Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Terms and acronyms used in this NOFO

HIV – Human immunodeficiency virus

PLWH – Person living with HIV

PLWOH – Person living without HIV (used to describe cohort participants who have been included for control or comparison purposes).

ART – Antiretroviral therapy (medications used to suppress the HIV virus in the body)

PrEP – Pre-exposure prophylaxis (medications used to prevent an HIV infection from beginning)

CRS – Clinical Research Site of the MWCCS.

DASC – Data Analysis and Sharing Center of the MWCCS.

LACC – Leadership and Coordination Center of the MWCCS

JUMP – Joint Unified Modular Protocol

DMSP - Data Management and Sharing Plan

LCAB – Local Community Advisory Board (typically comprised of study participants).

NCAB – National Community Advisory Board (comprised of representatives from all 13 LCABs).

Core-funded – This refers to planned operational and scientific activities which will be directly funded by the core NIH cooperative agreements for the 6-year grant period 2026-2032.

Ancillary-funded – This refers to planned operational or scientific activities which may be funded by ancillary grants (e.g. NIH R01 awards) during the 6-year grant period of the core cooperative agreements.

NIH ICOs – The individual Institutes, Centers, and Offices which together comprise the National Institutes of Health

Background

Over the past 40 years, remarkable progress has been made in the prevention and treatment of HIV in the U.S. and globally. Yet despite these advancements, today over 38 million people are living with HIV worldwide, with approximately 1.2 million new cases being diagnosed annually worldwide. In the United States, HIV incidence rates have declined, but scientific and public health advances have not benefited all populations evenly, with disproportionate negative impact of HIV on racial/ethnic and sexual/gender minorities, people with limited socioeconomic resources, and rural populations.

There have been significant improvements in both viral suppression rates among people living with HIV and the number of HIV-negative people prescribed HIV pre-exposure prophylaxis (PrEP) in the past ten years. According to CDC data, in 2019, 66% of people with diagnosed HIV in the U.S. were virally suppressed because of treatment with highly effective antiretroviral therapies (ART), an increase from 60% in 2015. Additionally, in 2019 nearly a quarter (23%) of people who could benefit from PrEP received prescriptions, an increase from 3% in 2015.

With the development of effective ART medications and wide access to them in the U.S., HIV infection has become a chronic disease, and PLWH are now surviving longer, aging, and requiring lifelong care and treatment. Currently in the United States, over 50% of PLWH are aged 50 and older, many of whom have been living with HIV for many years. At the same time, some people become infected with HIV later in life and need diagnosis and initial treatment at older ages. Across all age groups, PLWH are at increased risk of developing chronic comorbidities, coinfections, and complications, including noncommunicable diseases, as well as mental health and substance use disorders, even when HIV is suppressed.

Due to persistent viral reservoirs, inflammation caused by the virus, long-term use of ART, polypharmacy, and other pathological mechanisms that are not yet well-understood, older PLWH are at increased risk for multiple comorbidities. These comorbidities include cardiovascular disease, pulmonary disease, hematological disease, sleep disorders, malignancies, diabetes, mental disorders, sensory disorders, liver disease, cognitive impairment, and central nervous system complications. In addition, periodontal disease, alcoholism, and drug abuse are prevalent health issues among PLWH. Even with effective ART, many PLWH experience accelerated aging, altered metabolism, and chronic immunopathogenesis factors that converge and contribute to the development of several comorbidities and end-organ diseases.

Given the adverse trends in HIV-related health disparities and the growing numbers of older adults living with HIV, there is a continuing urgent need for basic, clinical, epidemiologic, behavioral, and translational research to understand the pathophysiology and treatment of HIV infection and its associated complications and comorbidities. This populomics approach can directly contribute to the scientific knowledge needed to develop, test, implement, and scale up multilevel, intersectional culturally-appropriate, community-engaged interventions, clinical practices, and guidelines to address the social and structural determinants of health and reduce disparities in HIV-related morbidity and mortality.

Project Origins

The MACS/WIHS Combined Cohort Study (MWCCS) is one of the world’s longest running cohort studies focused on the short and long-term effects of HIV. Since its inception, the MWCCS has yielded important findings to inform clinical practice and health policy including improvements in uptake and adherence to ART leading to reductions in morbidity and mortality for PLWH.

The Multicenter AIDS Cohort Study (MACS) of men was established in 1983 and the Women’s Interagency HIV Study (WIHS) began enrollment in 1994. In 2019, recognizing the evolving burden of HIV among aging populations, the NIH merged the MACS and WIHS to form the MACS/WIHS Combined Cohort Study (MWCCS) with primary program leadership by the National Heart, Lung, and Blood Institute (NHLBI) and co-funding and scientific guidance provided by 14 additional ICOs of the National Institutes of Health (NIH). Using a cooperative agreement mechanism, 13 clinical research sites (CRS) and a data analysis and coordination center (DACC) were funded for a 7-year project period in 2019, ending in 2026.

MWCCS is a deeply phenotyped and richly diverse cohort comprised of both PLWH and sociodemographically similar PLWOH. Women comprise half of the cohort, and more than 75% of participants recruited since 2019 are Black or Hispanic individuals, among whom HIV incidence rates are elevated compared with non-Hispanic whites. MWCCS includes the largest and longest running cohort of women living with HIV in the United States and is an exemplar of the priorities of the new White House Initiative on Women’s Health Research. With over 12,000 ever-enrolled study participants over a 40-year period, MWCCS has contributed significantly to our understanding of the pathogenesis and virology of HIV disease, and continues to address the psychosocial, socioeconomic, structural and behavioral factors that drive the HIV epidemic in the U.S.

