Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID) (http://www.niaid.nih.gov)
National Cancer Institute (NCI) (http://www.nci.nih.gov)

Title: Multicenter AIDS Cohort Study (MACS), Limited Competition (U01)

Announcement Type
This is a reissue of a limited competition to continue the longitudinal Multicenter AIDS Cohort Study (MACS)

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-AI-08-008

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.856, 93.393, 93.394, 93.395, 93.396, 93.399

Key Dates
Release Date: March 26, 2008
Letters of Intent Receipt Date: Not applicable
Application Receipt Date: June 10, 2008
Peer Review Date: October, 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: April 2009
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/  
Expiration Date: June 11, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary  

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

Section II. Award Information
  1. Mechanism(s) of Support
  2. Funds Available

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
  2.Cost Sharing or Matching
  3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Address to Request Application Information
  2. Content and Form of Application Submission
  3. Submission Dates and Times
    A. Receipt and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements and Information

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)     
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
    A. Cooperative Agreement Terms and Conditions of Award
      1. Principal Investigator Rights and Responsibilities
      2. NIH Responsibilities
      3. Collaborative Responsibilities
      4. Arbitration Process
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

The Division of AIDS (DAIDS) seeks to fund applications that cover the full scope of needed HIV/AIDS research. Towards that end, DAIDS supports clinical trial networks to address focused questions in selected populations; observational cohorts where highly standardized, quality-assured and extremely diverse data allow for research beyond standard clinical care in representative populations; and large clinical observational databases such as the North American International Epidemiologic Databases to Evaluate AIDS (IeDEA) network to study HIV outcomes under standard clinical care.

The MACS is a multi-site prospective epidemiology cohort study of men who have sex with men (MSM). Followed since 1983, the cohort is composed of men infected with HIV or at increased risk for such infection. The purpose of this FOA is to continue follow-up of the MACS cohort, the largest cohort study of HIV/AIDS in men in the U.S., thereby supporting studies of the natural and treated history of HIV infection in MSM as well as studies of emerging questions related to long-term HIV infection and treatment. These awards will support ongoing MACS research projects and the initiation of new projects on predictors of response to antiretroviral therapy, including host genomics, and long-term effects of HIV infection, the effects of long-term HIV infection and treatment on the aging process and the impact of HIV therapy on cardiovascular disease, liver disease, renal disease, neurocognitive impairment, cancer and other outcomes. Additionally, through the data and specimens collected, MACS awards will provide opportunities for expanded collaborations through independent, investigator-initiated research grants.

This FOA solicits applications from the Center/Coordination, Analysis and Management/MACS (CAMACS) and from each of the four MACS clinical sites. Because the MACS is an ongoing cohort study that has collected data and specimens from cohort participants since 1983, competition will be restricted to the current network of five funded sites. The application from CAMACS will describe the MACS scientific research agenda; it is expected that the principal investigators of all five MACS sites will contribute to the scientific research agenda. Based on that agenda, the CAMACS and clinical site applications will describe how each will support the overall MACS scientific research agenda.

This FOA is funded by the National Institute of Allergy and Infectious Disease (NIAID) and the National Cancer Institute (NCI).

BACKGROUND

HIV Infections among U.S. Men

The incidence and prevalence of HIV infection associated with male-to-male sexual contact in the United States remain high. The Centers for Disease Control and Prevention (CDC) estimates that in the United States in 2005, 53% of the 19,620 newly diagnosed cases of HIV infection and 47% of the 40,608 diagnoses of AIDS were in men who have sex with men (MSM). This number represents an 11% increase in the number of new HIV/AIDS cases in MSM since 2001. Minority men are particularly vulnerable with estimated incidence rates of 124.8 per 100,000 for African-American men and 56.2 per 100,000 for Hispanic men, compared to 18.2 per 100,000 for white non-Hispanic men. In a 2005 study of five large US cities, 46% of African American MSM were infected with HIV. Of the 12,140 AIDS deaths in 2005, 5,929 (60%) were MSM.  This number is in stark contrast to the 49,351 total AIDS deaths in 1995, 41,359 of whom were male. The introduction of highly active antiretroviral therapy (HAART) has transformed a once universally fatal disease into one that, while not curable, can be slowed dramatically. The estimated survival after an AIDS diagnosis has gone from approximately 1.6 years in 1988 to 14.9 years in 2003. Treated HIV infection has become a chronic disease bringing with it a new constellation of pathologies as HIV-positive individuals live longer and age with sub-optimal immune responses, chronic immunologic activation and the effects of long-term HAART treatment.

