as collection of all data associated with the biospecimens in a secure, customizable coordinated clinical data management system.

Unique Abilities: Describe special or unique strengths that may be relevant to specifically building, expanding, and maintaining the SCD in SSA Network infrastructure and research. These can include state-of-the art biomedical informatics systems (e.g., innovative tools, methods and algorithms), which may be shared or may be available to develop and expand scientific productivity; special administrative strengths or experience.

Other Attachments:

Past Performance: Provide a description of the SADaCC's accomplishments during the first phase of the program using the filename "Past Performance.pdf". The description should include challenges faced and how they were or will be addressed in the next phase of the program. The attachment must not exceed six pages.

Sustainability: Describe sustainability of the SADaCC beyond the current funding period and detail how the proposed activities will contribute to success in continuing the research efforts of the SCD in SSA Network using the filename "Sustain.pdf". This section of the application should refer to the letters of Institutional commitments (see Letters of Support) whichprovide an overview of the long-term prospects for sustained SCD-related bioinformatics and data and biospecimen activities.

The SADaCC PD(s)/PI(s) is expected to assemble a team with demonstrated expertise in multi-site coordination, project management, biomedical informatics, data management, biostatistics, clinical epidemiology, study design, and/or other relevant areas. The team should also include at least one to two members with demonstrated medical and scientific expertise in the area of SCD. Experience in coordinating multi-center groups, designing and implementing observational databases, Manual of Procedures development, biorepository collection, andprevious experience with phenotype harmonization and ontology developmentshould be described. Participation by the PD(s)/PI(s) or other proposed SADaCC staff in administrative aspects of clinical research (e.g., IRB, data and safety monitoring board or protocol review committee) should also be highlighted.

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

The operational budget including 8% Facilities and Administrative (F&A) costs should include, but not be limited to, the following items:

• PD(s)/PI(s) supervision of day to day operation and oversight of SADaCC professional activities.
• Collaborative Consortium staff training and certification in core operations and procedures.
• Conducting visits to each site each year. The SADaCC should assume two site visits (a total of five days each, including travel) for each of no fewer than seven sub-Saharan sites during the first year of the grant period and one to two site visits in each subsequent year. The applicant should plan to have one SADaCC participant at each site visit.
• Planning and conducting regular meetings and conference calls for the Consortium Sites, Steering Committee and Subcommittees and/or Working Groups, as appropriate:
  • The budget should specifically include costs for planning, meeting space, equipment, and coordination of the SCD in SSA Network Committee meetings that will be held twice a year, usually in Africa. Costs for Steering Committee meetings, held at the same time, should also be included. Steering Committee meetings are attended by PI and Co-PI of each Consortium site as well as the PIs, Co-PIs and Coordinators of the CCC and SADaCC. Network Committee meetings are attended by two to four people from the CCC, two to four people from SADaCC and two to four people from each of the Consortium sites, including those who also attend the Steering Committee meetings. (Specific information regarding numbers of attendees at these two meetings is covered below under travel costs.) OSMB meetings will be held exclusively via conference calls and will use web-based systems, as organized by NHLBI. The NHLBI OSMB will consist of about 7 members, including individuals from African nations and from the United States. SADaCC will be responsible for providing a $200 per call fee for each Board member and should assume three calls annually. The OSMB calls will be organized by NHLBI.
  • Costs for preparation and distribution of meeting and conference call minutes (but not the OSMB) should also be included in the budget.

Other costs include but are not limited to:

• Webinars, teleconferences, production of manuals etc.
• Development and maintenance of a secure private website for the distribution of program documents and reports.
• Development and maintenance of a public website for communications with outside interests, which shall be 508 compliant (https://www.section508.gov/about-us).
• Design of data collection forms, database structures, and implementation of systems for Registry and study(ies) data collection, including participant accrual, follow-up rates, and data quality that are available to sites on a 24-hour, 7 day a week basis with appropriate feedback, monitoring, backup, and security.
• Development of Manual of Operating Procedures (MOPs) for the SCD in SSA Network Registry and for each study to be conducted.
• Implementation of methods for timely monitoring and reporting of study events to ensure participant safety and confidentiality, including notification and reports to the NHLBI OSMB, and other appropriate agencies.
• Ensuring and monitoring attainment of informed consents from all participants before enrollment.
• Overseeing regulatory compliance at all Sites and the SADaCC. Ensuring that all appropriate ethical board approvals have been obtained before launching any Network study or the Registry.
• Providing resource management, including any needed subcontracts and outsourcing.
• Meeting other responsibilities as detailed in the strategy section.

