It is critical that applicants follow the Research (R) 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

Purpose

The purpose of this limited competition Funding Opportunity Announcement (FOA) is to support a Data Analysis and Coordination Center (DACC) for the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS-CCS). The DACC contributes critically to the study design, ensures appropriate adverse event monitoring and reporting, manages data, conducts statistical analyses, and helps with the dissemination of the results. As an active partner in the scientific endeavor, the DACC will serve as a member of the MACS/WIHS-CCS consortium to advance knowledge of the basic science, clinical science, and epidemiology of HIV infection in the US, with a focus on HIV-related comorbidities. A companion FOA, RFA-HL-19-008, will support the MACS/WIHS-CCS Clinical Research Sites.

Overview of the MACS/WIHS Combined Cohort Study

The success of antiretroviral therapy (ART) has ushered in a new era of clinical management for HIV patients. Today almost half of HIV infected patients in North America are over 50 years old. People with HIV infection can achieve nearly normal life-spans if treated with effective ART, in which case they are more likely to suffer chronic HIV-related comorbidities than AIDS-defining conditions. Despite this success, the impact of HIV, its treatment, and the legacy of immune suppression needs to be understood to optimize the health of people living with HIV.

The National Institute of Allergy and Infectious Diseases (NIAID) has been the primary steward for the MACS and WIHS since their inceptions in the 1980s and 1990s, respectively. In response to the changing epidemiology of HIV infection, NIH is shifting emphasis of support for the WIHS and MACS to research priorities focused on chronic HIV-related comorbidities. Beginning in 2019, the National Heart, Lung, and Blood Institute (NHLBI) will manage awards for the MACS/WIHS-CCS in close collaboration with eleven co-funding Institutes, Centers, and Offices (ICOs).

The MACS and WIHS are among the very few large, long-term cohorts of HIV-positive and HIV-negative age-matched controls that allow comparison of disease burden by HIV status, treatment, age, and other factors. MACS and WIHS participants have completed core assessments and research protocols at semi-annual visits during 150,000 cumulative person-years of follow-up. Follow-up of the MACS and WIHS cohorts (median age, 58 and 50 years respectively) provides insight into the impact of aging on HIV infection in the US. Some people at risk or living with HIV are also at higher risk for infection with hepatitis C and B viruses, herpes simplex virus, and human papillomavirus. Diabetes, mental illness, renal failure, and musculoskeletal disorders are also exacerbated among HIV-infected persons. Intertwined with these conditions is an elevated rate of substance use (alcohol, tobacco, and controlled substances), which increases infection risk, accelerates disease manifestations, and reduces adherence to treatment.

Data and specimens are available from men reporting sex with men (MSM) enrolled in three waves of the MACS, from 1984 to 2010 onward. In 2017 there were 2,165 MACS participants (46% HIV-negative and 54% HIV-positive) in active follow-up at Clinical Research Sites (CRSs) in Baltimore and Washington, DC; Chicago, IL; Pittsburgh, PA/Columbus, OH; and Los Angeles, CA. The WIHS study began in 1994, and has enrolled women in four waves including an expansion into southern states in 2014. In 2017, WIHS followed 2,339 women (30% HIV-negative and 70% HIV-positive) at CRSs in Atlanta, GA; Birmingham, AL/Jackson, MS; Bronx, NY, Brooklyn, NY; Chicago, IL; Miami, FL; Raleigh, NC; San Francisco, CA; and Washington, DC. MACS and WIHS data extend beyond routine care assessments. Included in the MACS and WIHS databases are longitudinal assessment of incident and fatal cancers, virologic and immunologic plasma and serum biomarkers, genome-wide association studies (GWAS) and deep sequencing on genes, and test results from affiliated studies. Future research can build on this depth of participant phenotyping.

MACS and WIHS investigators have produced over 2,300 publications on HIV-related topics that include ART toxicity, immunology, virology, pathogenesis, host genomics, prevention of HIV infection, neurocognitive function, mental health, substance abuse, sexual behavior, malignancies, metabolic and body composition complications, physical and immunologic aging, cardiovascular disease, renal dysfunction, hepatitis, dermatology, hearing loss, vestibular balance, impact of hormonal factors on HIV disease (e.g., perimenopause), physical impairment, quality of life, patient demographics, health care utilization, and statistical methods. Over 70 current NIH grants support MACS and WIHS internal and external investigators access to these resources, for both training and to investigate a multitude of research questions.

