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

Background

NIH established the International epidemiology Databases to Evaluate AIDS (IeDEA) program in 2006 to promote robust clinical epidemiology of ARV effectiveness and use through consolidation of clinic and patient data in seven regions: North America and Canada, South/Central America and the Caribbean, Asia Pacific, Southern Africa, West Africa, East Africa and Central Africa. The program supports epidemiologists, clinicians, data management specialists, bioinformaticians and statisticians to conduct research based on data from cohort studies, clinical trial networks, public and private clinics and hospitals, and private care providers. The regional data centers consolidate, curate and analyze these data to evaluate the delivery of care and clinical outcomes of people living with HIV/AIDS.

The initial awards (2006-2010), focused on building the data centers and beginning to work as a consortium, collecting consolidating and analyzing the data. As the databases became more established, IeDEA investigators in each regional data center worked to ensure the data were representative of the regions in which they were collected including expansion of the pediatric databases. The large databases from IeDEA have allowed for the development of novel statistical methods to describe and account for bias, which are key to maximizing the information that can be obtained from health data.

In the two succeeding award periods IeDEA bioinformaticians advanced IeDEA data harmonization and built the IeDEA data standard in collaboration with the European HIV Cohorts Data Exchange Protocol (HICDEP) and Harmonist to develop web-based tools for secure data exchange, data quality checking, and scientific project and portfolio management.

IeDEA has also concentrated on strengthening the quality of data in the regions. During these funding cycles, IeDEA also collaborated with global HIV care implementers and normative bodies to inform the implementation of HIV care globally. Currently the IeDEA databases include 1.7 million adults and children from 46 countries

Geographic Regions represented by Regional Data Centers include:

• North America, including Canada and the United States of America
• Central America, South America, Mexico and the Caribbean
• Australia, India, Pakistan, China and the rest of Asia
• West Africa Benin, Burkina Faso, Cape Verde, Chad, Cote d Ivoire, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, Togo
• Central Africa Burundi, Cameroon, Central African Republic, Congo, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Rwanda, Sao Tome & Principe
• East Africa Djibouti, Eritrea, Ethiopia, Kenya, Uganda, Somalia, Sudan, Seychelles, Tanzania
• Southern Africa Angola, Botswana, Comoros, Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, South Africa, Eswatini (formerly Swaziland), Zambia, Zimbabwe

IeDEA provides training and support to clinical/research staff in data management, data analysis, and statistical methods, as well as increased analytical capacity for the large datasets assembled within currently funded regions. By focusing on data and informatics infrastructure at the patient level, the regions have been able to collect high-quality data from participating clinics. This allows the regions to foster regionally relevant research by giving local investigators access to the data from their own clinics. Improved patient level data also leads to a higher level of care and a higher commitment to quality data.

In 2019, IeDEA initiated the Sentinel Research Networks (SRN) which is a prospective cohort of patients in each region. Changes in the management of HIV are resulting in decentralization of HIV care such that data consistency is at risk. Furthermore, the increased importance of non-communicable disease highlights gaps in data on these important co-morbidities. The SRN was developed to specifically strengthen HIV and non-infectious disease outcome data.

The response to the HIV epidemic continues to evolve. While the IeDEA program is expected to maintain its focus on HIV/AIDS and co-morbidities, NIH encourages opportunities to increase the impact of research resources by allowing investigators to leverage the IeDEA infrastructure to answer key questions of interest to the co-funding Institutes and Centers of importance in their community. It is recognized that leveraging the IeDEA infrastructure to study other diseases will necessitate the inclusion of populations at risk for these diseases. NIH is eager to support research across the HIV cascade, and this solicitation also encourages the enrollment of patients at all stages of HIV disease and of all ages.

The established Regional Data Centers also offer a unique opportunity to expand to include tuberculosis disease. Tuberculosis patients are anticipated to be frequently HIV co-infected but research on TB patients without HIV co-infection is also permitted.

Research Scope

The IeDEA Consortium, comprised of seven regional awards, strives to study the HIV epidemic globally, including both a vibrant and relevant epidemiologic research agenda in each region and globally. Toward these goals the consortium activities facilitate the accessibility and standardization of key variables, development of tools and methods for analysis and access to a global system of HIV and related clinical data.

Each regional award is expected to address the unique needs and opportunities provided by the HIV epidemic in their regions as well as the data sources available to them. Each regional award is also expected to be an integral contributor to the overarching goals of the consortium. This requires a level of commitment, communication and integration beyond that expected in traditional individual research grant awards.

