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

This Funding Opportunity Announcement (FOA) solicits applications as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to support Clinical Sites to improve the health and well-being of adolescents and adults with sickle cell disease (SCD) in the US through the development of multi-modal, multi-sector interventions aimed at improving the rate at which patients with SCD receive routine primary care. Applications that consist of multi-disciplinary teams of personnel from community and academic health-care institutions are highly sought.

In contrast to the prolongation of life achieved in children with sickle cell disease (SCD), there has been little progress in altering the natural history of SCD in adolescents and adults. Individuals with SCD experience a markedly increased mortality beginning in the second decade of life. The third and later decades of life are frequently associated with severe chronic pain, progressive organ damage and frequent hospitalizations. The provision of evidence-based and expert opinion-based care in SCD is complicated by the difficulties that many patients experience in obtaining access to the health care system, and receiving long-term care from knowledgeable providers. The disparities in the health care of individuals with SCD are due to multiple, overlapping factors that are common to many underserved populations at the individual, community and health care services levels. As demonstrated in the approach to care of other chronic diseases affecting underserved populations, maximal effectiveness in implementation of optimal care is achieved through multi-level and multi-modal interventions.

The lack of progress in the application of existing evidence-based guidelines together with the persistently high morbidity and mortality seen in many adults with SCD dictate that new research is needed to bring about improvements in clinical and behavioral outcomes in this underserved population.

The literature on disparities in health care has emphasized that equity can best be achieved by addressing barriers that exist at multiple levels (patient, community, provider/health care, organizational), and in taking into account the specific needs and resources that exist in particular care settings.

This FOA will support applications that propose a two-phased approach that consists of multi-disciplinary teams of personnel from community and academic health-care institutions to provide a greater understanding of SCD.

In the initial phase (Phase I), awarded Clinical Sites will utilize the methodologies of implementation research to 1) conduct a needs-based community assessment of the barriers to care for subjects with SCD, 2) design implementation research studies that address the identified issues of importance, and 3) participate in the development of a SCD Registry, in collaboration with the Data Coordinating Center and NHLBI. In Phase II, Clinical Sites will carry-out approved protocol(s) for implementation research studies that compare two or more multi-modal, multi-sector interventions that address important clinical issues, which will be facilitated by a Data Coordinating Center (DCC), described in the companion FOA (RFA-HL-16-011). Participation in the development of the SCD Registry will continue throughout Phase II.

While each applicant for a Clinical Site will propose protocol summaries in their individual applications, the final studies to be carried out by the SCDIC will be determined post-award through meetings of the SCDIC Steering Committee. Examples of potential implementation intervention strategies include, but are not limited to the following:

• Strategies to develop new models of continuous care from childhood to adolescence/adulthood.
• New models of coordinated community/academic multidisciplinary pain therapy.
• New strategies for subject identification and longitudinal care provision that exploit community outreach, leveraging of electronic health records, and development of computable phenotypes.
• Strategies to reduce hospital admissions and readmissions.
• An integrated care continuum for neurocognitive deficits extending from childhood through adult life.
• Effective strategies to train a cohort of primary care providers, nurse practitioners and patient care navigators in SCD management, and to incorporate technology (telemedicine) to extend care by specialist to providers in the community.
• Extension and adaptation of successful implementation strategies to different geographic settings (urban, rural, greater metropolitan areas).

Applications which do not include the following will be considered non-responsive and will not proceed to review:

• Key community stakeholders in the planning of the design, conduct and evaluation of the proposed Phase I and Phase II research
• Collaboration with representative patients, families, community organizations, school administrators, health care organizations, medical/nursing professional groups, and insurers
• Pre-existing data sharing networks

The SCDIC is a cooperative research program consisting of up to seven Clinical Sites, a Data Coordinating Center, NHLBI, The National Institute for Minority Health and Health Disparities (NIMHD), an Executive Committee, and a Steering Committee with attendant subcommittees.

Each Clinical Site will be comprised of a group of investigators based in a single contiguous geographic area, such as an entire city, or, in larger cities, a contiguous urban area, a city and adjacent suburbs, or a rural area with regional health facilities. The area must include a sufficient number of adolescent or adult subjects with SCD to permit enrollment, characterization, prospective follow-up, and participation in implementation research studies of a minimum of 300 adolescent or adult subjects with SCD. These subjects will also be consented for enrollment into the SCD Registry. Patients which respondents should attempt to identify within their catchment area should include subjects with sickle cell disease between 15.0 years of age and 45.0 years of age at the time of enrollment. For the purpose of this FOA, all genotypes (SS, SC, S/beta thalassemia/SC) regardless of clinical severity are considered as sickle cell disease syndromes. Sickle cell trait is not included in this group. Each Clinical Site will consist of a Research Team and an Advisory Group.