Supported Research Activities and Requirements

This limited competition FOA is restricted to the current Data Analysis and Coordination Centers (DACC) for the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). The unified science agenda is the proposed high priority scientific questions on HIV/AIDS, developed across the cohort consortium, that align with the science interests of co-funding Institutes, Centers, and Offices (ICOs). This FOA will also support DACC coordination of recruitment for new participants.

Supported Activities

This FOA will support DACC activities related to the core infrastructure of the MACS/WIHS-CCS including, but not limited to:

• Coordination of the ascertainment and adjudication of clinical events through appropriate review committees
• Planning and coordination of efficient cohort consortium examination cycles
• Maintenance and administration of data and biospecimen repositories
• Central support of study operations, internal and external collaborations, and data analysis
• Biospecimen collection, storage, and administrative management
• Data management, and administrative and communication tasks
• Coordination of a MACS/WIHS-CCS-wide recruitment plan to add up to 2,500 participants including both HIV-positive participants and HIV-negative participants with matched demographic and HIV-risk profiles.

The Unified Science Agenda

The unified science agenda outlines the common scientific aims for the MACS/WIHS-CCS consortium to complete during the seven-year funding cycle. The aims should address the highest priority scientific questions in HIV/AIDS patients, and should reflect the science interests of the co-funding ICOs, noting that many ICO interests are complementary. The application should scientifically justify the timing of proposed clinical tests, specimen collections, surveys, and other measures, the frequency of participant visits, and sampling from the cohort for substudies. This FOA supports research including but not limited to the following areas:

Cardiovascular

• Cardiac electrical conduction abnormalities including atrial fibrillation and long QT
• Vascular abnormalities and atherosclerosis
• Heart failure
• Incidence of myocardial infarction

Pulmonary

• Impaired lung function
• Chronic Obstructive Pulmonary Disease
• Asthma and its exacerbations
• Lung microbiome

Hematology

• Inflammation, hemostasis, thrombosis, fibrinolysis
• Hypercoagulation, platelet function, endothelial activation, hematopoiesis

Sleep

• Sleep disturbances and apnea

Implementation

• Comorbidities-related prevention and management guidelines in those with or at risk for HIV

Brain and Central Nervous System

• Brain structure and function
• Acute or delayed neurotoxicity
• Motor and neurocognitive abnormalities
• Behavioral or psychiatric abnormalities
• CNS reservoirs of HIV

Oral and Dental Health

• Dental caries and periodontal disease
• Soft tissue and salivary gland diseases
• Head and neck cancer, orofacial conditions

Women's and Men's Health

• Menopause, andropause
• Hormonal contraception
• Menstrual patterns and symptoms, premenstrual syndrome/dysphoria

Malignancies

• Cancer incidence, tumor stage, grade, histology
• Cancer treatments
• Cancer survivorship
• Cancer tissue blocks collection

Mental Health, Substance Abuse and Behaviors

• Mental health incidence, natural history, severity and treatment
• Substance abuse

Aging

• Physical function and frailty/disability, quality of life measures and biological/behavioral phenotypes such as accelerated-, normal-, and successful aging
• Etiology and mechanisms of comorbidities of HIV positive compared to HIV negative participants

Immune Response

• Chronic immune activation, inflammatory processes, immune system dysfunction
• Immunologic status of patients over the life span and the impact of HIV on infections, treatment of infections (i.e., HBV, HCV), and prevention of infections (i.e., response to influenza vaccine), or emergence of chronic infections (i.e., varicella zoster virus, cytomegalovirus)
• Basic science of immune activation and mechanisms of inflammatory pathogenesis

Viral Load

• Size and attributes of the HIV reservoir over time including identity of biological markers of the reservoir or novel ways to visualize viral distributions
• Understanding long term viral suppression or the emergence of HIV drug resistance

Social and Environmental Factors

• Role of social conditions such as socioeconomic factors, social support, trauma/violence, stigma, discrimination, life transitions, and food insecurity and the mechanisms of action through which they may affect health outcomes among people living with or at risk of HIV acquisition
• Complex interactions among multiple physiologic systems and a variety of human-level factors such as functional status, quality of life, health behaviors, and psychosocial issues

