National Heart, Lung, and Blood Institute (NHLBI)
93.840, 93.837, 93.838
This Funding Opportunity Announcement (FOA) invites applications for projects that propose to test late-stage (T4) implementation research strategies for optimally and sustainably delivering proven-effective, evidence-based multi--level interventions to reduce or eliminate cardiovascular and/or pulmonary health disparities, and that promote and improve population health in high-burden communities. For the purpose of this FOA, late-stage (T4) implementation research is defined as research to identify strategies to achieve sustainable uptake of proven-effective interventions in routine clinical and public health practice and community-based settings and maximize the positive impact on population health .
This FOA uses the bi-phasic, milestone-driven UG3/UH3 cooperative agreement mechanism and runs in parallel with a companion FOA ( RFA-HL-20-004 ), which seeks applications for a Research Coordinating Center (RCC). Awards made under this FOA will initially support a milestone-driven needs assessment and planning phase for up to three years, with possible transition to an implementation (UH3) phase of up to four additional years. Only UG3 projects that meet the scientific milestones and award requirements of the UG3 phase may transition to the UH3 phase. Applications submitted in response to this FOA must address both the UG3 and UH3 phases and are expected to include plans for project management and performance milestones for each phase.
March 11, 2019
30 days prior to the application due date
New Dates May 17, 2019; December 2, 2019, by 5:00 PM local time of applicant organization.All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
December 3, 2019
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.
The National Heart, Lung, and Blood Institute seeks UG3/UH3 cooperative agreement applications for projects that propose to test late-stage (T4) implementation research strategies for optimally and sustainably delivering two or more proven-effective, evidence-based multi-level interventions to reduce or eliminate cardiovascular and/or pulmonary health disparities, and that promote and improve population health in high-burden communities. For the purposes of this FOA, late-stage (T4) implementation research is defined as research to identify strategies to achieve sustainable uptake of proven-effective interventions into routine clinical practice and community-based settings and maximize the impact on population health .
This FOA uses the bi-phasic, milestone-driven UG3/UH3 cooperative agreement mechanism and runs in parallel with a companion FOA (RFA-HL-20-004), which seeks applications for a Research Coordinating Center (RCC). Awards made under this FOA will initially support a milestone-driven needs assessment and planning phase for up to three years, with possible transition to an implementation (UH3) phase of up to four additional years. Only projects that meet the scientific milestones and award requirements of the UG3 phase may transition to the UH3 phase. Applications submitted in response to this FOA must address both the UG3 and UH3 phases and are expected to include plans for project management and performance milestones for each phase.
Although life expectancy in the U.S. has increased significantly over the past five decades, key indicators of cardiovascular and pulmonary health outcomes continue to vary markedly by race, ethnicity, sex and/or gender, geographic location, and socioeconomic status (SES). Disparities in cardiovascular and pulmonary health are well-documented and account for a substantial proportion of preventable death and disability. In population groups defined by race/ethnicity, sex and/or gender, geography, and/or SES, disparities persist, and in some settings, are widening. Compelling evidence of this observation has been seen across epidemiologic cohort studies, including the Jackson Heart Study, Hispanic Community Health Study/Study of Latinos, and CARDIA study. Other studies from linked micro map plots and small-area analyses also suggest that large state-based, county-level cardiovascular disparities persist and are likely to worsen especially in the Southeastern and Appalachian regions of the U.S.
The 1985 Report of the Secretary’s Task Force on Black and Minority Health (i.e., the Heckler Report) highlighted the paradox of “phenomenal scientific achievement” and “steady improvement in overall health status,” on the one hand, and “persistent, significant health inequities” that existed for individuals from underrepresented racial and ethnic backgrounds, on the other. Despite numerous U.S. Department of Health and Human Services (HHS) initiatives aimed at reducing health disparities, including Healthy People 2010, Healthy People 2020, the National Stakeholder Strategy for Achieving Healthy Equity, and the most recent HHS Action Plan to Reduce Racial and Ethnic Health Disparities, disparities persist, particularly in cardiovascular and pulmonary health.
