National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Sickle Cell Disease in Sub-Saharan Africa: Data Coordinating Center (U24)
U24 Resource-Related Research Projects – Cooperative Agreements
Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
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) Data Coordinating Center (DCC) that will support the activities of the SCD in SSA Collaborative Consortium (RFA-HL-17-006). The Collaborative Consortium comprised of a Consortium Hub and at least two additional Collaborating Sites will be responsible for developing the infrastructure for a future SCD in SSA Research Network.
Applications that propose a feasible plan to provide overall project coordination, administration, data management, and biostatistical support, are of high programmatic interest. This FOA particularly seeks applications that plan for effective integration of DCC activities with those of the Collaborative Consortium, NHLBI, and review/monitoring bodies.
September 1, 2015
January 26, 2016
January 26, 2016
February 26, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
No late applications will be accepted for the Funding Opportunity Announcement.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
February 27, 2016
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.
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 had the S trait. A recent estimate predicts that in 2050, the number of newborns with Hb SS will increase to over 400,000. 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, Sß 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 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 U.S. children with SCD, 50-80% of affected African children die before the age of five years, often as a consequence of limited medical 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 for a Sickle Cell Disease (SCD) in Sub-Saharan Africa (SSA) Data Coordinating Center (DCC) to support the activities of the SCD in SSA Collaborative Consortium by providing overall project coordination, administration, data management, and biostatistical support. This FOA particularly seeks applications that plan for effective integration of DCC activities with those of the Collaborative Consortium, NHLBI, and review/monitoring bodies.
A full description of SCD in SSA Collaborative Consortium goals and activities is presented in the companion FOA (RFA-HL-17-006). In short, the Collaborative Consortium, composed of a Consortium Hub institution and at least two additional Collaborating Sites, will be responsible for developing the infrastructure for a future SCD in SSA Research Network that will advance SCD-related epidemiologic, translational, and clinical research.
Applications that address a comprehensive plan to provide overall project coordination, administration, data management, and biostatistical support, are of high programmatic interest. In particular, this FOA seeks applications that propose activities to meet the following goals:
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NHLBI intends to commit up to total costs of $853,200 for fiscal year 2017, $972,000 for fiscal year 2018, $972,000 for fiscal year 2019, and $799,200 for fiscal year 2020 to fund one award.
Application budgets may not exceed direct costs of $790,000 in FY2017, direct costs of $900,000 in FY2018, direct costs of $900,000 in FY2019, and direct costs of $740,000 in FY2020.
The budget needs to reflect the actual needs of the proposed project.
The maximum project period is 4 years.
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 African countries
Non-domestic (non-U.S.) Entities (Foreign Institutions) in
African countries are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations in African countries are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
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.
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:
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:
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)
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 a brief description of the features of the institutional environment that are relevant to the effective implementation of the proposed DCC. As appropriate, describe available resources, geographic distribution of space and personnel, and consultative resources. The applicant must also provide a description of the current capacity for 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 develop and make available a secure, customizable coordinated clinical data management system for collection, storage, and analysis of data from no less than 3 and up to 5 locations; to develop and provide a user friendly private web based system for subject enrollment and inter-site communication as well as a public system website to communicate information about Collaborative Consortium activities; to have computational sophistication for scaling the systems and tools to allow incorporation of these systems in a future, SCD in SSA research network that will include additional institutions; to address privacy and confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing as appropriate.
Unique Abilities: Applicants are encouraged to describe special or unique strengths that may be relevant to specifically building the SCD in SSA program 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.
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". Applicants should discuss the issue of future sustainability of their projects beyond the SCD in SSA program and how the DCC's activity will contribute to success in continuing the research efforts of sub-Saharan African SCD investigators. This section of the application should refer to the letters of Institutional commitments that provide an overview of the long term prospects for sustained SCD related bioinformatics and data activities.
All instructions in the SF424 (R&R) Application Guide must be followed. The following additional guidance should also be followed.
The DCC PD(s)/PI(s) is expected to assemble a team with demonstrated expertise in 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 sickle cell disease. When available, particular experience in coordinating multi-center groups, designing and implementing observational databases, previous experience with phenotype harmonization and ontology development, should be described. Participation by the PD(s)/PI(s) or other proposed DCC staff in administrative aspects of clinical research (e.g., IRB, DSMB, PRC) should also be highlighted.
All instructions in the SF424 (R&R) Application Guide must be followed. Also follow these additional instructions:
The operational budget including 8% Facilities and Administrative (F&A) costs should include, but not be limited to, the following items:
Other costs may be included, such as for:
Travel Costs (Suggested travel commitments for planning purposes):
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 DCC.