Treatment

• Pharmacologic agents that modify putative aging-related targets in HIV-infected individuals; e.g., metformin, statins, anti-inflammatory drugs, and neurotropics
• Developing, refining, and/or validating standardized drug efficacy, toxicity and co-morbidity phenotypes using dense SNP genotyping, targeted or whole exome/genome sequencing or other omic approaches (e.g., epigenomic)
• Management of disease symptoms affecting people living with HIV/AIDS (symptom science)

Omics

• Examination of differences in vaginal, oral, breast milk, or gut microbiome in HIV-infected versus uninfected people and impact on HIV pathogenesis, drug PK/PD, reservoirs, viral shedding and other STIs
• Preparing genomic and phenotyping data for analysis and deposition for research access by imputing genotyping data against appropriate reference populations, assigning phenotypes, correlating genetic variants with phenotypes, and other analytic processes
• Research utilizing omics approaches (e.g., genomic, epigenomic, microbiomic, proteomic, metabolomic) to identify physiological causes of symptoms such as but not limited to fatigue, impaired sleep, pain, nausea, dyspnea, and cognitive impairment

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

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

Eligibility is limited to current awardees of the Limited Competition Multicenter AIDS Cohort Study: Center for the Coordination, Analysis, and Management of the MACS award (RFA-AI-13-010) and current awardees of the Limited Competition - Women's Interagency HIV Study award (RFA-AI-12-002). Specifically, the eligible awardees are the Center for Analysis and Management of MACS Data (CAMACS) and WIHS Data Management and Analysis Center (WDMAC), collocated at Johns Hopkins University.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

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

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

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

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

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

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

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Email: [email protected]

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, with the following additional instructions:

Facilities and Other Resources: Applicants must include a brief description of the features of the institutional environment that are relevant to the effective implementation of the proposed DACC. As appropriate, describe available resources, geographic distribution of space and personnel, and resources relevant to the effective implementation of the unified science agenda.

Other Attachments: The attachments listed below must be completed or the application will not be peer reviewed. The names will be reflected in the final image bookmarking for easy access for reviewers.

1. Collaboration Plan

A Collaboration Plan must be provided as an attachment using the filename "Collaboration.pdf" and may not exceed 6 pages. The Collaboration Plan must clearly define the interactions between and integration of the MACS/WIHS-CCS, how information and resources will be exchanged, plans for communication, processes for making decisions on scientific direction, and procedures for resolving conflicts. Describe plans to enable scientific collaboration across CRS sites and with external investigators. Without repeating information from individual biosketches, describe plans to achieve synergy and interaction among key investigators to ensure efficient cooperation, communication and coordination across the CRSs. Describe communication plans for study leadership committees and science work groups.

2. Data Management Plan

A Data Management Plan must be provided as an attachment using the filename "Data Management.pdf" and may not exceed 5 pages. The Data Management Plan must describe internal and external data sharing strategies as appropriate and consistent with achieving the goals of the MACS/WIHS-CCS science interests. Where applicable, applicants are expected to describe plans for data harmonization, metadata generation, adoption/use of data standards or common data elements, and consortium-wide information technology infrastructure deployment.

3. Statistical Analysis Plan

A Statistical Analysis Plan must be provided as an attachment using the filename "Statistical Analysis Plan.pdf" and may not exceed 6 pages. The Statistical Analysis Plan should describe statistical design, power of overall study and studies restricted to subsets of participants, list outcome measures to be included in the unified science agenda, and describe innovative approaches to statistical analysis of prospective observational cohort data.

4. Biospecimen Plan

A Biospecimen Plan must be provided as an attachment using the filename "Biospecimen Plan.pdf" and may not exceed 5 pages. The Biospecimen Plan must clearly describe facilitation of biorepository access by MACS/WIHS-CCS and other investigators. The Biospecimen Plan should also describe how

study biospecimens will be collected, managed, analyzed, and stored. Applicants must include plans for maintenance and organization of existing and future biospecimens. Describe plans for adherence to Good Laboratory Practices (GLP). Opportunities to leverage institutional resources should be detailed, if applicable.

All instructions in the SF424 (R&R) Application Guide must be followed. All Key Personnel should demonstrate strong administrative, technical, and management expertise in the areas that are critical to the success of the application, including experience with working productively in collaborative environments. Key Personnel who are major contributors to the DACC must provide an NIH Biosketch whether or not they are budgeted. PD(s)/PI(s) other key DACC team members must have demonstrated experience in epidemiological cohort studies and HIV-related research, including expertise in HIV-related comorbidity research publications. Outline how much effort each PD/PI and key DACC team member will devote to the study.

