Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) issued by the Fogarty International Center (FIC) seeks to stimulate innovative ideas and impactful research to better understand the complexities around developing appropriate approaches for effective diagnosis, prevention, therapeutic interventions and integrated clinical care for HIV-associated non-communicable diseases (NCDs) in Low and Middle-Income Countries (LMICs). Specifically, this initiative will support research in the following areas: a) Basic sciences to address etiopathogenesis of NCDs in Persons Living with HIV (PLWH); b) Aging process in PLWH; c) Diagnostics tools for early detection of NCDs in PLWH; d) Therapeutic interventions to explore optimal drug regimens for PLWH with NCDs; e) Behavioral studies for better quality of life of PLWH with NCDs; and f) Clinical studies for better patient centered care for PLWH with NCDs. The R21 grant mechanism is intended to encourage exploratory/developmental research by providing support for the early and conceptual stages of project development and assessing feasibility of the proposed studies (https://grants.nih.gov/grants/funding/r21.htm ). It is hoped that this preliminary research will lay the foundation for larger studies that can lead to applications to other organizations or NIH institutes that support HIV-associated NCD research.

Background/Rationale:

NCDs are responsible for over 70% of deaths globally representing 41 million lives, of which 15 million people die prematurely between the ages of 30 and 69. Eighty-five percent of such premature deaths occur in LMICs and exert a substantial toll on the socio-economic structure of these resource-challenged communities, impeding any progress towards targeted prevention strategies (https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases). NCDs include, among many others, cardiovascular diseases, diabetes, obesity, chronic kidney, liver and respiratory diseases, cancer, alcohol and substance abuse and mental disorders. NCDs share the common feature that they are not transmissible and are often chronic in nature. While NCDs might have been triggered by an infectious agent, the chronic disease is often not dependent on the presence of the infectious agent and rather is the result of a combination of genetic, physiological, environmental and behavioral factors. Tobacco and alcohol use dependency, physical inactivity and unhealthy diets all increase the risk of dying from an NCD. WHO also recognizes that air pollution is a critical risk factor for NCDs (http://www.euro.who.int/en/media-centre/events/events/2019/04/WHO-conference-NCDs-Ashgabat-2019/key-questions-on-the-agenda). Detection, screening and treatment of NCDs, as well as palliative care, are key components of the response to NCDs. In 1981 when AIDS cases were first reported, there was the general assumption that people diagnosed with HIV would live 1-2 years. With the prescribed use of highly effective antiretroviral drugs and potent combination drugs, the life expectancy of PLWH has dramatically increased, and this population is living longer and relatively healthier lives. However, routine clinical care of these patients has shown increased risk of NCDs and life-style disorders and a new spectrum of comorbidities that raise new questions (https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm?;https://www.amfar.org/Non-AIDS-Defining-Illnesses-Impact-Health/).

The chronic nature of all NCDs has adverse health and economic consequences for the individual and the household, ultimately affecting the communities and nation as a whole, and that impact is more pronounced in resource limited settings such as LMICs. This concomitant presence of NCDs is more serious in PLWH where scientific evidence points to increased severity and compounded debilitating consequences of multimorbid conditions.

HIV infection results in a chronically inflamed physiological state and it is believed that monocyte activation likely is responsible for initiating the development of NCDs by promoting metabolic and cellular changes leading to early immune aging. The aging process itself is a risk factor for a number of NCDs and whether the presence of HIV infection compounds the risk factors is not well understood. In addition, HIV infection and the normal aging process share immune changes that result in the premature aging of HIV-positive subjects, which in turn increases their susceptibility to diseases associated with normal aging. Understanding these processes may help in the design of therapeutic interventions to stem the premature development of NCDs in HIV-infected subjects, especially in children, adolescents and young people. In addition, specific diagnostic markers to identify immune aging will be extremely useful in predicting the risk for developing a specific NCD.

There is a need for strong epidemiological, clinical and management related evidence that takes into consideration the differences in the disease epidemiology among different countries, the specific HIV-associated NCD and/or combinations of such diseases, and health system environment and types of services available towards developing a context specific integrated care model that is feasible, affordable, and effective in the specific LMIC.

The research priorities should be adapted to comprehensively understand the role of HIV in causing or exacerbating a wide range of diseases and the clinical manifestations of these diseases. Clinicians caring for patients with HIV will likely require new tools for optimal detection to prevent and to monitor for early signs of developing NCDs. The long-term goals for the FOA are to support locally relevant and catalytic research at LMIC Institutions in critical areas of HIV-associated NCDs to enhance research capacity building efforts at the LMIC institutions, and to build a network of researchers both within and across LMICs to collaborate and complement unique resources and strengths to build the scientific workforce locally.