The MACS

The MACS is in the third decade of research on MSMs with four clinical sites located in Baltimore, MD/Washington DC; Pittsburgh, PA; Chicago, IL; and Los Angeles, CA.  Between April 1984 and March 1985, 4,954 men were recruited into the study. Two additional waves of enrollment which targeted minority men were conducted in 1987-1991 and 2001-2003, bringing the overall enrollment to 6,972 men. Deaths in the years prior to HAART and loss to follow-up have resulted in a currently active cohort of 2,603 participants of which 47% are HIV-seropositive and 53% remain HIV uninfected. The median age of the cohort is 50 years old and 34% of the cohort is non-white. There have been more than 600 participants who have seroconverted to HIV since inception of the cohort, 36 of whom were enrolled since 2001. More than one million specimens collected at biannual visits throughout the nearly 25-year history of the MACS are stored in national and local MACS repositories.

MACS investigators have published more than 1000 peer-reviewed papers in their 25-year history. MACS research and publications have contributed to such findings as the link between risky sex and HIV seropositivity, low CD4 levels predicting progression to AIDS, the natural history of viremia after seroconversion, the effectiveness of HAART in preventing both primary and secondary opportunistic infections, lipid changes associated with HIV infection and use of HAART, and the HHS guidelines for Pneumocystis carinii pneumonia (PCP) prophylaxis and the use of antiretroviral agents. Key areas of current and continuing investigation include: HIV virology and host immunology; host and viral genetics; long-term effectiveness of antiretroviral therapy; long-term pathogenesis of HIV infection and treatment toxicities including neuropsychological, cardiovascular, renal and liver disease; co-morbidities and opportunistic infections, including HBV and HHV8; the synergistic effects of HIV infection, treatment and aging; AIDS-related cancer; behavior and quality of life; as well as novel statistical methods for analyzing data from prospective studies. 

The MACS Executive Committee (EC) is composed of: 1) voting members who are the Principal Investigators from each awarded site and the NIAID Project Scientist; and 2) ex officio non-voting members of the EC who are Project Scientists from co-sponsoring NIH Institutes. EC members help develop the specific areas of research and work with investigators outside the consortium who want to conduct research using MACS resources.  Study protocols and proposals for new research concepts for the cohort are reviewed by the entire EC and approved by the voting members of the EC.

MACS participants have been evaluated at six month intervals since enrollment. After obtaining the informed consent of the participant, the study visit includes the following elements:

Interview: Centrally scripted interviews are conducted at each visit, with some information also collected through an Audio Computer-assisted Self-Interviewing (ACASI) system. Each participant has greater than 7,500 variables collected at each visit. Self-reported data collection includes general medical history; antiretroviral therapy; health service utilization; sexual behavior; use of drugs, alcohol and cigarettes; and quality of life. Interview content is evaluated and revised every six months.

Additional Surveillance: All reports of AIDS-related diagnoses and non-AIDS diagnoses, such as cardiovascular and cerebrovascular disease, kidney and liver disease, lung infections, bacteremia, septicemia, malignancies and neurologic outcomes, are followed up with medical record abstraction.  State cancer registries and the National Death Registry are used to augment and confirm the outcome data.

Clinical Examination: Physical examinations conducted at each regular visit include standardized assessment of vital signs (e.g. blood pressure); anthropometric measures and assessment of lipodystrophy and neuropsychologic changes; and measures of frailty. Men needing further treatment are referred for care outside of the MACS.