Travel Costs (Suggested travel commitments for planning purposes):

• SCD in SSA Network Committee Meetings - The NIH plans to hold two meetings of Network program participants per year, and the applicant should request funds to travel to these meetings in their applications. Meetings will be held in Africa. It is expected that two to four people from CCC, two to four people from SADaCC and two to four people from each of the Consortium sites will attend Network Committee meetings, including those who will also attend the Steering Committee meetings. Appropriate travel funds for SADaCC participants at these meetings must be requested in the application. (CCC and Site participants will be supported by separate Collaborative Consortium funds.)
• Steering Committee Meetings - These will be held at the same time as the Network Committee meetings and involve only 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 the CCC and the same from SADaCC. It is expected that both the CCC and the SADaCC will have two people at the Steering Committee meeting. These individuals will also attend the Network meetings. Consortium Site and CCC participants will be supported by separate Collaborative Consortium funds.

Specific Aims: Describe a concise set of specific aims that explain the overall goals and expected outcomes of the SADaCC.

Research Strategy: Include detailed plans for SADaCC development and management with attention to how the SADaCC proposes to leverage the infrastructure that was developed in the first funding period of the Network. (NOTE: Relevant information that the applicant has provided in the SF424 R&R Other Project Information section may be referenced here as warranted.)

1. Overall SCD in SSA Network Coordination and Administrative Support

1A. Facilitation of Interactions and Functions: Describe plans for fostering connectivity to enrich overall research capacity and outcomes by effectively coordinating interactions between all the Network participants, including: the Collaborative Consortium Sites; the CCC; SADaCC; the Network and Steering Committees and their subcommittees and/or working groups; NHLBI; and other partners. Specifically address the following activities: 1) Scheduling meetings and calls, including those of the Collaborative Consortium sites, Network Committee, Steering Committee, and Subcommittees and/or Working Groups; 2) Preparing and distributing agendas; 3) Compiling and distributing review materials; 4) Preparing and distributing a list of action items within five working days of the meeting/call; 5) Preparing and distributing minutes for review and approval by associated PDs/ PIs, chairpersons, and NHLBI Program Officer(s) within five working days of the meeting/call; 6) Tracking and maintaining a central repository of minutes and materials relating to the functioning of the various sites and committees on the SCD in SSA Network internal website; 7) Informing SCD in SSA Network participants when minutes and materials are posted; 8) Developing, reproducing, distributing, and posting the Network’s Operating Procedures, as well as Study-specific and Registry-specific Manual of Procedures (MOPs) including updates; 9) Preparing and submitting reports regarding databases and datasets development, biospecimen collections, subject privacy, data capture/quality, data and performance of Collaborative Consortium sites to the Steering Committee and Observational Study Monitoring Board.

1B. Implementation of Network Activities at Consortium Sites: Describe plans to implement SADaCC support, and facilitate rapid implementation of Network activities, at sites that did not participate in the first phase of the Network and anticipated timelines. Describe plans to resume in as seamless a manner as possible support of Network activities at sites that participated in the first phase of the Network.

1C. Development and Maintenance of Network Operating, Registry- and Study-Specific Manual of Procedures: Describe plans to help the Network develop, maintain, and further revise, as appropriate, the SCD in SSA Network Operating Procedures and the Registry and study(ies) Manual of Procedures (MOPs). Operating Procedures for the Network include governance, coordination, communication, human subject considerations, publication policies, and processes to obtain all necessary ethical approvals and administrative/regulatory clearances; performance metrics for both the Collaborative Consortium and SADaCC; and any other overarching Network procedures. The SADaCC will help Consortium Sites develop Registry- and study(ies)-specific protocols with attention to the study design, statistical power/sample size, and statistical analytical sections. Additionally, the SADaCC is responsible for developing the Registry- and study(ies)-specific MOPs that include, but are not limited to, a description of the procedures related to database elements definitions, phenotype definitions, and ontologies, and information regarding data and biospecimen collection, quality control, processing, management, storage, security, and sharing.

