Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The expanded availability of antiretroviral (ARV) therapy globally has prompted NIH to develop programs to study ARV effectiveness and use across diverse settings. The differences in setting between where ARV therapies were tested and where they are used are vast, and an approach to evaluate effectiveness and care delivery was needed. The International epidemiology Databases to Evaluate AIDS (IeDEA) was first funded in 2006 to consolidate clinic and patient data in the following 7 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, data management specialists, bioinformaticians and statisticians to conduct research on collected clinical data. Sources of data include cohort studies, clinical trials networks, public and private clinics and hospitals, and private care providers. The regional data centers consolidate, curate and analyze data on care and treatment of HIV to evaluate the outcomes of people living with HIV/AIDS.

During the first award cycle of IeDEA (2006-2010), the regional data centers focused on building consortia, collecting data and ultimately consolidating and analyzing the data. As the databases became more established, IeDEA investigators worked to ensure the data were representative of the regions in which they were collected including expansion of the pediatric databases. Analytical methods to improve statistical inferences and the robustness of findings were advanced. Using these analytical approaches, IeDEA was able to use data from clinics where there were high rates of loss to follow-up and missing data.

In the second award cycle (2011-2015), IeDEA bioinformaticians developed the structure for data harmonization efforts and an IeDEA data standard. This framework was built in collaboration with the European HIV Cohorts Data Exchange Protocol (HICDEP).

IeDEA provides training and support to clinical/research staff in country, as well as increased analytical capacity for the large datasets assembled within currently funded regions. 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.

The IeDEA databases have expanded considerably; from 2009 through 2014 the databases expanded from 353,406 patients to over 1 million adults and children from 46 countries. 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 in-country 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.

Geographic Regions for Regional Data Centers

Applications will be accepted only from the regions defined below and from the institutions listed in the eligibility section.

Region 1 North America including Canada and the United States of America

Region 2 Central and South America and the Caribbean

Region 5 Australia, India, Pakistan and China and the rest of Asia

Region 8 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

Region 9 Central Africa Burundi, Cameroon, Central African Republic, Congo, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Rwanda, Sao Tome & Principe

Region 10 East Africa Djibouti, Eritrea, Ethiopia, Kenya, Uganda, Somalia, Sudan, Seychelles, Tanzania

Region 11 Southern Africa Angola, Botswana, Comoros, Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, South Africa, Swaziland, Zambia, Zimbabwe

Scope of Diseases and Populations

IeDEA is currently focused on HIV outcomes. However, NIH is interested in maximizing the efficiency of research resources by capitalizing on instances where investigators can leverage their existing resources to answer key questions in infectious diseases. IeDEA applicants are expected to retain a focus on HIV/AIDS and its co-infections and co-morbidities but may also demonstrate capacity to leverage the IeDEA infrastructure to include other infectious diseases important in their community.

IeDEA research populations should be primarily persons with HIV infection; however, some research questions may require inclusion of control populations. Furthermore, leveraging of infrastructure to study other related infectious 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 of all ages.

As IeDEA moves towards the third competitive segment, new challenges have emerged. Linkages between care settings and across the life span of a patient remain poor in most regions. Ideally, IeDEA will capture data from testing and throughout the HIV treatment cascade. Strengthening linkages, data collection, completeness, and depth remain goals of the consortium. Changes in support for HIV care under the President s Emergency Plan for AIDS Relief (PEPFAR) program realignment will present new challenges to care and to accurate evaluation of this care. IeDEA will need to be versatile in its approaches as these programs evolve. IeDEA is increasingly asked to address questions of importance to PEPFAR, the World Health Organization (WHO), the Institute of Medicine and other information consumers. IeDEA’s ability to interface with these information consumers is a key measure of its future success.

Research topics may include, but are not limited to:

• Studies that describe the clinical epidemiology of HIV, TB, viral hepatitis, cancer and other infectious diseases (HTHC&O) to inform care delivery, resource management and HIV prevention efforts.
• Development of novel approaches to improve the relevance of results by accelerating the pace of data curation and analysis such that they reflect the current state of the HIV epidemic and the global health response.
• Implementation science and cost effectiveness research on HTHC&O regionally and globally 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 re-alignment of funding.
  • 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
• Epidemiology of rare outcomes in persons with or at risk of HTHC&O
• Research from a life course approach that describes how patients move through the health care treatment cascade with the intent to improve retention along the course and to improve outcomes. This includes work on:
  • loss to care and failure to link to services including comparisons of methods to improve retention
  • retention across life transitions such as adolescence to adulthood, prevention of maternal-child transmission to adult care
• Inclusion of data from outside of HIV-care, such as cancer or non-communicable disease care.
• Epidemiology, including incidence, prevalence and predictors of adverse events
• Studies that inform reducing HIV transmission through treatment including:
  • linkages from testing to care to treatment
  • time to virologic suppression, and durability of suppression
  • antiretroviral adherence
  • monitoring of durability of drug regimens and emergence of resistance
• Epidemiology of behaviors that impact health outcomes such as smoking, alcohol use, illicit drugs, complementary and alternative medicines, stress and physical activity
• Novel biostatistical methods and models for the analyses of large databases

