Leadership for HIV/AIDS Clinical Trials Networks

RFA Number: RFA-AI-05-001 

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 Institute of Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov)
National Cancer Institute (NCI), (http://www.nci.nih.gov)
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov)
National Institute of Dental and Craniofacial Research (NIDCR), (http://www.nidcr.nih.gov)
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov)
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)
John E. Fogarty International Center (FIC), (http://www.fic.nih.gov)
National Institute of Nursing Research (NINR), (http://ninr.nih.gov)

Announcement Type
New

Updates: The following updates relating to this announcement have been issued:

Catalog of Federal Domestic Assistance Number(s)

93.855, 93.856, 93.395, 93.865, 93.121, 93.279, 93.242, 93.989, 93.273, 93.361 Nursing Research

Key Dates

Release Date: November 19, 2004
Letters of Intent Receipt Date(s): April 11, 2005
Application Receipt Date(s): May 11, 2005
Peer Review Date(s): October, 2005
Council Review Date(s) : January, 2006
Earliest Anticipated Start Date: March, 2006
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/daids/rfa/network06
Expiration Date: May 12, 2005

Due Dates for E.O. 12372
Not Applicable

Executive Summary

The objective of this RFA is to establish the Leadership of three to six HIV/AIDS Clinical Trials Networks to carry out the NIAID research agenda in the following areas: (1) Vaccine Research and Development; (2) Translational Research/Drug Development; (3) Optimization of Clinical Management, Including Co-Morbidities; (4) Microbicides; (5) Prevention of Mother-to-Child Transmission (MTCT) of HIV; and (6) Prevention of HIV Infection.

Each Network Leadership will consist of three components: (1) a Coordinating and Operations Center (CORE) to provide scientific and administrative leadership, central operations, and communications; (2) a Statistical and Data Management Center (SDMC) to provide biostatistical leadership and central data management; and (3) a Network Laboratory Structure to provide the laboratory services necessary to conduct the clinical research. These Network Leadership components may be combined in a single application or in separate, but linked applications. Resulting Networks may be funded through one to three Cooperative Agreements (U01). Clinical Trial Units will be solicited in a subsequent, linked RFA titled “ Units for HIV/AIDS Clinical Trials Networks ”. The resulting combination of a Network Leadership and affiliated Clinical Trial Units will constitute an HIV/AIDS Clinical Trials Network. Each Network will give high priority to collaborations with other NIH HIV/AIDS clinical research programs, the other Networks funded through this RFA and other HIV research entities in order to effectively develop and implement a clinically relevant, interdisciplinary and cost-efficient research program.

Eligible organizations include public or private institutions and organizations, for-profit or non-profit, such as universities, colleges, hospitals, and laboratories, units of State and local governments, and eligible agencies of the U.S. Federal government. Applicants may submit multiple applications under this announcement. Institutions and investigators with laboratory, statistical, data management, or administrative or operational expertise may collaborate with more than one Network.

Foreign institutions are not eligible to apply as the awardee institution. Foreign institutions are eligible to participate as collaborators within any of the three Network Leadership components.

NIAID and collaborating ICs anticipate awarding $150 million in FY2006 to fund the Leadership of approximately three to six HIV/AIDS Clinical Trials Networks. Networks are expected to vary substantially in size and scope of activities. For this reason, the amount of first-year awards is expected to vary; however, the range of awards is anticipated to be from $10 million to $20 million direct costs for the three Network Leadership components combined.

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html. Additional information and further instructions for preparation of application materials are available at the Division of AIDS application web site: http://www.niaid.nih.gov/daids/rfa/network06.

Public Briefing:

An informational session for investigators representing groups considering submission of applications in response to this RFA will be held. Details of the meeting will be announced on the NIAID web site (http://www.niaid.nih.gov) and in the NIH Guide to Grants and Contracts. Representatives from DAIDS and from the NIAID Division of Extramural Activities will provide information and answer questions pertinent to preparing applications in response to this RFA.