Laboratory Testing: All MACS participants have had blood taken for baseline laboratory tests: follow-up laboratory work is done at each six-month visit. As the study evolves, new areas of testing are identified and included. After approval by the MACS EC, these samples are made available for use by MACS investigators and by unaffiliated outside collaborators.

Since 1984 the Center/Coordination, Analysis and Management/MACS (CAMACS) has been at the Department of Epidemiology of the Bloomberg School of Public Health, the Johns Hopkins University. Data collected at the sites using paper forms are entered into a local data system for electronic transfer to CAMACS. A data manager at each site oversees data entry and works with CAMACS to ensure that datasets are complete and methods of recording the data are comparable between sites.

RELATIONSHIP TO OTHER PROGRAMS AND NIH INSTITUTES

The MACS plays an important role in the NIAID effort to foster studies of HIV infection and HIV-associated disease in relevant domestic populations. Studies of the treated history of HIV in men are critical for furthering our overall understanding of HIV infection and for assessing differences between HIV disease and treatment outcomes in men compared to women, in different racial and ethnic groups, and in aging populations. The MACS collaborates with other HIV-related research groups, including the Women’s Interagency HIV Study (WIHS), the International Epidemiologic Databases to Evaluate AIDS (IeDEA), and the Center for HIV-AIDS Vaccine Immunology (CHAVI). The MACS research platform serves as the source of data and samples for grants funded by the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), the National Institute on Deafness and other Communication Disorders (NIDCD), and the National Institute of Drug Abuse (NIDA).

RESEARCH SCOPE

The scientific agenda of MACS awardees may include, but is not limited to, the following areas of interest to the sponsoring NIH institutes:

The review will be conducted by the NIAID Division of Extramural Activities and may include a Reverse Site Visit (RSV).  In the event of an RSV, Principal Investigators and key staff will be invited to participate.  Potential dates, time, location and agenda of an RSV will be provided after receipt of all applications.

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the U01 cooperative agreement mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". Plans to continue of these cooperative agreement projects beyond the current funding opportunity are indefinite.

2. Funds Available

This initiative is a limited competition Funding Opportunity Announcement (FOA).  NIAID intends to commit $10 to $12 million in total costs in FY 2009 to fund  up to five MACS awards for a period of 5 years depending on scientific and technical merit as determined by peer review.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary. Although the financial plans of NIAID and the co-funding institute provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds. Funding beyond the first year of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

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

1.A. Eligible Institutions

Applications may be submitted by the five awardees-of the current four MACS clinical sites and the Center/Coordination, Analysis and Management/MACS (CAMACS).

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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 programs.

The principal investigator(s) of each MACS site must possess the skills, knowledge, resources and professional experience needed to carry out the proposed research as the PD/PI(s) are invited to work with their institution 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Not applicable

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

The Research Plan in each application should be completed as outlined in Section IV.6. Other Submission Requirements below.

Applications with Multiple PDs/PIs 

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: Not applicable
Application Receipt Date: June 10, 2008
Peer Review Date: October 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: April 2009

3.A.1. Letter of Intent

Not applicable.

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Eugene R. Baizman, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3126, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 402-1464
FAX: (301)-480-2408
Email: ebaizman@niaid.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIAID.  Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

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. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements and Information

Applications for this FOA should be divided into two parts. Part A will describe the overall MACS scientific agenda and research plan. Part B will describe participant retention activities and the ability of the site to contribute to MACS scientific activities.  The CAMACS application must contain both a Part A and a Part B. The individual MACS clinical site applications must contain only a Part B. Parts A and B must be prepared and structured as described below and follow the standard PHS398 application format.

CENTER/COORDINATION, ANALYSIS AND MANAGEMENT/MACS (CAMACS) APPLICATION (PARTS A AND B REQUIRED)

PART A. OVERALL MACS SCIENTIFIC AGENDA/RESEARCH PLAN

Part A of the MACS application will be limited to 125 pages and must address the following:     

1. Research Progress. This section should include key scientific contributions of the MACS during the current award period and progress to data on the current MACS scientific agenda. This section should be limited to no more than 25 pages.