1D. Management of Private and Public Websites: Describe plans for building on the existing website infrastructure developed in the first phase of the Network to provide and maintain the Network’s interactive, secure, scalable, flexible, and robust web-based information and administrative platform. The SADaCC must provide 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 Network. The private website should continue to contain all information pertaining to SCD in SSA Network activities and serve as a communication portal for the Network. Examples of documents would include, but are not limited to, protocols, Operating Procedures, MOPs, case report forms, subject accruals, Network and Steering Committees minutes, presentations, and manuscripts. The public website should include a description of the SCD in SSA Network and its objectives, a list of participants, a list of publications, contact information, and other information of interest to the general public. Note that all information and documents developed for the public website are required to be reviewed and approved by the Steering Committee and NHLBI before being posted on the public website. The website needs to be 508 compliant as required by Section 508 of the Rehabilitation Act and Section 255 of the Communications Act.

1E. Reporting to the NHLBI Observational Study Monitoring Board (OSMB) and Addressing NHLBI-approved OSMB Recommendations: Describe plans for reporting to the NHLBI OSMB and addressing NHLBI-approved OSMB recommendations.

1F. Coordination for the Network and Steering Committees: The Steering Committee 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. Steering Committee Meetings will be held two times a year in Africa along with the Network Committee meetings. The Network Committee meetings will be attended by all Steering Committee members as well as up to two more people from the CCC, up to two more people from SADaCC, up to two more people from each of the Consortium sites, and others such as advisors and community representatives. SADaCC will coordinate and organize both the Network Committee meetings and the SC meetings.

2. ?Needed Expertise for the Maintenance and Expansion of a Sickle Hemoglobinopathy Database (Registry database): Describe the intended approach for leveraging the centralized SCD Registry database infrastructure established in the first funding period of the Network, how implementation will be approached at new Consortium Sites, and provide an approach for expanding/updating the Registry as appropriate to meet the needs of the expanding network. Include: 1) Maintaining, and as appropriate updating the centralized, cumulative Registry database protocol developed in the first vanguard phase of the Network, subject to approval by the Steering Committee and the OSMB. 2) Designing data capture forms and preparing materials and documentation for SC, OSMB, NHLBI form/survey clearance; 3) Arranging for SC, OSMB, NHLBI review of these materials; 4) Addressing questions; 5) Reproducing and distributing Registry data base protocol, forms, MOPs, and updates and making them available on the private website. Maintain and update, as appropriate, the Registry MOP that was developed in the first phase of the network. The Registry MOP should contain a detailed description of the procedures for cumulative data collection, entry, and transmission; data compilation and management; data quality and security; and any other procedures relevant to the development, management, and analysis of the centralized cumulative database(s) for the Registry. Detailed guidance on the contents of the files to be delivered, as well as the mode and time line for data delivery should be included. Guidance on the demographic, clinical, and laboratory testing data fields and the field requirements, including acceptable codes and field sizes, will also be incorporated in the databases MOP.

The SADaCC should also be able to prepare appropriate materials and documentation needed to assist Consortium sites in obtaining all necessary administrative, ethical, and regulatory clearances relevant to the operation of the Registry database. The Registry database MOP and other materials will be reviewed, and approved by the SC, OSMB, and NHLBI upon implementation of the second phase of the SCD in SSA Network. It is anticipated that the centralized Registry database will be able to continue to capture data on SCD participants as soon as all ethical/regulatory approvals are obtained. Analyses of the Network Registry data collected in the first phase of the Network can be pursued upon appropriate approvals and it is anticipated that analyses that include phase 2 data may be able to be initiated in Year 2 of the phase 2 grant.

