It is critical that applicants follow the instructions in the Research Instructions for 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

Globally, hypertension is one of the risk factors associated with cardiovascular disease (CVD) and stroke accounting for approximately 7.6 million deaths per year worldwide. The majority of cardiovascular disease- (CVD) related deaths occur within low- and lower middle-income countries (Lower-MICs). The high burden of hypertension and stroke in Lower-MICs has not declined during the past decade. Although hypertension treatment and CVD screening are listed among the World Health Organization’s (WHO) most cost-effective strategies for addressing CVD and are also key elements of the WHO Global Action Plan 2013-2020, context-specific implementation strategies for the prevention, treatment, and control of hypertension within Lower-MICs are lacking. There is a clear need to determine the best strategies to scale-up effective interventions at the regional and national levels.

Although there are many evidence-based interventions for hypertension prevention, treatment, and control, these interventions are underutilized in low resource settings and for the purposes of this announcement, research in Lower-MICs where hypertension control for the general is suboptimal is of interest.

Late-stage T4 translation research designed to test sustainable implementation strategies to deliver evidence-based care and to achieve broad scale-up within Lower-MIC populations is needed. T4 translation research (T4TR) is defined as research that identifies implementation strategies to enhance sustainable uptake of evidenced-based interventions into real world settings. Thus, T4TR evaluates the salient implementation research outcomes for evidence-based interventions including acceptability, affordability, and appropriateness of interventions, cost, feasibility, fidelity, penetration, and sustainability of the intervention in specific contexts.

The purpose of this FOA is to support research that identifies and studies regional- or national-level implementation strategies for evidence-based interventions for the prevention, treatment, and control of hypertension in adults in World Bank defined Lower-MICs. Applications that address the following topics are of high programmatic interest:

• Execution of an evidence-based T4TR program using appropriate theoretical implementation frameworks (e.g. CFIR, RE-AIM, PRECEDE-PROCEED, PARIHS, K2A etc.) and leveraging preexisting hypertension prevention, treatment, and control interventions in Lower-MICs using these established implementation research frameworks.
• Implementation study designs that include multi-level (health care system, community provider(s), community-based organizations, HTN patients and their families) and multi-component interventions and may include appropriate community-based organizations.
• Components of the implementation research that are evidence-based and feasible for broad future implementation, and address system/facility, physician/provider, and patient barriers.
• Implementation research outcomes (e.g. acceptability, adoption, appropriateness, costs etc.) and collection of secondary outcomes that include treatment outcomes for hypertension prevention and control in Lower-MICs.
• Creation of robust multidisciplinary collaborative teams (led by Lower-MICs based academic institutions defined by World Bank, with inclusion of high income country partners ) to conduct T4TR for hypertension prevention, treatment, and control

This FOA encourages applications that will test implementation strategies to deliver evidence-based interventions within the regional (sub-national within one country) or national levels (among several countries) for the prevention, treatment, and control of hypertension utilizing a suitable theoretical or conceptual implementation framework. NHLBI is particularly interested in applications involving organizations or programs that can help researchers understand the barriers to scale-up of evidence-based hypertension interventions. Applicants are strongly encouraged to collaborate with appropriate institutions or organizations to achieve this end.

This FOA seeks applications that propose to:

• Create Lower-MICs strategic multidisciplinary collaborative teams that include team member(s) with proven T4 implementation science expertise from high income countries;
• Collaborate with major in-country academic health centers, public health agencies, Ministries of Health (MoH) or equivalent, and community organizations;
• Execute an actionable and context specific implementation research plan for hypertension prevention, treatment, and control in adults within a suitable theoretical or conceptual implementation framework;
• Implement a study design with a multi-level and multi-component intervention involving at least three or more levels that include the health care system, communities, the providers, patients with hypertension, and appropriate community-based organizations. Elements of the implementation study must be evidence-based and feasible for broad future implementation, and address system/facility, physician/provider, and patient barriers.
• Assess key implementation research outcomes for hypertension prevention, treatment, and control program; including assessment of treatment outcomes;
• Publish results in peer-reviewed literature and disseminate in clinical, public health, and community settings;
• Link implementation research programs to existing evidence-based hypertension prevention, treatment, and control programs in Lower-MICs. Approaches, including those that draw on successful local experience and those that lend themselves to adaptation to other environments, will be encouraged through this funding mechanism.

