Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)
National Cancer Institute (NCI)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)

Funding Opportunity Title

Limited Competition – Multicenter AIDS Cohort Study (MACS) Clinical Research Sites (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA-AI-08-008

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

RFA-AI-13-011

Companion Funding Opportunity

RFA-AI-13-010, UM1 Multi-Component Research Project Cooperative Agreements

Number of Applications

Only one application per applicant institution is allowed, as described in Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.855, 93.856, 93.399, 93.395, 93.394, 93.242, 93.279

Funding Opportunity Purpose

The purpose of this FOA is to renew the clinical research sites (CRSs) of the Multicenter AIDS Cohort Study (MACS) and continue support for clinical, epidemiologic and basic research on a cohort of men who report sex with men (MSM). The MACS will continue to characterize the long-term, natural and treated history of HIV infection in MSM, provide insight into the clinical epidemiology of HIV, and further our understanding of predictors of disease among HIV positive MSM. The MACS CRSs will also transition to a rolling cohort design to replace existing cohort members who die or otherwise are permanently lost to follow-up. Due to the demonstrated capacity to recruit and retain this unique population, the depth of data and specimens collected over decades, and the need for continued follow-up, this competition will be limited to the current four clinical awardee institutions for the MACS CRSs.   

Key Dates
Posted Date

March 8, 2013

Open Date (Earliest Submission Date)

June 11, 2013  

Letter of Intent Due Date(s)

June 11, 2013  

Application Due Date(s)

July 11, 2013, 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.

AIDS Application Due Date(s)

July 11, 2013, by 5:00 PM local time of applicant organization.   

Scientific Merit Review

November, 2013  

Advisory Council Review

January, 2014  

Earliest Start Date

April, 2014 

Expiration Date

July 12, 2013  

Due Dates for E.O. 12372

Not Applicable  

Required Application Instructions

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

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this FOA is to renew the clinical research sites (CRSs) of the Multicenter AIDS Cohort Study (MACS), and continue support for clinical, epidemiologic, and basic research on a cohort of men who report sex with men (MSM). The MACS will continue to characterize the long-term, natural and treated history of HIV infection in MSM, provide insight into the clinical epidemiology of HIV, and further our understanding of predictors of disease among HIV positive MSM. The MACS CRSs will also transition to a rolling cohort design to replace existing cohort members who die or otherwise are permanently lost to follow-up. Due to the demonstrated capacity to recruit and retain this unique population, the depth of data and specimens collected over decades, and the need for continued follow-up, this competition will be limited to the current four clinical awardee institutions for the MACS CRSs.

Background

Improvements in antiretroviral (ARV) therapies for HIV over the last 20 years have dramatically transformed HIV infection from an illness with nearly 100% fatality to a chronic disease. Therapy approaches have changed over time, drug toxicities have declined, and the benefits of earlier treatment have become more evident.  Clinical epidemiology and basic science research are needed to evaluate outcomes for different subsets of patients to better understand their clinical course of disease and to evaluate the causative factors.  Studies that compare people with and without HIV infection, people exposed to different ARV treatments, people of different ages, and people with various underlying characteristics and co-morbidities are necessary to properly attribute virus and therapy exposures to outcomes. Cohort studies that define participants by exposure group, and then follow them prospectively to measure outcomes, are optimal.

The HIV-1 epidemic in the U.S. continues to infect predominantly MSM, and in particular young African American men.  In 2009, MSM accounted for 61% of all new HIV infections among U.S. men and women.  Specifically, the U.S. Centers for Disease Control and Prevention (CDC) has reported 10,800 new HIV cases in African American MSM as of 2009, and of these 6,500 (60%) occurred among those age 13-29, a 48% increase for this age group than in 2006. Among 11,400 white MSM infected in 2009, the differences by age group are less striking with only a slightly higher number of cases among men age 40-49 years as compared to other age groups.  With regard to risk factors for HIV infection, CDC data also show 86% of all white men, 73% of all African-American men, and 81% of all Hispanic men with HIV were MSM as of 2009.  As improved ARV therapy has reduced HIV mortality, HIV/AIDS now affects men of all ages.  Older individuals with HIV are at high risk of HIV-associated morbidity and AIDS deaths.  Over one-third of all AIDS deaths in 2009 were among people over 50 years of age.