Clinically this research agenda includes understanding the clinical course of HIV, late stage complications, the interaction of HIV and aging, the syndemics of non-communicable diseases (NCDs), cancer other infectious disease and HIV, substance use research and mental health studies. IeDEA is also able to support modeling research and comparative effectiveness studies of the global HIV response. Research that evaluates the efforts to end the HIV epidemic are important parts of the IeDEA agenda. In that vein, IeDEA is expected to work with public health implementers at the clinic, national and global levels to ensure that the research is valuable for guiding their efforts. IeDEA is increasingly asked to address questions of importance to PEPFAR, the World Health Organization (WHO), the Institute of Medicine, in-country organizations and other information consumers. IeDEA’s ability to interface with these information consumers is a key measure of its future success. IeDEA is also committed to expanding research capacity in their regions and supports training at multiple levels.

IeDEA’s success depends on work to strengthen linkages, data collection, completeness, and depth of data. Individual level patient data is vital for high quality care and for evaluation of the care delivery. IeDEA research should highlight the importance of quality data and work to enhance data at multiple levels.

Research topics may include, but are not limited to:

• Epidemiology studies to inform care delivery and resource management for HIV, TB, and the manifestations of viral hepatitis, cancer and other diseases in the context of HIV infection (HTHC&O).
• Development of novel approaches to improve data curation and analysis to reveal the current state of the HIV epidemic and the global health response.
• Novel epidemiology and statistical approaches to include data from non-clinic care settings, population surveys, surveillance data, or registry data to inform on patient status and program success as well as social determinants such as stigma, poverty, violence on a community/regional basis.
• Novel biostatistical methods and models for the analyses of large databases
• Epidemiology, including incidence, prevalence and predictors of adverse events
• Studies to monitor the durability of drug regimens and emergence of ARV resistance
• Comparative effectiveness and cost effectiveness research on HTHC&O including:
• Assessments of barriers and enhancements to care
• Evaluations of outcomes regionally and with respect to changes in care delivery programs as a result of changes in program funding, policies, or guidelines.
• Studies on cost-effectiveness of different diagnostics and treatments regionally
• Observational comparative effectiveness research on HTHC&O including comparisons of different therapy regimens or different care settings and approaches
• Research utilizing a life course approach that describes the impact of syndemics on a patient's success in achieving health. This work should focus on finding individual and structural approaches to improve health outcomes including loss to care and failure to link to services including comparisons of methods to improve retention across life transitions such as adolescence to adulthood, prevention of maternal-child transmission to adult care
• Epidemiology of behaviors that impact health outcomes such as tobacco use, alcohol use, illicit drugs, complementary and alternative medicines, stress and physical activity
• Studies that describe HIV prevention efforts and the global roll out of Pre-exposure prophylaxis (PrEP).
• Studies that inform reducing HIV transmission through treatment (prevention in Positives and U=U) including:
• linkages from testing to care to treatment
• time to virologic suppression, and durability of suppression
• antiretroviral adherence

IeDEA regions are expected to continue the SRN research to improve gaps in data and data quality to more effectively address questions in HIV/AIDS care. The SRNs are equally focused on the epidemiology of non-communicable diseases in HIV populations as well as risk behaviors and co-morbidities impacting health outcomes. Reflecting the co-funding Institutes and Centers' research agendas, IeDEA Regional Data Centers may include SRNs to address research on diabetes, hypertension and other cardiovascular disease (CVD), hepatitis, alcohol and substance use, and lung health in the context of HIV. Examples include but are not limited to:

• Enhancement of adverse event data
• Assessment of co-infections such as hepatitis
• Access to medical record information on TB or cancer events and their treatment.
• Data to measure the impact of diabetes, cardiovascular disease, and depression in patients and to understand the impact of these co-morbidities on quality of life and HIV viral suppression.

NIAID seeks to expand the established IeDEA program to understand the epidemiology of tuberculosis infection including research on TB progression and outcomes in persons globally. To accomplish this, NIAID encourages the inclusion of cohorts of patients seen at tuberculosis facilities with or without HIV co-infection. In keeping with the structure of IeDEA, TB data is intended to serve as a platform for other research in basic science or trials. Specimen collection is not expected, and clinical trials are not allowed. Data eligible for inclusion in this cohort includes:

• Persons receiving treatment for primary TB
• Persons receiving re-treatment for TB because of poor adherence, or poor susceptibility to the original therapy.
• Persons on Isoniazid Preventive Therapy (IPT) due to HIV infection
• Persons exposed to TB

The IeDEA TB research plan is encouraged to include collaboration with TB-RePORT sites currently funded by NIAID bilateral programs (https://www.reportinternational.org/about). Regions are encouraged to include additional sites, or other sources of TB data of importance to the IeDEA region.