Research Strategy: Include detailed plans for the DCC development and management. (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 Program 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: 1) The Consortium Hub and the Collaborating Sites; 2) The Collaborative Consortium and the DCC; and 3) The Collaborative Consortium/DCC and the Steering Committee (SC), Observational Safety Monitoring Board (OSMB), NHLBI, and partners.
Applicants should specifically address the following activities: 1) Scheduling meetings and calls, including those of the Collaborative Consortium sites, SC, its subcommittees, and the OSMB; 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 supervisory NHLBI scientists within ten 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 website; 7) Informing SCD in SSA program participants when minutes and materials are posted; 8) Reproducing, distributing, and posting Operating Procedures, including updates; 9) Preparing and submitting reports regarding database development, subject privacy, data capture/quality, data and performance of Collaborative Consortium sites to the SC and OSMB.
1B. Development and maintenance of SCD in SSA Operating Procedures: Describe plans to help the Collaborative Consortium develop SCD in SSA Operating Procedures during the first year of the DCC. Operating Procedures include governance, coordination, communication, and the development and approval of data base elements, phenotype definitions, and ontologies. The Operating Procedures should also provide information regarding data collection, management, security, and sharing; human subject considerations; statistical and analytical requests; publication policy; processes to obtain all necessary approvals and administrative/regulatory clearances; and performance metrics for both the Collaborative Consortium and the DCC.
1C. Creation and management of private and public websites: Describe plans for the development and maintenance of an interactive, secure, scalable, flexible, and robust web-based information and administrative platform. The DCC 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 program.
A private website would contain all information pertaining to SCD in SSA program activities and serve as a communication portal for the program. Examples of documents would include, but are not limited to, protocols, Operating Procedures, , case report forms, subject accruals, Steering Committee minutes, presentations, and manuscripts.
A public website would include a description of the SCD in SSA program 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.
1D. Coordination for the Observational Study Monitoring Board (OSMB) and Steering Committee (SC): The NHLBI will establish the Observational Study Monitoring Board to review data base materials and potential study protocols. The OSMB will review progress related to the database including enrollment, case report form submission, adverse events, etc. The OSMB will make recommendations to the NHLBI Director regarding Consortium continuation and potential modifications. The OSMB will consist of five members including individuals from African nations and from the United States. Meetings will be held via conference calls and will use web-based systems. There will be approximately three calls annually, each 3 hours in duration, with a $200 per call honorarium for each Board member distributed by the DCC. The DCC will be responsible for providing administrative and logistic support for OSMB calls; preparing and presenting data reports during the open and closed sessions of the OSMB; compiling minutes of the open and closed sessions.
The Steering Committee (SC) will consist of representatives from the Consortium Hub, Collaborating Sites, DCC, NHLBI, and H3 Africa program, as well as an External Chair. The External Chair will not be an NHLBI staff member but will be appointed by NHLBI staff. Meetings will be held two times a year in Africa. The DCC will coordinate and support SC meetings. The DCC will be responsible for reimbursing the Chair at 15% fulltime professional effort and supporting the Chair's travel and administrative expenses.
2. Needed Expertise for the Creation/Maintenance of a Sickle Hemoglobinopathy Database
2A. Expertise and intended approach for the development of centralized database protocols and associated materials and services. Include: 1) Developing centralized, cumulative database protocols that will be subject to approval by the Steering Committee (SC) and the Observational Study Monitoring Board (OSMB). 2) Designing data capture forms and for 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 data base protocols, forms, Manual of Operating Procedures, and updates and making them available on the private website.
The Manual of Operating Procedures (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 centralized cumulative databases. Detailed guidance on the contents of the files to be delivered, as well as the mode and time line for data delivery would also be included. Guidance on the demographic, clinical, and laboratory testing data fields and the field requirements, including acceptable codes and field sizes, would also be incorporated in the databases’ MOP.
The DCC should also be able to prepare appropriate materials and documentation needed to assist consortium sites in obtaining all necessary administrative and regulatory clearances relevant to the operation of the database.
The databases’ MOP and other materials will be reviewed, and approved by the SC, OSMB, and NHLBI in the first year of the SCD in SSA program. It is anticipated that the centralized database will be built and ready for initial analyses by the end of Year 2 of the grant.
2B. Ability to provide data management, compilation, and tracking systems: Describe plans to develop and implement secure and robust data collection, tracking, management, and storage procedures for all data compiled by the SCD in SSA program and provide necessary data management systems to the Collaborative Consortium sites. The DCC will be responsible for implementing innovative, cost effective procedures that take advantage, whenever possible, of existing data platforms at Collaborative Consortium sites; incorporate 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 DCC by the individual Collaborative Consortium sites, under the auspices of the central Hub site. The DCC 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 its Operating Procedures.
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 DCC 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 should include, but not be limited to, demographic, clinical, and laboratory data. Data on enrolled subjects should be entered routinely by the sites in a web-based data entry system provided by the DCC. The DCC will be responsible for monitoring and evaluating data base enrollment and for developing site performance metrics and corrective actions for under-performance.