Over the next five years, based on the age structure of the cohort alone, MACS men are expected to experience significantly increased numbers of diseases and deaths.  Transition to a rolling cohort will allow MACS to accrue men who are more representative of the U.S. epidemic; i.e., those recently infected and not yet on therapy, and men treated under today’s therapy regimens. As noted at the proceedings of the Office of AIDS Research Advisory Council (OARAC) meeting in November 2011, the continued severity of the HIV epidemic among MSM, and psychosocial issues impacting MSM at most risk for acquiring HIV infection, remain important areas of research. The MACS is well positioned to evaluate the natural and treated history in men infected decades ago in order to determine if there are important differences in the HIV disease process as treatments for HIV evolve and the duration of infection increases. 

History of the MACS and Contributions to HIV and AIDS Research

The MACS has been able to chronicle the HIV-1 epidemic from its inception, through early therapy eras, and to today’s highly effective ARV therapies.  In the early years of the study the MACS conducted basic research in virology and immunology, documented the clinical epidemiology of HIV, and investigated the pathology between HIV, related co-infections, and the host immune system. Equally striking since the relentless devastation and clinical failure of patients in the no-therapy era, is the success of current highly effective and less toxic medications that have substantially reduced viral replication in blood down to undetectable levels and have normalized many immune functions.  Today HIV infection is best characterized as a chronic disease causing long-lasting immune deficiencies.  The character of these deficiencies, and the pathologies that may develop, are dependent on a range of factors including personal characteristics (genetics and behavior), HIV treatment patterns (treated early vs. late, and with more toxic vs. less toxic and more convenient regimens), and a patient’s underlying co-infections and co-morbidities.  The MACS cohort, with its breadth of data on men over the course of their infection and treatment, is uniquely able to study the complex interactions between these factors. MACS research has sought to define the clinical epidemiology of HIV among aging MSM, and to evaluate the predictive value of clinical tests to differentiate those patients at highest risk of poor outcomes. 

Enrollment to the MACS began in 1984.  Data and specimens are available from nearly 7,000 MSM enrolled in two major waves, one at study inception and another group of men from 2001-2003.  As of October 2012, active follow-up (one semiannual study visit in the last year) continues on over 2,291 men (50.6% HIV-negative and 49.3% HIV-positive).  The two visits per year include an extensive interview, administered face-to-face by trained interviewers.  Those components of the questionnaire that include questions about behavior and ascertainment of HIV and non-HIV-related care are administered by audio computer assisted self-interview (ACASI).  The study visit also includes a comprehensive physical examination and the collection of biological specimens linked to a large, high-quality national repository.  The nearly 28 years of clinical and interview data have created a large database, with over 90,000 person-years of follow-up.  The database includes evaluations beyond standard of care assessments such as carotid intimal media thickness, duel energy xray absorptiometry (DEXA) scan measurements, iohexol clearance derived renal function measures, medical record confirmation of key outcomes, standardized measures of physical functioning, results from intensive clinical testing, and novel research testing.  For example, the database includes longitudinal assessment of virologic and immunologic plasma and serum laboratory markers, genome-wide association studies (GWAS) and deep sequencing analyses on genes hypothesized to impact HIV susceptibility and disease progression.  Because laboratory and other test results from affiliated studies must be deposited into the overall MACS database, the depth of cohort data increases over time as these highly characterized participants remain in follow-up. Therefore, future research can build upon existing data and specimens without having to repeat tests, making data available to all investigators cost-effective and efficient.

The inclusion in MACS of HIV positive MSM but also a large comparator population of age-matched, HIV-negative MSM allows the study to sort out the effects of HIV from its treatment and morbidities related to age.  Because both groups of subjects undergo the same MACS protocol assessments, the study data can be adjusted for the contribution of confounders in the etiology of AIDS and other outcomes of interest.  In particular, as persons with HIV in the U.S. age, understanding the interactions between HIV and aging under long-term antiretroviral treatment requires controlling for HIV status, age, HIV progression and treatment history, and for other risk factors.  As of October, 2012 the median age of current MACS participants was 55 years (with about 70% greater than or equal to 50 years of age).  Continuing follow-up on the existing MACS MSM cohort of HIV-positive and HIV-negative age-matched controls, the only such long-term, longitudinal HIV cohort in existence, will be crucial for understanding the impact of the aging process on HIV infection, particularly as long-term outcomes increase in the near future.  