Telecommunications for the hearing impaired: TTY 301 451-5936

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
    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
      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

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
    3. Merit Review Criteria
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative 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. Award Criteria
    4. 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

The National Institute of Allergy and Infectious Diseases (NIAID) and collaborating ICs solicit applications from domestic institutions to serve as the Leadership for HIV/AIDS Clinical Trial Networks focused on therapeutics, vaccines and prevention. Through this RFA, the Leadership of three to six HIV/AIDS Clinical Trials Networks will be established to carry out the NIAID research agenda in the following areas: (1) Vaccine Research and Development; (2) Translational Research/Drug Development; (3) Optimization of Clinical Management, Including Co-Morbidities; (4) Microbicides; (5) Prevention of Mother-to-Child Transmission (MTCT) of HIV; and (6) Prevention of HIV Infection. Each Network Leadership will consist of three components: (1) a Coordinating and Operations Center (CORE) to provide scientific and administrative leadership, central operations, and communications; (2) a Statistical and Data Management Center (SDMC) to provide biostatistical leadership and central data management; and (3) a Network Laboratory Structure to provide the laboratory services necessary to conduct the clinical research. Clinical Trial Units will be solicited in a subsequent, linked RFA titled ‘ Units for HIV/AIDS Clinical Trials Networks '. The resulting combination of a Network Leadership and affiliated Clinical Trial Units will constitute an HIV/AIDS Clinical Trials Network.

Each resulting HIV/AIDS Clinical Trials Network will work cooperatively with the Division of Acquired Immunodeficiency Syndrome (DAIDS), NIAID and collaborating ICs to implement a research agenda focused on the most important clinical research questions defined by DAIDS. Each Network also will be expected to give high priority to collaborations with the other DAIDS-sponsored Networks funded through this RFA, other NIH HIV/AIDS clinical research programs, and other HIV research entities in order to effectively develop and implement a clinically relevant, interdisciplinary and cost-efficient research program. To foster these interdisciplinary collaborations, this RFA also identifies the HIV/AIDS scientific research priorities of other NIH Institutes and Centers and opportunities to collaborate with other HIV/AIDS clinical trials groups or conduct interdisciplinary collaborative research.

1. Research Objectives

I. Current HIV/AIDS Clinical Trials Networks and Accomplishments to Date

Since its inception in 1987, the Division of AIDS, NIAID has designed, developed and sponsored extramural Clinical Trials Networks to develop and optimize therapies, vaccines and prevention modalities for HIV/AIDS. These Clinical Trials Networks have played a vital role in HIV and AIDS research, providing the critical mass and infrastructure for both quality and continuity in collaborative, protocol-driven clinical research. The contributions and progress made by these Networks and their antecedents, the Adult and Pediatric AIDS Clinical Trials Groups (ACTG), the AIDS Vaccine Evaluation Group (AVEG), and the HIV Network for Prevention Trials (HIVNET), have been unparalleled and have advanced HIV clinical science around the world. The current NIAID-sponsored HIV/AIDS Clinical Trials Networks and the accomplishments of each are described below:

Information about the current DAIDS-supported HIV/AIDS Clinical Trials Networks, their organizational components and clinical trial sites, and ongoing and planned clinical trials is located at DAIDS application web site: http://www.niaid.nih.gov/daids/rfa/network06. DAIDS also supports contracts with several organizations to provide clinical research support to sites conducting DAIDS-sponsored research. Activities conducted by these contractors include clinical site monitoring, drug distribution, laboratory quality assurance, specimen storage, training, and regulatory assistance. Additional information about the current and planned contracts can be found at the DAIDS application web site: http://www.niaid.nih.gov/daids/rfa/network06.