NCI Specific Objectives:

NCI seeks to continue support for projects that incorporate understanding of the impact of HIV on incidence, prevalence, spectrum of cancers and survival in the regions supported by IeDEA. Building on IeDEA collection of information on cancer as a co-morbidity in HIV patients, NCI supports research in the following areas

• epidemiologic assessment of the risk for cancer based on developing rigorously linked data sources that track patient-level information with cancer outcomes
• patient-level risk factors
• HIV-related risk factors
• epidemiologic assessment of cancer based on linkages with cancer registries and other sources of data (such as insurance databases and electronic medical records)
• epidemiology of co-infections with potentially oncogenic viruses
• evaluations of oncology care received by cancer patients, including implementation science, comparative effectiveness and cost-effectiveness research
• regional epidemiology of clinical outcomes in cancer patients including:
• comparison of cancer outcomes in HIV positive and negative patients
• assessment of gaps in care that negatively impact cancer patients
• impact of cancer screening and care on survivorship

To maximize the benefits of the investment, NCI also encourages infrastructure development at the local level including:

• support for developing tools for better cancer data collection
• dissemination of cancer data
• dissemination of instruments for data collection
• development of upgraded cancer diagnosis
• development of strategies to facilitate access to tissue resources for in-depth analysis of biological underpinnings of cancer in HIV-infected individuals globally

NICHD Specific Objectives:

NICHD seeks to continue support for the collection of data on HIV infection in pregnant women and infants, children, and adolescents. While the North American IeDEA region does not support a pediatric cohort, coordination with the existing NIH NICHD pediatric database program funded by NIH in North America is encouraged. Research applications may include, but are not limited to, the following areas:

• Research on epidemiology of pediatric HIV infection, including:
• pediatric diagnostic approaches and strategies
• extent and type of treatments of HIV-infected children
• pediatric response to therapy
• changes in the natural history of HIV pediatric infection
• associated co-infections and co-morbidities of HIV and their treatment in children
• effect of co-morbidities (i.e., malnutrition, malaria, TB, neurocognitive dysfunction) on HIV pediatric disease and treatment outcomes
• pediatric transition to the adult healthcare setting
• implementation science research on barriers to pediatric and adolescent diagnosis and care
• implementation science research on barriers to and models of successful transition from pediatric to adult HIV care
• implementation science research on barriers to prevention and elimination of mother-to-child transmission (PMTCT) and early infant diagnosis
• adolescent and young adult cohorts in IeDEA SRNs

Additionally, linkage of maternal and pediatric data is critical to assess the efficacy of interventions to eliminate mother-to-child transmission (MTCT) and to evaluate the short- and long-term effects of prevention interventions on both maternal and child health. NICHD is interested in supporting research in the following areas:

• studies on pregnant women with HIV
• pregnancy outcomes (including infant infection status)
• effects of long-term therapy on maternal health and subsequent pregnancy
• studies on HIV-exposed but uninfected children
• evaluation of short- and long-term consequences of in-utero and neonatal exposure to ARVs

NIMH Specific Objectives:

NIMH seeks to continue to support IeDEA for projects that will incorporate methods to increase understanding of the impact of HIV on incidence, prevalence, and spectrum of mental health and neurobehavioral disabilities in regions covered by IeDEA. Impaired mental health and neurobehavioral dysfunction occur as significant co-morbidities in HIV patients. It is recognized that data on mental health and neurobehavioral functioning is lacking, and that IeDEA will need to develop novel methods to collect and capture relevant data. NIMH seeks to support projects in mental health such as, but not limited to, the following areas:

• Epidemiologic assessment of the risk for mental health and neurobehavioral dysfunction at the individual patient and regional level accounting for:
• patient level risk factors
• regional and environmental level risk factors including social determinants such as stigma, violence, poverty and disease-related risk factors
• Epidemiologic assessment of mental health and neurobehavioral dysfunction based on linkages with other sources of data (such as insurance databases)
• Assessment of the continuum of care both for HIV and mental health and their interrelation
• Harmonization of valid and reliable instruments and measures used to assess and report mental health and neurodevelopmental function across regions
• Evaluation of mental health and neurobehavioral care received by patients identified with disabilities in these domains, including determinations of capacity uptake and response to therapy
• Evaluation of the effect of other co-morbidities (i.e., malnutrition, malaria, TB, substance use) on mental health and neurobehavioral dysfunction and care in the context of HIV infection.
• Regional epidemiology of clinical outcomes in patients with mental health and neurobehavioral disabilities
• Comparison of mental health and neurobehavioral outcomes in HIV positive and negative patients
• Assessment of gaps in mental health care that negatively impact HIV and mental health outcomes in patients
• In addition, NIMH also encourages the development at the local level of valid and reliable evaluation methods to assess mental health and neurobehavioral functioning.

