Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Sickle Cell Disease (SCD) is a recessively inherited disorder that affects hemoglobin. Hallmark complications of the disease include hemolytic anemia, acute vaso-occlusive pain, sepsis, and widespread chronic end-organ damage. Unlike most Mendelian conditions, SCD is associated with considerable and largely unpredictable phenotypic heterogeneity. Currently approaches to care are mostly preventive and effective interventions are few.

The worldwide burden of this serious illness is rising. In 2010, over 300,000 neonates were born with homozygous hemoglobin’s (Hb SS) disease and just under 5.5 million were heterozygous for hemoglobin S. A recent estimate predicts that in 2050, the number of newborns with Hb SS will increase to over 400,000 per year. Between 2010 and 2050, it is expected that about 14.2 million affected babies will be born worldwide. Importantly, these estimates do not reflect the incidence of other sickle hemoglobinopathies (hemoglobin SC, SE,’s thalassemia etc.) nor numbers of all age-affected individuals.

In the U.S. and other high income nations, scientific infrastructure and technical expertise have supported the discovery and implementation of some effective SCD therapeutic and preventive strategies. Patients with SCD living in these countries have benefited from newborn screening, preventive care practices, ongoing comprehensive care, and the use of hydroxyurea. Nonetheless, these individuals still die prematurely and their adult quality of life is often compromised by additional debilitating complications. The comparatively slow progress of SCD research in high income nations has been attributed, at least in part, to a low disease prevalence that makes epidemiologic and clinical research studies difficult to pursue.

More than 75% of SCD births occur in sub-Saharan Africa where the presence of a heterozygous sickle mutation provides protection against severe falciparum malaria. In sharp contrast to children with SCD in the U.S., 50-80% of affected Africans now die before the age of five years, often as a consequence of limited health resources and infrastructure. Examples include a widespread lack of newborn screening programs, pneumococcal vaccines, and penicillin prophylaxis regimens. In addition, while high regional disease prevalence would be expected to facilitate epidemiologic, translational, and clinical research, most sub-Saharan African nations lack the means and capacity required to pursue such investigations.

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications that propose to develop a Sickle Cell Disease (SCD) in Sub-Saharan Africa (SSA) Collaborative Consortium. The Collaborative Consortium will be responsible for engaging in capacity building activities and for developing a comprehensive plan to establish an infrastructure upon which a future SCD in SSA Research Network that will advance SCD-related epidemiologic, translational, and clinical research can be built. The Collaborative Consortium will be comprised of a Consortium Hub (applicant institution) and at least two Collaborating Sites located in sub-Saharan African countries separate from that of the applicant institution.

The Collaborative Consortium will be expected to work closely with an associated Data Coordinating Center (DCC) that will be supported by a separate funding mechanism (RFA-HL-17-007).

Applications that address a comprehensive plan to establish an infrastructure upon which future SSA SCD Research Network operations can be built are of high programmatic interest. In particular, this FOA seeks applications that propose to oversee the activities necessary to meet the following goals:

• Formation of a centralized, electronic, patient-consented, sickle hemoglobinopathy database that will facilitate registration and follow-up of SCD patients and serve as the backbone of the future SCD in SSA Research Network operations.
• Creation of shared database elements as well as harmonized SCD phenotype definitions and ontologies.
• Integration of Collaborative Consortium activities with those of the DCC, NHLBI, Steering Committee, Observational Monitoring Board, and any existing training programs.
• Development of SCD standards of care appropriate to regional resource availability and clinical needs.
• Organization of research and clinical skill development activities.
• Planning for future SCD cohort studies, implementation of preventive/therapeutic practices, and the inclusion of new African Sites to constitute the SCD in SSA Research Network.
• Accomplishment of Collaborative Consortium activities over 4 years, with a 2 year development phase, a 1 year pilot/planning phase, and a 1 year implementation phase.