Phenotyping in MWCCS is both comprehensive and frequent, with annual study visits that include clinical exams, labs, and interviews. The biorepository contains about 5.4 million specimens, and there is a robust -omics research program including substudies and linked NIH grants focused on proteomics, DNA methylome, and microbiome, and other factors associated with a number of comorbidites and with mortality. Scientific productivity of the MWCCS has remained high since the cohort merger in 2019, with about 500 scientific publications since 2019, many in high impact journals, and currently over 100 active ancillary studies. NIH-funded ancillary studies include 30 active training awards.

Purpose and Organization of the MWCCS Renewal

Purpose: The purpose of this NOFO and its two companion NOFOs is to renew the MWCCS for a 6-year project period (2026-2032). Continuation of this epidemiological study of middle-aged and older PLWH, along with comparable PLWOH, will enable the sustained follow-up of a deeply phenotyped cohort of approximately 5,700 participants from across the United States. This initiative will utilize a populomics approach, i.e., examination of health determinants across multiple scales of influence (e.g. molecular, cellular, physiological, lifestyle/behavioral, household, neighborhood, environmental, cultural, and sociopolitical) using multi-disciplinary methods to investigate the web of influences impacting the health, quality of life, and survival of adults living with HIV.

Renewal of the MWCCS aligns with the NIH Strategic Plan for HIV and HIV-Related Research and the White House initiative “Ending the HIV Epidemic (EHE): A Plan for America”, which provide a roadmap for the NIH HIV/AIDS research program, ensuring that funds are allocated per established NIH scientific research priorities. Aligned with these goals, the MWCCS will continue to serve as a reliable, valid and standardized platform for collaborative and independently-funded HIV populomics research for both MWCCS investigators and the broader scientific research community.

Organization: For the renewal period (2026-2032), there will be 3 highly integrated, collaborative, and cooperative components to the MWCCS, each funded via a distinct award mechanism:

Leadership and Coordination Center (LACC): NIH intends to fund a single LACC via an open competition. The purpose of the new LACC will be to improve clinical guidance and oversight of the cohort and create an enhanced structure for scientific leadership, scientific work group support, participant outcomes ascertainment, internal training, operational accountability, community and participant engagement, and promotion of the cohort to external stakeholders. Additional information about the LACC can be found in the companion NOFO RFA-HL-26-011 (Leadership and Coordination Center (LACC) for the MACS/WIHS Combined Cohort Study (MWCCS) (U01 Clinical Trials Not Allowed)).

Clinical Research Sites (CRS): NIH intends to renew funding via a limited competition NOFO for up to 13 clinical research sites. Each CRS will be expected to retain cohort enrollment of all MWCCS participants who gave informed consent during the period 2019-2025 and continue to track and solicit participation from any remaining MACS or WIHS participants who have neither declined nor agreed to enroll in the MWCCS. In addition, the 5 CRS whose investigators participated in the STAR Cohort of HIV in Reproductive Age Women have the option to invite STAR cohort participants (only those who meet all inclusion criteria for MWCCS) to join the MWCCS. Inclusion of STAR participants in MWCCS is not a required activity, and NIH encourages applicants to carefully consider their CRS resources and scientific priorities before making a decision. If a CRS does choose to solicit enrollment of eligible STAR Cohort participants, NIH expects that the consent process would involve transfer and integration of all STAR data and biospecimens for those participants to the MWCCS archive and biorepository. Additional information about the CRS can be found in the companion NOFO RFA-HL-26-009 (Limited Competition: Clinical Research Sites (CRS) for the MACS/WIHS Combined Cohort Study (MWCCS) (U01 Clinical Trials Not Allowed)).

Data Analysis and Sharing Center (DASC): NIH intends to fund a redefined MWCCS Data Analysis and Sharing Center (DASC) via this limited competition NOFO. The DASC will prioritize systems modernization, more rapid and accessible data sharing, and enhanced biostatistical support to investigators and scientific working groups, while coordinating, standardizing, and integrating all core data collection, processing, storage, and analytic activities of the cohort. The DASC will also serve as a resource to the scientific community to enable and promote broad use of the MWCCS data to advance HIV populomics science. NIH expects applicants for the DASC to include, but not be limited to, the following areas of responsibility in their proposal:

1. Systems Modernization
2. Data Security
3. Data Management and Sharing
4. Data Dissemination and Training
5. Biospecimens Protection
6. Cohort Multisite Collaboration Plan
7. Program Monitoring, Evaluation, and Quality Control
8. Analytical Innovations

Scientific Priority Areas

The MWCCS renewal initiative will support activities under two broad umbrellas: (1) continuation of the MWCCS as a cohort study platform that will collect and make publicly available high-quality risk factor and outcome data on HIV and associated comorbidities in middle-aged and older adults in the United States; and (2) investigations of highly significant scientific research questions that are of interest to the MWCCS investigators and which are well-aligned with the scientific priorities of the co-funding NIH ICOs.