Clinical Site Research Teams

The Clinical Site Research Team will include all personnel whose efforts will be supported by the award. Clinical Site Research Teams will work collaboratively with NHLBI, NIMHD, the DCC, and the other funded Clinical Sites within the SCDIC. Clinical Site Research Teams will consist of at least one or more members with expertise in implementation research, clinical trials, primary care and hematology (pediatric and adult providers), and community-based primary care. Additional members could include epidemiologists, health care policy specialists, emergency department professionals, bioinformatics specialists, and/or administrators. Pediatric clinical providers will play a crucial role in the development of programs that enable transition to adult hematologic and general medical care providers. One or more members of the Research Team should have expertise in participating and collaborating in large multicenter programs.

Clinical Site Advisory Groups

Clinical Site Advisory Groups should consist of representatives from participating community and academic medical centers within their pre-defined catchment area; this group may include, depending on the types and affiliations of the institutions located in the catchment area: members of health maintenance organizations, AHRQ-funded practice based research networks, institutions that are HRSA-funded sickle cell disease demonstration projects, as well as the representation of community organizations, health care systems, providers, patients, and third party payers. It is highly recommended that two or more academic medical centers located in proximity to each other (each of which also is within the geographic catchment area) be members of the same Clinical Site.

Other constituents of the SCDIC will be as follows:

Data Coordinating Center (DCC)

The DCC will facilitate and support the research efforts of the SCDIC. The DCC will be responsible for: coordinating the SCDIC program and providing administrative and operational support; helping develop the SCDIC Registry and protocols; developing the SCDIC operating procedures and manuals of operations for each protocol; developing and implementing web communication tools; data management and associated training; data compilation into databases; analysis of data; and helping with the development of presentations and publications. For more details, refer to the companion FOA for the SCDIC Data Coordinating Center (HL-16-011).

NHLBI

The National Heart, Lung, and Blood Institute (NHLBI) will be responsible for organizing the program, providing oversight of the monitoring of implementation research studies through an NHLBI Observational Study Monitoring Board (OSMB), overall monitoring of interim data and safety issues, providing representation on the Steering Committee, and collaborating with the DCC and the SCDIC investigators in the development and implementation of the SCD Registry.

NIMHD

The National Institute for Minority Health and Health Disparities (NIMHD) will be responsible for providing Program Officer (PO) representation on the Steering Committee and collaborating with NHLBI on providing expert guidance to the Steering Committee on the issues pertinent to minority health and disparities.

Steering Committee
The Steering Committee for the SCDIC will be composed of each Clinical Site PD/PI and one additional investigator, the PD/PI of the DCC, NHLBI and NIMHD scientific staff, and an independent chairperson appointed by the NHLBI. Each Clinical Site will have one vote on the Steering Committee. The committee will identify issues that have broad applicability across the program. Initial recommendations regarding program level organization (overall SCDIC procedures), and an evaluation of where studies can achieve consistencies (e.g., data element capture) will be made by the Steering Committee. It is expected that the Steering Committee will review the protocols developed by the Clinical Sites in collaboration with the DCC and NHLBI, and provide comments to optimize the protocol designs. Such recommendations might involve areas such as study design, standardized aspects of informed consent, sharing of expertise in implementation strategies, optimizing stakeholder involvement, data collection, data sharing and data Quality Control plans. Protocols that have been reviewed and approved by the SCDIC Steering Committee will then undergo review by the NHLBI Protocol Review Committee before they can be implemented.

Executive Committee

An Executive Committee, consisting of the chair of the Steering Committee, the DCC PD/PI, the NHLBI and NIMHD Program Officer(s) and, on a rotating basis (every ten months), one of the Clinical Site PDs/PIs will meet via teleconference on a weekly or bi-weekly basis in the beginning of the program, and potentially less often later on in the program (depending on progress).

Protocol Review Committee (PRC)
A PRC will be appointed by NHLBI and NIMDH. The membership of this committee will consist of members with expertise in implementation research, sickle cell disease, biostatistics, health care administration, health care disparities, and ethics. The PRC will review protocols after they have been reviewed by the Steering Committee. Recommendations from the PRC will be given to NHLBI for approval, before a study can be launched by a Clinical Site.

Observational Study Monitoring Board (OSMB)

An independent program-wide OSMB will be appointed by the Director of NHLBI. Members of the OSMB will advise the Institute regarding study feasibility, participant burden, data monitoring, and successful achievement of milestones for each project. The DCC will budget travel and honoraria for the OSMB.

Publications Committee

A sub-Committee of the Steering Committee will serve as the Publications Committee. The Publications Committee will follow a publications policy approved upon by the Steering Committee at the beginning of the program period and will be responsible for review of all abstracts, presentations, and manuscript submissions by SCDIC investigators.