Multiple respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), display significant socioeconomic and racial/ethnic disparities. While studies like the FLOW (The Function, Living, Outcomes, and Work) study provide valuable description of the magnitude of disparities in health outcomes, the relationship between race–ethnicity, SES and COPD health outcomes remains poorly characterized. Low SES is also thought to be an independent risk factor for impaired respiratory health, especially as it relates to the prevalence of asthma. Despite advances in asthma care and our understanding of risk factors for the disease, the burden of disease remains persistently and disproportionately high in non-Hispanic Blacks and Puerto Ricans. While the sense of urgency to fully investigate evidence-based interventions that target asthma prevention and treatment is quite clear, the fact remains that few large-scale intervention studies have been conducted to examine the feasibility of reducing and/or eliminating these disparities. Similarly, the occurrence of obstructive sleep apnea (OSA) is higher among racial/ethnic groups than in Whites. For instance, in pediatric populations, African American children have a four to six times higher prevalence and more severe OSA than White children, and are less likely to experience resolution of sleep-disordered breathing after adenotonsillectomy, the primary treatment. Partial attribution of the higher incidence and severity in children from racial and/or ethnic backgrounds is associated with living in lower SES neighborhoods. Undiagnosed and/or untreated sleep disorders could lead to greater collective burden of disease over the life course. Overall, African Americans experience more negative health outcomes, including higher rates of hypertension when first diagnosed with OSA that may contribute to the lifetime burden from having sleep disorders earlier in life. Proven-effective interventions, like CPAP, are available, but are underutilized in underserved, low SES communities.
Research is urgently needed to understand the barriers to implementation, optimize delivery strategies, identify diverse multidisciplinary stakeholders who need to be engaged, and maximize strategies for sustaining use of proven-effective interventions. Few studies have focused on the implementation, scale-up, and maintenance of intervention delivery for prevention and treatment of cardiovascular and pulmonary diseases, in general. Even fewer studies have focused on addressing disparities in high burden communities, specifically. Community-based participatory research approaches, in which researchers and communities partner as equitable peers to address locally-identified health issues of greatest importance to the community, have the best potential to foster acceptance, adoption of interventions, and sustained support for interventions being broadly implemented long-term.
Increasingly, there is recognition that single-level interventions are not adequate to reduce health inequities. Multilevel interventions are encouraged to better understand and appropriately intervene to eliminate health disparities. For the purposes of this FOA, multilevel interventions are defined as those that have multiple components designed to affect factors at two or more levels of the social ecological spectrum that contribute to wellness or with the goal to effect changes within and between levels. Dynamic interventions involving individual, family/group, neighborhood, state, or national levels may account for multidimensional influences on individual risk factors and population-level social factors. For example, evidence suggests that population-level behavior changes can be best achieved by changing physical and social environments for key risk factors, including, but not limited to tobacco use, unhealthy diet, and lack of physical activity. Multilevel interventions that consider complex interactions at multiple ecological levels can better address the social determinants of health that contribute to health disparities. Similarly, community-based participatory approaches in which researchers and communities partner as equitable peers to address locally-identified issues of greatest importance to the health of the community, have the best potential to foster acceptance and adoption of interventions, and provide support for broad sustainable implementation.
Research Scope and Objectives
The objective of this FOA is to support late-stage T4 implementation projects to test strategies for the optimal uptake and continued sustainability of proven-effective interventions that will provide generalizable knowledge to reduce or eliminate disparities in cardiovascular and pulmonary health, disease, and disease risk factors in high-burden communities in the U.S. Applications are expected to propose projects that: (1) capitalize on community-based participatory research approaches; (2) leverage current knowledge of the most prevalent cardiovascular and/or pulmonary risk factors to address disparities within high-burden U.S. communities; (3) identify barriers to and facilitators for uptake of proven-effective interventions; (4) develop effective community partnerships that will drive intervention uptake and long-term sustainability of model approaches; and (5) enhance implementation research capacity-building within high-burden U.S. communities.