2. Scientific Agenda. The scientific agenda should address the key areas of interest as determined by the MACS principal investigators taking into account the areas of NIH interest identified in RESEARCH SCOPE in Section 1. Funding Opportunity Description. The scientific agenda of the MACS should be limited to no more than 80 pages and address the following:

Provide a copy of the MACS certificate of confidentiality in the appendix.

3. Organizational Structure. This section should describe the organizational structure and scientific oversight mechanisms of the MACS and discuss how the MACS administrative structure facilitates the conduct of the MACS scientific agenda, including coordination across all MACS sites. This section should be limited to 10 pages.

4. All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project. This section is limited to 10 pages.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

PART B. CENTER/COORDINATION, ANALYSIS AND MANAGEMENT/MACS (CAMACS) APPLICATION

The Research Plan items 2-5 in Part B of the CAMACS application is limited to 35 pages and must address the following:

A description of the role played by CAMACS as the coordinating center for epidemiology research, statistical analysis and management of both datasets and study protocols. This section of the application should address the following topics:

-- Progress and achievements of CAMACS during the current funding cycle. This section should describe the role of CAMACS in implementing the MACS scientific agenda. 

-- The approaches needed to maximize data accessibility to achieve increased scientific usefulness of MACS data.

-- The methods by which CAMACS, in collaboration with other MACS Principal Investigators, allocates resources for data analysis to support the MACS scientific agenda in terms of presentations and publications.

-- The methods by which CAMACS provides leadership and intellectual input about epidemiologic and statistical issues in the design of studies. This description should include development of novel design and analytic approaches, estimating sample size requirements for specific research questions, planning and performing interim and final analyses, and preparing reports that summarize the results of such analyses.     

-- The mechanism by which collaborations with the clinical sites are maintained, assuring data quality by developing appropriate study protocols, conducting clinical site monitoring visits, and monitoring data forms and study results submitted to CAMACS.

-- The role played by CAMACS in providing close and effective coordination of MACS-wide research, e.g., organizing the MACS website and conference calls, and coordinating with federal contractors the semi-annual MACS-wide scientific meetings in which study results are presented and discussed and collaborations are fostered. 

-- The role played by CAMACS in assuring protection of the human subjects participating in this research.   

-- The role played by CAMACS in assuring relevant and quality data annotation of biological samples collected by the NIAID repository.

PART B. MACS CLINICAL SITE APPLICATION

The Research Plan items 2-5 is limited to 35 pages for each clinical site application and must address the following:

(1) Progress and achievements of the MACS site during the current funding cycle. This section should describe both the site’s role as a clinic site for recruitment and retention of participants and its role in implementing the MACS scientific agenda. Each site application should include standardized tables describing the cohort’s recruitment, retention, missed visits and missing data and specimens.

(2) Description of the site’s participation as a clinic site for the conduct of the MACS cohort study. Specifically, each site application should describe the following:

- The means used to maintain high participant retention rates and community outreach.

- The means by which MACS participants at each site are referred for clinical care and how relevant data related to clinical care are incorporated into the study database.

-  The methods used to encourage participation of MACS subjects in individual studies and the means by which collaborations with outside investigators are incorporated into the existing MACS protocol.

- How the site will provide leadership for and collaborate in MACS-wide epidemiologic and/or clinical investigations with MACS data according to the MACS agenda.

- Arrangements for specimen handling, including testing and storage at the site, and specimen shipping.

- The site’s organization, management and methods of communication, including outreach efforts with the community.

- The methods used by the site to insure the protection of human subjects including assurances of appropriate use of genetic data and other sensitive data regarding drug use.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".  

(3) All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Appendix Materials

All paper PHS 398 applications submitted for May 25, 2008 and subsequent due dates must provide appendix material on CD only, and include five identical CDs in the same package with the application.  Paper applications submitted for due dates prior to May 25, 2008 may voluntarily provide the appendix on five identical CDs; if submitting CDs it is not necessary to include a paper appendix. (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information


1. Criteria

Only the Review Criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID in accordance with the review criteria stated below.