For the purposes of this FOA:

• NCD is defined as a chronic condition that may or may not have emerged from an infectious pathogen, but the chronic condition is not dependent on the presence of an active infection and hence is not communicable .
• HIV-associated NCD refers to an NCD whose emergence, severity and/or pathogenic course is influenced by HIV infection and/or anti-HIV drugs.
• HIV-associated NCD can also include a disease, disorder or condition affecting a person exposed to high risk environments who remains uninfected by HIV. An example of such a situation is the effects of stigma and associated mental health and depression suffered by Exposed/Uninfected individuals.
• Where needed, it may be required to disentangle the effects of HIV infection on NCD incidence from the confounding disease. Therefore, comparison studies with demographically and behaviorally similar uninfected individuals will be needed.

Objectives:

The objective of this FOA is to enhance understanding of the complex mechanisms leading to an increased susceptibility to NCDs, drug-induced metabolic disorders leading to a higher risk for developing NCDs, and an accelerated aging process in PLWH that may lead to better design of future interventions aimed at decreasing the effects of such co-morbidities. In vitro studies and use of applicable animal models are allowed; however, the relevance of these studies to human disease should be clear. The areas of focus under each topic area may include but are not limited to:

• Basic sciences:
  • Address etiopathogenesis of NCDs in PLWH
  • Conduct mechanistic studies to understand the cause for the accelerated disease in PLWH
  • Investigate the biological, physiological, biochemical and metabolic processes that are affected by HIV infection resulting in the exaggerated pathology
• Aging process in PLWH:
  • Investigate causes for early onset of NCDs in the stable PLWH population on antiretroviral therapy (ART) in relation to the time of HIV diagnosis and starting on ART
  • Understand the mechanisms of immune aging that may be helpful in designing appropriate interventions to stem the aging process initiated by HIV
• Diagnostics:
  • Develop better tools for early diagnosis of NCDs in PLWH
  • Identify early markers of NCDs in PLWH who start on ART post diagnosis
• Therapeutic interventions:
  • Explore optimal drug regimens and drug-drug interaction (DDI) which complicate therapy decisions in PLWH with NCDs
  • Explore the role of drug-drug interactions resulting in ineffective treatment outcomes and developing alternate drug regimens,
  • Explore the role of nutritional imbalance and nutritional supplementation in therapeutic uptake and health outcomes of PLWH with NCDs
• Behavioral studies:
  • Examine long-term options for better quality of life in PLWH with NCDs, including decreasing the effects of stigma, mental health and neurocognitive disorders
• Clinical studies:
  • Develop approaches for better patient centered care and care outcomes
  • Conduct implementation research for more integrated care management of HIV and HIV-associated NCD
  • Develop research-based evidence needed for integrating HIV and HIV-associated NCD care for future decisions on health care delivery and policy

In keeping with the suggested research topics above, the following lists some specific focus areas of interest to the partner ICs in HIV-associated NCDs.

• NIAMS is interested in observational, translational, and basic/pre-clinical research focusing on how the presence or treatment of HIV/AIDS impacts systemic rheumatic, musculoskeletal and skin disease progression and pathogenesis with a focus on utilization of existing HIV cohorts and repositories.

• NIDCR is interested in research that addresses gaps in our knowledge of the combined effects of HIV, antiretroviral therapy (ART), and NCDs on oral health, and identification of approaches for prevention and treatment of oral diseases and assessment of treatment outcomes in PLWH with NCDs
• NIDDK is interested in basic, translational, clinical, and epidemiologic research on AIDS-related noncommunicable comorbidities within its mission. These include loss of gastrointestinal immune and microbial homeostasis, enteropathy and gastrointestinal diseases; liver diseases; kidney, urologic, and hematologic diseases; and metabolic perturbations, obesity, diabetes and associated complications

Through this initiative FIC seeks to support exploratory research on the interplay between HIV and development of NCDs in PLWH and uncovering to what extent HIV infection influences the pathogenic effects of comorbid conditions. Applicants will also be expected to address the needs of collaborating LMIC institutions to develop capacity for carrying out research in this field. The FOA is intended to foster partnerships between HIV and NCD researchers to develop interdisciplinary collaborations that may also include policy makers, health economists, and health systems experts. Research teams should contain an appropriate mix of the relevant disciplines to accomplish the proposed studies. It is expected that this small research grant mechanism will initiate new ideas and determine feasibility of studies of novel approaches to understand and reduce the long-term suffering from the comorbid disorders.

Proposed studies must be consistent with the NIH Office of AIDS Research high and medium priorities for HIV research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-137.html).

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

Other

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

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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. 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.

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.