Unique responsibilities of CCC, SADaCC and Consortium sites:

• SADaCC will provide data management system, training and technical support to the sites
• The sites to provide data to the CCC for compilation and quality control
• The CCC to provide complied data to SADaCC for further/final quality check and clean up, storage and analysis
• SADaCC will also be responsible for developing the public-use data sets at completion of the program per data sharing plan

3. Additional Expertise for Research Planning, Design, Execution and Reporting:
For SCD cohort studies and implementation research of new preventive/therapeutic practices: SADaCC will help develop all Network protocols with attention to study design, power and sample size, data management, and statistical analysis sections. The SADaCC will therefore need to provide substantial statistical and analytical capability. Since the SADaCC will be assisting the Collaborative Consortium sites as they develop plans for database analyses, SCD cohort studies, and the implementation research of new preventive/therapeutic practices, the application must describe the proposed SADaCC's expertise in study design, sample size and power calculations, as well as the ability to conduct simple as well as complex, and sometimes novel analyses. For optimal functioning, the SADaCC should also have one to two staff members with scientific and medical expertise relevant to sickle cell disease.

Unique responsibilities of CCC, SADaCC and Consortium sites in management of biospecimens (including their aliquots):

• SADaCC will provide a repository management system for biospecimens, training and technical support to the sites, including specimen tracking
• The sites to 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 to provide compiledrepository data to SADaCC for further/final quality check and 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

4. Data Management
4A. Ability to continue to provide and, for new studies, develop and implement, data management, compilation, and tracking systems: Describe plans to provide secure and robust data collection, tracking, management, and storage procedures for all data (Registry and study-specific) compiled by the SCD in SSA Network, and provide necessary data management systems to the Collaborative Consortium sites. SADaCC will be responsible for implementing innovative, cost effective procedures that take advantage, whenever possible, of existing data platforms at Collaborative Consortium sites, and incorporating new approaches to database support and management to reduce the burden of rising costs of software.
Describe approach to collecting, organizing, and storing data from the individual sites and assuring the quality of the study data submitted and stored. All data will need to be entered and transmitted to the SADaCC by the individual Collaborative Consortium sites, under the auspices of the CCC. The SADaCC should be able to devise and provide a Data Management Plan, a Data Quality Control/Quality Assurance Plan, and a Data Security Plan to be included in each MOP.

The computer programs, data management systems, databases, and other resources developed through this cooperative agreement will need to be compliant with terminology and data standards established by the NIH. The SADaCC should be able to ensure that the computer hardware and software procedures comply with all relevant regulations of the countries in which sites are located as well as those of the United States.
Data to be collected, managed, and analyzed are expected to include, but not limited to, demographic, clinical, and laboratory data. Data on enrolled subjects should be entered routinely by the sites in web-based data entry systems provided by the SADaCC . The SADaCC will be responsible for monitoring and evaluating data base enrollment and for developing site performance metrics and corrective actions for under-performance in Registry or study-specific activities..
The SADaCC should also be able to provide scalable infrastructure. Describe ability to provide a scalable system that will be able to accommodate additional sites and data in the future.

4B. Bioinformatics skills: Describe ability to deliver innovative and flexible biomedical informatics that can specifically support the creation of data base elements, harmonized SCD phenotype definitions and ontologies, 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.

4C. Ability to ascertain, compile, and enforce human subject research regulations and informed consent requirements specific to each participating country: Describe how SADaCC will reliably identify unique regional consent regulations and ensure compliance with all requirements as they are stipulated by each participating African nation.

4D. Capacity for database training and site visits: Describe how SADaCC will train staff at each individual Collaborative Consortium site in procedures delineated in each MOP. This includes training and consultation regarding data collection, entry, storage, and transmission procedures. The SADaCC should be capable of establishing procedures for quality control/improvement and certification of data management at Collaborative Consortium sites, and conducting site visits to address and remedy issues in the conduct of SCD/SSA Registry and study databases related activities.
The SADaCC should assume two site visits (five days each, including travel) for each of no fewer than 7 sub-Saharan sites during the first year of the grant period and one to two site visits in each subsequent year. The applicant should plan to have one SADaCC participant per site visit.

4E. Creation of public use data sets: Should the SCD in SSA Network end after the 5 year period (or earlier as directed by the NHLBI), describe how SADaCC 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 the participating sites, NHLBI, and be made available to the scientific community. These datasets must be de-identified and must be appropriate for independent use by an investigator external to the study.

5. Dissemination of Results:
Assistance with the preparation of scientific reports and publications: The SADaCC will participate in the development of scientific abstracts, presentations and publications; coordinate Publications Committee calls, and other relevant subcommittees calls; check all reports, abstracts, presentations, and publications data for accuracy; and post presentations and publications on the website.
The applicant should 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.