The review will be conducted by the NIAID Division of Extramural Activities and may include a Reverse Site Visit (RSV).  In the event of an RSV, Principal Investigators and key staff will be invited to participate.  Potential dates, time, location and agenda of an RSV will be provided after receipt of all applications.

As part of the initial merit review, all applications will:

The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

CAMACS-PART A: OVERALL MACS SCIENTIFIC AGENDA AND RESEARCH PLAN

Significance:  Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Does the MACS address important problems relevant to HIV-1 epidemiology and pathogenesis in MSM? Has the applicant appropriately addressed the most important questions and potential solutions that the MACS expects to encounter in the coming years?  Does the scientific vision set forth by the MACS leadership delineate the most important ways in which the data and specimens obtained from the cohort will continue to advance the scientific communities understanding of HIV-1 infection, disease and treatment? Does the agenda sufficiently address how the MACS will study issues relevant to the HIV-1 epidemic?  Is the MACS suited to use the cohort structure to address new questions in the field as they arise, and is there potential for the effect of the proposed studies on the concepts or methods to drive the field?  If the aims of the application are achieved, why will the information provided be significant?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Does the applicant present a well-developed and well-integrated conceptual framework, design, methods, and analysis plan appropriate for this cohort of MSM with, or at risk for, HIV infection?  Does the applicant acknowledge potential problem areas and consider alternative tactics?  Are the scientific goals set forth in this application feasible considering the size and make-up of the cohort?  Are the core laboratory procedures well coordinated, with adequate and appropriate quality control?  Has the MACS demonstrated flexibility and strength in its structure and data collection system so that it will remain well suited to address new questions which are not yet anticipated?  Does the scientific and organizational structure of the MACS facilitate the conduct of the MACS scientific agenda?  Does this structure foster collaborations with investigators outside the MACS?  Is the structure of the MACS flexible enough to address new questions related to HIV as they arise?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?  Does the scientific agenda, presented by the investigators, represent innovative study designs?  Does the project develop areas of research important for understanding the long term treated history of HIV?  Does the structure of the MACS foster innovative responses to address new questions related to HIV as they arise?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?  Are the investigators well-suited to engage in highly collaborative interactions with other MACS investigators and with investigators external to the MACS who wish to utilize MACS data and specimens, in collaboration with the MACS?  Is the work proposed appropriate to the experience level of the Principal Investigator and other MACS researchers? 

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  Will the scientific environment in which the work will be done contribute to the probability of the success of MACS-wide scientific agenda/research plan?  Do the proposed analyses take advantage of unique features of the MACS scientific environment or optimize useful collaborative arrangements?

CAMACS PART B: CAMACS RESEARCH PLAN

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Has CAMACS successfully served as the CAMACS data management and analysis center over the past 5 years?  Does CAMACS fulfill other roles and duties that are critical to the success of MACS-wide scientific studies and to the work of external collaborators?  Is the role of CAMACS in the design of future MACS analyses adequate and appropriate?  Does CAMACS propose cutting-edge analytical methods to optimize the use of observational data to inform on key questions?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Is the approach for managing MACS data and ensuring its security appropriate and optimal?  Are the approaches to ensuring the close coordination of MACS-wide research and of research performed by external collaborators appropriate and optimal?  Does the applicant acknowledge potential problem areas and consider alternative tactics?  Is the approach for the research proposed by CAMACS appropriate? Has CAMACS appropriately addressed the responsibility of developing the logistics necessary for the EC to develop and coordinate the MACS scientific agenda?  Has CAMACS appropriately addressed the logistics necessary to ensure that MACS data and specimens are collected, stored and shipped in a standardized fashion?  Has CAMACS demonstrated how appropriate training is conducted to ensure consistent data collection?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators:  Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator (s)and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?  Are there key personnel in place, and is their level of effort sufficient to conduct MACS research including study design, analysis, and development of novel epidemiologic and statistical methods?  Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers?  Have the Principal Investigator(s) and key personnel budgeted sufficient time to ensure that adequate attention is paid to the MACS-wide scientific issues?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? 