DAIDS supports a contract to develop and implement the DAIDS Enterprise System (DAIDS-ES). DAIDS-ES is a comprehensive data management system to support the business functions, management and oversight responsibilities of the Division of AIDS. The current and planned components of the DAIDS-ES include: DAIDS Training Calendar, DAIDS Master Contact System, DAIDS Expedited Adverse Event Reporting System (DAERS), and DAIDS Protocol Management System. Successful applicants will be required to interface, integrate or adapt their information system(s) to interact with these and future components of the DAIDS-ES as necessary. Additional information about these components and timelines for availability is available at: http://www.niaid.nih.gov/daids/rfa/network06.

II. Other NIH HIV/AIDS Clinical Trials Programs In addition to the above Networks, the NIH sponsors other HIV/AIDS Clinical Trials Programs. Applicants are strongly encouraged to include proposed collaborations with these Programs in their applications. These NIH sponsored Programs include:

III. The Changing HIV Epidemic and the NIAID Scientific Agenda DAIDS supports research that will help lead to the end of the AIDS epidemic. Current estimates are that 38 million people were living with HIV infection at the end of 2003 and that the epidemic continues to expand in almost all regions of the world, with approximately 4.8 million new infections in 2003 (UNAIDS 2004 Report on the Global AIDS Epidemic). The burden of disease in this pandemic is disproportionately high among women and those who live in poverty. The proportion of infected persons who are women has increased steadily during the epidemic so that now more than 50% of those living with HIV are female. Adolescents and young adults aged 15-24 years account for half of all new infections worldwide: girls and young women are particularly vulnerable. In Sub-Saharan Africa, women account for 57% of infected adults and 75% of the infections in young adults.

Though a large proportion of HIV-infected adults in the U.S. are men, women now account for 25% of all HIV infections in North America. Some minority groups within the U.S. also are disproportionately affected. For example, approximately 50% of those living with HIV/AIDS are black and 10% are Hispanic (HIV/AIDS Surveillance Report 2002). The geographic distribution of people living with AIDS also has changed as the epidemic has become more generalized. By the end of 2002, 39% of persons living with AIDS in the U.S. resided in the South, 29% in the Northeast, 19% in the West, 10% in the Midwest, and 3% in the U.S. territories.

Women, adolescent and young adults, and minorities continue to be under-represented in clinical research because of social, cultural, and geographic barriers. This lack of involvement in research diminishes access to quality health care, hampers widespread adoption of available preventive approaches, limits safe and effective management of HIV treatment and associated complications, and jeopardizes the ability of researchers to generalize findings to those most in need. The scientific research plans of the DAIDS Networks must reflect current realities in capitalized and resource-limited settings and develop innovative approaches for the prevention and treatment of HIV infection that recognize the role of family, household and community as participants in a successful clinical research process. These approaches also should have worldwide applicability.

Achieving the mission of ending the HIV epidemic requires a carefully coordinated clinical research plan aimed at preventing new infections and reducing HIV morbidity and mortality in those already infected in the U.S. and internationally. Though substantial progress in the development of strategies to prevent and manage HIV infection has occurred, less than 20% of individuals who need prevention services have access to them and only 7% of HIV-infected persons in low and middle-income countries can access antiretroviral medications (UNAIDS 2004 Report on the Global AIDS Epidemic). Development of safe and effective vaccines, microbicides and other protection methods, improvement of regimens to safely prevent the transmission of HIV from mother to child, and continued development of new therapeutic agents are essential to halting the spread of HIV and optimally treating those already infected. Significant questions remain, especially in resource-limited settings, regarding the most effective ways to use currently available anti-HIV agents to attain long-term health maintenance, prevent the development of resistance, preserve immune function, manage co-infections and complications of HIV and HIV therapy, and prevent the spread of HIV. Though these areas of inquiry have been advanced significantly through the existing Clinical Trial Networks supported by DAIDS (e.g. vaccine development, prevention sciences, therapeutics), avenues of future research must cut across the traditional Network boundaries to ensure the most efficient and effective use of available resources and to achieve the mission of DAIDS.