MACS investigators have produced over 1,200 publications  including studies on the following HIV-related topics: antiretroviral therapy, immunology, virology and HIV pathogenesis, co-morbidities, neuropsychology and psychiatry, malignancies, metabolic and body composition complications, physical and immunologic aging, cardiovascular disease, renal dysfunction, hepatitis, sexual behavior, dermatology, prevention of HIV infection, quality of life, health care utilization, HIV and host genomics, statistical methods for analysis of longitudinal data, drug and alcohol use and abuse, patient demographics, hearing loss and vestibular balance.  Because participants are seen twice per year, the design of the MACS can be modified to rapidly address new questions as they arise.

In addition to its long-standing role in informing HIV and clinical epidemiology, MACS conducts and supports research in basic sciences.  The stored specimens and clinical data are available to basic science investigators within and outside of the MACS, and have been used to answer questions on virology, viral evolution, immunology, co-infections, responses to therapy, genetics, and clinical disease markers.  The depth and quality of the repository make the study a unique resource for the research community. Data and specimens are available at no cost to any investigator including those with no ties to the MACS investigative teams.

The MACS core infrastructure also supports internal and external investigators through training and access to the cohort’s infrastructure, and repository, thereby allowing them to obtain ancillary grant awards to investigate a multitude of research questions.  MACS investigators have demonstrated a history of collaboration with several NIH-funded cohorts such as the Women's Interagency HIV Study (WIHS), the North American AIDS Cohort Collaboration on Research and Design  (NA-ACCORD), the Center for HIV/AIDS Vaccine Immunology (CHAVI), the AIDS Linked to the Intravenous Experiences (ALIVE), the Cohort Study of Chronic Kidney Disease in Children (CKiD), the HIV-CVD Collaborative, the Centers for AIDS Research (CFARs), as well as NIH Intramural programs of the NCI and NIAID. 

The requirements for the unified MACS Scientific Agenda is described in the FOA, Limited Competition Multicenter AIDS Cohort Study: Center for the Coordination, Analysis, and Management of the MACS (CAMACS) (UM1), and must reflect a research plan constructed by PDs/PIs of all CRSs and CAMACS.  

Overview of MACS and Science Management

Cohort Description: The current MACS clinical research site consortia are located in Los Angeles, CA (University of California at Los Angeles), Baltimore, MD (Johns Hopkins University), Chicago, IL (Northwestern University), and Pittsburgh, PA (University of Pittsburgh).  Each clinical site represents the population of HIV-infected MSM in the local metropolitan area.  The study began before HIV was identified, with an initial enrollment at the four clinical research centers of 5,622 MSM (2,196 HIV-positive and 3,426 HIV-negative but at risk).  In 1994, NIAID administratively censored 1,710 HIV negative men as a cost saving measure.  Additional enrollment of 1,350 MSM (688 HIV-positive and 662 HIV-negative) took place from 2001-2003, and more recently the Pittsburgh MACS consortium began recruiting highly active ART-naïve, AIDS-free MSM 18-30 years of age in Pittsburgh, PA (and a satellite clinic at the Ohio State University in Columbus, OH). 

Working Groups: Specific areas of scientific focus are cultivated by collective groups of investigators with common research interests and goals, collectively known as the MACS Working Groups (WG). Each WG will include the PD(s)/PI(s), local project managers and clinical experts, as well as senior and junior investigators at participating institutions (with outside consultants included as needed). The WG’s are expected to shepherd cohort-wide projects through completion, encourage the organization of related efforts across the clinical sites, promote collaboration across the different disciplines represented by the various WG’s, and explore current and future scientific questions germane to that area of the overall MAC Scientific Agenda.

MACS Executive Committee: The MACS Executive Committee (EC) is responsible for the overall common scientific aims of the Program and the progress of WGs.  The EC is composed of the PD(s)/PI(s) from each awardee institution, and the Project Scientists from each NIH co-funding institutes and centers.  EC members are expected to prioritize the MACS Scientific Agenda, oversee the completion of research within MACS and assist external investigators who wish to conduct research using current, or to-be-collected, data, specimens, and/or other resources.  In addition, changes to existing study procedures, and proposals for new research (submitted by internal and external investigators) are reviewed with approval and prioritization based on a consensus decision of the EC.  On rare occasions when consensus is not achieved, approval and prioritization may be based on a majority vote of the EC. 

