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 for a Data Coordinating Center (DCC), as part of the Sickle Cell Disease Implementation Consortium (SCDIC), to support Clinical Sites that propose 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 (see RFA-HL-16-010).

In contrast to the prolongation of life achieved in children with 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.

The SCDIC is a cooperative research program that will promote the development and evaluation of strategies that take a multi-modal, multi-sector approach 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 Clinical Sites and the NHLBI. Each Clinical Site will be expected to enroll and follow at least 300 adolescents and adults with SCD into the SCD Registry.

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 to develop the SCD 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.

Needs Assessment (Phase I):

• Create and manage a database to support the needs assessment data from each Clinical Site.
• Enter the needs assessment data provided by each Clinical Site into a database.
• Analyze data in collaboration with Clinical Sites to identify major gaps and barriers to care.
• Identify potential strategies which could address barriers to care.
• Conduct implementation research studies.

Development of the SCD Registry (Phases I and II):

• Establish a SCD Registry using data collected on SCD patient characteristics and outcomes, health care access and utilization, and providers and health care systems characteristics and practices.
• Use existing research resources to expedite development of Case Report Forms (CRFs)
• Conduct analyses of the information collected in the SCD Registry database including comparative studies in relation to guidelines and recommendations, including the NHLBI evidence-based management of SCD (http://www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/quickguide.pdf).

Implementation research studies to test the effectiveness of interventions in real-world settings (Phase II):

• Provide expertise and support for Clinical Sites in the design and conduct of implementation research studies to test interventions under real-world or usual conditions. Studies should test behavioral and/or clinical interventions at the patient, family, community, provider or health care system level and collect and analyze outcomes at these levels.

The SCDIC is a cooperative research program consisting of up to seven Clinical Sites (described in the companion FOA, RFA-HL-16-010), a DCC, NHLBI, NIMHD, an Executive Committee, and a Steering Committee with attendant sub-committees.

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. Each Clinical Site will consist of a Research Team and an Advisory Group.

The overall structure of the SCDIC will be as follows:

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, consisting of at least one or more members with expertise in implementation research, clinical trials, as well as pediatric and adult providers (primary care and hematology), and community-based primary care providers, could consist of, 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.

Each Clinical Site must include 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 is strongly encouraged. Pre-existing data sharing networks are also encouraged.

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 (see the PHS 398 Research Plan for specific DCC task requirements).

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 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 the Clinical Sites in order 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, 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 Protocol Review Committee will be appointed by NHLBI and NIMHD. 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. Include the following additional information:

Applicants are encouraged to suggest collaboration strategies with CTSA sites and how collaboration would enhance performance, productivity and cost-effectiveness of the SCDIC program.

In such a case, a description of the CTSA and how the applicant proposes interacting with it should be included, as well as a letter of agreement from either the CTSA, Program Director or PD/PI (see Letters of Support.)

All instructions in the SF424 (R&R) Application Guide must be followed. Include the following additional information:

Facilities & Other Resources

Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by the NIH National Center for Research Resources should identify the resources that could be available to support the proposed SCD implementation initiative DCC, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency. In such a case, a description of the CTSA and how the applicant proposes interacting with it should be included,

All instructions in the SF424 (R&R) Application Guide must be followed. Include the following additional information:

Describe previous or current skills in leading and managing a DCC including: administrative support and coordination of multicenter research programs; research protocol development, feasibility assessment, and research design; data management; data analysis; timely coordination, implementation, and management of collaborative implementation research studies. Describe experience in and ability to estimate appropriateness and reasonableness of resources required for individual projects and to manage resources efficiently. Provide evidence of successful performance as a DCC for multicenter federally funded clinical studies within the past three years.

Describe expertise in implementation research, including developing a conceptual framework, conducting needs-based assessments, and devising multi-faceted interventions that address specific community requirements.

All instructions in the SF424 (R&R) Application Guide must be followed. Include the following additional information:

Additional Budget Information

For budget planning assume that during Phase I the major activities will include a needs-based assessment, evaluating barriers to care for subjects with SCD, developing interventions to address these barriers utilizing multi-level, multi-modal strategies, supporting the Clinical Sites in developing at least one implementation research project protocol that will be completed prior to the end of the Phase I project period, and collaborating with NHLBI in implementing the PhenX Toolkit for SCD Research. In addition, budgetary support for the development of the SCD Registry will be necessary in Phase I.

During Phase II the DCC will support the ongoing SCD Registry and approved implementation research studies. It is anticipated that there may be as many as seven simultaneous implementation research studies underway.

The budget justification for each year should include a table that assigns direct costs among core costs and research design and initiation costs. Core costs include essential personnel, facilities and other services to address the scope of activities described in this FOA not involving research design and initiation or research execution and close-out (described below). Research design and initiation costs include costs associated with research design and preparations required to initiate, receive and process data from implementation research studies.