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

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) in sub-Saharan Africa are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations in sub-Saharan Africa 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: [email protected]

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

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

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

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

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

Facilities & Other Resources: Applicants must include information regarding the existing facilities and particular expertise at the Consortium Hub and at each Collaborating Site. Include a detailed, well-documented description of existing institutional infrastructures and special capabilities. With regard to the Consortium Hub (applicant 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 Consortium Hub. Describe any plans the institution may have for further development of its research administration capabilities.

Other Attachments:

Organization Structure: Applicants should include a strategy for organization structure that is no more than one page. Applications that exceed this limit will be withdrawn. This attachment should be entitled "Org_Structure.pdf" and will be reflected in the final image. Describe the organizational structure of the Collaborative Consortium, and the plans for administering, managing, tracking, and coordinating its activities.

Sustainability: Applicants should include a strategy for Sustainability that is no more than one page. Applications that exceed this limit will be withdrawn. This attachment should be entitled "Sustain.pdf". Discuss the issue of future sustainability of the Collaborative Consortium beyond the funding period and how the proposed activities will contribute to success in continuing the research efforts of the SCD in SSA program participants. 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 by the Collaborative Consortium and each of its components.

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional guidance should also be followed:

Applicants are expected to assemble a Collaborative Consortium team whose members demonstrate experience and expertise in relevant areas including the diagnosis and care of individuals with SCD, administration and coordination, data base 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 operational budget including 8% Facilities and Administrative (F&A) costs 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 Consortium
• Staff training and certification in core operations and procedures
• Reasonable administrative costs
• Developing a Manual of Operating Procedures (MOP) for the SCD in SSA program; this will be done in concert with the DCC
• Budgeting for site subcontracts is permissible
• Include travel costs for two persons from the Consortium Hub and one from each Collaborating Site to attend Steering Committee (SC) and SCD in SSA in program meetings (held simultaneously), two times a year, in a convenient African location. Include travel costs for an additional one to two people from the Consortium Hub and one to two people from each Collaborating Site to attend the program 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 DCC application budget and are not part of this application.

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

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

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

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

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

1. Operations and Governance:

Applicants should briefly outline the planned infrastructure logistics for inter-site communications as well as interactions with the DCC, local Ministries of Health and Education, NIH, the Steering Committee (SC), Observational Study Monitoring Board (OSMB), and potential partnering programs. Additional details will have been provided in the "Facilities and Other Resources" section of the application.

2. Data Base Development:

Applicants should outline how they, with the help of the DCC, intend to build a centralized, electronic, patient consented, sickle hemoglobinopathy database that will facilitate registration and follow-up of SCD patients. The following information should be included:

• Anticipated roles (distinct and shared) to be played by the Collaborative Consortium and the DCC
• Steps that the Collaborative Consortium will pursue to incrementally build and expand the database
• 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
• Consent procedures: How the Consortium Hub will ensure that each Collaborating Site adheres to its own unique regional consent regulations
• The feasibility of enrolling the total number of subjects (representing all the sites) as presented in the Enrollment reports
• How local regulatory approvals relevant to the protection of human subjects will be obtained
• Additional ethical, legal and social issues (ELSI) relevant to the conduct of regional SCD data acquisition and research, and how these will be addressed

3. Consistent Standards of Care:

Applicants should describe the methods they would use to establish 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
• How the Collaborative Consortium would establish consensus regarding standards of care and how it would allow for Collaborating Site-specific modifications based upon regional feasibility/resources

4. Skill Development Activities

4A. Participation in existing training programs: Applicants are encouraged to take advantage of current programs that are supported by other NIH entities, as well as other agencies, and societies. Individuals from the Consortium Hub and/or Collaborating Sites may participate. Some examples appear below. Other similar programs may be accessed. Applicants should briefly describe any intent in this regard and identify which programs will be pursued.

• Medical Education Partnership Initiative (MEPI): http://www.fic.nih.gov/programs/Pages/medical-education-africa.aspx. Where possible, applicants are encouraged to collaborate with MEPI grantees in order to take advantage of the training infrastructure and opportunities available through MEPI.
• Fogarty International's Global Health Program for Fellows and Scholars: http://www.fic.nih.gov/Programs/pages/scholars-fellows-global-health.aspx. This program provides supportive mentorship, research opportunities and a collaborative research environment for early stage investigators from low-and middle-income countries (LMICs), to enhance their global health research expertise and their careers.
• American Society of Hematology (ASH) Visitor Training Program (VTP): https://awards.hematology.org/. 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.