In the table below, NIH platform priorities (i.e. priorities for new or continued data collection) and investigational priorities (i.e. priority topics and questions for analysis, publication, and dissemination) are listed by co-funding ICO. Many ICO scientific priorities may be both overlapping and complementary, and applicants are advised that duplicative priorities are not always listed in the table in the interest of brevity. Specific areas of HIV populomics science which will be supported by the initiative include but are not limited to:

TABLE OF NIH SCIENTIFIC PRIORITIES FOR THE MWCCS RENEWAL

Joint Unified Modular Protocol (JUMP) and Example Timeline

For the MWCCS renewal, NIH expects the MWCCS investigators, led by the new LACC, to develop a joint unified modular protocol (JUMP) that will detail specific data items to be collected during Visits 107-111, including clinical measurements, questionnaires, laboratory testing, biospecimen collections, medical and hospital record abstractions, and dataset linkages to obtain health outcome data. NIH expects the JUMP to employ an alternating modular design which will result in a shortening of each annual visit in terms of duration and effort for the participants, while creating time and opportunity to address current data gaps through collection of new data on multiple risk factors and outcomes of scientific importance.

Implementing biennial and/or triennial content modules while maintaining a much briefer core annual exam (needed for blood draws and outcomes ascertainment) will help address and reconcile 3 important competing priorities: (1) contain the time and effort burden on aging participants with significant vulnerabilities; (2) expand data collection to cover important data gaps across multiple areas of HIV comorbidity science; (3) increase the number of participants who complete high-intensity data modules such as cardiac echocardiography, pulmonary function tests, and sleep actigraphy. In addition the JUMP plan will create time and opportunity for the future addition of ancillary-funded modules, without overburdening study participants.

Finalization of the JUMP will not occur until after the MWCCS renewal cooperative agreement awards are made in early 2026. The first six months of the new grant period will be used by the new LACC leadership, in coordination with the Executive Committee, the DASC, and NIH Project Scientists and Collaborators, to review and finalize a consensus version of the JUMP. Therefore, in addition to content details of their proposed JUMP, LACC applicants should explain and justify the relevant principles, scientific priorities, and consensus process they have employed for developing the JUMP. CRS award recipients and the DASC recipient will be expected to fully participate and cooperate with the JUMP finalization process which will be led and coordinated by the team which is awarded the LACC cooperative agreement. A detailed proposed JUMP should be included in the applications for the LACC cooperative agreement, but not in the CRS or DASC applications.

Example of a JUMP modular design

One example of a possible JUMP protocol design is shown in the Table below. In this example, there are two non-overlapping biennial modules (B and C, collected every 2 years), three non-overlapping triennial modules (D, E, and F, collected every three years), and one annual module of essential core data items (module A, collected every year). Under the requested 6-year grant period, the investigators would be able to complete five annual study visits (V107-V111) in five years (Oct 2026-Sep 2031). This example JUMP plan would permit collection of module A five times, module B three times, and modules C, D, and E twice. Module F would be collected once during V109. 

The specific scientific data content of all of the proposed modules in the JUMP should reflect both the scientific priorities of the co-funding NIH ICOs (see Table of NIH Scientific Priorities above), as well as be well-aligned with the scientific expertise of the study investigators and the research priorities and investigational specific aims of each CRS applicant.

The example JUMP timeline above is for illustrative purposes only, and the LACC applicants are expected to weigh all contributing factors in proposing and justifying the frequency of data collection for each proposed content module. However, a proposed JUMP protocol in which the majority of content modules are scheduled to be collected on an annual basis will be considered non-responsive to the requirements of the LACC NOFO.

Limitations and Requirements

Cohort Participants

The following groups of individuals are eligible cohort participants for the renewal period:

1. Persons who were ever enrolled in the MWCCS from 2020 to 2025.
2. Persons who were ever enrolled in the original MACS or WIHS cohorts and who completed at least one in-person study visit prior to 2019.
3. Women who were ever enrolled in the STAR cohort (via study sites funded under RFA-HD-19-024) and who meet all current eligibility criteria for enrollment in the MWCCS. Recruitment and enrollment of former STAR cohort participants is an optional activity which is not a requirement for any applicant.

Annual Visits

The MWCCS Renewal will not provide support for semi-annual participant clinic visits for the purposes of data collection. NIH expects all core-funded data collection to occur during the annual visits, beginning with V107 in the fall of 2026.

However, CRS applicants may choose to propose and budget for more frequent participant contacts for the purposes of ensuring participant retention, engagement, education, and/or safety and well-being. Similarly, NIH anticipates that future ancillary-funded data collection modules could be timed to either coincide with the core-funded annual visit, or alternatively to occur at a 6-month visit or other time point.

Special Considerations

Use of Common Data Elements in NIH-funded Research

Many NIH ICs 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 ICs 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" (http://cde.nih.gov/) 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 NIH ICs strongly encourages investigators that plan to collect phenotype and/or environmental exposure data about their study participants to utilize standard protocols included in the PhenX Toolkit (http://www.phenxtoolkit.org).

Limited Competition

This NOFO is limited to institutions funded under RFA-HL-19-007 and will fund a single Data Analysis and Sharing Center (DASC) for the MWCCS.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible institutions are limited to those organizations which were previously funded under RFA-HL-19-007.

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active 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 their organization to develop an application for 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 How to Apply-Application Guide.

A multiple PI (mPI) leadership structure is required. The DASC mPI team should include individuals with demonstrated expertise in epidemiology, biostatistics, and data science. Individuals may not apply to be an mPI of both the DASC and the Leadership and Coordination Center (LACC) (RFA-HL-26-011). Applications without an mPI leadership structure will be considered incomplete and will not proceed to peer review.

Eligible PD/PIs are limited to those associated with organizations which were previously funded under RFA-HL-19-007.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Health, Lung, and Blood Institute
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

Applicants should include “MWCCS” in the title of their submission as the first word.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Facilities and Other Resources (Required): Applicants must include a succinct description of the aspects of the institutional environment that are relevant and necessary to the effective functioning of the proposed DASC. Describe geographic distribution of working spaces, personnel, equipment, and computing resources. In particular, provide details about computer network and data security features which will ensure safety of participant health and medical care data from hacking and other data breach/theft risks. Describe computing security measures in place for home-based telework and other off-site personnel working environments, as relevant.