NIDA Specific Objectives:

NIDA seeks to support research to increase the understanding of the influence of substance use (SU) on HIV incidence, prevalence, and treatment outcomes in order to better incorporate substance use services into clinical care settings and programs. NIDA has particular interest in African regions that are experiencing rapid increases in injection and non-injection illicit drug use and are generally under-resourced for SU services. NIDA also has interest in regions of Asia where stimulant use continues to be a significant driver of sexual risk and opiate injection persists as a source of HIV transmission.

NIDA seeks to support projects in substance use research including, but not limited to, the following areas:

• Development of outreach models, assessment methods, and ways to use existing data resources to improve SU-related data capture, with the goal of enhancing strategies in integrated HIV-SU care approaches.
• Epidemiologic assessment of SU effects on HIV acquisition, transmission and treatment outcomes at individual and population levels, including consideration of local and regional indicators of SU and other efforts to model individual and ecological contributions.
• Assessment of SU effects (including effects of time-varying changes in patterns of SU) on longitudinal HIV clinical outcomes, including retention in care, viral suppression, and co-occurring conditions such as viral hepatitis.
• Assessment of the effectiveness of SU treatment and integrated treatment HIV-SU venues as strategies for treatment as prevention.
• Evaluation of the impact of utilizing substance use treatment or harm reduction approaches on HIV prevalence and the spectrum of HIV treatment outcomes.
• Evaluation of novel methods to characterize SU-related behavior and use of SU services (e.g., medication-assisted treatment, syringe services) over time at both individual and system levels
• Characterization of SU among other key populations (men who have sex with men (MSM), transgender (TG) persons, etc.) and other HIV-affected populations.
• Studies that consider SU and SU trajectories in the context of HIV-related reproductive health and clinical conditions co-occurring with HIV (e.g., STIs, viral hepatitis).
• Studies that facilitate discovery of emerging SU epidemics (e.g., dissemination of synthetic opioids such as fentanyl) that may be implicated in changes in HIV acquisition, transmission, and management.
• Implementation science and cost effectiveness research related to reducing SU care barriers or enhancements and changes in care delivery as they relate to SU and HIV.

In addition, NIDA encourages the local and regional development of valid and reliable methods for capturing SU data in a timely, inexpensive manner to build HIV/SU sentinel surveillance systems. NIDA also encourages methodologic development and the use of innovative methods to capture the variable course of SU over time, such as latent class analysis, time-varying effect models, and new algorithms for mediation and moderation in longitudinal samples, along with the use of novel small sample statistics that enable investigation of effects in small, but epidemiologically important subpopulations of substance users (e.g., MSM, young injectors, adolescents who are poly-substance users).

NHLBI Specific Objectives:

NHLBI seeks to support an increased understanding of the prevention and management of HIV-associated comorbidities, coinfections and complications in heart, lung, and blood disease areas. Specific areas of interest may include biomarkers for HIV-associated comorbidities in heart, lung and blood, such as heart failure, ischemic heart disease, atherosclerosis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and anemia.

As sudden cardiac death has been found to account for a majority of cardiac and non-AIDS related deaths in HIV-infected patients, with a higher prevalence of cardiomyopathies and heart failure among those deaths, this is of particular interest to NHLBI. NHLBI recognizes that this area of research is more complicated in that interventions have to be more targeted, particularly for ischemic heart disease, chronic obstructive pulmonary disease and obstructive sleep apnea. Therefore, research applications may also include implementation science research addressing impediments to uptake, scale-up, and sustainability of evidence-based interventions in various contexts.

NHLBI encourages tracking of all forms of smoking, inclusion of measures such as ambulatory oximetry, and assessment of sleep and circadian variables.

In continuing existing work of the SRNs, NHLBI is interested in the prevalence of HIV-associated cardiovascular and pulmonary comorbidities and relevant risk factors in participants from both urban and rural clinic sites.