Interaction with Community Advisory Boards (CABs):  An optimal interaction between MACS sites and communities from which participants are drawn is critical.  The MACS EC is responsible for ensuring that individual MACS sites maintain ties to their patient communities and interact in the spirit of collaboration that is mutually responsive.  Each MACS site is responsible for budgeting appropriate expenses for the support of these interactions.

MACS Data Collection

MACS participants are evaluated every six-months within a prescribed window of time called the “visit wave.”  Clinical Research Sites must continue to demonstrate the capacity to conduct the core MACS data and specimen collection protocol and MACS-wide substudies.

Interview: Centrally scripted interviews are conducted at each visit.  Self-reported data collection includes the following:  sociodemographic information; health care utilization; general medical history; use of prescription and non-prescription medications such as a complete antiretroviral medication inventory; use of alcohol, tobacco and illicit drugs; sexual risk behaviors; beliefs regarding HIV and its treatment; neuropsychological status; assessment of daily living activities.  Interview content is evaluated and may be revised every six months by the EC.  To maximize data quality, centralized training is conducted by CAMACS or external consultants.  Training, periodic assessment of quality and the development of question-by-question guidance materials are the responsibility of CAMACS working with the investigative team leading a specific research project.

Clinical Outcome Confirmation/Ascertainment:  All reports of AIDS-related diagnoses are confirmed by medical record abstraction.  State cancer registries and the National Death Registry are used to augment and confirm the outcome data that are collected.

Clinical Examination:  Physical examinations are conducted at each regular visit by a health care practitioner who has completed the MACS physical exam training.  The exams include standardized assessment of vital signs (e.g., blood pressure); anthropometric measures; a skin and oral examination; an examination of lymph nodes and abdomen; and measures of frailty.  The MACS protocol currently includes anal pap smear specimen collection referral for anoscopy and/or biopsy when indicated.  Men needing further treatment are referred for care outside of the MACS, using referral mechanisms that take into account the participant’s insurance coverage and ability to cover associated costs.

Laboratory Testing:  All MACS participants are asked to provide urine and fasting whole blood samples for baseline and follow-up laboratory monitoring.  As new areas of inquiry are identified, additional samples may be requested. 

National and Local Repositories: Urine, plasma, serum, lymphocytes and cell pellets are collected and stored at local MACS CRSs and nationally at the NIAID HIV/AIDS Specimen Repository.  Requests from internal and external investigators to access reposited samples are made to the MACS EC using the concept sheet submission process.  In addition, available tissue biopsy samples are to be provided to the AIDS and Cancer Specimen Resource.

Data Entry and Management:  Currently, data are collected at the sites on paper forms that are entered into a web-based data system updated each visit cycle and maintained by CAMACS.  A data manager at each clinical site must oversee data entry, and must work with CAMACS to ensure that datasets are complete and ensure methods for recording the data are comparable between sites.  CAMACS staff members are responsible for the central management of data, which includes data quality oversight, creation of summary variables to facilitate harmonized analysis, analyzing data for MACS research, and preparing analytical datasets for external investigators who will perform analyses.

Research Scope of the MACS

The data and specimens collected and archived by the MACS provide the basis for a wide-ranging Scientific Agenda of interest to the NIAID and partnering components who co-sponsor the study.  These include the following focused areas, although this list is not exhaustive as other areas of interest may be identified in the future.

HIV Disease Pathogenesis: Proposed research may take advantage of reposited specimens collected across key time points, may use data already generated on participants including genetic and longitudinal data on immune markers, or may be prospective in nature requiring additional specimen collection and testing.

Antiretroviral (ARV) Treatment: The composition of the MACS cohort will reflect therapy use patterns representative of the U.S. HIV-positive population.  Therapy use in the cohort is therefore likely to be diverse, and differences in therapy exposure, effectiveness, and program delivery are of particular interest.

Comorbidities:   Research in MACS will be able to maximize use of the existing and new cohort members, specimens and data repository to account for the complex interrelationship between covariates, for example, genetics, co-infections, co-morbidities, ARV therapy, behavior, and aging.