Other Attachments: The following attachments must be completed as instructed and attached or the application will not be peer reviewed. All page limits are inclusive of any references deemed necessary by the applicant. Applicants should use the filenames exactly as specified below to facilitate the peer review process. The filenames specified below will be reflected in the final image bookmarking for easy access by reviewers. The purpose of these attachments is to permit applicants to include technical details and specifications which are too lengthy to include as part of the main proposal Research Strategy (see Section PHS 398 Research Plan below). Each of the required attachments described below must not exceed 5 pages in length, inclusive of any necessary references or citations.

1. Systems Modernization Plan (Required) (DASC_systems.pdf): The DASC Systems Modernization Plan must describe system features, technical details, and timelines for staff training and implementation for upgrading and modernizing the MWCCS data collection interfaces and software. The following elements are recommended:
   1. Infrastructure Upgrades, including a recommended transition to a cloud-based architecture for enhanced scalability and reliability.
   2. Standards, Harmonization, and Interoperability: Compliance with the NIH FY23 Data Sharing Policy and suggested adoption of standardized data formats and protocols as well as common data models used for patient observations and outcomes.
   3. Automation: Implementation of automated workflows for real-time data collection and validation.
   4. User-Friendly Interfaces
   5. Biospecimen Look-up Tool: Electronic access for investigators to facilitate easy look-up of biospecimen availability for specific participant groups and study visits.
   6. Scalable Data Storage
   7. Data Integration Tools
   8. Data Quality and Governance: Implementation of automated data validation rules, data lineage tracking, and compliance with General Data Protection Regulation and HIPAA.
   9. Training and Support
   10. Timeline and Milestones: Clear timeline with phases for planning, development, testing, training, and full deployment.
        
2. Data Security Plan (Required) (DASC_security.pdf): The DASC Data Security Plan must include technical details about the combined elements and redundancies that will ensure safety and privacy of the large amounts of participant data that are collected, stored, analyzed, and shared by the DASC on behalf of the entire cohort and all the CRS. These elements are recommended to include hardware security, software security, security protocols, encryption at rest and in transit, access control, incident response plan, regular audits, staff training, contingency plans, and regular reports to the Executive Committee and to NIH.
    
3. Biospecimens Protection Plan (Required) (DASC_biospecimens.pdf): The DASC Biospecimens Protection Plan must include details about the collection, processing, storage, shipping, and archiving of all types of participant biospecimens which will be added to the MWCCS biorepository. Details should be included about documentation (both physical records and electronic computer files), and processes and safeguards in place to protect participant confidentiality and to ensure that various types of possible errors in specimen retrieval and use do not occur. Plans to facilitate ease of electronic look-up of biospecimen availability for targeted groups of participants and/or particular study visit years should also be included.
    
4. Monitoring, Evaluation, and Quality Control Plan (Required) (DASC_monitor.pdf): The DASC Monitoring, Evaluation, and Quality Control Plan must propose specific metrics that will be used to track overall cohort performance in the arenas of (1) participant recruitment, engagement, retention, and completion of data collection protocols; (2) completeness and usability of specific data modules which are tied to scientific priority areas; (3) effectiveness of the operational working groups in ensuring quality control and high fidelity adherence to the JUMP by all MWCCS staff and investigators.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

Biographical Sketch: All mPIs, co-investigators, and the Project Director should be listed as key personnel with biosketch included. The biographical sketch should describe educational qualifications, technical and/or clinical certifications and licensure, relevant training, HIV comorbidities research experience, and specific experience with the MWCCS.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

Salaries and effort of all personnel should be commensurate with effort and responsibilities. Because mPI responsibilities include both local and cohort-wide activities under the cooperative agreement funding mechanism, the minimum effort for each individual mPI must be at least 20% (2.4 months).

Applications must include budget support for the following activities and personnel:

• Travel funds for the mPIs, the Project Director, and other DASC investigators and staff as appropriate, to attend an annual project meeting in Bethesda MD.
• Travel funds for selected DASC investigators and staff to participate in CRS site visits for the purpose of data systems training and quality control monitoring.
• All costs associated with required outreach and training activities to promote wider use of the MWCCS data archive by the HIV scientific research community.

Budget Justification:

The budget justification for each person (whether or not they are key personnel) must include a statement about which specific aims they will be responsible for or contributing to. Blanket statements such as “all investigators will contribute to all specific aims” are not acceptable. Rather, statements must be specific and defined. For example, “Ms. Robinson will lead Specific Aim 3.a and contribute to Specific Aim 4.”

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Applicants should consult the list of detailed responsibilities for the DASC, including Areas of Joint Responsibility, in Section VI. Cooperative Agreement Terms and Conditions of Award as they prepare the Research Plan section of their application.

Specific Aims

DASC Specific Aims should be detailed and measurable, and cover all areas of DASC core responsibilities as described in this NOFO, including any additional activities or initiatives not specified here.