IV. Objectives and Scope

The NIAID HIV/AIDS Clinical Trials Networks must be configured with sufficient flexibility and linkages to enable efficient response to new scientific opportunities and outreach to communities in which key questions around HIV/AIDS prevention and treatment research must be addressed to safeguard the public health. By competing these Networks under a single RFA, DAIDS aims to: 1) develop a consortium of linked Clinical Trials Networks; 2) establish priorities across a broad range of clinical research activities; 3) coordinate activities across Networks to ensure high caliber science; 4) increase efficiency through resource sharing; 5) flexibly allocate and distribute resources in response to priority research opportunities, and; 6) leverage complementary strengths and resources within and outside the Networks. The research activities of the funded Networks will be closely coordinated with other complementary programs within DAIDS (e.g. Comprehensive International Programs for Research on AIDS (CIPRA), the Centers for AIDS Research (CFAR), the NIAID (e.g. programs in the Division of Microbiology and Infectious Diseases and NIAID's intramural research program), as well as ongoing and planned HIV/AIDS research programs ongoing/planned in other NIH Institutes and Centers, other Federal agencies (e.g. Center for Disease Control and Prevention, Health Resources and Services Administration , the U.S. Agency for International Development), and other sponsors (e.g. other governments, institutes, non-governmental organizations, community-based organizations, charitable organizations, pharmaceutical/biotechnology industry, etc.).

A. The NIAID Research Agenda for HIV/AIDS Treatment and Prevention Clinical Research

1. Vaccine Research and Development

Vaccine research and development remains the number one priority of DAIDS, with the ultimate objective of identifying a safe vaccine that will protect all persons against infection and/or disease progression, and will also protect the public against further transmission throughout the world and against all clades of HIV and routes of transmission. NIAID expects to be supporting two to three Phase I/II vaccine trials by 2006. There also will be a number of additional candidate vaccines in Phase I/II trials, including several that are multi-clade or seek to induce strong cellular immune responses and that have shown promise in non-human primate models. During the period 2006-2013, this vaccine development effort will need a clinical research mechanism that can pursue a number of priorities. These include the following:

NIDCR has identified the following research priorities (additional review criteria apply - see Section V.2.IV):

NIMH research priorities include the investigation of factors that affect understanding about product efficacy, its impact on acceptance and use of HIV vaccines, and the impact that vaccine availability might have on adherence to risk reduction guidelines.

Vaccine testing in adolescents and collaboration with the NICHD Adolescent Trials Network for vaccine testing are research priorities for NICHD.

The Partnership for AIDS Vaccine Development (PAVE), http://www.pave.org, a collaboration between the NIH, the Centers for Disease Control and Prevention (CDC) and the Department of Defense (DoD), and the recently announced “Global Vaccine Enterprise,” are alliances of multiple independent entities to develop and execute an integrated global vaccine evaluation plan. DAIDS will continue to play a key role in these groups. Network collaborations with these other HIV vaccine groups may be of great importance in addressing critical challenges in vaccine research and development, such as identifying, recruiting, and retaining the highest risk populations, implementing advanced product development and manufacturing, developing the necessary facilities and infrastructure for clinical trials, and training a larger cadre of scientists to conduct research. Development of prevention messages are also an important component of vaccine protocols because they can anticipate and address potential increases in risk behavior after vaccine rollout. In addition, some individuals will become infected during a vaccine trial, and there may be a scientific and ethical need to follow these cases for many years, if not for the life of the participant, at considerable cost.

2. Translational Research/Drug Development

A long-term goal of DAIDS is to develop therapeutics that prevent progression and death from HIV disease, prevent and manage the complications related to HIV disease and its therapies, prevent the emergence of HIV drug-resistant variants, block the transmission of HIV, and ultimately “cure” HIV infection by eradicating the virus and eliminating reservoirs. DAIDS will need to address the highest public health priorities and collaborate with pharmaceutical companies to assure rapid development of the most promising agents. In addition, this clinical research must be conducted in all appropriate populations in order to facilitate licensure (such as pharmacokinetic and safety studies in children, adolescents, and pregnant women) and to optimize use. During the next decade, it is anticipated that drugs will be developed against at least two new HIV targets, fixed-dose combinations will become the standard of care, and noticeable progress will be made in integrating therapies to enhance immunity. This will be accomplished by conducting studies to:

Research efforts in this area should complement and expand research performed by industry and will require close collaboration with other NIH institutes. NICHD supports an extensive research agenda relevant to the treatment of HIV and its complications in infants, children, adolescents, pregnant and non-pregnant women, domestically and internationally. NICHD anticipates continued collaboration and integrated research efforts between NIAID sponsored clinical trials networks and the NICHD Pediatric/Perinatal Network and additional collaborations with the NICHD ATN.

NCI supports an extensive research agenda relevant to cancer treatment in HIV-positive persons of all ages. It is anticipated that NCI and NIAID-sponsored networks will collaboratively develop and implement studies in areas of mutual scientific interest, including HPV and hepatitis.

3. Optimization of Clinical Management, Including Co-Morbidities

Optimization of clinical management to reduce disease progression and minimize co-morbidities is a high priority treatment research area for DAIDS. The reduction of peak viremia and long-term viral load suppression, reconstitution of the immune system, and mitigation of ART toxicities are essential in achieving these objectives. This will be accomplished by the following:

NIDCR has identified the following research priorities (additional review criteria apply - see Section V.2.IV):

Participation of other NIH institutes, as well as other Federal agencies and international partners (e.g., DoD, European Union, World Health Organization, CDC, World Bank and others) is essential to be able to carry out DAIDS scientific agenda in this area. Other NIH Institutes have indicated their interest in participating in the following research areas:

4. Microbicides

The objectives of DAIDS microbicides research are to identify a microbicide that is safe and at least partially effective in preventing HIV acquisition and transmission, determine the correlates of short- and long-term safety, and evaluate and optimize product acceptability and adherence to its appropriate use. By 2006, DAIDS expects to have launched an efficacy trial of two candidate topical microbicides. Additional candidates are in earlier stages of the developmental pipeline with a significant number expeditiously advancing toward clinical evaluation. In collaboration with NIAID's Division of Microbiology and Infectious Diseases and other partners, DAIDS envisions a Clinical Trials Network capable of conducting all stages of clinical research and collaborating closely with entities involved in clinical research and development. DAIDS' focus is on products that are safe enough for daily use and that incorporate multiple mechanisms of attack. Behavioral research will be a key component, as will exploration of candidates that may permit delivery to be dissociated from sexual activity. This research agenda will be accomplished by the following:

The NIDCR has identified the following research priority (additional review criteria apply - see Section V.2.IV):

NICHD supports studies related to microbicides and genital mucosal immunity. The NICHD's Contraceptive and Reproductive Health Branch supports the Contraceptive Clinical Trials Network (CCTN), which conducts clinical trials on oral, injectable, implantable, or topical contraceptive drugs/devices and microbicides, as well as on genital mucosal immunity. The Demographic and Behavioral Sciences Branch at NICHD conducts studies related to behavioral aspects of microbicide use, including determinants of sexual behavior and of microbicide acceptability by individuals and communities.

The research area of microbides will require extensive coordination with the NIAID Division of Microbiology and Infectious Diseases, the NICHD, microbicide developers, and other research organizations to: (i) ensure the most efficient and effective use of available resources; (ii) pursue the highest priority candidate microbicides; and (iii) help ensure that the global clinical research agenda is maximally comprehensive and minimally duplicative. NIAID and NICHD sponsor the Integrated Preclinical/Clinical Program for HIV Topical Microbicides and NICHD supports the Microbicide Quality Assurance contract; collaborations with these researchers and others who are advancing microbicide candidates through preclinical development or conducting pharmacological or other relevant research are essential.