All instructions in the SF424 (R&R) Application Guide must be followed. Applications must include budget support for the following:

• Publication, data sharing, and dissemination of results.
• Travel funds for the DACC PD/PI to attend the annual two-day meeting of MACS/WIHS-CCS investigators in Bethesda, Maryland
• All costs (travel, honoraria, and teleconference/webcast) associated with the activities of the OSMB and External Advisory Board.

Costs to support teleconferences/webcasts, protocol teams, and all technical and other committees supporting the MACS/WIHS-CCS.

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:

Specific Aims: Provide a summary of the unified science agenda and indicate how the completion of the unified science agenda will advance the MACS/WIHS-CCS science interests of ICOs outlined in Part 2, Section 1 of this FOA.

Research Strategy: The Research Strategy attachment of the application should include sections A and B.

Applicants must provide an overview of the core science activities and cohort infrastructure support to be provided throughout the project period by the DACC. Describe DACC activities regarding the planning, implementation, and management of cohort consortium protocols. Applicants must specifically address:

A. DACC Core Activities

• Regulatory oversight: Describe how oversight of participants will be implemented, including IRB approvals and the consent/assent process. Applicants are encouraged to review NIH Human Subjects Policies and Guidance in the informed consent process. Include plans for compliance with the NIH Policy on the Use of a Single Institutional Review Board permitted by local regulations, as applicable.
• Training/monitoring: Describe plans for training/monitoring of CRS sites and personnel to implement research protocols and core exam components
• Protocols: Process(es) to support development and implementation of MACS/WIHS-CCS-wide protocols
• Quality management: Describe how data collection activities will be managed, including quality control measures.

B. Unified Science Agenda

• Provide an overall description of the unified science agenda and indicate how it will advance the MACS/WIHS-CCS science interests of ICOs outlined in Part 2, Section 1 of this FOA.
• Scientifically justify the timing of proposed clinical tests, specimen collections, surveys, and other measures, the frequency of participant visits, and sampling from the cohort for substudies.
• Describe innovative or novel approaches to address research questions not specified elsewhere in the application.
• Describe planned methods to capture participant vital and health status, risk factors, and other individual-level information. For example, describe plans to use participant-completed forms, face-to-face interviews, or audio computer assisted self-interviews to accomplish these activities.
• Estimate participant time burden (time required to complete study visits)
• Include a plan for data linkages to ascertain events of clinical significance and the process to coordinate review committees' efforts to adjudicate clinical events

Letters of Support: Provide all appropriate letters of support, including any letters necessary to demonstrate the support of site participants and other collaborators. If co-funding or in-kind support is planned from non-NIH sources, letter(s) outlining details of the commitment (e.g., type, amount, and source of support), signed by a business official on organization letterhead must be included in the Letters of Support section.

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:

• Data collected under this FOA, along with previously collected data, are expected to be widely shared. Metadata, common data elements, consortium-wide information technology, protocols, manuals of procedures, and other documentation necessary to describe the study and resultant data are expected to be widely available.
• Justification will be required to allow data to be withheld from wide distribution. Applications must describe how the DACC will facilitate compliance with the unified science agenda data sharing plan. If research participants are assured that their data will not be shared with other researchers, the application should explain the reasons for such promises. Such promises should not be made routinely and without adequate justification.
• For the most part, it is not appropriate for the initial investigator to place limits on the research questions or methods other investigators might pursue with the data. It is also not appropriate for the investigator who produced data to require co-authorship as a condition for data sharing.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 with the following additional instructions:

Section 2 - Study Population Characteristics:

2.4 Inclusion of Women, Minorities, and Children

Additional instructions:

Provide a table summarizing important demographic and clinical attributes of active participants in the MACS/WIHS-CCS cohort.

2.5 Recruitment and Retention Plan

Additional instructions:

Briefly describe the relevance of the cohort to proposed research on HIV infection and HIV-related comorbidites in the ART era. Include a description and justification of MACS/WIHS-CCS plans to recruit across racial, gender, age and geographic subgroups to meet unified science agenda interests.