Communities of Interest:
The NHLBI anticipates research will focus on reduction or elimination disparities in populations in at least one of the following communities with a high burden of cardiovascular and/or pulmonary health disparities:
Efforts to make evidence-based health care for cardiovascular and/or pulmonary diseases equitably available in communities with high burden of disparities requires dedicated infrastructure and partnerships, especially collaboration among researchers, service end-users, health delivery systems, local communities, and governmental and non-governmental organizations and agencies that will implement and sustain ongoing efforts. The NHLBI expects applications to focus on implementation strategies that will be adaptable and responsive to community needs, sensitive to local contexts, embrace cultural and organizational factors, and support community-engaged, community-based participatory research approaches.
This FOA is intended to support applications that propose to utilize partnerships within the communities of interest with representatives from: (1) one or more research organizations; (2) one or more key community public sector organizations, particularly stakeholders with access to and knowledge of high-burden populations and that provide access to service user viewpoints so as to be responsive to local needs, interests, and capacities (e.g., regional or local community organizations, businesses, civic leadership, NGOs); (3) one or more local and state public health agencies; and (4) one or more health care delivery entities, health systems, payors, and/or health care provider organizations.
The NHLBI envisions that, as a group, awardees will constitute a research alliance capable of addressing research questions about the delivery of evidence-based prevention, early intervention, treatment, and care for reducing and/or eliminating disparities and improving cardiovascular and pulmonary population health in high-burden communities, and for fostering the development and long-term sustainability of evidence-based cardiovascular and pulmonary related policy and programs. Additionally, this FOA seeks to address implementation research capacity-building by requiring plans for skills development in implementation research and dissemination and implementation research methodologies to address health disparities in high-burden communities.
Implementation Research Elements
This FOA is intended to support applications that propose to : (1) employ validated theoretical or conceptual implementation research frameworks (e.g., Consolidated Framework for Implementation Research (CFIR); Promoting Action on Research Implementation in Health Services (PARiHS); Pragmatic-explanatory continuum indicator summary (PRECIS); Reach Effectiveness Adoption Implementation Maintenance (RE-AIM); PRECEDE-PROCEED, K2A, etc.); (2) include implementation research study designs (e.g., experimental, quasi-experimental, observational, modeling, cluster randomization, stepped-wedge, Type III hybrid effectiveness, etc.); (3) include implementation measures as primary research outcomes (e.g., acceptability, adoption, appropriateness, affordability, costs, feasibility, fidelity, penetrance, and sustainability etc.; and (4) inform understanding of key mediators and mechanisms of action of the implementation.
Applicants proposing to conduct a clinical trial under this FOA should review NHLBI’s requirements for clinical trials research (See https://www.nhlbi.nih.gov/health-topics/about-clinical-trials).
Applications that include plans to leverage existing and/or previous efforts to address disparities (e.g., Million Hearts, Evidence Now, CDC Racial and Ethnic Approaches to Community Health (REACH), etc.), leverage previous NIH-funded research data resources (e.g., SPRINT, DASH Diet, etc.), foster sustainability, and include information to enable others to optimize successful strategies are strongly encouraged.
Applications that also include a core group of measures related to disparities burden including, but not limited to population-level lifetime cardiovascular and/or pulmonary risk, geospatial profiles of community disease burden, community indicators of the social determinants of health, and predicted and currently observed regional mortality rates are encouraged. Additionally, projects utilizing research that leverages annual county-level health assessments, small area analysis data, and community health status indicators are strongly encouraged.