5. Planning Activities (Year 3)

5A. Cohort studies: Applicants should broadly describe three feasible cohort studies and why these would represent consortium priorities. The following list provides some examples. This list is meant only to provide guidance; it is not exhaustive and appropriate topics are not limited to the examples 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
• Perform clinical trials of a new SCD treatment

5B. Implementation of new preventive/therapeutic practices: Applicants should identify three new clinical practices and broadly describe them. Applicants should explain why these practices would represent Collaborative Consortium priorities, what implementation barriers they foresee, and what additional resources would be needed. (The following list provides some examples of SCD related preventive/therapeutic practices. This list is meant only to provide guidance; it is in no way exhaustive and appropriate topics are not limited to the examples given here):

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

5C. Integration of Additional Collaborating Sites: Applicants should discuss how the Collaborative Consortium would go about soliciting new members and which sub-Saharan regions of the continent they would anticipate including.

6. Milestones and Metrics

The applicant should discuss how the Collaborative Consortium will be assessed and how success and impact will be defined and determined. To facilitate monitoring and evaluation, applications should include a well-defined set of yearly milestones for the proposed activities. Such milestones should conform to the timeline described below as continued support during years 2-4 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 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.

Timeline - Applicants will be expected to conform to the established timeline:

Development Phase: Years 1 and 2

• Establish structure, operations, and meeting schedule for Collaborative Consortium members
• Set up working relationships and operating procedures with the DCC, Ministries of Health & Education, the NHLBI, review/monitoring bodies, and other partners
• Develop (with assistance from the DCC) agreed upon data base elements, phenotype definitions, and ontologies
• Work with the DCC to create and maintain a centralized, electronic, patient consented, sickle hemoglobinopathy database
• Establish ethical, legal and social issue (ELSI) guidelines
• Compile locally feasible and consistent SCD standards of care
• Complete regulatory approvals
• Prepare Collaborative Consortium operating manuals
• Where applicable, begin participation in independently funded training programs

Pilot/Planning Phase: Year 3

• Finalize data base and associated operations in concert with the DCC
• Complete pilot data base patient registration and data entry
• Plan for future introduction of feasible practices, based upon Collaborative Consortium priorities
• Plan for the future initiation of SCD cohort research studies, guided by Collaborative Consortium priorities and in collaboration with the DCC
• Plan for network engagement of additional African SCD centers
• Prepare application(s) for further funding

Implementation Phase: Year 4

• Enhance the database in response to pilot experiences and in collaboration with the DCC
• Complete full registration and data entry
• Continue training activities
• Submit new application(s)

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 program. 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. Appropriate letters regarding the Consortium Hub and each Collaborating Site should be included.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. Applicants should include a strategy for Data Sharing Plan. Describe an initial plan for sharing data and resources generated by the Collaborative Consortium and DCC. For the purposes of this initiative, data and resource sharing will be limited exclusively to participating African Collaborating Sites and the DCC during the years (four) 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 four, 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 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 program. The initial plan must be approved by NHLBI program staff before the application can be funded. Notably, after the Collaborative Consortium 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 Collaborative Consortium 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.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about r. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

This initiative is not subject to intergovernmental review.

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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 NHLBI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the project address an important problem or a critical barrier to progress in the field? 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?

If successful, will the proposed project establish the necessary infrastructure to develop a future SCD in SSA Research Network?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

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

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?

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

Operations and Governance:

Is a sound organizational structure proposed? Are Data Sharing/Release Strategies appropriate for the goals of the program? Will the logistics associated with inter-site and inter-group interactions promote communication and synergy?

Data Base Development:

Recognizing that substantial input will be provided by the DCC, does the application provide approaches to database construction and the development of phenotype/ontology definitions? Does the application define SCD and 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?