NIDDK Specific Objectives:

NIDDK seeks to support epidemiologic and syndemic research associated with HIV-related coinfections, comorbidities, and complications (CCCs) within NIDDK Research Areas. Systemic complications of HIV infection directly affect many of the organ systems and physiologic or metabolic processes of interest to the NIDDK. These include enteropathy and loss of gastrointestinal homeostasis; liver diseases and viral hepatitis coinfections; kidney, urologic, and hematologic diseases; and the recently emerging non-communicable burden of obesity, diabetes, and associated metabolic complications. NIDDK seeks to support projects within NIDDK Research Areas including, but not limited to, the following:

• Detection of emerging comorbidities, coinfections, and complications for the benefit of data consumers as well as for interrogation of the underlying causes contributing to their increased incidence.
• Identification of biological pathways contributing to CCCs to inform further translational research.
• Elucidation of the pathways through which societal factors, the built environment, and stigmas contribute to CCCs.
• Capture of health care utilization, including medications, procedures, and vaccines for diseases and conditions.

FIC Specific Objectives:

The Fogarty International Center (FIC) supports basic, clinical and applied research and training for U.S. and foreign investigators working in the Low- and Middle-Income Countries (LMICs). Coordination with international programs funded by the Fogarty International Center (FIC) is highly encouraged. FIC will support collaborative, multi-institutional linkages with international sites where Fogarty HIV Research Training Programs are active. Towards this objective Fogarty seeks to support the Fogarty IeDEA Mentorship Program (F-IMP) as it continues to expand training and mentorship opportunities across the LMIC regions.

Research Collaboration

Essential to the success of the overall program is the strong collaboration, cooperation and communication between and among the Regional Data Centers to achieve program-wide objectives while supporting regional efforts. This collaboration relies on a robust administrative structure and shared vision for the collaboration. It is expected that regions will apportion the different shared responsibilities across the network. Regional applications are expected to participate in IeDEA through:

• Participation in the Executive Committee and working groups at the global and regional levels.
• Supporting the administrative tools used to manage the network
• Contributing to the internal and external portions of the IeDEA website.
• Promptly supplying publications information to the consortium
• Providing information on regional findings and other news for the IeDEA newsletter.
• Submitting and reviewing research concepts to ensure scientific feasibility, rigor, and appropriateness in the regional and global context.
• Adherence to all IeDEA EC standard operating procedures and practices.
• Contribution to and adherence with the IeDEA DES for global research.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

This limited competition is open to the following organizations/institutions only:

Only renewal applications from the current IeDEA Regional Data Centers may be submitted in response to this FOA:

Foundation for AIDS Research (New York, NY) Asia Pacific region
Indiana University (Indianapolis, IN) East Africa region
Johns Hopkins University (Baltimore, MD) North America region
ADERA (France) West Africa region
Vanderbilt University (Nashville, TN) Central, South America and Caribbean region
University of Bern (Switzerland) Southern Africa region
Albert Einstein College of Medicine (New York, NY) Central Africa region

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) 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.

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:

Bruce Sundstrom, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5045
Email: sundstromj@niaid.nih.gov

, with the following exceptions or additional requirements:

For this specific FOA, the Research Strategy section is limited to 30 pages.

Within the biosketch, applicants should describe the unique capabilities of the proposed investigators and staff by including:

• record of collaborations, especially in HIV/AIDS epidemiology studies, within the past five years
• strengths of the proposed staff in:
• biostatistics, particularly in the analysis of longitudinal data and the development of innovative statistical methods
• bioinformatics, data management, data analysis, and project management and relevant experience in performing these functions in collaborative researc
• the contributions of the proposed regional data center team in preparing manuscripts from previous research collaborations

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

with the following additional instructions:

Within the budget section, applicants should develop budgets to reflect activities being managed by the Regional Data Center for the overall program. and within the budget justification, articulate how those activities will address regional coordination needs specific to the IeDEA program shared.

Research Strategy:

Applicants should discuss how the proposed research is innovative and will lead to new findings in HIV/AIDS; other infectious diseases, non-communicable diseases, mental health and/or cancer. Applicants should describe capabilities and commitment to collaborate in multi-center biostatistical and epidemiological research. Multi-regional analyses may be proposed.

Epidemiology research: Applicants should describe the epidemiological, statistical and administrative methods used to produce innovative and significant research. Describe the populations and sources of data included in their region, its generalizability to the epidemic in the region and its appropriateness for the proposed research agenda. Describe completeness, quality and broad research potential of the data, as well as how the data may be used to advance novel research approaches. A summary of the data may be provided, including but not limited to, number of patients, variables, frequency of data collected and strategies for describing patient transfers, retention, survival/death. Where appropriate, applicants should describe how IeDEA data can be combined with other data sources to build more robust understanding of patient outcomes, e.g., patient registries, DHS surveys, PHIA and other PEPFAR data, census data and prospectively collected data as well as modeling exercises that derive parameters from IeDEA databases.