Malignancies: The incidence of many cancers will continue to increase as MACS participants continue to age.  Reposited specimens provide an ideal mechanism to study predictors prior to the cancer diagnoses.  MACS is expected to contribute specimens to the AIDS and Cancer Specimen Resource repository, and to collaborate with other HIV researchers where needed to ensure sufficient statistical power to address rare cancers and pre-malignant conditions.

Substance Use: Substance use and abuse remain an underlying issue for risk of HIV acquisition and HIV disease progression among MSM.  Current or historical use of alcohol, tobacco, illicit drugs and other substances relate to other behavioral issues for the cohort including abuse, mental health status, and educational level.  Research in all areas of the MACS Scientific Agenda can take into account the impact of substance use, in both integrated and specifically focused research studies.  Both the determinants and the consequences of substance use are of interest to the extent that they may help explain substance use effects related to HIV, its treatment and its biologic, clinical and/or behavioral outcomes.

Epidemiological and Statistical Methods:  Innovative methodological approaches for the conduct, design and analysis of cohort studies of HIV/AIDS are needed to maximize the use of observational data to inform on health outcomes.  Novel ways to improve the quality of self-reported data, to improve linkages between health care data (clinical care and pharmacy data), and standardize collection techniques and harmonize data bases are needed to improve research.  Development of new statistical approaches to account for the complexity of MACS data is also encouraged.

Through this FOA, NIAID will support epidemiology of HIV infection and its treatment including the range of acute and chronic pathologies in MSM over the full course of their adult life with HIV.  The FOA also supports research on behavioral components of HIV care including how younger MSM access care, remain in care, initiate HIV therapy, suppress virus, and maintain viral suppression.

It is also expected that the MACS consortium will continue to provide a platform for collaborations that lead to independent, investigator-initiated research projects.  MACS is also expected to continue established collaborations with the Women’s Interagency HIV study to facilitate research on gender related differences in HIV.   

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

Renewal

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

 NIAID and partner ICs intend to commit an estimated total of $17.9M to fund four CRS awards and the current Center for the Coordination, Analysis, and Management of the MACS (CAMACS).

Award Budget

Application budgets are limited to $4.2M in total costs per year, but must reflect actual needs of the proposed project.

Award Project Period

The maximum project period for each award is five years.  

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Only applications from the current MACS clinical research sites (CRSs) may be submitted in response to this limited competition:

Foreign Institutions

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 allowed.

Required Registrations

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.

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

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

Applications proposing Multiple PD(s)/PI(s) are particularly appropriate for this program, including those with diverse expertise in clinical infectious diseases and HIV epidemiologic research. 

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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.

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:

The letter of intent should be sent to:

Tracy A. Shahan, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3140, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS mail)
Telephone: 301-451-2606
Email:  TShahan@niaid.nih.gov

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

PHS 398 Cover Letter

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Specific Aims of the CRS application should reflect the aims of the proposed consortium.

Research Strategy: Start each section with the appropriate heading in order, addressing Significance, Innovation, and Approach, and including the appropriate information.  Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

Under the appropriate headings within the Research Strategy section:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification: 

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

3. Submission Dates and Times

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

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

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.   

6. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.    

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Has the applicant demonstrated success in utilizing the existing cohort to advance our understanding of HIV infection and related outcomes? Does the CRS applicant demonstrate capacity to enroll MSM appropriate for the research agenda proposed?  Does the application demonstrate leadership in HIV/AIDS research through a strong publication record?  

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  Do the proposed PD(s)/PI(s) possess the skills, knowledge, commitment, and professional experience in observational clinical research needed to carry out the proposed research plans?  Have the PD(s)/PI(s) demonstrated a history of productive working relationships as scientific collaborators?  Are the time commitments of staff appropriate to accomplish the stated aims?  Do the PD(s)/PI(s) propose an organizational structure that facilitates collaboration within and outside of the MACS? Have the PD(s)/PI(s) and site investigators demonstrated productivity as first or senior authors on MACS publications? 

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application provide innovative ways to integrate local and MACS-wide aims among the proposed projects including the use of technology, non-MACS sources of clinical data, and other sources of funding to achieve the stated scientific goals? Does the application demonstrate flexibility such that the applicant is likely to be able to respond with innovative systems to address new questions related to HIV as they arise? 