This FOA is intended to support projects that:

• Utilize appropriate theoretical and/or conceptual implementation frameworks (e.g., CFIR, RE-AIM, PRECEDE-PROCEED, PARIHS, K2A, etc.) to:
• Assess key implementation research outcomes including acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration and sustainability, in secondary outcomes from treatment.
• Collaborate with at least one institution in the US or other high income countries (HIC) to develop T4TR teams;
• Utilize a variety of approaches such as experimental and quasi-experimental study designs, mixed methods studies, comparative case studies, economic and mathematical modeling, and/or combined approaches.
• Address system barriers at three or more levels (e.g., patient, family, community, provider, health system(s), policy and/or environmental levels) to hypertension prevention, treatment, and control and how these can be addressed.
• Demonstrate an appropriate plan for knowledge translation and exchange included as a component of the project. This should include a training and implementation science capacity-building component.

The types of studies that are considered responsive to this FOA include, but are not limited to implementation research focused on multi-level and multi-faceted prevention, treatment, and control of hypertension in adults through multi-strategy and multi-level interventions that:

• Address lifestyle and environmental risk factors (e.g., high salt intake) through multi-strategy and multi-level interventions.
• Examine the initiation of treatment for individuals with hypertension with proven lifestyle and pharmacological interventions utilizing T4 implementation science frameworks (treatment).
• Address sustaining treatment, self-efficacy and self-care management of hypertension interventions until the treatment goals are achieved.
• Identify individuals at risk for secondary stroke and address the need for aggressive secondary prevention measures (awareness).
• Analyze implementation research outcomes for the initiation of treatment that controls hypertension and other stroke risk factors for individuals with recent stroke or transient ischemic attack (TIA) with proven lifestyle, diet, and pharmacological interventions (treatment).
• Analyze implementation outcomes for sustaining effective treatment and self-care management to prevent secondary stroke (control).

These types of projects will be considered non-responsive to this FOA, and applications proposing such projects will not be reviewed:

• Applications that propose a single-level intervention or a unidimensional approach.
• Applications for infectious diseases research (e.g., HIV, tuberculosis, or malaria).
• Applications that use non-evidence based approaches to hypertension prevention, treatment, and control in Lower-MICs.
• Applications without HIC collaborators and/or collaborators with T4 translation research expertise.
• Applications without a theoretical or conceptual implementation framework(s) for hypertension prevention, treatment, and control in Lower-MICs and significant justification for the use of said framework.
• Applications in which the implementation research will be conducted in non-Lower-MICs.

See Section VIII. Other Information for award authorities and regulations.

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

Non-domestic (non-U.S.) Entities (Foreign Institutions)

Eligibility is limited to institutions from lower-MICs. Institutions from high income or middle income countries as defined by the World Bank are not eligible but are encouraged to collaborate with Lower-MICs.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

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

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

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).

Applications from Lower-MICs must collaborate with institution(s) in the US or other high income countries (HIC) to develop T4 implementation research teams; collaborating HIC institutions must have demonstrated knowledge and expertise in T4 implementation research and collaborate with Lower-MICs institutions in developing the relevant T4 implementation research agenda for hypertension prevention, treatment, and control. The multidisciplinary collaborative research team should contain broad membership from in-country institutions to conduct local needs assessments and create an actionable, context-specific T4 implementation research plan for hypertension prevention, treatment, and control.

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the instructions in the Research Instructions for 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
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

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

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

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

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

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

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

Applicants are required to assemble a collaborative research team whose members have demonstrated experience and expertise in relevant areas including T4 translation research, global health, hypertension, CVD expertise in low resources settings, as well as research planning, project administration, implementation, and monitoring.