Non-U.S. based HIC investigators are not eligible as PD/PIs but may be included as consultants, especially if they present special opportunities for furthering research programs, with unusual talent or provide resources relevant to the proposed project that either are not readily available in the eligible LMIC or the U.S. institution or which augment existing resources.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

Letter of Intent

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:

Geetha P. Bansal, Ph.D.

Fogarty International Center

Telephone: 301-496-1492

Email: [email protected]

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

This FOA provides an avenue for investigators in the LMICs and in the U.S. with interests in studying the intersection of HIV/AIDS with chronic NCDs to establish research collaborations and research capacity strengthening activities at the LMIC institution. It is expected that collaborating investigators will provide complementary expertise in proposing studies to investigate HIV-associated NCDs.

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

Applicant should budget funds for at least one PD/PI or designated co-Investigator to attend the annual program network meeting per year in Bethesda, MD.

The R21 grant will provide support to assess needs, to initiate preliminary studies and strengthen research capabilities at the LMIC institution, and to organize, plan, prepare, and assemble or solidify partnerships, additional expertise, information and data as needed for an application for a more comprehensive research grant (e.g. a R01). The application should define an exploratory research project and associated plan for assessing, developing and strengthening research capabilities .

Research Strategy:

Justify the relevance of the proposed research to the HIV-related health outcomes of people in the LMIC setting.

Collaboration:

The purpose of this grant is to foster initial development of collaborative work focused on HIV-associated N?C?D?s relevant to LMICs; accordingly, investigators are not required to demonstrate in the application any history of prior collaboration. However, those factors in the investigators' background and/or institutional circumstances that will facilitate success in such collaboration, beyond the information stated on individual biosketches, should be clearly delineated. The role of each key personnel and institution and the plans for the coordination of the research activities should be noted.

In the case of a collaboration between researchers in an LMIC and a U.S.-based institution, the application should include plans for coordination of research (and activities to strengthen LMIC research capabilities) between the partner institutions, which should be described and should include regular meetings (virtual and/or physical). Collaborations between two or more LMIC investigators must describe plans to expand the network and build research capacity in their proposed research area.

Networking

All applicants are encouraged to become familiar with other relevant research and research training being conducted at the LMIC institution, and more widely within the country and region as feasible. Applicants may discuss the potential to take advantage of synergies for networking and collaboration for research and for activities to strengthen research capabilities.

Such activities may include but are not limited to:

- leveraging NIH or other funder investments already in place in specific foreign countries,

- using common measures/data elements across research studies in a country/region,

- sharing or pooling data or creating data repositories,

- making efficient use of local/regional oversight bodies such as IRBs, DSMBs

- sharing education platforms to develop expertise across programs.

Capacity Building

Applicants should show evidence of institutional support for capacity building in this area. Such support may take many forms, such as by encouraging networking seminars and symposia, by facilitating communications and partnership with other Institutional leaders to consider joint funding opportunities, and other similar avenues.

Letters of Support: Letters of support should be provided by each collaborator and collaborating institution.

The following modifications also apply:

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

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.

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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.

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Section V. Application Review Information

1. Criteria

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 R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Significance

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?

In addition, for applications involving 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?

Investigator(s)

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 for this FOA: Is there an appropriate mix of HIV and NCD researchers whose combined expertise will provide an integrated approach to working on the proposed project?

In addition, for applications involving 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?

Innovation

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?

In addition, for applications involving 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?

Approach

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?

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?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable

Study Design

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?

Environment

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 for this FOA: Is there evidence of Institutional support to PI(s) to build research capacity in HIV-associated NCDs?

In addition, for applications involving clinical trials:

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?

Study Timeline

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)?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Applications from Foreign Organizations

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 also assess the potential for research capacity building at the PI Institution by considering the extent of Institutional involvement in supporting HIV-associated NCD activities

Select Agent Research

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).

Resource Sharing Plans

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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review , 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.

• 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.

• 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.
• Geographical balance of projects.
• ?Programmatic balance i?n scientific topics.

3. Anticipated Announcement and Award Dates

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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 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).

2. Administrative and National Policy Requirements

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.

3. Reporting

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.

Section VII. Agency Contacts

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Geetha P. Bansal, Ph.D.
Fogarty International Center (FIC)
Telephone: 301-496-1492
Email: [email protected]

Heiyoung Park, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: ?301-594-5032
Email: ?[email protected]

Peter Perrin, Ph.D.?
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-3759
Email: ?[email protected]

Anais Stenson, Ph.D.
National Institute of Mental Health (NIMH)
Email: [email protected]

Geraldina Dominguez, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-781-3420
Email: [email protected]

Mark Rubert, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-806-6596
Email: [email protected]

Jane Blom
Fogarty International Center (FIC)
Telephone: 301-496-5710
Email: [email protected]

Timothy Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-7760
Email: [email protected]

Jeni A Smits
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-4020
Email: ?[email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information