The epidemiologic methods and administrative oversight necessary for this collaborative study should include descriptions of the types of data available, methods used to merge, harmonize, share, explore and validate the database, and how the regional data center proposes to enhance data to answer significant questions.

Specific Institute Interests: Each application must provide a specific description of their proposed research to the priority areas for each of the participating institutes.

Sentinel Research Network: Each LMIC Regional Data Center application region should describe how the SRN is conducted in their region, including how sites and patients are chosen. Further, applicants should show how they will use SRN data to bring generalizable knowledge about HIV outcomes in their region. The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) is invited to show how more intensive data available from some sites is used to develop similarly generalizable results for the North American research.

Epidemiology of TB: Each LMIC Regional Data Center application should describe how they plan to pursue clinical epidemiology research of TB. IeDEA regions should describe the sites that will be included in their IeDEA-TB program and the cohort enrollment approach. Existing Tuberculosis Regional Prospective Observation Research for Tuberculosis (TB-RePORT) clinics are encouraged to participate in the IeDEA collaboration. Collaborations between the two programs are encouraged to advance the epidemiology agenda of IeDEA and the clinical trial and basic science agenda of TB-RePORT.

IeDEA data exchange standard: Describe how the region will support continued development of the IeDEA data exchange standard (IeDEADES.org) and its usability through collaboration with the Harmonist project. Regions are encouraged to create tools to visualize the data for non-research audiences and improve access to clinic level data by clinical staff to accelerate availability of these data to inform the public health response. Applicants should describe how core data elements are chosen and the process by which the standardized definitions for clinical outcomes and events are derived.

Training and capacity building: Recognizing the importance of the site level cadre of researchers, applications should describe how the proposed projects strengthen existing structures and capacity. Applicants from LMIC regions should describe how training is accomplished under the Fogarty IeDEA Mentoring Program (F-IMP). Descriptions of how applicants are chosen, how they are mentored, and metrics to evaluate the success of the mentoring program should be included.

Management Structure: Discuss the management structure of the individual regional datacenters as well as the IeDEA Program overall network.

Communication and collaborations: Describe how the region will coordinate and communicate between and among the IeDEA Regional Data Centers. Describe how the region will participate in the regional and global working groups and attend face-to-face meetings. Regionally supported mechanisms to facilitate interregional activities are expected. The regional centers should describe how they will address the global network responsibilities for cross regional activities. These responsibilities include at least the public- and internal-facing website, administrative management of the global network internal and external collaborations, conference calls, publications, and management of IeDEA -wide program meetings.

Describe how the region will adhere to the IeDEA process for submission, review and approval of research proposals submitted by IeDEA Regional Data Center investigators and outside investigators. Describe the mechanisms for regional stakeholders to review questions to ensure the research agendas remain responsive to regional needs.

If subcontracts are proposed, applicants should describe the activities to be subcontracted, the method and level of integration between the regional data center and the proposed subcontractor(s), and the expected advantages of such an approach.

Letters of Support

The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).

Applicants are encouraged to include letters of support from sites to highlight their capacity to be a strong contributor to the region’s research agenda. Letters of support may describe commitments from sources of regional data indicating willingness to provide data and an agreement that the data can be used in aggregate for regional, multiregional and IeDEA program-wide analyses. Collaborators may provide details regarding the individual country's policies on sharing data, human subjects protection, privacy and confidentiality, but applicants are required to follow all NIH Data Sharing policies and human subjects protection requirements. Sources of data for regional databases may come from hospitals, clinics, national surveillance programs, and clinical trials or cohorts. The completeness, quality and broad research potential of the data may be described, as well as how the data may be used to answer questions not available from the data currently in the region. A description of the data may be provided, including but not limited to, number of patients, variables, frequency of data collected and strategies for patient retention. In addition, a description of the data facility may be included (availability of space, computer equipment, etc.)

Letters documenting institutional commitment to the project may be included addressing support of infrastructure, subcontracting, establishment of agreements for data usage, etc. Letters of support must be provided in English or accompanied by English translation.

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive 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.

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?

Specific to this FOA:

Is the proposed research likely to make significant contributions to important global issues related to HIV, TB, viral hepatitis, cancer NCDs, and other infectious diseases (HTHC&O) epidemics among adults and children?

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 to this FOA:

Are the PDs/PIs' training and experience to perform the data management, data analyses, study design and coordinating roles that are central to the functioning of the Regional Data Center appropriate and strong? Are the skills, training, experience and level of effort of key personnel sufficient?

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?

Specific to this FOA:

Are novel approaches to data aggregation proposed, such as use of registries or other non-clinic-based sources of data, which will enhance the quality and breadth of data available to the Program? Does the application demonstrate innovative approaches to maximize communication across data centers for multiple regions?