6. Milestones and Metrics:
The applicant must describe plans 1) to monitor and evaluate the administrative performance of both the Collaborative Consortium and SADaCC, and 2) to determine how the overall project will be assessed and how success and impact will be defined. The applicant must provide a well-defined set of yearly milestones for proposed activities. These 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 SADaCC's performance and progress.

Timeline: The applicant will be expected to conform to the established timeline:

Years 1 to 2 (including support for the development phase of the new Collaborative Consortium sites as appropriate)

• Provide overall coordination and administrative support to the Network
• Set up working relationships with the Consortium sites including the CCC, Ministries of Health & Education, the NHLBI, review/monitoring bodies, and other partners
• Develop the Network’s Operating Procedures and study MOPs
• Work with the Collaborative Consortium sites to continue implementing and further update, as appropriate, the centralized, secure, electronic, patient consented, sickle hemoglobinopathy database (Registry database) that was developed in the first phase of the Network using agreed upon database elements, phenotype definitions, and ontologies, as appropriate
• Assist the Collaborative Consortium as it prepares ethical, legal and social issue (ELSI) guidelines for the study
• Support the Collaborative Consortium with research planning, study-specific protocol development and MOPs, design and execution of approved SCD cohort studies and implementation research of new preventive/therapeutic practices. Pilot studies may be considered and conducted in preparation for the launch of the main studies. It is anticipated that some studies will be launched in Years 1-2, while others may need to be launched in later years of the Network, per timelines.
• Establish study-specific data management systems
• Assist Collaborative Consortium members with regulatory approvals
• Provide training as appropriate on study-specific or Registry procedures to Consortium sites
• Construct and design skills development programs appropriate to each site; prepare educational materials
• Provide biostatistical and analytic support

Years 3 through 5

• Provide overall coordination and administrative support
• Refine data infrastructure, data entry, and management procedures as needed
• Support the conduct of approved SCD cohort and implementation research studies
• Support and maintain the Registry
• Maintain data bases and associated operations, including procedures for quality assurance
• Provide additional biostatistical, design, implementation, and analytic support to the Collaborative Consortium as needed
• Conduct statistical analyses
• Support Publication Committee calls and help disseminate results through participation and review of abstracts, presentations, and publications

Letters of Support: The applicant must provide a statement that addresses how institutional commitment will be established and sustained, and how the SADaCC 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 SADaCC 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. The letter should also briefly discuss the institution's plans for sustaining an active program of SCD related data management subsequent to the end of the SCD in SSA Network. The application should also include letters of support from the 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. The applicant is expected to propose an initial plan for sharing data and resources generated by the Collaborative Consortium and SADaCC . For the purposes of this initiative, data and resource sharing will be limited exclusively to participating African Collaborative Consortium members and the SADaCC during the years (five) of grant support. In addition, this limitation will continue for at least one year after the funding period ends or, in the event of termination, at least one year after the date of termination. (Subsequent plans and timing for appropriate 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.)

The applicant is only expected 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 program staff before the application can be funded. Notably, after the Collaborative Consortium and SADaCC awards have been made, these entities and the NHLBI/NIH will develop a unified initial policy for data and resource release, consistent with applicable NIH policies, laws, regulations, and rules and with achieving the goals of the Network. Final, uniform policies will ultimately be determined by the Steering Committee. The application must include a statement that the SADaCC 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 non-responsive 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.

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

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?

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:
Does the team have the ability to help design and implement observational databases, to develop and conduct cohort studies, or to help implement new medical approaches?

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:
Is the proposed program sufficiently innovative to ensure that the SADaCC infrastructure will be capably established, able to promote planned operations, and sufficiently flexible to support the additional Consortium members and planned activities?

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:
Is the infrastructure developed in the first phase of the program effectively leveraged? Is the applicant's plan likely to result in the successful development of useful Operating Procedures and Manuals of Procedures? Has the applicant provided a well-defined set of yearly milestones for the proposed SADaCC activities? Does the plan lay out a comprehensive approach to the provision of data and biospecimen management, compilation and tracking? Does the applicant provide evidence of sufficient experience to successfully execute proposed plans? Does the applicant describe what kind of assistance they will provide to the Collaborative Consortium as it plans and conducts SCD cohort studies and the implementation research of new preventive/therapeutic practices? Are the proposed data and biospecimen management and tracking systems scalable and able to accommodate expansion for additional sites, and data and specimens? Are milestones clearly delineated and sufficiently comprehensive?