Core costs include funds to execute actions described in the scope of activities not involving research design and initiation or protocol execution and close-out, including, but not limited to:

• PD/PI supervision of day-to-day operation of DCC.
• Investigators contribution and oversight of DCC professional activities.
• Conducting site visits as deemed necessary to evaluate the data quality reported in the SCD Registry as the research evolves.
• Planning and conducting meetings and conference calls for the Steering Committee.
• Developing and maintaining a secure web site for the distribution of project or program documents and reports, and an open-access public web site that provides information about the SCD implementation program.
• Developing the operating procedures for the overall SCDIC program.
• Coordinating other collaboration responsibilities as detailed in scope of activities.

Research design and initiation costs include costs associated with research study design and preparations required to initiate, receive and process data from implementation research studies. For budget planning, assume that implementation studies will include approximately 300 participants at each Clinical Site.

Research design and initiation costs include, but are not limited to:

• Designing electronic Consent Report Forms, and database structures for the developmental SCD Registry.
• Developing protocol/study-specific manual of operations/procedures for the SCD Registry and approved implementation research studies.
• Developing templates for study monitoring reports (e.g., participant accrual, follow-up rates, adherence to protocol, and data quality).
• Serving as central resource for IRB approval and overseeing regulatory compliance at all Clinical Sites

Protocol execution and close-out costs include, but are not limited to:

• Training Clinical Site research coordinators at beginning of each protocol.
• Maintaining program databases, including documentation of variables and collection procedures, and insuring appropriate confidentiality and security.
• Analyzing and presenting research data collected during the program to NHLBI, the Steering Committee, other SCDIC committees and the NHLBI OSMB.
• Employing new statistical methodology as required to address issues that emerge.
• Maintaining data quality control at, and monitoring performance of, the Clinical Sites.
• Reporting (e.g., adverse event report compilation and distribution; recruitment performance).
• Logistical support of data collection-specific costs--DCC resource management, including subcontracts and outsourcing.
• Data analyses and taking appropriate leadership in preparation of scientific reports and manuscripts and publication and presentation of findings.
• Data and resource sharing.
• Dissemination of research findings.

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:

Research Strategy: A typical research strategy description is not expected as part of this DCC application, instead, the following items should be addressed satisfactorily by the applicant:

Program Coordination and Administrative Support

Describe proposed strategies to:

• Develop and implement a coordinated plan to achieve SCDIC program objectives. Participate as a member of the Steering Committee, the Executive Committee, and the Publication Committee, as appropriate.
• Provide meeting/conference call support for SCDIC Committees and the OSMB, as well as other organizational units, through provision of materials and documentation, meeting planning and logistics, conference call coordination, and taking and distributing minutes of the meetings/calls. Two face-to-face meetings per year of the Steering Committee in Bethesda, MD are expected. Regular monthly Steering Committee meetings as teleconferences or web-based presentations are also expected. Support for additional calls as necessary based on the needs of the program (e.g., the Steering Committee, the Executive Committee, and the Publications Committee).
• Develop and maintain operating procedures for SCDIC. The SCDIC operating procedures must address governance; coordination; communication; development and approval of research protocols; data collection, management, security, and sharing considerations; data quality assurance procedures; statistical and analytical support; publication policy; human subject considerations; and processes to obtain all necessary oversight board approvals and administrative/regulatory clearances, as appropriate.
• Develop and maintain a public and private SCDIC website. 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. The private website shall contain all information pertaining to SCDIC activities and will serve as a communication portal for the program. Examples of documents include but are not limited to protocols, operating procedures, manuals of operations, consent report Forms (CRFs), Steering Committee minutes, presentations and manuscripts. The public website should include a description of the SCDIC program and its objectives, a list of participants, a summary of the SCDIC research studies, a list of SCDIC publications, contact information, and other information of interest to the general public. All information and documentation developed for the public website shall be reviewed and approved by the Steering Committee and NHLBI before being posted on the public website. The computer programs, databases, and other resources developed through this FOA shall be compliant with terminology and data standards established by NHLBI. The DCC will ensure that the SCDIC computer hardware and software procedures comply with all Federal and State regulations.
• Coordinate and convene the SCDIC Protocol Review Committee (PRC) and OSMB. Administer budget for honoraria and travel expenses for PRC and OSMB. Help coordinate and convene the SCDIC protocol review Committee and OSMB.
• Regularly interact with NHLBI program officers on programmatic research activity issues.