Research team should possess the following characteristics:

• Extensive research experience with the proposed populations.
• Extensive experience in T4TR and/or implementation science, hypertension, cardiovascular disease and conducting research with patients in Lower-MICs.
• Extensive experience in working with the healthcare organizations in resource poor settings, serving these populations and relevant experience engaging patients and stakeholders in implementation research, health services research, clinical trial research and conducting randomized trials.
• An independent capacity for data analysis.

All instructions in the SF424 (R&R) Application Guide must be followed. The operational budget including 8% Facilities and Administrative (F&A) costs should include, but not be limited to the following items:

• PD(s)/PI(s) supervision of day to day operations and oversight of the professional activities of the proposed skills development
• Reasonable administrative costs
• Necessary project management costs
• Costs of developing needs assessment document for dissemination purposes
• Costs of developing a hypertension specific needs assessment document for dissemination purposes
• Subcontracts as necessary
• Travel costs for two persons (including PD(s)/PI(s) or their delegate) to attend program meetings to be held two times each grant year, in a location to be determined (for budgeting purposes, assume Johannesburg, Republic of South Africa)

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: Organize the Research Strategy in the subsections identified below.

1) Background and Significance

• Define the problem to be addressed, including type(s) of interventions that will be targeted.
• Outline the proposed implementation framework that will be utilized and its potential to improve hypertension prevention, treatment, and control for adults living in Lower-MICs.
• Summarize record of research at the lower-MIC applicant institution relevant to addressing a hypertension prevention, treatment, and control program that will maximize the use of both high and low income country institutional research environments,

2) Investigator Team(s)

Address the management and the coordination of efforts in all the required areas listed below and describe how the expertise and experience of the investigator team(s) will be leveraged, organized, and managed to meet the study objectives:

• Engagement of patients and other relevant stakeholders to participate actively in all phases of the study, including design, implementation, evaluation, and reporting of results.
• Monitoring of study processes to ensure the quality of the hypertension intervention and fidelity to the protocol.
• Access to a sufficient number of clinics and participants to ensure adequate statistical power.
• Suitability and relevance of the research endeavor in a Lower-MIC.
• Ensure the screening, detection, diagnosis, and treatment of hypertension can be locally managed or treated in Lower-MICs setting.
• Global or national healthcare delivery as demonstrated by established collaborations with health care workers at the local sites.
• Establishment of successful partnerships with various stakeholders (e.g., MoH, community organizations, health systems etc.) to execute implementation studies in Lower-MICs,

3) Approach

Applicants must describe plans for:

• Activities to take place during a one-year (first year) planning period including local needs assessment.
• Protocol development, including developing collaborations and refining the protocol based on results of the one-year planning period activities.
• Efficient execution of quantitative and qualitative research to identify local needs and capacity for hypertension prevention, treatment and control.
• Collection of key implementation research outcome data and measures.
• Standard metrics and/or protocols that will be used for examining implementation research outcomes and for assessing features of the health care system, community, clinic, and the broader context.
• Formation of in-country strategic T4TR collaboration teams that include major in-country academic health centers, public health agencies, Ministries of Health (MoH) or equivalent, community organizations, patient and other key stakeholders as research partners in the conduct of the implementation study.
• Development of T4TR regional and global collaborations across Lower-MICs, upper middle and high income countries.
• Primary outcome of the implementation study which must assess key implementation research outcomes/barriers that impede scale-up of hypertension prevention, treatment, and control in Lower-MICs.
• A clearly justified implementation study design based on a theoretical framework (e.g. Cluster randomized designs, adaptive or other trial designs to address inadequate response to the active intervention or its components, especially among population subgroups, randomization at the individual patient level).
• Evidence-based interventions with one or more well-defined comparator groups.
• Incorporation of multi-level and multi-component interventions that include involvement of leadership of the health care system, practitioners, patients with hypertension, and appropriate community-based organizations.
• Implementation of the intervention(s) in low resource settings.
• Effectively restricting participation to participants with uncontrolled blood pressure or hypertension
• Leveraging context specific knowledge to engage patients and families, and to ensure that broad future implementation is feasible.
• Data collection and possible barriers for data collection will be mitigated for system/facility, community, clinician, and patient.
• Data analysis
• How the implementation study will assess the tailoring of patient factors that result in increased adherence and engagement such as context, preferences, and language.
• Addressing major obstacles that are more common among high risk populations.
• Possible innovative use of technology
• How different components of the multi-component intervention may be directed at different levels such as the leadership of the health care system, providers, patients, and appropriate community groups or resources.
• Determining whether there are specific subgroups for which specific components of the intervention are ineffective for controlling hypertension.