Research Strategy

The following broad topic areas should be included in this section, organized and titled as deemed appropriate by the applicants. Overall, applicants should integrate review of past accomplishments and milestones for the 2019-2025 period with reflections on, and plans for, innovations and improvements to optimize the essential services that the DASC will provide to the CRS, the LACC, the scientific working groups, NIH, and the broader scientific community. Applicants will provide 4 separate technical attachments on important activity areas (Systems Modernization, Data Security, Biospecimens Protection, and Monitoring, Evaluation and Quality Control). Therefore, the Research Strategy section of the proposal should not repeat language from the technical attachments, but rather should be written for a broadly multidisciplinary audience of peer reviewers and NIH program staff.

Data Systems and Data Collection: Include justifications, timelines, and specific plans (avoiding technical intricacies which should be included in the supplements as needed) for essential core activities related to (1) modernization and major improvements in Gemini or conversion to a cloud-based system (e.g. RedCap), (2) data security (including encryption, secure data transfer protocols, remote work and access control, ongoing cohort-wide staff training and credentialing, security audits, and security incident management and reporting), contingency plans for likely problem scenarios, and (3) other information as deemed appropriate by the applicants.

Data Processing, Quality Control, Archiving, and Biospecimens Protections: Describe planned improvements and enhanced efficiencies for these core activities, in the context of the new JUMP annual visits which will commence in October 2026. Include plans for training CRS staff and investigators on key issues and responsibilities. CRS applicants have been instructed to budget funds for in-person staff trainings at the DASC as needed. In addition to in-person trainings, innovative and complementary training modalities may be proposed (e.g. establishment of training manuals, a perpetual video training library, help-desk office hours, live zoom training webinars, etc).

Collaborations and Communications: Establish plans to work collaboratively and communicate effectively with the LACC, the CRS, scientific and operational working groups, NIH staff, and outside investigators. Describe and justify any new or continuing operational working groups that will provide critical advising and oversight to the DASC for key areas of responsibility.

Data Dissemination and Training: At least one public data release annually for the length of the award is mandatory. Annual MWCCS data releases should employ the NHLBI-recommended Data Freeze Approach. Each annual public data release should be accompanied by comprehensive and end-user friendly data dictionaries and codebooks (supported by standardized vocabulary mapping and metadata) which are accessible to outside investigators as well as MWCCS investigators and staff. Describe new and innovative strategies planned to provide training (at multiple levels of technical expertise) to MWCCS investigators and staff and outside investigators (including ESIs and trainees) and ongoing technical support for the duration of the project period. Leveraging of available NHLBI tools, such as BioData Catalyst, is recommended.

Program Evaluation: Describe plans (including frequency and timelines) to evaluate internal cohort progress toward meeting operational and scientific specific aims in the arenas of: (1) participant recruitment, engagement, retention, and completion of data collection protocols; (2) completeness and usability of specific data modules which are tied to scientific priority areas; (3) research productivity of MWCCS scientific working groups and investigators; (4) effectiveness of the operational working groups in ensuring quality control and high fidelity adherence to the JUMP by all MWCCS staff and investigators.

Analytic Leadership and Innovations: Provide a comprehensive data analytic strategy which addresses important methodological, statistical, and data science issues relevant to the MWCCS cohort. Relevant analytic topics include but may not be limited to:

• Statistical approaches to, and empirical justifications for, parsimonious data redaction and masking in all publicly released data files with the goal of ensuring protection of participant identities while minimizing negative impacts on data usability.
• Analytic approaches to etiologic research which investigates multilevel influences on HIV comorbidities and outcomes (e.g. biological, individual, familial, neighborhood, region).
• Statistical approaches to non-response bias, missing data over multiple cohort visits and multiple data domains, and participant mortality and loss-to-follow-up.
• Rigorous analytic strategies to compensate for any non-comparability of study groups in analyses which compare PLWH and PLWOH.
• Innovations in data visualizations for both internal (operational) and external (public data dissemination) purposes.
• Innovations in longitudinal cohort outcomes analytic techniques.
• Innovations in training and dissemination such as the use of scientific analysis notebooks (e.g. Jupyter Notebooks, Google Collab) to provide step-by-step analytic approaches.

This section should also include justification for any DASC-supported co-investigators and discussion of how they will support MWCCS investigators and staff with data analyses, data visualizations, and co-authoring of concept sheets and scientific publications.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Additionally, applicants should consult and incorporate the NHLBI Supplement to the NIH Policy for Data Management and Sharing into their DMSP as applicable. This includes, but is not limited to, plans to share scientific data through existing NIH-supported Scientific Data Repositories, Ancillary Studies, and the Data Freeze Approach.

Data Repositories

NHLBI-supported researchers are expected to share scientific data through existing NIH-supported Scientific Data Repositories or other repositories that have the desired characteristics described in the Supplemental Information to the NIH Policy for Data Management and Sharing: Selecting a Repository for Data Resulting from NIH-Supported Research. NHLBI encourages submission of data into NHLBI BioData Catalyst (BDC), especially for data from studies that must comply with NHLBI’s Accrual of Human Subjects (Milestones) Policy and for those projects supported by funding opportunity announcements that encourage data deposition into BDC. NHLBI also encourages the submission of data into BDC for NHLBI projects and ancillary studies to NHLBI parent studies subject to the NIH GDS Policy. For data submitted to repositories other than BDC, an appropriate globally-unique, persistent identifier with sufficient metadata should be shared with NHLBI to promote FAIR principles and populate a master index for data generated from all NHLBI-supported research.

NHLBI discourages the deposition of data in multiple places, which may incur issues of version control and excess storage costs. If researchers need to deposit data generated from NHLBI support into more than one repository, the rationale for this need should be provided within the Data Preservation, Access, and Associated Timelines element in DMS Plans. When approved for deposition in multiple repositories by appropriate NHLBI staff, for data deposited in repositories other than BDC, an appropriate globally-unique, persistent identifier for each repository, with sufficient metadata, should be provided to the NHLBI to promote FAIR principles.