Regional Standards of Care:

Are plans to establish three regional SCD standards of care adequately explained and are they feasible?

Skill Development Activities:

Are proposed plans for skill development activities appropriate and compelling?

Planning Activities:

Are plans for the three cohort studies, implementation of new practices, and integration of additional sites well described? Are they feasible?

Milestones and Metrics:

Are plans to assess the success and impact of the Collaborative Consortium reasonable and feasible? Do milestones conform to the timeline described in Section IV.2? Is it likely that milestones will be met as described?

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 children, justified in terms of the scientific goals and research strategy proposed?

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?

Does the application identify and plan to leverage unique resources and expertise at the Collaborative Consortium Hub and Collaborating sites? Does the application plan to take advantage of existing programs currently supported by other NIH entities, agencies, and societies?

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

The Collaborative Consortium as an Integrated Effort

Are the proposed Collaborative Consortium structure and communication/coordination plan conducive to achieving early program goals?

Sustainability

Do the letters of institutional and national commitment suggest that the overall environment is conducive to a sustained research network enterprise? Do the collaborations between the Consortium Hub and Collaborating Sites suggest viable long-term partnerships and an ability to expand the program's membership in the future?

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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

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

Reviewers will comment on whether the 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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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

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

As part of the scientific peer review, all applications:

• 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.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• How well the application addresses the goals of the SCD in SSA program.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the 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:

Awardee(s) will have the primary responsibility for the conduct of Collaborative Consortium activities, including supervision of Consortium sub-contracts and site performance, modifications of project 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.

Awardee(s) will agree to the governance of the Collaborative Consortium through the Steering Committee and recommendations from the OSMB.

Awardee(s) will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."

Awardee(s) will provide information regarding Collaborative Consortium goals and progress toward those goals to NHLBI staff annually and will ensure that the data produced meets the quality standards agreed upon at the beginning of the project.

Awardee(s) will ensure that Consortium activities are well integrated and coordinated with those of the DCC.

Awardee(s) and, where appropriate, Collaborative Sites, and/or the DCC, will retain custody of, and have primary rights to, the data 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:

Two NHLBI Project Scientists and one H3Africa program (http://h3africa.org/) scientist will serve on the Steering Committee (SC). NHLBI project scientists may serve on sub-committees or working groups, e.g., data sharing, data release, quality control etc., as appropriate. The NHLBI members may work with Consortium members on issues coming before the Steering Committee and other sub-committees and working groups.

The NHLBI Project Scientists 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 Scientists will serve as liaison between the Awardee, as well as the DCC, the OSMB, other Councils, and the larger international scientific community; will attend all Steering Committee meetings with one scientist having one vote on the Steering Committee; 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 will periodically report progress about the Collaborative Consortium to the Director of the NHLBI.

Additionally, the NHLBI Project Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Project Officer may also serve as an NHLBI Project Scientist.

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 there are human subject ethical issues that may dictate a premature close-out.

Steering Committee (SC) Responsibilities:

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 OSMB will be responsible for safeguarding the interests of study participants, ensuring data quality, and monitoring the overall conduct of the Collaborative Consortium and DCC Programs.

The OSMB is asked to make recommendations to the Office of the Director, NHLBI about:

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 plan; amendments to the data acquisition protocols and consent forms; performance of the Hub, individual sites, and the DCC; participant safety, including review of consent forms; notification of, and referral for, unexpected findings; the Consortium's progress toward SCD in SSA program goals, continued NIH support, and necessary program changes.

Communication with the OSMB members will be primarily through the NHLBI Program Office. It is expected that study investigators will not communicate with OSMB members about the study directly, except when making presentations or responding to questions at OSMB meetings or conference calls.

Each OSMB is assigned an 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 are held at least three times a year via conference call using web based processes.

Areas of Joint Responsibility include:

The 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 DCC staff 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 DCC 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.

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

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Norma B. Lerner, MD, MPH
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0080
Email: [email protected]

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

Dianna Jessee
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0154
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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