MACS CLINICAL SITES:

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Has this MACS clinical site successfully served as the source for MACS data and specimens?  Has this MACS clinical site successfully recruited and retained sufficient numbers of participants?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Are the design and methods for cohort maintenance, data and specimen collection adequately developed, well-integrated, and appropriate to the aims of the MACS?  Does the applicant acknowledge potential problem areas and consider alternative approaches? Are the plans for maintaining the cohort, obtaining data and sending data to CAMACS, and for obtaining biological specimens and sending these to the NIAID Specimen Repository feasible and adequate?  Are the plans for working with CAMACS to ensure appropriate standardization and quality control of data collected at each site adequate? 

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Are there key personnel in place to conduct MACS research including epidemiologic expertise in study design and analysis?  Have the Principal Investigators budgeted sufficient time to ensure appropriate oversight of their clinical site and the MACS-wide scientific agenda?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information


1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See Also Section IV.5. Funding Restrictions.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 (U01), 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.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining the research objectives, approaches and details of the projects within the guidelines of the FOA, and for conducting scientific projects.  Specifically, awardees have primary responsibility as described below.

A. Responsibilities of CAMACS: 

The CAMACS awardee is responsible for all the activities necessary to achieve the project's Research Objectives, including the following:

- Establish and maintain relationships with the MACS sites, NIAID and the other NIH co-funding institutes to facilitate the achievement of the objectives.

- Maintain the system developed for tracking MACS research in collaboration with the MACS Executive Committee (EC).  Maintain and regularly distribute a list of all publications, manuscripts in progress and presentations using MACS data.  The CAMACS PI is a voting member of the EC.

- Provide semi-annual reports at the MACS EC meetings

- Monitor adherence to clinical and laboratory protocols, and coordinate implementation of any new or modified protocols that the EC approves during the course of the study.  CAMACS will be responsible for preparing and updating operations manuals and data collection forms as well as coordinating the revision of existing MACS questionnaires, and the development and testing of new questionnaires for utilization in the MACS, including the standardization of procedures for data collection.  They will also be responsible for providing adequate teaching and training to MACS personnel at the clinical sites to assure that the questionnaires continue to be administered in a uniform, standardized fashion, performing site visits as necessary.  In particular, CAMACS will be responsible for the following evaluations: interview skills and procedures, HIV pre-test and post-test counseling, specimen collection skills and procedures, and data management at local sites.

- Work with the NIAID specimen repository contractor to ensure that an accurate inventory of specimens is available and that repository usage is tracked.  CAMACS will conduct training and provide updates about the web-based tracking system to ensure that MACS investigators can access the specimen database.  Manage requests for specimens from MACS investigators and work with the repository contractor to prioritize requests for samples and facilitate timely delivery of samples to investigators.

- Collect, edit, clean and store data collected from MACS clinical sites; provide centralized storage, security, processing and retrieval of MACS data; ensure the continued quality of the data management system and its adequacy to the expanding needs of the MACS.

- Provide recruitment and retention data to inform sites about current cohort status.  The data must be supplied on a regular basis so that cohort retention problems can be readily corrected.

- Prepare and submit progress reports to NIH.  A summary of CAMACS activities and progress and the results of site monitoring evaluations must be sent annually to program officers at NIAID and the other NIH co-funding institutes.

- Make drafts of manuscripts available for review (electronically or in hard-copy) by the Project Scientists for NIAID and the other NIH co-funding institutes at the time they are circulated to co-authors and when the final manuscripts are submitted for publication.  Copies of the published articles should be forwarded to program officers at NIAID and the other NIH co-funding institutes.

- Prepare and submit a MACS public-use data electronic file with the data from up to three years before the file's creation.

- Maintain a searchable web-based archive of MACS publications.

-  Work with the WIHS Data Center (WDMAC) to organize the semi-annual MACS meeting.