Ancillary Studies

NHLBI defines ancillary studies as studies that collect new data or derive data for purposes that are separate from the main “parent” study. The goal of ancillary studies is to extend scientific knowledge beyond the parent study’s original scope. NHLBI ancillary studies are primarily supported by NIH funds but may also be funded, in part or whole, by other sources such as non-profit and private sector organizations. Studies approved as ancillary, regardless of funding sources, to an NHLBI-funded parent observational study or clinical trial (including studies co-funded by multiple institutes, centers, and offices or to which NHLBI provides administrative oversight) are required to adhere to the parent study’s data sharing policies as a condition of approval. The requirements of data sharing agreements between NHLBI-funded parents and their ancillary studies should be consistent with the principles of the NIH DMS Policy.

Data sharing requirements are outlined in the agreement between the parent and respective ancillary study, and it is the responsibility of the ancillary study principal investigator to state in writing to the parent study steering committee any special circumstances that would preclude or limit data sharing. As specified in contract terms or award terms, designees from the parent studies shall submit updated and new ancillary data to an NHLBI-approved data repository on the same data submission timeline as the parent data (for example, core exam data, annual event surveillance, etc.). Ancillary study principal investigators should get advance approval from the parent study steering committee for any plans to share data with other repositories which have characteristics consistent with those described in the Supplemental Information to the NIH Policy for Data Management and Sharing: Selecting a Repository for Data Resulting from NIH-Supported Research.

Data Freeze Approach

To maximize the value of data sharing with the biomedical research community and control study and repository costs, NHLBI allows Institute-supported studies to use a comprehensive data freeze approach to meet NIH Data Management and Sharing policy requirements. This approach requires sharing comprehensive data freezes of scientific data throughout the funded project periods in advance of publications rather than sharing small subsets of extensive data on a per-publication basis. For more information on the Data Freeze Approach, see the FAQ page

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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, NHLBI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group convened by the NHLBI, in accordance with NIH peer review policies and practices, 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 NOFO.

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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 Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

• Each U01 CRS project, the U01 (DASC, and the U01 LACC will receive a separate award, and the mPIs of each respective award will have control over their project's operating budget.
• All recipients will be required to attend annual cohort meetings and participate in the cooperative nature of the cohort.

The Clinical Research Sites will have primary responsibility for:

• The CRS mPI(s) will be responsible for the scientific and technical direction of the project and agree to abide by cohort policies and guidance. This includes accepting the actions and recommendations approved by the Steering Committee, the Executive Committee, and the Observational Study Monitoring Board. In addition, each CRS mPI must agree to accept participation of and close coordination and cooperation with the following stakeholders: NIH Program Staff, the LACC, and the DASC in those aspects of management of the project as described below.
• Specific responsibilities of the CRS include but are not limited to:
  • Collaboratively 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) as needed
  • Participating fully in required activities and responsibilities of the MWCCS Executive Committee
  • Accepting and implementing the policies approved by the MWCCS Executive Committee consistent with applicable grant regulations
  • Monitoring CRS staff and investigator adherence to clinical and laboratory protocols
  • Obtaining all requisite study and protocol IRB approvals
  • Scheduling participant clinic visits, capturing study-specified outcomes, and completion of study visit components including consent, questionnaires, in-person examinations, and collection of biospecimens
  • Tracking retention and follow-up of participants at the CRS and making these data available to the LACC and the DASC on a monthly basis
  • Close monitoring of participant safety and unexpected adverse outcomes
  • Collaborating closely with the LACC and the DASC to establish and implement quality assurance and control processes in all study activities, including data analyses led by the CRS
  • Participating in all relevant staff trainings and ongoing evaluation of CRS personnel interview skills, HIV counseling, and examination techniques
  • Implementing training, ongoing evaluation, and quality control for all CRS laboratory staff and procedures for handling and testing of participant specimens, including web-based tracking of delivery to central repository
  • Implementation and maintenance of strict data security procedures for the collection, storage, analysis, and archiving of participants' personal health information
  • Taking rapid corrective actions for all supported activities when deficits or problems are identified
  • Cooperating fully with the LACC, the DASC, and NIH programmatic, technical, and administrative staff
  • Providing research opportunities and mentorship to early career investigators, including those at the pre-doctoral, post-doctoral, and early independent career stages
  • Developing and supporting collaborations with external investigators, as appropriate
  • All other specific required activities described in RFA HL-26-009 but not listed here
• Recipients will retain custody of, and have primary rights to, the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. However, recipients will implement the approved Data Management and Sharing Plan (see Submitting an Application), which will be incorporated as an additional term of award and will be expected to share (make available) these data both within the consortium and with the scientific community. Recipients should comply with their institutional intellectual property policies and practices as approved in the award.