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.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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. Include the following additional information:

Describe how the research infrastructure will support the implementation of interventions, and provide access to, engagement of, and follow-up of adolescents and adults with SCD.

All instructions in the SF424 (R&R) Application Guide must be followed. In addition, Clinical Site Research Teams must consist of at least one or more members with expertise in implementation research. Include a description of expertise in implementation research for relevant person profile(s).

All instructions in the SF424 (R&R) Application Guide must be followed. In addition, the budget should:

• Include costs for two Steering Committee meetings to be held in Bethesda, Maryland in each year of the program. The Steering Committee will otherwise meet by teleconferences.
• Include clinical costs for the SCD Registry and any subsequent associated costs.

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: Define the goals of the needs assessment, and describe how collaborators and stakeholders will be engaged in the program, in the establishment of a SCD Registry, and in the identification, development, and evaluation of interventions to address major barriers to care as well as implementation of evidence based or best practices based guidelines as set forth in the NHLBI Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014: http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines.

Research Strategy: In the initial phase (Phase I), Clinical Sites are required to utilize the methodologies of implementation research to 1) conduct a needs-based community assessment of the barriers to care for subjects with SCD, 2) design implementation research studies that address the identified issues of importance, and 3) participate in the development of the Sickle Cell Disease (SCD) Registry, in collaboration with the Data Coordinating Center and NHLBI. Each Clinical Site will be expected to enroll and follow at least 300 adolescents and adults with sickle cell disease into the SCD Registry. Applicants are expected to demonstrate collaboration with representative patients, families, community organizations, school administrators, health care organizations, medical/nursing professional groups, and insurers.

After administrative review by NHLBI and NIMHD program staff, awardees that have met the scientific milestones for Phase I will be eligible for transition to the second phase (Phase II). In this phase, Clinical Sites will carry-out completed protocol(s) for implementation research studies that compare two or more multi-modal, multi-sector implementation interventions that address important clinical issues, which will be facilitated by a Data Coordinating Center (DCC), which is described in the companion FOA (RFA-HL-16-011). Participation in the SCD Registry will continue throughout Phase II.

Phase I (two or three years)

Applicants should describe their plans to carry-out a systematic needs assessment for patients with SCD at the individual, community, and health care organizational levels to identify barriers to ongoing care within a defined geographic area. Account for the different sectors that contribute to the care of adolescents and adults with SCD including home environment, family, school, work, community, as well as academic and community-based sites of health care. Include a description of the community, the identification and roles of participants and intended means of engaging and maintaining participants, as well as plans for data collection and analysis. Include a map of the targeted geographic area proposed, with justification as to how the boundaries were chosen and why they were selected.

Applicants should describe their plans to enroll and follow at least 300 adolescents and adults with SCD into a Registry. Include plans for prospective evaluation and participation in specific implementation research protocol(s) with attention to the use of validated instruments to optimize data quality, standardization, and harmonization of collected data elements. Include a plan, if applicable, to use retrospectively collected data on the same subjects.

Phase II (three to four years)

Describe plans for ongoing participation in the SCD Registry.

Describe plans for the identification and development of proposed interventions, including integration into the overall program. The proposed multi-sector, multi-modal implementation intervention strategies must be evidence or best practices-based and should address important issues in health care provision, natural history and epidemiology, and consider social, academic and employment-related issues and needs. At least one intervention should address the integration of a maximal number of subjects with SCD who are not currently followed on a regular basis in any out-patient facility into longitudinal regular care or should address strategies to increase the percentage of subjects who take hydroxyurea on a regular basis (using CBC and Hb F levels to determine compliance).

Include the conceptual implementation framework(s) or model(s) that underlie the anticipated implementation strategies as well as plans for evaluation. Provide a summary of a potential implementation research study to evaluate different implementation strategies. The summary, while not a full protocol, must include the following: a) population, including how adolescents and adults who are currently not in regular longitudinal care will be identified within the community, the size of the community to be studied, and what the comparator group is and why it is appropriate, b) study design, including treatment assignment (if appropriate) and duration, c) interventions that represent the following sectors: home, school, or work, emergency department, outpatient clinics and inpatient settings, d) plans for integrating the programs of care around the individual needs of each subject, and e) SCD outcomes and implementation research outcomes.