2.7 Study Timeline

Additional instructions:

The Study Timeline must describe the sequential timing of each protocol that is part of the proposed unified science agenda during the next seven-year MACS/WIHS-CCS funding cycle. For each sequential participant visit, estimate the time allotted for participants to complete all planned visit components (e.g., consent, physical exam, specimen collection, protocol procedure, break time, interviews and surveys, and other measures). For sequential visits, estimate time needed to collect questionnaire data by NIH science interest area. For protocols of the unified science agenda involving subsets of participants, describe the procedure, required time, number to be enrolled, selection criteria, and visit cycle when the protocol will occur. Estimate the participant time burden (time required for a participant to complete each study visit).

Section 3 - Protection and Monitoring Plans

3.5 Overall Structure of the Study Team

Additional instructions:

Include a description of the following:

• DACC Study Team Structure to advance the MACS/WIHS-CCS research agenda
• DACC staffing for information technology, data management and quality control, CRS staff training, and other MACS/WIHS-CCS wide support
• DACC staffing to enable investigator access to MACS/WIHS-CCS biorepository materials
• DACC staffing to support MACS/WIHS-CCS statistical analyses and methods development
• DACC staffing to enhance data sharing with non-MACS/WIHS-CCS funded (external) investigators
• Plans to evaluate the effectiveness of DACC research support activities
• Describe the proposed governance structure for the MACS/WIHS-CCS consortium to include, but not limited to committee structures to manage the MACS/WIHS-CCS such as the Executive Committee, Scientific Leadership Committee, Developmental Award Research Committee, and Community Advisory Board. Describe each entity's functions, how often they will meet and how they will communicate with the consortium to fulfill their respective responsibilities.

Delayed Onset Study

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

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Many NIH ICOs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICOs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a "Common Data Element (CDE) Resource Portal" to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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.

The merits of both the DACC Core Activities and the Unified Science Agenda, Parts A and B of the Research Strategy, respectively will be considered.

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

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

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

In addition, specific to this FOA:

How does the proposed MACS/WIHS-CCS Unified Science Agenda maximize the potential of the overall cohort to advance understanding of HIV-related outcomes in the ART era?

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?

In addition, specific to this FOA:

Do the proposed PD(s)/PI(s) possess the essential experience and expertise to manage DACC science contributions, coordination of centralized activities, and cohort support role?

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

In addition, specific to this FOA:

Are approaches to project and DACC core activities and infrastructure innovative?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

In addition, specific to this FOA:

How likely is it that the DACC application will foster collaborations with both MACS/WIHS-CCS and external collaborators?

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?

In addition, specific to this FOA:

Does the environment foster collaboration? Does the scientific environment in which the work will be done contribute to the probability of success? Is there evidence of institutional support?

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

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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

As part of the scientific peer review, all applications:

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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.

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. Specific tasks and activities may be shared among the awardees and the NIH as defined below.

The DACC PD(s)/PI(s) will have primary responsibilities for:

• Advancing the research objectives, and supporting the technical approaches and details of research projects within the guidelines of the FOA, as an active participant in every scientific project
• Defining objectives and approaches of the research
• Establishing and maintaining productive working relationships with the cohort sites
• Supporting project design and protocol development
• Working collaboratively with investigators who propose ancillary study components
• Implementing uniform methods to capture participant data on vital and health status, risk factors, and other personal information
• Supporting data linkages to ascertain events of clinical significance
• Coordinating review committees' efforts to adjudicate significant clinical events
• Performing centralized data analyses to support the MACS/WIHS-CCS unified science agenda
• Developing innovative approaches to statistical analysis of prospective observational cohort data
• Tracking recruitment and retention of participants at each CRS and making these figures available to the Executive Committee (EC) and representatives of co-funding institutes in annual progress reports
• Updating CRSs about current cohort status in a timely manner
• Collecting, editing, cleaning, and storing data collected from CRSs; providing centralized storage, security, processing and retrieval of cohort data; providing quality control of the data management system and addressing evolving data needs of the cohort study
• Preparing a final annotated dataset for delivery to NIH or an NIH designated institution of the complete cohort dataset (all data included in the cohort dataset)
• Performing data audit site visits on a routine basis at a minimum of once every three years
• Ensuring accurate inventory of specimens in repository; train and provide updates on the web-based tracking system; manage requests for specimens from investigators; prioritize requests for samples; facilitate timely delivery of samples to investigators
• Releasing clinical and GWAS data to the scientific community in a timely manner
• Developing a dossier and agenda to be distributed at the semi-annual EC meetings; attending and participating in EC meetings
• Facilitating the activities of the cohort Executive Committee
• Providing summary tracking of submitted site-specific and MACS/WIHS-wide concept sheets
• Establishing a process for annual strategic planning of scientific and management priorities to ensure that funding is allocated to meet local and cohort-wide aims
• Arranging, conducting, and distributing documentation for regular conference calls for Scientific Work Groups (SWG), EC and other committees, and semi-annual meetings of cohort investigators
• Monitoring adherence to clinical and laboratory protocols, and coordinating implementation of new or modified protocols that the EC approves during the study
• Preparing and updating operations manuals, data collection forms, coordinating the revision of existing questionnaires and development and testing of new questionnaires for use in the cohort, including the standardization of procedures for data collection
• Providing teaching and training to cohort personnel at the CRSs to assure that the questionnaires continue to be administered in a uniform, standardized fashion
• Collecting and tracking study and protocol approvals, including IRB approvals and renewals
• Providing a forum for posting, circulating and consolidating input on draft manuscripts to co-authors, NIH co-funding ICO Project Scientists and Program Officers
• Maintaining the system for tracking cohort research and providing study progress reports at the semi-annual investigator meeting
• Maintaining and distributing a searchable list of all MACS/WIHS-CCS publications, manuscripts in progress and presentations using cohort data at a minimum semi-annual frequency
• Maintaining internal and public websites, posting study documents on internal website