The Leadership and Coordination Center will have primary responsibility for:

• Clinical and scientific guidance and oversight of the MWCCS as a whole, including scientific leadership, scientific working group support, operational working group support, training pertaining to the clinical protocol and participant interactions, operational accountability, community and participant engagement, and promotion of the cohort to external stakeholders
• Establishing and maintaining congenial, respectful, and productive working relationships with each of the CRS, the DASC, the NCAB, and NIH Program Staff
• Collaborating closely with the mPIs of the DASC to ensure clear delineation of responsibilities, frequent communications, and smooth central functioning of various aspects of cohort management and support of the CRS for both cohort operational specific aims and scientific investigational aims
• Serving as permanent co-chair(s) of the MWCCS Executive Committee, with an additional co-chair elected or selected by the CRS mPIs, in order to facilitate leadership continuity over time, accountability, and timely communications
• Developing and leading a consensus process for finalizing and implementing the Joint Unified Modular Protocol (JUMP)
• Collecting and tracking study and protocol approvals, including IRB approvals, ancillary studies, and renewals
• Providing clinical, scientific, and operational leadership, accountability, and technical assistance to the cohort-wide efforts to ascertain and adjudicate significant clinical events and outcomes for all ever-enrolled participants (e.g. major adverse cardiovascular events (MACE), incident cancers, HIV/AIDS-related comorbidities, hospitalizations, deaths), as allowable per participant consents
• Coordinating, facilitating, and monitoring clinical review committees' efforts to adjudicate all significant clinical events in a timely fashion
• Actively participating in specific scientific investigations when appropriate
• Working collaboratively with investigators proposing ancillary study components
• 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 resources are allocated to meet local and cohort-wide aims
• Arranging, conducting, and distributing documentation for regular conference calls for Scientific Work Groups (SWG), Executive Committee (EC) and other committees, and annual meetings of cohort investigators
• Ensure high-fidelity adherence and quality outcomes for all clinical and laboratory protocols, via development of enhanced resources for staff training, guidelines for credentialing, regular monitoring and oversight for quality control purposes, and additional approaches as proposed by the LACC mPIs
• Coordinating implementation of new or modified protocols approved by the Executive Committee
• Consult and coordinate with the DASC on all areas of protocol implementation, tracking, quality control, and data collection which involve overlapping areas of responsibility (e.g. the overlap between clinical techniques and collection of clinical data). Providing teaching and training to cohort personnel at the CRSs to assure that the questionnaires continue to be administered in a uniform, standardized fashion
• Providing a forum for posting, circulating and consolidating input on draft manuscripts to co-authors, NIH co-funding ICO Project Scientists and Program Officers
• Planning and hosting an annual symposium or workshop to inform the broader research community about scientific progress of the MWCCS and provide an opportunity for development of collaborations with outside investigators
• All other specific required activities described in RFA HL-26-011 but not listed here

The Data Analysis and Sharing Center will have primary responsibility for:

• Modernizing and maintaining all data collection systems for the MWCCS, with continual quality-improvement updates to facilitate CRS data collection activities.
• 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
• Implementing uniform methods to capture participant data on vital and health status, risk factors, and other personal information
• Developing data linkages with health information exchanges, clinics, and medical centers to ascertain events of clinical significance, ideally through automated data collection.
• Performing centralized data analyses to support MWCCS scientific investigations
• 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
• 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 repository 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
• Collaborate with the biorepository to ensure accurate inventory of specimens in the 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, consistent with NIH and NHLBI policies
• Producing an annual study progress report to be distributed at the annual EC meeting in collaboration with the LACC.
• Maintaining the system for tracking cohort research and providing study progress reports at the semi-annual investigator meeting
• Maintaining an ongoing, up-to-date web-based searchable list of all MWCCS publications, manuscripts in progress and presentations using cohort data
• Maintaining internal and public websites, posting study documents on internal website
• All other specific required activities described in RFA HL-26-010 but not listed here

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

The NHLBI Project Collaborator will have substantial involvement in the conduct of this activity through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. In addition to the NHLBI Project Collaborator, other NHLBI Program Officials and Grants Management Officers will oversee the normal program stewardship of the cooperative agreements. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property will reside with Senior Institute management, separate organizational components, and/or oversight committees. Other NHLBI staff members such as direct line supervisor 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.

In addition, each co-sponsoring institute will nominate at least one Project Collaborator, Scientist, or Program Officer to provide scientific oversight, technical assistance, and coordination aligned with their institute’s scientific priorities for the MWCCS. NIH Program Staff activities will include but may not be limited to:

• Participating in the NIH Scientific Oversight Committee (N-SOC) which will be comprised of representatives from all MWCCS co-funding ICOs, the Office of AIDS Research (OAR), and other NIH stakeholders as appropriate
• Participating in study leadership via voting membership in the MWCCS Executive Committee, close and regular consultations with the LACC and the DASC, and regular communication with NIH stakeholders in the MWCCS
• Reviewing all relevant study protocols and data
• Monitoring study progress, results and quality assurance across all sites
• Participating in selected Scientific Working Groups and Operational Working Groups as appropriate
• Providing technical assistance and advice to the recipients as appropriate
• Providing mentoring and counseling to MWCCS investigators, including trainees and early stage investigators, as appropriate and needed
• Assisting with the development of research protocols
• Ensuring disclosure of conflicts of interest and adherence to NIH policies
• Facilitating collaborations between the recipients and other NIH-sponsored programs investigators, or organizations that may contribute to the study's goals
• Assisting in the interaction between the recipients 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

Areas of Joint Responsibility include, but may not be limited to:

MWCCS Executive Committee

The EC is the primary decision-making body for this multi-site collaborative research study. All MWCCS stakeholders will have representation on the EC and participate in sharing decision-making on all topics of broad important to cohort operations. One or more of the LACC mPIs will serve as permanent EC Chair, with an additional EC Chair chosen by the CRS mPIs.

As an explicit condition of their NIH cooperative agreement awards, all recipients must agree to both actively participate in the EC and to collegially abide by its decisions and policies pertaining to all aspects of study operations.