The funding institutes recognize that gaps in data and data quality will require new approaches and additional resources. With this in mind, regional data centers may propose methods to enhance the quality of data within their region. Applicants may choose to support selected sites that, with increased support, could provide enhanced data to address key questions. Activities should be highly focused and limited in scope. Applicants may propose a variety of approaches to enhance data including sentinel cohort sites, one-time data collections, or database registry matches.

Examples include but are not limited to:

• enhancement of adverse event data
• assessment of co-infections such as hepatitis
• improvement of patient follow-up between care sites
• access to other medical record information on TB or cancer events
• evaluation of the effect of antiretroviral drug use during pregnancy on pregnancy outcome (e.g., congenital defects, preterm delivery, and low birth weight)
• long-term effects of antiretroviral drug use on uninfected, HIV-exposed children
• enhancement of data to better clarify loss to follow-up

Data harmonization remains a core element of the IeDEA consortium. Regional centers must demonstrate commitment to the IeDEA standard and demonstrate how they will support and expand the potential of the global data standard.

NCI Specific Objectives:

NCI seeks to continue support for projects that incorporate understanding of the impact of HIV on incidence, prevalence, and spectrum of cancers in the regions covered by IeDEA. Building on initial awards that included core mechanisms for the 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)
• 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 outcomes in HIV positive and negative patients
  • assessment of gaps in care that negatively impact cancer patients

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

• dissemination of cancer data
• dissemination of research tools such as data collection instruments
• development of upgraded cancer diagnosis
• development of tissue resources to facilitate in-depth analysis of biological underpinnings of cancer in HIV-infected individuals globally

NICHD Specific Objectives:

NICHD has co-funded IeDEA since 2006 to include pediatric patients in the database. For this FOA, NICHD is continuing to target pediatric data collection in the 4 African, the Asian, and the South American regional networks. There is already an existing pediatric database program funded by NIH in North America. The purpose of NICHD’s involvement in IeDEA is to continue support for the collection of data on pediatric HIV infection. Research applications may include, but are not limited to, the following areas:

• Research on epidemiology of treated HIV infection, including:
  • extent and type of treatments of HIV-infected children
  • response to therapy
  • changes in the natural history of HIV infection
  • associated co-infections and co-morbidities of HIV and their treatment
  • effect of co-morbidities (i.e., malnutrition, malaria, TB, neurocognitive dysfunction) on HIV disease and treatment outcomes
  • transition to the adult healthcare setting
• complications of therapy as perinatally-infected youth are exposed to chronic therapy
• implementation science research on barriers to pediatric and adolescent care, with treatment and potential solutions to those barriers
• implementation science research on barriers to and models of successful transition from pediatric to adult HIV care
• implementation science research on barriers to prevention of mother-to-child transmission (PMTCT) and early infant diagnosis and potential solutions to those barriers

Additionally, linkage of maternal and pediatric data is critical to assess the efficacy of interventions to prevent mother-to-child transmission (MTCT) and to evaluate the short- and long-term effects of prevention interventions on both maternal and child health. The IeDEA consortium has had limited data collection on antiretroviral drug use in pregnancy and the efficacy of interventions to prevent MTCT to date. With expanded WHO recommendations on antiretroviral prophylaxis for women and expanded treatment recommendations, it will be important to evaluate the efficacy of these interventions, the effect on pregnancy outcome, and the effect on long-term maternal and child health, including those children who are uninfected but exposed to antiretroviral drugs in utero. NICHD is interested in supporting research in the following areas:

• studies on HIV-infected pregnant women
  • pregnancy outcome (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 intends to initiate support of 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 the 4 African 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 is lacking, and that IeDEA will need to develop methods to collect 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 level accounting for
  • patient level risk factors
  • regional and environmental level risk factors
  • HIV-related risk factors
• Epidemiologic assessment of mental health and neurobehavioral dysfunction based on linkages with other sources of data (such as insurance databases)
• Evaluation of mental health and neurobehavioral care received by patients identified with disabilities in these domains, including determinations of capacity and response to therapy
• Evaluation of the effect of other co-morbidities (i.e., malnutrition, malaria, TB) 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 outcomes in HIV positive and negative patients
  • assessment of gaps in mental health care that negatively impact HIV and mental health outcome 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 initiate support for research which will increase understanding of the influence of substance use (SU) on HIV incidence, prevalence, and treatment outcomes in order to better incorporate substance use into clinical care settings and programs. NIDA has particular interest in focus on African regions 10 and 11 (East Africa and Southern Africa), as under-resourced regions which are experiencing rapid increases in injection and non-injection illicit drug use. 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 use of existing data resources to improve SU-related data capture, with the goal of enhancing strategies for linkage to testing and HIV treatment, and improvement in integrated care approaches
• Epidemiologic assessment of substance use effects on HIV at individual and population levels, including consideration of local and regional indicators of substance use and other efforts to model individual and ecological contributions
• Assessment of substance use effects (including effects of time-varying changes in patterns of substance use) on longitudinal HIV clinical outcomes, including retention in care, viral suppression, and co-occurring conditions associated with substance use, such as psychiatric disorders and viral hepatitis
• Assessment of the effectiveness of substance use treatment and integrated treatment venues as strategies for treatment as prevention
• Evaluation of the impact of utilizing drug treatment or other available harm reduction approaches on HIV prevalence and the spectrum of treatment outcomes relative to in-country health delivery systems
• Evaluation of novel ways to characterize substance use-related behavior and use of substance use services (e.g., pharmacologic treatment, syringe services) over time at both individual and system levels
• Implementation science and cost effectiveness research related to care barriers or enhancements and changes in care delivery as they relate to substance use and HIV

In addition, NIDA encourages the development at the local and regional level of valid and reliable methods for capturing substance use data in a timely, inexpensive manner to build sentinel surveillance systems. NIDA also encourages methodology development and the use of innovative methods to capture the variable course of substance use 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 (e.g., MSM, young injectors, adolescents who are poly-substance users).

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

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) Region 5
Indiana University (Indianapolis, IN) Region 10
Johns Hopkins University (Baltimore, MD) Region 1
ADERA (France) Region 8
Vanderbilt University (Nashville, TN) Region 2
University of Bern (Switzerland) Region 11
Albert Einstein College of Medicine (New York, NY) Region 9

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

Applicant Organizations

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

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

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

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

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

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

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed , with the following additional instructions: Biosketches should describe the unique capabilities of the proposed investigators and staff by including:

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

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

As there will not be a separately funded coordinating center, budgets should reflect the additional responsibilities associated with these activities, as outlined in Part 2, Section VI of this FOA under the heading Coordinating Activities .

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

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

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

Research Strategy: Applicants should discuss how the proposed research is innovative and will lead to new findings in HIV/AIDS; other infectious diseases, neurology and 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.

Applicants should describe the epidemiological, statistical and administrative methods used to produce the most innovative and significant research. They should describe the populations and sources of data included in their region and its appropriateness for the proposed research agenda. Information on the establishment and maintenance of the research collaborations should be included. 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 datacenter proposes to enhance data to answer significant questions. The application should describe how the region will support continued development of the IeDEA data standard and its usability through creation of analytic and quality assurance code. Regions are encouraged to create code to visualize the data for non-research audiences, and improve access to clinic level data by clinical staff. Applicants should describe key information ( core data ) to be obtained across the regional data centers and develop standardized definitions for clinical outcomes and events and how the region proposes to accelerate availability of these data to inform the public health response.

Recognizing the importance of the site level cadre of researchers, applications should describe how the proposed projects strengthen existing structures and capacity. A plan for the review and approval of IeDEA Consortium and non-Consortium research proposals should be included, as well as a description of the mechanisms by which regional stakeholders can pose questions to ensure the research agendas remain responsive to regional needs. Applicants may identify discrete areas of responsibility for which they plan to utilize subcontracts. This approach is encouraged if it allows the applicant to more efficiently carry out the numerous responsibilities of the regional data center. 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.

Applicants are asked to discuss plans for coordination and communication across the seven IeDEA Regional Data Centers. It is expected that each region participates in global executive committee conference calls, and participates in global IeDEA face to face. Regionally supported mechanisms to facilitate interregional activities are encouraged. As there will not be a separately funded coordinating center, plans for facilitation and management of the IeDEA central website should be included.