Awardees retain custody of and have primary rights to data and software developed under

these awards subject to Government rights of access consistent with current DHHS, PHS, and

NIH policies. Awardees agree to the governance of the study through an Executive Committee and to

accept and implement decisions approved by the Executive Committee (see "Joint

Responsibilities" section below). Awardees are expected to make their data widely available to other investigators, per NIH/NHLBI data sharing policies: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_policies.html; https://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing.

Study investigators are strongly encouraged to publish and disseminate results, tools, resources, and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely manner to the scientific community.

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources; citing the name of study or NHLBI support; or special access to study results, data, findings or resources requires notification and concurrence by NHLBI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification to and concurrence by NHLBI.

Other Collaborations: The MACS/WIHS-CCS CRS Principal Investigators primary responsibilities:

The PD(s)/PI(s) assume(s) responsibility and accountability to the applicant organization officials and to the NHLBI for the performance and proper conduct of the research supported by the U01 award in accordance with these terms and conditions of the award. As such, the awardee PD(s)/PI(s) will be responsible for all aspects of the study and cohort, as well as any modification(s), unless otherwise provided for in these terms or by action of the Executive Committee.

Specific responsibilities include:

• Defining objectives and approaches of specific research protocols
• Providing leadership in protocol development for specific research protocol(s), and/or serving as an expert Reading Center or Laboratory for specific research protocol(s)
• Participating in the activities of the cohort Executive Committee
• Accepting and implementing the policies approved by the cohort Executive Committee consistent with applicable grant regulations
• Performing all activities of the unified science agenda
• Implementating any additional EC approved MACS/WIHS-CCS protocols
• Monitoring CRS adherence to clinical and laboratory protocols
• Obtaining all requisite study and protocol approvals
• Scheduling participant CRS visits, capturing study-specified outcomes, and completion of study visit components including consent, questionnaire and examinations
• Tracking recruitment, retention, and follow-up of participants at the CRS and making these data available to the DACC for inclusion in annual progress reports.
• CRS safety monitoring
• CRS data quality control
• Evaluating CRS personnel interview skills, HIV counseling, and examination techniques
• Proper CRS staff handling of specimens, web-based tracking of delivery to central repository
• Assuring data security in the collection of participants' personal health information
• Taking corrective actions for all supported activities as needed
• Cooperating with NIH programmatic, technical, and administrative staff
• Attending and participating in the complete agenda of the semi-annual EC meetings
• Providing mentorship and training to early career investigators at the CRSs
• Coordinating with the MACS/WIHS Developmental Award Advisory Committee (DARC) for early career investigator training
• Developing and supporting collaborations with external investigators

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

Project Scientists and Program Officers from the co-funding institutes have substantial involvement in the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants. Each ICO will select at least one NIH Project Scientist and Program Officer. These individuals are responsible for study involvement specific to their ICOs related to the following tasks:

• Participating in Executive Committee meetings
• ICO programmatic staff will coordinate with investigators, particularly on issues to their specific domains, in cooperation and coordination with other NIH programmatic staff
• Monitoring study results and quality assurance across all sites
• Reviewing all appropriate study protocols and data
• Facilitating collaborations between the awardees and other NIH-sponsored programs investigators, or organizations that may contribute to the study's goals
• Assisting in the interaction between the awardees and investigators at other institutions, as appropriate for the cohort
• Promoting collaborative research efforts that involve interactions with other NIH-supported projects, programs, and centers and helping with the coordination of such efforts
• Facilitating harmonization of data and biospecimen resource optimization
• Participating in Scientific Work Groups' meetings
• Providing technical assistance and advice to the awardees as appropriate
• Assisting with the development of research protocols
• Monitoring study progress
• Ensuring disclosure of conflicts of interest and adherence to NIH policies

In addition to the NHLBI Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components, and/or oversight committees. Other NHLBI staff members such as direct line supervisor and/or other Senior NHLBI Program management staff may serve as agency Program Officials as needed with responsibility for the normal scientific and programmatic stewardship of the award.

The NHLBI/NIH reserves the right to withhold funding or curtail the study if any of the following occur:

• Substantial shortfall in participant recruitment, follow-up, data reporting, or quality control
• Major breach of the protocol or substantive changes in the agreed-upon protocol, methodologies, and/or tools with which the NHLBI/NIH cannot concur
• Failure to develop or implement a mutually agreeable protocol
• Human participant ethical issues that may dictate a premature end of the award
• Results that substantially diminish the scientific value of study continuation

MACS/WIHS-CCS Executive Committee (EC): The EC Chair is appointed by the EC. The EC consists of Principal Investigators from each Clinical Research Site, the DACC, and Community Advisory Board members. Program Officers or Project Scientists from each NIH co-funding institute will have voting representation, based on processes developed by the EC Principal Investigators and ICO representatives. Each Principal Investigator from the CRSs and DACC is a voting member of the EC. In the case of multiple Principal Investigators in either an CRS or the DACC, the Principal Investigators should reach consensus on their position to cast a single vote representative of their site. Awardee members of the Executive Committee will be required to accept and implement policies approved by the EC. The members of the cohort EC will be responsible for:

• Holding recurring scheduled conference calls.
• Discussing the status of the existing cohort, including retention, changes in consensus protocol procedures, quality control of data, reviewing updates of the SWGs and other matters of interest to all institutions affiliated with the MACS/WIHS-CCS; assessing scientific progress and establishing scientific priorities and timelines.
• Optimizing a mechanism for rapid access to data for exploratory work or manuscript preparation, including clearance and prioritization of requests by the EC.
• Promoting the use of biological specimens and other survey and experimental data by investigators outside of cohort; considering and approving requests to use biological specimens and cohort data by investigators outside of cohort; approving concept sheets submitted by cohort and external investigators.
• Ensuring that individual cohort sites maintain ties to their patient communities and interact in a spirit of collaboration that is mutually responsive.
• Providing oversight and review of the cohort publication policy. The policy will be reviewed in the first six months of the funding cycle, and amended by the EC if necessary, to achieve overall fairness and timeliness in the formal reporting of research results.
• Support DACC planning of cohort-wide meetings. Semi-annual cohort-wide meetings, of up to three full-days in duration, will be convened to gather the EC, Working Groups, study coordinators, data managers, statisticians, NIH Program Staff and other key members. The meeting location will rotate between the cohort sites, with the spring season meeting held in the greater Washington, DC area.

Scientific Leadership Committee (SLC): The SLC is comprised of previously selected members of the MACS/WIHS-CCS consortium including the Chair of the Executive Committee, Investigators, Project Directors, Working Groups (WGs) chairs, and ICO representatives. The purpose is to reduce time demands on the EC by rapidly and efficiently assembling the SLC, on an as need basis, to address emerging study issues and management issues. The SLC reports to the EC during the EC call.

Developmental Award Advisory Committee (DARC): The DARC is comprised of members of the Scientific Working Groups (SWG) appointed by the Executive Committee to serve on this committee with other subject matter experts also serving as ad hoc reviewers when necessary. DARC members will choose one of their members to chair this committee. The DARC reviews and prioritizes developmental fund applications submitted to the cohort study as funds are identified and made available from within MACS/WIHS-CCS institutions, NIH, or other sources. MACS/WIHS-CCS CRSs will allocate 5% of their annual direct costs to support DARC awards. Support for developmental awards, DARC meetings, and travel, will be managed by the DARC in coordination with representatives from NIH co-funding ICOs and MACS/WIHS-CCS institutions. Recognizing the key role that developmental awards play in advancing novel research and supporting and mentoring early stage investigators, NIH places high value on support for developmental awards.