Each applicant must submit milestones that are specific to their proposed implementation study. These should be quantifiable and the metrics to measure success fully explained in the application. Additional milestones may be negotiated with NIH Grants Office before and after funding decisions have been made.

The proposed implementation study should build on the findings of ongoing interventions for hypertension prevention, treatment, and control programs in Lower-MICs. All applicants should provide a thoughtful analysis of barriers to obtaining their implementation research outcomes

in the patient and provider populations and study organizations they intend to target. Applicants should provide realistic solutions about how they plan to address these obstacles and challenges to help assure successful study. For example, factors which might present obstacles for implementation research could include: turnover of clinicians, staff and leadership in healthcare organizations; lack of Information Technology (IT) infrastructure to provide electronic feedback and information needed for the trial.

With the purpose of increasing the potential of adoption and uptake of the findings by other healthcare providers/systems, describe relevant plans for leveraging available staff and facilities and also community resources that are representative of real-world (present and potential) linkages to the practices engaged in the trials. If proposing to include community resources to augment healthcare, applications must include a description of how the community resources will be integrated into healthcare delivery keeping in mind that referral alone, without active follow-up, to community programs by the healthcare system or staff is not, in itself, adequate.

Letters of Support: Attach letters of support relevant to the project. If applicable, provide a letter of agreement with institution(s) or organization(s) that identifies the collaboration and level of involvement. If proposing to include community resources to augment healthcare, provide letter of support that confirms that the community program or policy is directly linked to healthcare delivery through a formal agreement, reimbursement, and regular communication about patient progress and outcomes.

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 PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 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 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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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? Is there a strong scientific premise for the project? 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:

How strong is the case that successful completion of the proposed aims will support assessment of the key T4 implementation research outcomes (e.g. acceptability, adoption, appropriateness, costs etc.) and collection of secondary outcomes including treatment outcomes for hypertension prevention and control in Lower-MICs?

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?

Specific to this FOA:

Has the applicant(s) demonstrated a commitment to collaborating with stakeholders in the T4 space within country, and across low and high income countries? Has the applicant(s) demonstrated a track record of strong scientific collaborations? Does the team of investigators have the acknowledged expertise in T4 translation research, global health, hypertension, and other relevant areas?

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:

How well have the applicant(s) described their theoretical or conceptual implementation framework (e.g. CFIR, RE-AIM, PRECEDE-PROCEED, PARIHS, K2A etc.) to address hypertension prevention, treatment, and control in adults in Lower-MICs?

How carefully have the applications justified their implementation study design and are the study designs practical with high likelihood of success based on past experience or feasibility studies in Lower-MICs?

To what extent have the applicant(s) utilized a variety of approaches such as experimental and quasi-experimental study designs, mixed methods studies, comparative case studies, economic and mathematical modeling, and combined approaches?

Has the applicant(s) described an implementation study which involves a multi-level and multi-component intervention involving the healthcare system, communities, the providers, patients with hypertension, and appropriate community-based organizations?

How well has the applicant(s) demonstrated the ability to conduct a health priority needs assessment of ongoing in-country hypertension prevention, treatment, and control programs and assess the appropriate baseline implementation measures (e.g. fidelity, penetration, sustainability etc.) and secondary treatment measures for interventions identifying potential barriers to regional or national scale-up?