Specific areas of responsibility for EC members include but may not be limited to:

• Protection of participant safety via regular monitoring and responsive corrective action when needed
• Promotion of scientific integrity, validity, and excellence in all areas of study operations and scientific investigations
• Facilitation of rapid and regular data sharing with the broader scientific community to increase the pace, significance, and impact of MWCCS HIV populomics research.
• Participation in regular EC video calls, annual cohort meetings, and ad-hoc trainings, research meetings, and other gatherings as needed
• Assistance to and support of the NCAB
• Substantive contributions to, and participation in, Scientific Working Groups and Operational Working Groups as appropriate for individual areas of expertise.
• Cooperation and collaboration with the LACC and the DASC on relevant areas of study operations and scientific investigations

MWCCS Steering Committee

The SC is a subset of the EC which meets more frequently than the full EC and advises the EC on important operational and scientific issues. All MWCCS stakeholders (CRS mPIs, CRS Project Directors, LACC mPIs, DASC mPIs, NIH Program Staff, NCAB members) should have at least one representative on the SC. The EC Co-Chairs will also serve as SC Co-Chairs.

Scientific Work Groups

SWGs are comprised of subject-matter scientific experts from the CRS, the LACC, the DASC, and NIH who collaborate on new and continuing scientific investigations which will result in public presentations and peer-reviewed publications. SWGs should also include and provide mentorship opportunities for early-stage investigators, including pre-doctoral and post-doctoral trainees. The LACC will provide scientific leadership and coordination of operations (e.g. scheduling of meetings, maintenance of records, facilitation of communications), while the DASC will monitor SWG productivity and outputs via monitoring of agreed-upon productivity metrics and regular reporting to the EC. The number and topic areas of the SWG will be determined by the MWCCS investigators (LACC and EC); however NIH expects that these topic areas will be well-aligned with the NIH scientific priority areas detailed in Section 1 of this NOFO. Furthermore, NIH expects that there will be no gaps in coverage – in other words there should be no NIH priority area which is not covered by at least one SWG.

Operational Work Groups

OWGs have the purpose of bringing together scientific and methodological experts from among MWCCS investigators and staff, as well as NIH staff as appropriate, to consider and advise the LACC, the DASC, and the EC on topics of significance to cohort operations. For example, a Laboratory Measures Working Group might have the mandate of reviewing and ensuring quality and high-fidelity adherence to study protocol in the collection, processing, storage, and analysis of participant biospecimens. The number and topic areas of the OWGs will be proposed by the LACC and the DASC and agreed to by the EC. Coordination, administrative support, and monitoring of the OWGs will be the responsibility of either the LACC or the DASC, depending on the specific topic area.

National Community Advisory Board

MWCCS investigators and staff from the CRS, LACC, and DASC and NIH staff will collaborate to support the NCAB, its members, and its planned activities as requested by NCAB leadership. The LACC will provide leadership and coordination for cohort support of the NCAB, including centralized administration and payment of stipends and travel reimbursements to NCAB members for required annual national meetings.

Observational Study Monitoring Board

The OSMB is an independent board of scientific, clinical care, and bioethics experts who monitor MWCCS progress and advise the Director of NHLBI on matters of study performance, participant safety, return of clinical results, informed consent, participant burden, and overall study success. All MWCCS stakeholders collaborate to support the OSMB through provision of any requested data or information about study operations and scientific investigations, including making presentations and/or preparing topic-specific reports as requested by the OSMB members.

Violations of Terms and Conditions of Cooperative Agreement Awards

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

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

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Dr. Elizabeth Pathak
National Heart, Lung, and Blood Institute (NHLBI)
Email: [email protected]

Paul Anthony Burns, Ph.D., M.S.
NIMHD - NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES
Phone: 301-451-4509
E-mail: [email protected]

Elizabeth Anne Barr, Ph.D.
ORWH - Office of Research on Women's Health
Phone: 301.402.7895
E-mail: [email protected]

Gregory Greenwood, Ph.D.
National Institute of Mental Health (NIMH) 
Telephone: 240-669-5532
Email: [email protected]

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

Richard A Jenkins
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 301-443-6504
E-mail: [email protected]

Trinh T Ly
NIDCD - NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Phone: 301-827-0007
E-mail: [email protected]

Ann Namkung Lee, MPH
National Institute of Aging (NIA)
Telephone: 301-496-6838
Email: [email protected]

Geraldina Dominguez, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3420
Email: [email protected]

Hiroko Iida, DDS, MPH
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-594-7404
E-mail: [email protected]

Leigh A. Willis, PhD, MPH
National Institute of Nursing Research (NINR)
Telephone: 240-687-1634
Email: [email protected]
 

Gerald B. Sharp, Dr.P.H.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3217
Email: [email protected]

Kendall J. Bryant, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA) 
Telephone: 301-402-0332
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
Email: [email protected]

Lynn Rundhaugen
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-4546
Email: [email protected]

Priscilla Grant, J.D.
NIMHD - NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES
Phone: 301-594-8412
E-mail: [email protected]

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

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Pamela G Fleming
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 301-480-1159
E-mail: [email protected]

Samantha J Tempchin
NIDCD - NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Phone: (301) 435-1404
E-mail: [email protected]

Laura Pone
National Institute on Aging (NIA)
Telephone: 301-451-9956
Email: [email protected]

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: [email protected]

Gabriel Hidalgo, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: [email protected]

Jenna Briggs
National Institute of Nursing Research (NINR)
Telephone: 301-480-0639
Email: [email protected]
 

Robert Kirker
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-3176
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Section VIII. Other Information

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 2 CFR Part 200.