B. Responsibilities of MACS Clinical Sites:

The quality of the MACS research will largely depend on the degree of collaboration between and among the MACS sites and CAMACS.  The generation of high-quality data in a multi-center setting will require continuous feedback by the sites to CAMACS for data management and protocol implementation.  The responsiveness of the sites in providing information to CAMACS will be the responsibility of the MACS Principal Investigators.  All MACS Clinical Site PIs will be voting members of the Executive Committee.

Specifically, sites will be responsible for:

- Quality of data and of publications involving the awardee’s site.

- Research design and implementation, data collection, final data analysis and publication in collaboration with the other MACS sites and CAMACS, within the guidelines established by the MACS EC.

- Establishing, in collaboration with CAMACS, appropriate mechanisms for quality control and monitoring and for follow-up of MACS participants in terms of disease outcomes specified by the EC.

- Collecting and submitting biological specimens specified in the MACS protocol to the repository contractor with appropriate documentation and labels.

- Anticipating and responding to repository cost issues.

- Establishing and maintaining relationships that facilitate the achievements of the study objectives with other MACS sites and with the NIH institutes funding the MACS

- Preparing and submitting annual progress reports and manuscripts to the NIH. 

- Drafts of manuscripts at the time they are circulated to co-authors, final manuscripts being   submitted for publication, and copies of published articles should be sent to the Project Scientists for NIAID and the other NIH co-funding institutes for comment, in accordance with publication policies established by the MACS EC.

- The MACS clinical sites will also be responsible for maintaining an optimal collaboration with    CAMACS.

Specifically, the clinical sites will be responsible for:

- Providing adequate and timely response to all pertinent requests by CAMACS concerning past, ongoing, or planned research activities.

- Immediate reporting of problems in data collection, record abstraction and information flow.

- Immediate reporting of relevant staff changes.

- Staff attendance at training sessions.

- Submitting complete and clear MACS abstract and manuscript concept sheets.

- Maintaining optimal working condition of hardware and software and coordinating changes and/or upgrades.

- Ensuring that all requests to CAMACS are timely and well documented.

The PI will retain custody of, and have primary rights to the data information and software developed under the cooperative agreement, subject to Government rights of access consistent with the current HHS, PHS, and NIH policies. Publication and copyright agreements and the requirements for financial status reports, retention of records, and terminal progress reports will be as stated in the NIH Grants Policy Statement.  

C. Responsibilities of MACS Clinical Sites and CAMACS:

ACCESS TO DATA.  The EC, in collaboration with CAMACS, will be responsible for optimizing a mechanism for rapid access to data for exploratory work or manuscript preparation. Requests by investigators for raw and summary data will be managed by CAMACS after clearance and prioritization by the EC. Prior to approval and release of data, research plans submitted to the EC will be evaluated to determine if they are in accordance with the informed consent signed by the MACS participants.  A MACS public-use data set will be created yearly by CAMACS and will contain data covering the period up to three years prior to the data set’s creation.

BIOLOGICAL SPECIMENS.  In view of the importance of biological specimens for current and future studies, their number and volume should be regularly monitored by CAMACS and reported to the EC. Each site's annual report to NIAID and the other NIH co-funding institutes should include a CAMACS summary report on biological specimens and a detailed status report of any local repository. Problems with specimen collection at individual sites should be brought to the attention of the EC, through CAMACS and the working groups, for appropriate remedial measures. Requests for specimens by MACS investigators should describe in detail the study for which specimens are sought, their number and volume, in accordance with a standardized MACS Data and Specimen request form. MACS specimens may also be made available to independent investigators upon approval of requests by the EC.  The EC will actively promote wider and optimal utilization of MACS specimens by outside investigators. Prior to approval and release of specimens, research plans submitted to the EC will be evaluated to determine if the research is in accordance with the informed consent signed by the MACS participants and that necessary IRB approvals have been obtained. EC approval is not necessarily applicable to specimens in local repositories. However, notification of the EC about studies being conducted on local repository specimens is expected, and compliance with human subjects regulations is required.