Has the applicants(s) included appropriate plans for knowledge translation and exchange as a component of the project?

Has the applicant(s) included appropriate plans and designed the research study to allow for generalizability of the research results for other Lower-MICs, and/or low income countries?

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

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.

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.

Not Applicable

Not Applicable

Not Applicable

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

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

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

Cooperative Agreement Terms and Conditions of Award

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

• Providing effective leadership and management.
• Developing and defining study approach, plans, conduct and analysis.
• Meeting goals, timelines, and milestones.
• Collaborating with NHLBI Program Officer (PO) and Project Scientist (PS) in all aspects of scientific and technical research needed for the management of the study.
• Agreeing to participate and abide by the governance of the Steering Committee (SC).
• Accepting and implementing recommendations made by the SC.
• Ensuring participation by their site in SC meetings, support committees, task forces, and advisory panels as needed.
• Ensuring all third party participants compliance (field centers, single institution or consortiums) in implementing the guidelines developed by the SC.
• Design and development of an implementation research program for hypertension prevention, treatment, and control, in Lower-Middle Income Countries.
• Submitting operations updates as established by the SC.
• Attendance in all annual meetings, teleconferences, workshops, and working groups.
• Note: The PD(s)/PI(s) should plan for at least one in person meeting in the Washington DC Metro area annually.
• Publishing and releasing publicly and disseminating results, tools, protocols, resources and other products, in accordance with established protocols and governance of the SC.
• Note: It is expected that all methods, analyses, and data (e.g., software, and algorithms) will be made available in a timely manner to the scientific community.

NHLBI staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards as described below:

NHLBI staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress and negotiate goals. Monitoring may include: regular communication with the PI and his staff, periodic site visits for discussion with awardees' research team, observation of development and management techniques, fiscal reviews, and other relevant stewardship matters.

For each award, there will be a NHLBI Program Officer (PO) and a member of NHLBI staff responsible for the normal scientific and programmatic stewardship of the award. The PO will be named in the award notice. The NHLBI will also retain its typical stewardship role, including its authority and discretion to withhold or reduce support or take other enforcement action, such as if the awardee fails to achieve its goals or fails to comply with the Terms and Conditions of the award.

In addition, there will be an NHLBI Project Scientist (PS) assigned to the award. The PS will have substantial and programmatic involvement during the conduct of this activity. The PS will have primary responsibility for:

• Serving as a resource to provide scientific/programmatic support during the accomplishment of the implementation study by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or participating in the preparation of publications.
• Assisting in the development and modification of study protocols.
• Providing assistance, coordination and facilitating interactions and collaborations among the recipients of the Hy-TREC initiative and providing technical assistance and advice as appropriate.

The NIH reserves the right to phase out or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting. Failure to achieve minimally acceptable milestone levels may result in the withholding of future support and or negotiating an orderly close-out of this study.

Areas of Joint Responsibility Include:

The awardees, NHLBI staff and other stakeholders agree to the governance of the study through a Steering Committee (SC). The SC will have primary responsibility for the conduct of protocols and preparation of publications. The SC will facilitate coordination and synergy across the entire program; and develop recommendations for uniform procedures and policies, participate in the monitoring of issues relating to recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of the annual reports, site visits, patient logs, etc.

The SC membership will include the NHLBI PS and the PD(s)/PI(s) of each award. The SC Chair will not be an NHLBI staff member but will be appointed by NHLBI. Additional members may be added by action of the SC. Other government staff may attend the SC meetings, if their expertise is required for specific discussions. As necessary, NHLBI staff will partner with Recipients to create appropriate subcommittees to handle interests that may be specific to a set of awardees funded by this FOA.

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. The three members will be: a designee of the SC 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.

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.

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.

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: https://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 Center Telephone: 800-518-4726

Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

LeShawndra N. Price, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-451-0164
Email: leshawndra.price@nih.gov

Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Mary Baylor
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0480
Email: baylorm@mail.nih.gov

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.