The DCC should also be able to provide scalable infrastructure. It is anticipated that the initial vanguard group of Collaborative Consortium site investigators will be joined by those from other institutions after the first four years of program funding. The DCC will need the ability and resources to expand the size and scope of its operations to meet future needs.
2C. 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.
2D. Ability to ascertain, compile, and enforce consent requirements specific to each participating country: Describe how the DCC will reliably identify unique regional consent regulations and ensure compliance with all requirements as they are stipulated by each participating African nation.
2E. Capacity for database training and site visits: Describe how the DCC will train staff at each individual Collaborative Consortium site in procedures delineated in the MOP. This would include training and consultation regarding data collection, entry, storage, and transmission procedures. The DCC 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 database related activities.
The DCC should assume two site visits ( five days each, including travel) for each of three to five 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 DCC participant per site visit.
2F. Creation of public use data sets: Should the SCD in SSA program end after the initial 4 year period (or earlier as directed by the OSMB), describe how the DCC will transform the centralized database and datasets into public use datasets that will be delivered (at a time specified by the NHLBI) with associated detailed documentation to NHLBI and be made available to the scientific community. These datasets must be de-identified and must be appropriate for independent use by an investigator external to the study.
3. Additional Expertise for Future Planning and Reporting
3A. Assistance with Collaborative Consortium planning for SCD cohort studies and implementation of new preventive/therapeutic practices: The DCC will need to possess substantial statistical and analytical capability. Since the DCC will be assisting the Collaborative Consortium sites as they develop plans for database analyses, future SCD cohort studies, and the implementation of new preventive/therapeutic practices, the application must describe the proposed DCC'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 DCC should also have one to two staff members with scientific and medical expertise relevant to sickle cell disease.
3B. Database expansion: Describe ability to provide a scalable system that will be able to accommodate additional sites and data in the future.
3C. Assistance with the preparation of scientific reports and publications: The DCC should be able to participate in the development of scientific abstracts, presentations and publications; coordinate Publications Committees, and other relevant subcommittees’ calls; check data for accuracy; post presentations and publications on the website.
Applicants 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.
4. Milestones and metrics
Applicants must describe plans 1) to monitor and evaluate the administrative performance of both the Collaborative Consortium and the DCC, and 2) to determine how the overall project will be assessed and how success and impact will be defined. Applicants 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 2-4 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 DCC's experience and progress.)
Timeline: Applicants will be expected to conform to the established timeline:
Development Phase: Years 1, 2
Pilot/Planning Phase: Year 3
Implementation Phase: Year 4
Letters of Support: Each DCC applicant must provide a statement that addresses how institutional commitment will be established and sustained, and how the DCC efforts will be given a high priority within the institution. The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the DCC Director, assignment of space, and/or other ways proposed by the applicant institution. Letters from a high-level institution official(s) (e.g., Dean of the School of Medicine, President, or Vice President for Research) should be attached confirming this commitment. 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 Initiative Program.
Applications 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.
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 are expected to propose 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 Collaborative Consortium members 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 appropriate 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. )
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 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/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 program. Final, uniform policies will ultimately be determined by the Steering Committee. The application must include a statement that the DCC 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 a. 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.
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?
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?
More specifically, has the applicant assembled a team with demonstrated expertise in biomedical informatics, data management, biostatistics, clinical epidemiology, study design, and/or other relevant areas? Does at least one investigator have substantial scientific and medical expertise in sickle cell disease? Does the applicant team have any experience coordinating multi-center groups? Does the team have the ability to help design and implement observational databases? To plan future cohort studies? Help implement new medical approaches? Has there been previous experience with phenotype harmonization and ontology development? Has there been participation by the PD(s)/PI(s) or other proposed DCC staff in administrative aspects of clinical research (e.g., Institutional Review Board, Data Safety and Monitoring Board, Scientific Review Board etc.)?
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 DCC infrastructure will be capably established, able to promote planned operations, and sufficiently flexible to support future Consortium members and planned activities? How innovative are proposed approaches to the activities outlined in the strategy section?
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?
Overall SCD/SSA Initiative coordination and administrative support
Does the applicant outline a reasonable plan to facilitate interactions among participants in the Initiative, the NHLBI, Steering Committee, OSMB, and partners? Does the plan include how functions noted in the strategy section will be pursued? Is the applicant's plan likely to result in the successful development of useful Operating Procedures? Does the plan for developing and sustaining public and private websites appear appropriate to program goals? Does the plan for coordinating the OSMB make sense? Has the applicant provided a well-defined set of yearly milestones for the proposed DCC activities? Do milestones conform to the timeline described in the research plan of this FOA?