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?

Specific to this FOA:

Does the research demonstrate a solid approach to data management, integration and harmonization from different sources? Does the analysis approach have a strong likelihood of producing valid answers to questions proposed? Does the analysis plan present the strengths and weaknesses of the proposed research approach and suggest alternative analysis techniques to address the weaknesses?

Are the data to be made available representative of the regional population and of sufficient quality and quantity to fulfill the research aims? Does the application describe how enhanced data collection, i.e. sentinel cohorts, would be performed? Do any enhanced data collection or approaches to accelerate data availability add significantly to the aims of the application?

Is the plan for the review and approval of research proposals from within and without the IeDEA program appropriate? Are there mechanisms by which regional stakeholders can pose questions to ensure the research remains responsive to regional needs? Is the proposed plan for coordination and communication across the seven IeDEA Regional Centers that constitute the program adequate and appropriate? Does the application demonstrate strength in the capacity to manage the IeDEA site assessment process and commitment to the data harmonization process?

Are the regional collaborations appropriate, feasible and optimal? Is the plan for obtaining sufficient, relevant data to answer a broad range of the questions in HTHC&O research strong? Are the plans for site development and ensuring consistent data collection strong? Do the plans for a region-specific website and the IeDEA Program-wide website support strong communication and collaboration?

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 to this FOA:

Do the letters of support indicate an appropriate level of commitment by collaborators?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories 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

For Renewals, the committee will consider the progress made in the last funding period.

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.

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

• 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.

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that 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.

2. Administrative and National Policy Requirements

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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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. 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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides 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/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• 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.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

Data Management. Each Regional Data Center will be responsible for all data management functions, including the following:

• Prospectively obtaining, editing, merging, and storing data from local collaborators
• Accelerating the access to key data fields to ensure that IeDEA reflects the current status of the HIV epidemic as much as possible
• Participating in IeDEA Program Executive Committee (EC) coordinated site assessments to describe the participating site in the network.
• Providing routine feedback to local collaborators on data quality and completeness, variable selection, and clinical event/outcome definitions
• Conducting training to strengthen and augment data collection and management at sites within the region, where needed
• Ensuring the continued quality of the data management system and protection of PII and its adequacy to the needs of the region and the IeDEA network and establishing a system for regular evaluation of reliability, validity, and completeness of data
• Participating in the development and enhancement of the IeDEA data harmonization standard, including creation of quality assurance code to improve the quality of data.
• In concert with the IeDEA EC, developing the optimal mechanism(s) to ensure that internal and external investigators have access to the data as approved by the IeDEA EC

Data Analysis. The Principal Investigator will provide analytical support to regional investigators in the formulation of research ideas and in writing formal requests to conduct these analyses known as concept sheets , analysis of data, and the preparation of manuscripts. This support will include instances when the Principal Investigator or co-Investigator is the lead author, the Regional Data Center provides full analytic support, or the Regional Data Center ensures access to data for other collaborators. In addition, the awardee will:

• Perform epidemiologic and methodological investigations and develop novel methodological approaches utilizing data from the Regional Data Center and from the IeDEA network.
• Develop analytic code for the IeDEA data standard, to improve visualization of data to show among other things temporal trends to non-research audiences and improve access to clinic level data by clinical staff.
• Provide semi-annual reports at the IeDEA EC meetings
• Make drafts of manuscripts available for review (electronically) to the NIH Project Scientist and other NIH staff at the time they are circulated to co-authors and when the final manuscripts are submitted for publication
• Provide regional data/information to IeDEA EC as requested

Participation in IeDEA Executive Committee (EC). The PD/PI will be a member of the IeDEA EC and as such will:

• Participate in IeDEA EC teleconferences and meetings
• Along with other collaborative key personnel, attend semi-annual IeDEA EC meetings
• Assist in the identification of key variables to collect across IeDEA regions
• Assist in the development of standardized clinical outcomes/events definitions and the IeDEA data harmonization standard
• Assist in the development of the IeDEA network scientific agenda, identifying research questions to be answered and the methods by which those questions can be addressed at the regional, multi-regional or network level
• Determine the common variables of a merged multi-regional dataset to be made available for public use

Publications. The PD/PI will be responsible for the timely presentation and publication of abstracts, manuscripts and reviews authored and/or co-authored by regional investigators and supported in part or in total under this Cooperative Agreement.