Scientific Work Groups (SWG): Subject matter experts within the MACS/WIHS-CCS consortium serve as SWGs to strategize on research priorities and opportunities within their domain, train early career investigators, develop protocols, facilitate training of CRS staff on protocol implementation, and operate protocol related reading centers and laboratories. These groups drive the innovative work and their functioning will therefore be critical for the success of the MACS/WIHS.

Community Advisory Board (CAB): Constructive interactions between CRSs and the communities in which participants live are critical to the science. Individual CRSs sites maintain ties to their patient communities and interact in a spirit of collaboration that is responsive to local perspectives. The CRS will cultivate constructive relationships with their local CAB on any relevant issues, including participant recruitment to facilitate community engagement, and are responsible for budgeting to support these interactions. CAB members review study direction, attend meetings and participate on calls to assure local support. A participant from each CRS catchment will be chosen to represent that site as CAB members. These CAB members form the National Community Advisory Board (NCAB. One or more members of the NCAB serve on the EC.

Observational Study Monitoring Board (OSMB): The OSMB is an independent advisory body. Members of the OSMB are appointed by NHLBI to advise the NHLBI and co-funding ICOs on study performance, participant safety and risk, informed consent, progress, burden and overall scientific direction. MACS/WIHS-CCS consortium staff, such as PD(s)/PI(s) and other key investigators from the study, are invited as needed to present reports during the annual OSMB open session.

Areas of Joint Responsibility:

MACS/WIHS-CCS PD(s)/PI(s) in the DACC and CRSs are expected to work collaboratively with investigators proposing ancillary study components.

NIH staff and MACS/WIHS-CCS PD(s)/PI(s) in the DACC and CRSs will work collaboratively with appropriate MACS/WIHS-CCS committees to re-assess the priorities of the unified science agenda in the event of budgetary or resource constraints.

Where applicable, the awardee will work with the NHLBI and/or other suitable NIH ICOs' on efforts to harmonize data and use common data standards and elements across all MACS/WIHS-CCS CRSs and the DACC. For instance, NHLBI can partner with the PD(s)/PI(s) to prepare a dataset and documentation for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) as described in the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies and the Guidelines for NHLBI Data Set Preparation. BioLINCC or another mutually agreed upon NIH-based data repository may be used for the wide sharing of study data to enable public access to MACS and WIHS data. Large-scale genomic data generated via ancillary studies are to be deposited along with associated phenotype data into the database of Genomic and Phenotype Data (dbGaP) in accordance with the NIH Genomic Data Sharing Policy.

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-945-7573

Rick Berzon, DrPH
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8949
Email: [email protected]

Sean Altekruse, DVM, MPH, PhD
National Heart, Lung, Blood Institute (NHLBI)
Telephone: 301-435-1290
Email: [email protected]

Geraldina Dominguez, PhD
National Cancer Institute (NCI)
Telephone: 240-781-3291
Email: [email protected]

Ebony Madden, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: (301) 503-5620
Email: [email protected]

Basil Eldadah, MD, PhD
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: [email protected]

Carolyn Williams, PhD, MPH
National Institutes of Allergy and Infectious Disease (NIAID)
Telephone: 301-402-2305
Email: [email protected]

Denise Russo, MD
Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6871
Email: [email protected]

Gallya Gannot, DMD, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-451-5096
Email: [email protected]

Richard Jenkins, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1923
Email: [email protected]

Pim Brouwers, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-627-3863
Email: [email protected]

May Wong, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: [email protected]

Rebecca Henry
National Institute of Nursing Research (NINR)
Telephone: 301-594-5976
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: [email protected]

Erin Davis
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8026
Email: [email protected]

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

Deanna Ingersoll
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: [email protected]

Lesa McQueen, M.Sc.
National Institute on Aging (NIA)
Telephone: 301-402-7738
Email: [email protected]

Ann Devine
National Institutes of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: [email protected]

Bryan Clark, MBA
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone:301-443-2805
Email: [email protected]

Tijuanna DeCoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9531
Email: [email protected]

Kelli Oster
National Institute of Nursing Research (NINR)
Telephone: 301-594-2177
Email: [email protected]

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.