Protocol Development
Describe proposed strategies to:

• Coordinate and participate in the development and finalization of SCDIC protocols [needs assessment protocol, Registry protocol, and SCDIC-specific implementation research study(ies) protocol(s)] and develop corresponding manuals of operations. Provide appropriate and capable leadership and expertise in developmental study design, project management, data management, biostatistics, and data analysis.
• In collaboration with investigators and SCDIC staff, finalize and distribute research study protocols and related documents for study implementation, e.g., CRFs and manuals of operation.
• Review successive draft protocols and protocol-related documents and make recommendations for modification/improvements. Arrange for and coordinate the review of successive versions and final research protocols and protocol-related documents by investigators and SCDIC staff as well as by the NHLBI PRC.

The primary responsibility for protocol development for SCDIC studies rests with the SCDIC Clinical Sites, with the DCC providing expert advice and assistance in particular regarding study design with attention to the biostatistical (sample size and power calculations) and analytical sections. The DCC has primary responsibility for the development of the manuals of operations.

Program Initiation and Management
Describe proposed strategies to:

• Provide all necessary data management systems or work with Clinical Site members to use their existing, functioning, and compatible data management system(s) to compile data provided by the Clinical Sites into databases stored by the DCC.
• Provide a tracking system for biospecimens, in the event that such materials will be needed for certain studies.
• Use existing research resources, as part of data management responsibilities, to expedite development of CRFs and to optimize data quality, standardization and harmonization. Existing NIH resources include the Patient Reported Outcomes Measurement Information System (PROMIS), the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), the Common Data Elements Portal, and Consensus Measures for Phenotypes and Exposures (PhenX), notably the PhenX-Sickle Cell Disease supplement.
• Assist in planning and developing materials for and participate in study initiation meetings, teleconferences, webcasts, and/or video casts, to provide standard and study-specific training for research site personnel in data collection instruments and procedures for data collection, entry, management, validation, quality control and submission, and standard and study-specific procedures and instructions for Adverse Events (AEs), Severe Adverse Events (SAEs), and Unanticipated Problems (UPs) reporting. Coordinate planning and materials development for study initiation activities with other appropriate SCDIC groups, NHLBI program staff and research investigators.
• Plan and conduct training programs for research personnel covering regulatory requirements and standard practices for human subject research, DHHS (Department of Health and Human Services), NIH and NHLBI policies and procedures study development, implementation, monitoring and reporting.

Data Management
Describe proposed strategies to:

• Participate in the development of Data Monitoring Plans (DMPs).
• Compile SCDIC data in databases and ensure quality of the data in collaboration with the Clinical Sites. The main databases that need to be compiled by the DCC include: 1) the needs assessment database comprised of the needs assessment data done in Phase I at each Clinical Site; 2) the SCD Registry that will be comprised of data collected prospectively as well as retrospectively (if possible) on adolescent and adult patients with SCD; and 3) the datasets corresponding to each implementation research study or observational study that will be conducted in the program. Conduct regular reviews of active research studies to assess multiple performance factors, e.g. subject accrual and retention, adherence to protocol-specific requirements, etc.
• Document action items, problems, and deficiencies and recommend improvements.

Bioinformatics Support

Applicants must describe plans to to harness benefits of biomedical informatics opportunities to support operations, administration and research activities, including a strategy for ongoing assessment of informatics performance across Clinical Sites.

Statistical Support and Analysis
Describe proposed strategies to:

• Provide biostatistical support during protocol development and analyze study data collected by SCDIC. In collaboration with the Clinical Sites, the DCC will manage and analyze data collected by the program to, in particular, answer important research questions about adoption and sustainability of tested interventions that improve patient outcomes including reduced mortality.
• Provide expert assistance regarding comparative effectiveness/implementation research study, the SCD Registry, and the needs assessment efforts in terms of study designs, sample size/power calculations, and data analysis plans.
• Assist in the preparation and/or review of the appropriateness and adequacy of the study designs for proposals from SCDIC-supported research teams for SCDIC.
• Develop and refine study designs and statistical analysis plans for approved implementation research studies.
• Prepare interim and final statistical analyses of all needs assessments, Registry, and specific implementation research studies data in collaboration with SCDIC-supported investigators.
• Review the accuracy and completeness of statistical data for abstracts, manuscripts, and presentations reporting on the results of research conducted by SCDIC.
• Prepare regular statistical reports such as periodic study status reports for SCDIC Committees, and the OSMB reports. Assist in preparing materials for and make oral presentations at OSMB meetings/teleconferences regarding interim and final data.
• Prepare and distribute SCDIC assessment reports in collaboration with NHLBI.

Dissemination of Results

Assist the Steering and or Publications Committee in preparation of scientific reports for publication and presentation.

Management Capabilities
Describe planned strategies to modify the proposed organizational systems to assign and adjust resource allocation during program execution, including potential outsourcing to increase efficiency or to address short-term demands. Describe strategies to meet deadlines (e.g., NHLBI and national meetings, Steering Committee meetings, DSMB or OSMB meetings, Protocol Review Committee meetings).