Phases of Award
The UG3 phase will support the following planning activities focused on sustainable uptake of proven-effective interventions throughout the community of interest:
Milestones and Transition to UH3 Phase
Delineation of milestones is a key characteristic of this FOA. The application is expected to propose a well-defined set of milestones for the UG3 phase as well as the UH3 phase. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be performance-based to enhance the likelihood that the project will be completed on-time and on-budget. It is understood that the proposed milestones for the UH3 phase may be revised as activities in the UG3 phase progress. In the event of an award, the PD/PI and NHLBI staff will negotiate the final list of milestones for each year of support. At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 phase. Satisfactory completion of UG3 milestones will be assessed administratively to determine eligibility to transition to the UH3 implementation phase. The quality of the planning, design, and documentation products for the UH3 phase will be given key consideration when the NHLBI considers the transition to the UH3 implementation phase. If at any time the project fails to make progress toward meeting milestones (e.g., developing a final protocol and/or manual of procedures including a detailed description of study procedures and process details; completing training of study staff, etc.), the NHLBI may consider ending support and negotiating an orderly close-out of the award. Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding. An administrative review of the extent to which peer-reviewed milestones are met in the UG3 phase will determine whether the UH3 phase award will be issued, subject to NHLBI funding availability.
Examples of projects that are of interest to NHLBI and responsive to this FOA include but are not limited to those that clearly identify a high burden community or population; assemble a broad-based research team that is inclusive of all key community members; tests optimal and sustainable interventions delivery strategies suitable for the local context and that are of high priority for the community being studied.
The following types of projects will be considered non-responsive to this FOA and will be returned without review.
Projects that propose to:
Close interaction with the NIH and with the RCC will be required to accomplish the goals of this program. The RCC will assist in dissemination of policies and processes that enable research in partnership with healthcare systems, patients, and practitioners.
Applications that propose multi-site studies with multiple domestic sites are subject to the new NIH Single IRB policy as indicated in NOT-OD-16-094.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NHLBI intends to fund up to 8 awards, corresponding to total costs of up to $7,875,000 in FY 2020 and $10,500,000 per year in FY 2021 through 2026.
Application budgets may not exceed direct costs of up to $635,000 in Fiscal Year (FY) 2020, and up to $850,000 per year in FY 2021 through FY 2026.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
All instructions in the SF424 (R&R) Application Guide must be followed.
Start Up Meeting
Budgets must include funds for the PD/PI and two additional key personnel to participate in a two-day start-up meeting in Bethesda, Maryland at the NIH during the first year of the award (within the UG3) phase.
Budgets must include funds for the PD/PI and two additional key personnel to attend annual 3 day meetings of key staff of each award, appropriate NHLBI staff, RCC key personnel, and selected experts in year 2 through the end of the award period and should include costs for hosting one of these annual meetings at the activity site of one of the awardee projects on a rotating basis.
In order to equitably engage the community of interest in the research activities under the award, applications should budget for local community meetings or other appropriate activities.
Provide a concise description of the aim of the implementation research study to be conducted. In particular, explain how the study will address optimally and sustainably delivering proven-effective, evidence-based multi-level interventions to reduce or eliminate cardiovascular and/or pulmonary health disparities.
Describe how the study design will inform the understanding of key mediators or mechanisms of action of the implementation and/or sustainment effort.
UG3 Planning Phase
Community and/or Population and Interventions
UH3 Implementation Phase
Without repeating information from the individual biosketches, describe how the expertise and experience of the investigator team will be leveraged, organized, and managed to meet the objectives of the proposed project. Address the management and coordination of efforts. Identify the collaborative process for engagement and involvement of stakeholders and patients to participate fully in all phases of the implementation strategy, including design, deployment, testing, and reporting of results. Describe the governance/management plan for the proposed project.
Letters of Support
To be considered complete, applications must include letter(s) of support from collaborating community-based partners, healthcare provider(s), and/or other organization(s) indicating their relevant expertise and commitment to participate. Applications without the required letter(s) of support will not be reviewed.
If partial funding is to be provided by sources other than NHLBI, provide letter(s) of support from the source(s) signed by an authorized representative.