Does the applicant provide evidence of sufficient experience to successfully execute proposed plans?
Is the initial plan for sharing data and resources generated by the Collaborative Consortium reasonable and feasible? Is it consistent with achieving the goals of the SCD in SSA program?
Creation and maintenance of a centralized, electronic, patient consented, sickle hemoglobinopathy database
Does the plan reflect an ability to develop and manage appropriate database protocols and services? Does it lay out a comprehensive approach to the provision of data management, compilation and tracking? Are the bioinformatics skills and approaches sufficiently sophisticated? Will the applicant be able to reliably identify unique regional consent regulations and ensure compliance with the all requirements? Are approaches to data base training and site visits reasonable and likely to be successful? Is the approach to the creation of public data sets a good foundation upon which to develop a final plan? Does the applicant provide a reasonable initial resource and data sharing plan consistent with achieving the goals of the program?
Does the applicant provide evidence of sufficient experience to successfully execute proposed plans?
Biostatistical and analytic support
Does the applicant describe what kind of assistance they will provide to the Collaborative Consortium as it plans for future SCD cohort studies and the implementation of new preventive/therapeutic practices? Does the applicant provide plans demonstrating the requisite statistical, analytical, and study design capabilities? Is the proposed system scalable and able to accommodate expansion for additional sites and data? Does the applicant outline an approach to the preparation of scientific reports and associated activities?
Does the applicant provide evidence of sufficient experience to successfully execute proposed plans?
Milestones and metrics
Does the applicant propose an effective approach to performance monitoring? Are milestones clearly delineated and sufficiently comprehensive? Do they conform to the timeline described in Section IV.2? Are they feasible?
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?
Are the institutional environment (resources, space, personnel) and organizational structure (management, coordination, tracking) appropriate for implementing the proposed DCC plan? Is the grants administration capacity adequate?
Are there sufficient clinical data management resources to support the development of a secure system for collection, storage, and analysis of data from no less than 3 and up to 5 locations? Does the application demonstrate the ability to develop private and public web based systems? Is there sufficient computational sophistication for scaling the systems and tools to allow incorporation of these systems computational sophistication for scaling the systems and tools to allow incorporation of these systems in a future, SCD in SSA research network that will include additional institutions? Does the application adequately address privacy and confidentiality issues related to database management, distributed computing, and multiple levels of data sharing as appropriate and consistent with achieving the goals of the program?
Does the application describe unique strengths that may be specifically relevant to building the SCD in SSA program infrastructure and research? Does the application describe a proactive plan to incorporate existing data platforms and take advantage of existing resources at Collaborating Sites?
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 SCD in SSA Program as an Integrated Effort
Is the proposed structure of the DCC conducive to achieving early program goals? Are there adequate mechanisms proposed for regular communication and coordination among investigators within the DCC and those in the Collaborative Consortium? Are adequate administrative structures in place for the day-to day management of the DCC and its communication with the Collaborative Consortium?
Do the letters of Institutional and National commitment suggest that the overall environment is conducive to a sustained DCC enterprise that will be able to support a larger SCD research network? Do the planned collaborations between the DCC and the Collaborative Consortium suggest viable long-term partnerships and an ability to expand the network'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.
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:
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:
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:
The Data Coordinating Center (DCC) PD(s)/PI(s) will have the primary responsibility for:
Conducting DCC activities, including supervision of site performance, modifications of DCC 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 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 DCC goals and progress toward those goals as requested by NHLBI staff and insurance that the data produced meets 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 Hub 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 10 working days after each meeting
Providing administrative and logistic support for OSMB calls; preparing and presenting data reports during the open and closed sessions of the OSMB; preparing minutes of the open and closed sessions; paying for OSMB costs; 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 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 (NHGRI) 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 and the DCC 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 DCC activities and the development of DCC policies.
The NHLBI Project Officer will serve as liaison between the Awardee, the Hub, 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 Project Officer will periodically report about the progress of the DCC 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.
Additionally, an agency program official or 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.
Steering Committee (SC) Responsibilities:
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 OSMB will be responsible for safeguarding the interests of study participants, ensuring data quality, and monitoring the overall conduct of the Consortium and DCC Programs.
The OSMB will be asked to make recommendations to the Office of the Director, NHLBI about: 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 DCC, Hub and individual sites; participant safety, including review of consent forms; notification of, and referral for, unexpected findings; the DCC's progress toward SCD in SSA program goals, continued NIH support, and necessary program changes.
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 will be held via conference calls using web-based processes.
Areas of Joint Responsibility include:
The DCC 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 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.
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.
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)
GrantsInfo (Questions regarding application
instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Norma B. Lerner, MD, MPH
National Heart, Lung and Blood Institute (NHLBI)
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
National Heart, Lung and Blood Institute (NHLBI)
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.
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