The PD/PI and co-investigators are requested to submit draft manuscripts to the NIH Project Scientist prior to submission for publication so that an up-to-date summary of program accomplishments can be maintained and coordinated press releases prepared. Publications require appropriate acknowledgement of NIH support and adherence to EC defined IeDEA network authorship rules

Coordinating activities. In collaboration with each other, grantees are asked to support IeDEA-network meetings, maintain a centralized website, conference calls and participate in coordinating meetings and conference calls on a global level.

The PD/PI Each grantee will be responsible for the oversight and maintenance of an IeDEA Regional Data Center public website and support the IeDEA network website. It is anticipated, but not required, that these websites will have controlled access areas that also serve the communication needs of the IeDEA EC.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

During performance of the award, the NIH Project Scientist, with assistance from other NIH scientific staff (including staff from other participating ICs), may provide appropriate assistance, advice and guidance by: participating in the design of the activities; coordinating or participating in the analysis of data; advising on management and technical performance; or participating in the preparation of publications.

The Project Scientist(s) will serve as a liaison/facilitator between the awardee, and other NIH components and will serve as a resource for scientific and policy information related to the goals of the awardee's research. The role of NIAID and cosponsoring NIH institutes will be to facilitate and not to direct the activities. It is anticipated that that NIH staff will be given the opportunity to offer input into decision processes.

The NIH Project Scientists will also:

• Provide input to decision making
• Monitor study results and quality assurance across all regions to ensure the production of high-quality unbiased results that are comparable across regions
• Ensure and facilitate access to IeDEA datasets for all approved internal and external research collaborators
• Have access to and may periodically review study protocols and data
• May request that data be generated from the Regional Data Center for use in preparing internal reports on IeDEA activities. It is expected that NIH Program Staff will have substantial scientific input and may at times be responsible for the generation of research presentations and publication of IeDEA data, as directed by the IeDEA EC
• Serve as a voting member of the Regional IeDEA ECs
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

IeDEA Network Executive Committee (EC):

The Principal Investigators of the Regional Data Centers and the NIH Project Scientists will serve as members of the IeDEA EC; the agency program official or IC program director will not be a member of the EC. The IeDEA EC chairperson will be elected from among the non-Federal IeDEA EC members and rotate at the discretion of the EC. Each region, and the Chief of Epidemiology, NIAID, have one vote on the EC. In addition to regional meetings, it is anticipated that the IeDEA EC, along with other appropriate key personnel, will meet on a semi-annual basis and that the meetings will be held on a rotating basis, as determined by the IeDEA EC, at the sites of the Regional Data Centers or in conjunction with major international meetings. Awardee members of the IeDEA EC will be required to accept and implement policies approved by the IeDEA EC.

The IeDEA EC will be required to encourage collaboration with investigators external to the IeDEA network. To facilitate this, the IeDEA EC will maintain public communication forums, such as the IeDEA website.

The IeDEA EC is responsible for making recommendations on all scientific, policy and organizational issues concerning development and implementation of both internal and external research concept sheets, publications and access to data. The IeDEA EC also will be responsible for developing and implementing policies and procedures to ensure access to data for exploratory work or manuscript preparation. Requests by internal or external investigators for raw and summary data will be in a standardized format and will be reviewed by the IeDEA EC and evaluated to determine if the research is scientifically aligned with the overall objectives of the IeDEA Network. The individual Principal Investigators will be responsible for ensuring and demonstrating to the IeDEA EC that their Regional Data Center contributes to the overall effort.

Dispute Resolution:

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 agreementsare 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:GrantsInfo@nih.gov(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:support@grants.gov

Lori Zimand, MBA, MPH
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3212
Email: lzimand@niaid.nih.gov

Geraldina Dominguez, PhD
National Cancer Institute (NCI)
Telephone: 240-781-3291
Email: domingug@mail.nih.gov

Richard Jenkins, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1923
Email: jenkinsri@mail.nih.gov

Nahida Chakhtoura, MD MsGH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
Email: nahida.chakhtoura@nih.gov

Pim Brouwers, PhD
National Institute of Mental Health (NIMH)
Telephone: 240-627-3863
Email: pb56u@nih.gov

Aynur Unalp-Arida, MD, MSc, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8879
Email: aynur.unalp-arida@nih.gov

LeShawndra Price, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8166
Email: leshawndra.price@nih.gov

Kendall Bryant, PhD
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0332
Email: kbryant@mail.nih.gov

Laura Pone
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2951
Email laura.pone@niaid.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: pfleming@mail.nih.gov

Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email SiscoR@mail.nih.gov

Ms. Jeni Smits
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-4020
Email: Jeni.Smits@nih.gov

Lynn Rundhaugen
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-4546
Email: lynn.rundhaugen@nih.gov

Judy Fox
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Section VIII. Other Information