DISSEMINATION OF STUDY RESULTS.  The existing MACS publication policy should be followed. The policy will be reviewed in the first six months of the funding cycle, and amended by the EC if necessary, to achieve overall fairness and timeliness in the formal reporting of research results. The timely dissemination of study results to the communities involved is strongly emphasized. The support of the NIH Institutes funding the MACS should be acknowledged and the NIH grant numbers included in all publications.

MEETINGS: Semi-annual MACS-wide meetings, to be held in the Spring and the Fall of each year of the award period, will convene the EC and Working Groups at the same location. A Spring meeting will always be held in the Washington, DC area, with rotation of the Fall meeting to each MACS site or to other cost-effective sites. A substantial portion of each meeting will be devoted to assessing scientific progress and establishing scientific priorities and timelines. CAMACS should ensure the availability of updated summary data for these meetings.

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.

2.A.2. NIH Responsibilities

NIAID and NCI assistance will be provided by the Project Scientists for each Institute. The Project Scientists 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, as described below.

NIH Project Scientists will:

-  Be members of the Executive Committee. The NIAID Project Scientist will be a voting member of the EC, the NCI Project Scientist will be an ex officio, non-voting member of the EC. 

- May, at times, serve a leadership role in the conduct of a particular area of scientific research.

- Monitor study results and quality assurance across all sites, in order to ensure the production of high-quality, unbiased results that are comparable across sites.

- Ensure and coordinate access to MACS datasets for presentations and publication of study-wide data to ensure that the MACS sites have equal access to MACS data and participants. 

- Have access to and review all study protocols.

- Oversee the collection, storage and cataloging of samples to ensure that appropriate access to the NIAID contractor-maintained repository of biological specimens, a key resource for the entire scientific community, is provided.

- In collaboration with the MACS EC, may have data generated from the MACS for use in preparing internal reports on MACS activities. 

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

The MACS is managed by an Executive Committee (EC) comprised of the Principal Investigators from the four clinical sites, the Principal Investigator from the Center/Coordination, Analysis and Management/MACS (CAMACS), the Project Scientist from NIAID and ex officio members including the NCI Project Scientist. Ex officio members will not be voting members of the EC but will serve as confidential advisors to review and discuss proposed scientific activities.  The EC will meet by teleconference twice monthly and in person twice a year to discuss changes in protocols, new protocols, study results, retention of the cohort, quality control of data, requests to perform research using MACS data or samples, specimen preservation and distribution from the NIAID repository, and other matters of interest to all institutions affiliated with the MACS.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

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 arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

In addition, through CAMACS, the MACS EC must submit, in electronic format, an annual progress report to the program officers at the NIH co-sponsoring institutes that includes the following:

- Tables recording recruitment and retention over the past year for both the overall MACS Study and for each clinical site (by race/ethnicity as delineated by NIH policy: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html)

 - The number and type of specimens collected and sent to the NIAID repository

- A brief report of progress in ongoing MACS research projects over the past year

- A listing of publications either published or in-press for the year being reported

- A listing of abstracts and presentations made in the past year exclusive of the list of published and in-press publications

- A brief summary of recruitment and retention activities conducted at each site

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

NIAID:

Robin E. Huebner, Ph.D., M.P.H.
Division of AIDS
Room 4104, MSC-7626
6700-B Rockledge Drive
Bethesda, MD 20892-7626
Telephone: (301) 402-4239
FAX: (301) 402-3211
Email: rhuebner@niaid.nih.gov

NCI:

Rebecca Liddell Huppi Ph.D.
Office of AIDS Malignancy Program
Room 6119, MSC-8337
6120 Executive Boulevard
Bethesda, MD 20892-8337
Telephone: (301) 496-4995
FAX: (301) 480-4137
Email: liddellr@exchange.nih.gov

2. Peer Review Contacts:

Eugene R. Baizman, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3126, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 402-1464
FAX: (301)-480-2408
Email: ebaizman@niaid.nih.gov

3. Financial or Grants Management Contacts:

Mollie Shea
Division of Extramural Activities
Room 2234, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 402-6576
FAX: (301) 493-0597
Email: mshea@niaid.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


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