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:
Is there sufficient computational sophistication for scaling the systems and tools to allow incorporation of these systems in a SCD in SSA research network that will include additional institutions? Does the application describe a proactive plan to incorporate existing data platforms and take advantage of existing resources at Collaborative Sites?

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 SCD in SSA Network as an Integrated Effort: ?
Are adequate mechanisms proposed for regular communication and coordination among investigators within the SADaCC and those in the Collaborative Consortium?

Past Performance: ?
How well does the application describe accomplishments and how well did the team address challenges faced in the first phase of the program? How likely is that the team will effectively fulfill the responsibilities of the SADaCC in the next phase of the SCD in SSA Network program?

Sustainability:
How adequate are the Letters of Support in demonstratinginstitutional and national commitment? How likely will the proposed planned collaborations between the SADaCC and the Collaborative Consortium sustain 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 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 Sickle Africa Data Coordinating Center (SADaCC) PD(s)/PI(s) will have the primary responsibility for:

• Conducting SADaCC activities, including supervision of site performance, modifications of SADaCC design, quality control, data analysis and interpretation, preparation of publications, and collaborations with other partners, unless otherwise provided for in these terms or by action of the Steering Committee, or recommendations from the OSMB.
• Accepting governance from the Steering Committee and NHLBI-approved recommendations from the OSMB.
• Accepting coordination, cooperation, and participation of NHLBI staff in aspects of scientific and technical project management as described under "NHLBI Program Staff Responsibilities"
• Providing information regarding SADaCC goals and progress toward those goals as requested by NHLBI staff and insurance that the data produced meet the quality standards agreed upon at the beginning of the project.
• Ensuring that activities are integrated and coordinated with those of the Consortium.
• Ensuring, in collaboration with the CCC awardee, that data are deposited in the appropriate databases at the appropriate times, that resources developed as part of this project are made publicly available according to program policies, and that findings are published in a timely manner.
• Adhering to policies regarding intellectual property, data release and any additional policies that might be established during the course of this activity consistent with applicable NIH policies, laws, and regulations.
• Retaining custody of, and have primary rights to, software and data management approaches developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Scheduling the time for and coordinating the Steering Committee meetings and teleconferences; preparing concise (3 to 4 pages) conference summaries; delivering summaries to members of the group within 5 working days after each meeting.
• Preparing and presenting data reports during the open and closed sessions of the OSMB; paying for OSMB members consultant fees; communicating with the OSMB members primarily through the NHLBI Program Office and not directly except when making presentations or responding to questions at OSMB meetings or conference calls.

NHLBI Program Staff Responsibilities

NHLBI 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 Consortium members and the SADaCC 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 SADaCC activities and the development of SADaCC policies.
• The NHLBI Program Officer/Project Scientist will serve as liaison between the Awardee, the Consortium CCC and sites, the SC, 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 Program Officer/Project Scientist will periodically report about the progress of the Consortium and SADaCC to the Director of the NHLBI.
• 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 NIH.

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 discuss progress in meeting goals; facilitate coordination and synergy across the entire program; develop recommendations for uniform procedures and policies.
The Steering Committee will meet twice a year in Africa with additional intermittent teleconferences; 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 SADaCC 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 data base enrollees; adherence to established procedures; completeness, quality, and analysis of data base measures; the data and statistical analysis plans; amendments to the data acquisition protocols and consent forms; performance of the SADaCC, CCC and individual sites; participant safety, including review of consent forms; notification of, and review of, unexpected findings and severe adverse events; SADaCC's progress toward SCD in SSA Network program goals, continued NIH support, 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 SADaCC awardee will retain custody of and have primary rights to data 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 investigators 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, 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 SADaCC protocols 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:[email protected](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:[email protected]

Shimian Zou, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8301
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Taryn Cobb
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-827-8025
Email: [email protected]

Section VIII. Other Information