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Does the applicant propose a feasible scientific research agenda that capitalizes on the MACS structure to achieve significant results? Are the proposed aims likely to foster significant scientific collaborations? Does the applicant propose a research area that is sufficiently flexible to address new research questions as new findings are released? Does the application propose a cohort that will appropriately address the research agenda in a representative population of US MSMs? Does the application demonstrate ability to access and recruit MSM who are in and out of HIV care? Are the scientific goals feasible given the size and make-up of the cohort? Are the core laboratory procedures well-coordinated, with adequate and appropriate quality control? 

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there sufficient access to target patient populations for replacing those lost to follow-up; are there established interactions with community advocacy groups?  Does the institution demonstrate a commitment to support the MACS investigators? Does the environment foster collaboration with other HIV/AIDS research scientists? 

Ability to Conduct the MACS Protocol

Does the application demonstrate successful ability to perform the standard processes for the core MACS data and specimen collection protocol, and MACS-wide substudies? Has the CRS applicant demonstrated capacity to access and recruit the target population? Does the CRS applicant describe how the team would be able to enroll and retain MSM in the current era?

Additional Review Criteria

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.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

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

Revisions

Not Applicable

Additional Review Considerations

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.   

Applications from Foreign Organizations

Not Applicable 

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases, 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:

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

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

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

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

Section VI. Award Administration Information

1. Award Notices

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

Project Scientists from NIAID and partnering components will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants or cooperative agreements. 

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

NIH Project Scientists will be responsible for:

A primary funding agency Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the NIH award notice.

Areas of Joint Responsibilities include:

MACS Executive Committee (EC):  The MACS EC consists of PD(s)/PI(s) from each CRS, CAMACS, and staff from the NIH co-funding ICs. Each PD/PI (CRS and CAMACS) is a voting member of the EC. In the case of multiple-PD(s)/PI(s), the PD(s)/PI(s) 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 MACS EC will be responsible for:

MACS Working Groups (WG): The MACS WG consists of PD(s)/PI(s) of each awardee, senior and junior investigators of awardees and outside consultants as needed.  The members of the MACS WG will be responsible for:

Intellectual Property

The awardee is solely responsible for the timely acquisition of all appropriate propriety rights, including intellectual property rights, and all materials needed for the awardee to perform the project.

Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any propriety rights, including intellectual property rights, or any materials needed by the awardee to perform the project.

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Program Generated Data, Software and Other Resources

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

The Programs funded under this FOA are expected to follow the requirements and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx) as well as those in the Data Sharing Guiding Principles for the NIAID/DMID Systems Biology Program (http://www.niaid.nih.gov/LABSANDRESOURCES/RESOURCES/DMID/SB/Pages/DataReleaseGuidelines.aspx) Program-generated data and software should be made available through publicly accessible web and database sites, including the Web Portal, the BRCs (http://www.niaid.nih.gov/dmid/genomes/brc/default.htm), the NCBI (http://www.ncbi.nlm.nih.gov/) and/or other public repositories, as identified by the Steering Committee in consultation with the NIAID.

Program-generated data and software include, for example:

Whenever possible, the awardee shall provide software certified by the Open Source Initiative (http://www.opensource.org/licenses/), to guarantee the right of others to read, redistribute, modify, and freely use the software.

Program-generated novel reagents (e.g., expression vectors, mutant strains, libraries, protein clones), should be made available through NIAID-supported repositories, such as the NIAID BEI Resources (http://www.beiresources.org/) or in other repositories as identified by the Steering Committee in consultation with the NIAID.

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 individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)

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

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Joana Roe, B.A.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-3759
Email: jroe@niaid.nih.gov  

Kishor Bhatia, Ph.D., FRCPath
National Cancer Institute (NCI)
Telephone: 301-496-4995
Email: bhatiak@mail.nih.gov

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

Deborah Colosi, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-8542
Email:  colosida@mail.nih.gov

Peer Review Contact(s)

Tracy A. Shahan, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2606
Email:  TShahan@niaid.nih.gov

Financial/Grants Management Contact(s)

Mollie Shea
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-6576
Email: MShea@niaid.nih.gov

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

Maryellen Connell
National Institute on Drug Abuse (NIDA)
Telephone: 301-774-3803
Email: mconnell@nida.nih.gov

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

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.

Authority and Regulations

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 Parts 74 and 92.


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