The following modifications also apply:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
In addition, for applications involving clinical trials:
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
For this particular announcement, note the following:
The UG3/UH3 phased innovation cooperative agreement supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. A UG3/UH3 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Reviewers will assign a single impact score for the entire application, which includes both the UG3 and UH3 phases.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA:
To what extent will the outcomes of the proposed research inform the reduction and elimination of cardiovascular and/or pulmonary and promote and improve population health in high-burden communities? How appropriate is the proposed T4 implementation strategy for the selected high-burden community of interest? To what extent will the outcomes inform optimal and sustainable uptake of the proven-effective interventions to reduce or eliminate disparities in cardiovascular and pulmonary health, disease, and comorbid risk factors in the participating high burden communities?
What is the likelihood that the project design will enable uptake and/or scale-up? What characteristics of the project demonstrate readiness for the implementation phase? What is the quality of the provided documentation/justification for targeting the community of interest?
In addition, for applications proposing clinical trials:
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific to this FOA:
How strong is the implementation research expertise of the PD(s)/PI(s) and Key Personnel and capacity to foster and coordinate multilevel collaborations to test the implementation strategies? Is there strong evidence that the PD/PI has experience leading a multidisciplinary team and managing administrative functions? How adequate is the methodological and statistical expertise on the investigative team? Do the investigators commit adequate effort to successfully fulfill the proposed projects’ needs? Does the research team include appropriate representatives from organizations and agencies that can ensure uptake of research findings and ensure public health relevance for that setting? How well does the application demonstrate that all stakeholders will be actively involved in the research process including in the selection of the interventions and the research design? How strongly does the experience of the PD/PI demonstrate the ability to coordinate, monitor, and manage all activities, including appropriate research milestones?
In addition, for applications proposing clinical trials:
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific to this FOA:
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
In addition, for applications proposing clinical trials:
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
Specific to this FOA:
How well does the proposed project demonstrate a solid understanding of implementation research principles? How fitting is the conceptual framework underlying the proposed implementation delivery strategy? To what extent will the plans for developing partnerships with stakeholders contribute to adequate testing of the implementation delivery strategy? How strong is the plan for recruiting and engaging a sufficient pool of eligible participants in a timely manner? How well are the identified implementation facilitators and barriers key to adoption, adaptation, integration, scale-up and sustainability of the proven-effective intervention or guideline? How likely is the proposed implementation strategy to be adaptable and responsive in the context of the selected high-burden community, and how adequately does the strategy account for cultural and organizational factors? How strong are the plans for handling data collection and missing data, and for data analysis? To what extent will the proposed plans have the potential to optimize sustainability of the implementation delivery strategy beyond the funded project period? What is the quality of the governance/management plan for the proposed project?
How likely are the go/no-go milestones to be achieved in the 3-year period of the UG3 grant? How well will the design proposed in the UG3 phase move the intervention delivery strategy appropriately forward to the larger UH3 phase? How likely is it that s ufficient data will be collected in the UH3 phase to determine overall improvement of population health in the high burden community of interest? Are the applicant’s overall approaches to overcoming obstacles and limitations sound and feasible? Are the overarching milestones applicable to the overall program and integrated with the milestones for the UG3 and UH3 phases? Do the milestones present quantifiable measures for the achievement of intended outcomes for the program as a whole in a timely manner? What is the quality of the plans for collaboration, communication, coordination, management, administration, conflict prevention and resolution, financial and resource allocation, and publication approach among team members?
In addition, for applications proposing clinical trials:
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Specific to this FOA:
How well does the environment support timely completion of both the UG3 and UH3 phases? Are the sites and/or facilities where research will be conducted within the participating communities of interest appropriate for the research?
In addition, for applications involving clinical trials
For all CT FOAs, add the following questions, after the standard questions for the Environment review criterion.
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the 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 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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
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).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
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 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.
Information regarding the disposition of applications is available 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.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety
Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at HHS grant administration regulations at 45 CFR Part 75 and other HHS 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.