Staffing Expertise and Capabilities
Propose an operational structure for providing and coordinating all DCC functions for conducting at least seven implementation research studies simultaneously, including lines of responsibility for professional staff. Describe plans to meet timelines efficiently when managing multiple studies within a multi-center program.

Describe proposed management strategy to ensure that NHLBI funds are properly and efficiently deployed including:

• Estimating appropriate and reasonable resources needed for individual projects in its role as a DCC of implementation research studies.
• Managing program resources and budget efficiently.
• Assigning and adjusting resource and budget allocation during program execution and potential for outsourcing to meet short-term requirements.
• Reporting resource allocations to NHLBI on a quarterly basis.

Particular Strengths of PD/PI or Institution
Applicants are encouraged to describe special or unique strengths that may be relevant to the SCDIC 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 of the SCDIC program; an understanding of methods to develop consistent standards for representing SCD research data; and special administrative strengths or experience. Participation by the PD/PI or other proposed DCC staff in administrative aspects of implementation research should be highlighted.

Willingness to Collaborate

Describe strategy to promote collaboration across Clinical Sites, and investigators involved in NHLBI-funded implementation research programs to accelerate translation of study findings to the scientific community and clinical practice as well as stimulate identification of salient research questions from experiences in clinical practice.

The DCC will work with the NHLBI/NIH program staff to implement the PhenX Toolkit for SCDIC program (https://www.phenxtoolkit.org/), which includes common data elements, patient-reported outcomes instruments and organ-system specific elements into a common data collection system to be used by the participating Clinical Sites.

Examples of potential collaborative opportunities may include, but are not limited to:

(1) Use of a Web-based virtual collaborative work environment to exchange information and ideas, such as new research findings, with other researchers and clinicians, communication from practicing clinicians to researchers that inform and shape the research agenda, and interactive discussion groups to stimulate ideas and answer important questions from the research and clinical communities.

(2) Automated methods for rapidly identifying relevant research findings that can be integrated into the guidelines development process to ensure that guidelines are updated regularly.

(3) Promotion of standardized methodologies for reporting research findings to facilitate more rapid and efficient translation of research findings into clinical practice.

(4) Contribution to data repositories and evidence tables that can be accessed by clinicians and researchers.

Letters of Support

The departmental and/or institutional commitments to participate in research should be clearly documented with letters of support from appropriate individuals. Support in areas of grants management, personnel management, space allocation, data coordination and confidentiality, information technology, procurement, and equipment, and general support of research, should be described along with evidence of previous research support.

Applications that plan to collaborate with a CTSA funded by NIH or other federally funded research centers should provide a letter of agreement that identifies the level of support. The letter should be from the PD/PI or program director of the center(s).

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? Does the applicant have demonstrated experience with data management and collection for implementation research studies?

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?

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?

Does the applicant propose adequate plans for program initiation, program management and protocol development?

Does the applicant address specific strategies to ensure data quality?

How strong is the proposed plan to coordinate DCC staffing expertise (internal and external) to meet changing demands and workloads of the SCDIC program?

Is there a well-developed plan to develop and sustain a public and internal web site?

How strong is the plan for promoting communication and collaboration across the SCDIC program and NHLBI to identify, standardize and harmonize common data elements, procedures and outcome measurements?

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?

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.

Not Applicable

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:

The Data Coordinating Center will be responsible for:

• Designing and performing proposed work compliance with the requirements of this FOA.
• Reporting on study conduct, safety measures, data collection and analysis to the NHLBI-appointed OSMB.
• Organizing and participating in on-going meetings and teleconferences such as the quarterly Steering Committee meeting and regular conference calls with the NHLBI Project Scientist to engage NHLBI staff for the needs of the program.
• Retaining 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.
• Coordinating the SCDIC program and providing administrative and operational support.
• Developing the SCDIC operating procedures and manuals of operations for each protocol.
• Developing and implementing web communication tools.
• Development of the Sickle Cell Disease Registry, in collaboration with NHLBI Project Scientist.

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

• Providing voting and non-voting 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.
• Appointing an independent OSMB.
• Providing overall monitoring of interim data and safety issues.
• Providing a NHLBI Project Scientist other than the NHLBI Program Official to 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.
• Monitoring the implementation research studies throughout each project year with the expectation that research plans will be modified if needed.
• Overseeing the normal scientific and programmatic stewardship (NHLBI Program Official) of the award and will be named in the award notice.
  
  

Areas of Joint Responsibility Include:

• Participating in OSMB meetings which 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 awardee, 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. Although a decision to fund or not to fund the UH3 portion of the study will be based in part on scientific issues, Dispute Resolution will not be used to resolve disagreements regarding funding decisions for the UH3 award, since NHLBI retains full authority for this intrinsically governmental function.

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.