Other Submission Requirements

As applicable, regions should include specific research agendas to address the interests of the the individual participating ICs (National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute for Child Health and Human Development).

Letters of Support: If letters of support are in a language other than English, they must be accompanied by an English translated version. Sites may take this opportunity to highlight their capacity to be a strong contributor to the region’s research agenda. Letters of support may include, but are not limited to, a commitment from each source of regional data (e.g., the local investigator, institution or organization) indicating willingness to provide data and an agreement that the data can be used in aggregate for regional, multiregional and IeDEA consortium-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' protections 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.)

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the proposed research have a high probability of success in answering questions of importance in the HIV, TB, viral hepatitis, cancer and other infectious diseases (HTMC&O) epidemics among adults and children?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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? How strong is the evidence provided that the experience level of the PD/PI and other scientific and technical staff is appropriate for the proposed work?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are 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 consortium? Does the application demonstrate innovative approaches to maximize communication across multiple regions?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Does the 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? 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? Does any enhanced data collection or approaches to accelerate data availability add significantly to the aims of the application? Does the analysis plan present the strengths and weaknesses of the proposed research approach and suggest alternative analysis techniques to address the weaknesses? Is the plan for the review and approval of IeDEA Consortium and non-Consortium research applications 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 consortium 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?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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 HTMC&O research strong? Do the letters of collaboration indicate an appropriate level of commitment by collaborators? Are the plans for site development and ensuring consistent data collection strong?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

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

Not Applicable

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIAID, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR 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/PI will have the primary responsibility for:

Data Management. The 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 pace of access to key variables to ensure that IeDEA reflects the current status of the HIV epidemic as much as possible.
• participating in global Executive Committee (EC) coordinated site assessments to describe the participating site in the consortium.
• 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 PII and its adequacy to the needs of the region and the IeDEA Consortium 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 preparation of 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 Consortium
• 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
• Prepare and submit annual progress reports
• 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
• In accordance with the IeDEA EC, provide regional data/information to 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 all 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 scientific agenda, identifying research questions to be answered and the methods by which those questions can be addressed at the regional, multi-regional or Consortium 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 submission of all 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 joint press conferences prepared. Publication or oral presentation of work performed under this Cooperative Agreement is the responsibility of the Principal Investigator and co-investigators and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.

Coordinating activities. In collaboration with each other, Regional Data Center grantees are asked to take over coordination responsibilities previously managed by the IeDEA coordinating grant. This includes support for global meetings, maintaining a centralized website, conference calls and participation in coordinating meetings and conference calls on a global level. The IeDEA regions will be responsible for the existence and maintenance of an IeDEA public website. It is anticipated, but not required, that this website will have password-protected 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 scientific program staff who are designated based on the research topic and their relevant expertise (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, the pharmaceutical and biotechnology industries, and other government agencies (e.g., FDA, USDA, CDC, OGAC) and will serve as a resource for scientific and policy information related to the goals of the awardee's research. However, the role of NIAID and cosponsoring NIH institutes will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and that NIH staff will be given the opportunity to offer input into this process. The manner of reaching consensus and final decision-making authority for the Regional Data Center will rest with the Principal Investigator.

The NIH Project Scientists will also:

• 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:

Global Executive Committee (EC):

The Principal Investigator of each Regional Data Center and the NIH Project Scientist 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 member, including the NIH Project Scientist, will have one vote. 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 around 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 consortium. 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 appropriate and in agreement with the overall objectives of the IeDEA Consortium. The individual Principal Investigators will be responsible for ensuring and demonstrating to the IeDEA EC that their Regional Data Center adequately contributes to the overall effort.

Collaboration with Other Projects and Federal Agencies:

Where scientifically appropriate, NIAID or another co-funding IC may propose that the awardee collaborate on scientific initiatives with other NIAID, NICHD, NIMH or NCI-funded projects and/or U.S. government agencies, such as CDC, OGAC, FDA, USAID and HRSA.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

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Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

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

Geraldina Dominguez, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-496-3204
Email: Gd130a@nih.gov

Rohan Hazra, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6868
Email: hazrar@mail.nih.gov

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

Pim Brouwers, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3863
Email: Pb56u@nih.gov

Kelly Poe, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5036
Email: kelly.poe@nih.gov

Julia Shriner
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2972
Email: shrinerj@niaid.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 301-496-8791
Email: woodwars@mail.nih.gov

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

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-8729
Email: pfleming@mail.nih.gov

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

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 .