2.A.1. Awardee and Principal Investigator Rights and Responsibilities
The PD(s)/PI(s) will have the primary responsibility for defining the research objectives, approaches, and details of the research within the guidelines of the FOA and retain primary responsibility for the performance of all UG3/UH3 supported research activities. The PD/PI will be responsible for:
PD(s)/PI(s) agree to participate in the cooperative research program, including serving on the Steering Committee, participating in Steering Committee meetings and teleconferences, adhering to steering committee policies and decisions, attending all annual awardee meetings and workshops, and accepting the close coordination, cooperation, participation and assistance of NHLBI and NIH staff in accordance with the guidelines described in this section (Section VI.2. “Cooperative Agreement Terms and Conditions of Award”).
All awardees proposing clinical research must comply with federal, state, and local regulations regarding clinical research and monitoring of clinical trials and oversee that all training requirements for the protection of human subjects are in compliance.
The PD/PI will ensure that on-site administrative structure, scientific capacity, and training are available to enable the research team, including local research investigators and partners, to perform the research activities proposed in this grant application.
The PD/PI will ensure that research and research capacity-building activities conducted under this cooperative agreement employ an approach that identifies optimal and sustainable strategies to deliver proven-effective interventions into routine clinical and public health practice and community-based settings to achieve maximal population health impact. The PDs/PIs will provide a process for assessing ongoing research and research capacity building projects and modifying, redirecting, and/or curtailing ongoing research activities to reflect local changes/shifts based on emerging needs or changing epidemiological conditions within the participating high-burden communities of interest. PDs/PIs will ensure the development of research-based strategies for use by government agencies, non-governmental agencies, community public sector organizations, public health agencies, health care delivery entities, health systems, and/or health care provider organizations.
The PD/PI will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by members of the grant and supported in part or in total under this cooperative agreement. Manuscripts shall be submitted to the NIH Program Official within two weeks of acceptance for publication and must comply with the NIH Public Access Policy . Publications or oral presentations of work performed under this cooperative agreement will require appropriate acknowledgement of NHLBI support. Timely publication of major findings is encouraged.
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.
2.A.2. NIH Responsibilities
An NHLBI Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The role of the NHLBI Project Scientist will be to facilitate and not to direct the activities. It is anticipated that the NHLBI Project Scientist will offer advisory input. The NHLBI Project Scientist will facilitate liaison activities for partnerships and aid with access to NIH-supported resources and services. Other appropriate NHLBI program staff assistance will be coordinated by the NHLBI Project Scientist, which may include Medical Officer(s), clinical operations and regulatory, biostatistics, and other expertise as required. The NHLBI Project Scientist, with support of the appropriate staff and expertise, may provide coordination and assistance to the awardees to meet the requirements for clinical protocol content and conduct. The NHLBI Project Scientist with substantial programmatic involvement may:
A network Scientific Advisory Group (NSAG) may be appointed and supported by NHLBI to review the progress and provide scientific advice for the intersecting and joint activities of all grants that receive funding under this FOA. The NSAG will be comprised of no more than seven federal and non-federal experts selected by the NHLBI to participate in NSAG activities in an advisory capacity, when appropriate. When convened, the NSAG will meet at the annual meeting of awardees.
Additionally, an agency Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
2.A.3. Collaborative Responsibilities
A steering committee (SC) will serve as the governing board for DECIPHeR awardees. All participants in the DECIPHeR program are bound by the policies and procedures developed by the SC; adoption of such policies and procedures requires a majority vote. Awardees under this FOA will be required to accept and implement policies approved by the SC. Membership on the SC will include the PI of each DECIPHeR award, or a designated representative in the case of a Multiple PI award. Each designated representative will have one vote. The NHLBI Project Scientist will be a voting member of the SC. The chair will be chosen by a majority vote of the SC, with years of service as chair determined by the committee. The chair is responsible for preparing meeting agendas, for scheduling and chairing meetings, and for preparing concise minutes which will be delivered to SC members within 21 days of the meeting. Virtual meetings are appropriate. The NHLBI Project Scientist may not serve as Chair of the SC.
Steering Committee responsibilities will include:
2.A.4.. Dispute Resolution Process
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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. 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.
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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
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