Milestones used to determine Clinical Sites' transition to Phase II include the following:

• Evidence of the extent of stakeholders' engagement
• Evidence of the research team's commitment and ability to collaborate across Clinical Sites and within the SCDIC.
• Active participation in the Steering Committee and its subcommittees.
• Provision and entry of high quality data from the needs-based assessment into a comprehensive database, in adherence with SCDIC procedures and description of methodologies used to conduct the needs assessment.
• Identification of interventions that can be implemented to address the identified needs of the community; including conceptual framework(s) or model(s) used to develop the research implementation studies and what will constitute their successful conduct.
• Completed protocol(s) for implementation research study(ies) that compare two or more multi-modal, multi-sector implementation interventions that address important clinical issues.
• Cooperation with the DCC in developing the manual of operation(s) and in submitting IRB applications in a timely manner.
• Consent and enroll at least 300 adolescents and adults with SCD into the SCD Registry.

Milestones will be finalized prior to award and subsequently incorporated into the Notice of Award.

Protection of Human Subjects: Address the research conducted in the community needs assessment (Phase I & Phase II).

Inclusion of Women and Minorities: Address the research conducted in the community needs assessment (Phase I & Phase II).

Inclusion of Children: Address the research conducted in the community needs assessment (Phase I & Phase II).

Letters of Support: The departmental and/or institutional commitments to participate in research should be clearly documented with letters of support from appropriate individuals.

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, with the following modification:

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

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.

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 Key Dates. 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 components of participating organizations, 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.

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? To what extent does the research team demonstrate expertise in implementation research?

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? Would implementation of the project potentially lead to substantial changes in the care of adolescents and adults with SCD?

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?

Is the approach to the community needs assessment likely to be representative of the population of adolescents and adults with SCD?

Are the proposed multi-sector multi-modal implementation intervention strategies evidence or best practices-based and do they address important issues in health care provision, natural history and epidemiology, with consideration of social, academic and employment-related issues and needs?

Does the applicant provide adequate plans for achieving yearly milestones described in the Research Strategy section of this FOA?

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? Is there documentation of previous or ongoing efforts to implement evidence based guidelines into usual care for other chronic conditions (besides SCD)?

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?

Will the research infrastructure support the implementation of interventions, and provide access to, engagement of, and follow-up of adolescents and adults with SCD?

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.

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.

Not Applicable

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 NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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 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.

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.

Grants awarded under this FOA will be excluded from automatic carryover. All carryover requests must be reviewed and approved. Grants awarded under this FOA will not be provided the authority to automatically extend the final budget period one time for up to 12 months beyond the original expiration date shown in the Notice of Award. All extensions, including the first extension, will require NHLBI prior approval.

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 recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below:

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

• Creation of the programs of care for adolescents and adults at high risk of poor outcomes in SCD.
• Designing and performing their proposed clinical trial in compliance with the requirements of this FOA.
• Reporting on study conduct, safety measures, data collection and analysis to the NHLBI-appointed OSMB.
• Regular conference calls with the NHLBI Project Scientist to engage NHLBI staff for the needs of the program.
• Participation in the SCDIC Steering Committee calls and activities (see additional information in Joint Responsibility). The PD(s)/PI(s) will serve as a voting member of the Steering Committee.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

An NHLBI Project Scientist will be responsible for:

• Providing voting and scientific representation on the Steering Committee that oversees the operations and determines the scientific directions of the overall program.
• Providing oversight of the monitoring of implementation research studies through an NHLBI Observational Study Monitoring Board (OSMB).
• Collaborating with the DCC and the SCDIC investigators in the development and implementation of the SCD Registry.
• Monitoring the implementation research studies throughout each project year with the expectation that research plans will be modified if needed.

Additionally, the Program Official, named on the Notice of Award, will be responsible for the normal programmatic stewardship of the award.

An independent OSMB will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues. Meetings of the OSMB will be held regularly by teleconference. A NHLBI scientist other than the NHLBI Program Official will serve as Executive Secretary to the Board. Because the OSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with OSMB members regarding study issues, except as authorized by the board's Executive Secretary.

The NHLBI reserves the right to phase out or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature phase out of the award.

Areas of Joint Responsibility Include:

• Participating in OSMB meetings will be held regularly by teleconference
• Attending conference calls as part of an SCDIC Steering Committee with other awardees and NHLBI Project Scientist to meet the following requirements:
• Defining the metrics to evaluate the implementation of their program. The same metrics will be used for all programs.
• Determining the criteria for inclusion of specific interventions in a guide of best practices for the care of adolescents and adults with SCD and creating a report to document these best practices.
• Reporting (at least annually) the results of quality assessments and stakeholder feedback as well as the trial modifications to be undertaken to address the data.
• Defining the metrics to assess sustainability in the final year of the program/Phase II.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to dispute resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the grantee, one NIH designee, and a third designee with expertise in the relevant area that is chosen by the other two. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 Service Desk (Questions regarding ASSIST, 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

Harvey Luksenburg, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0050
Email: [email protected]

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

Ron Caulder
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0148
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.