5. Prevention of Mother-to-Child Transmission (MTCT) of HIV

The research objectives for preventing mother-to-child transmission (MTCT) of HIV are to: (i) identify safe, practical and more effective approaches to further reduce MTCT, especially in resource-limited settings; (ii) define treatment options for pregnant and breastfeeding women and their newborns, both separately and as a unit; and (iii) develop knowledge to ensure the prolonged success of MTCT programs without compromising future treatment options for women. One of the success stories in MTCT is the effectiveness of nevirapine (NVP) in preventing transmission, and several trials are currently underway to evaluate the use of NVP to prevent transmission from breast milk and to optimize combination ART in NVP-exposed mothers and infants. In addition, several new candidate HIV vaccines will soon be ready for testing in HIV-exposed infants. Priorities for MTCT research in the years 2006-2013 will be to optimize treatment regimens both for mothers who are not yet on ART drugs, and for mothers who are already taking ART for their own care. In both cases, the goals will be to simplify delivery of care while improving the health of HIV-infected pregnant women, minimizing toxicity and drug resistance, and decreasing the risk of HIV transmission to their infants. Another priority will be to evaluate the safety and pharmacokinetics of new drugs, combinations and vaccines in women, including those who are pregnant, and in HIV-exposed infants. This will be accomplished by conducting studies to:

Participation of other NIH institutes, particularly the NICHD, as well as other Federal agencies (e.g. CDC and DoD) and other international partners (e.g. Elizabeth Glaser Pediatric AIDS Foundation (http://www.pedaids.org) and the MTCT-Plus Initiative (http://www.mtctplus.org) is essential to be able to carry out the NIAID scientific agenda. NICHD supports an extensive research agenda relevant to the prevention of mother-to-child HIV transmission focused on pregnant women, postpartum and breastfeeding women, and infants, domestically and internationally, that can be accessed at (http://www.niaid.nih.gov/daids/rfa/network06/default.htm). NICHD anticipates continued collaboration and integrated research efforts between NIAID-sponsored clinical trials networks and the NICHD Pediatric/Perinatal Network and additional collaborations with the NICHD ATN.

6. Prevention of HIV Infection

The DAIDS objectives in the area of prevention research are to: (1) identify practical, safe and effective approaches to halt the spread of HIV, especially in domestic and international populations at greatest risk; (2) develop integrated behavioral and biomedical prevention models that are efficacious, cost-effective, locally-appropriate, and sustainable; and (3) demonstrate the generalizability of integrated prevention programs to different cultural contexts and the feasibility of scaling up. Clinical trials are already underway to evaluate several drug-based prevention strategies, the protective value of adult circumcision, community-based voluntary counseling and testing (VCT) programs, and a community-based social diffusion prevention program to prevent epidemic spread. However, because incident HIV infections are driven by individuals with acute early HIV infection, greater availability and use of antiretroviral therapies, VCT, and behavioral prevention strategies targeted at seropositive individuals may lower transmission risks to uninfected persons, particularly those in resource-limited settings. Thus, the priority of prevention research will be to target newly-infected individuals and their partners and to test culturally-appropriate prevention science that integrates biomedical and technological advances, behavioral prevention strategies and interventions, sexually transmitted disease treatment, and provision of antiretroviral therapy. This will be accomplished by conducting studies to:

This research area will require extensive collaboration with NIH Institutes that conduct and sponsor prevention research (e.g. NICHD, NIDA, NIMH) and with researchers that they support. The NICHD supports an extensive research agenda relevant to the prevention of HIV through investigations related to women's health, and social and behavioral studies of the acceptability of various interventions and delivery methods for prevention of HIV in men, women and youth, domestically and internationally. NICHD anticipates continued co-sponsorship with NIAID of clinical trials networks focused on HIV prevention and encourages additional collaborations with the NICHD ATN. NINR has identified the development of prevention interventions based on biobehavioral and sociocultural dynamics in diverse populations such as adolescents, women and minorities as high priority research areas. Coordination with other research organizations and sponsors is required to help ensure that the global clinical research agenda is maximally comprehensive and minimally duplicative.

B. Options for the Scope of Applications

Through this solicitation and a forthcoming solicitation for Units for HIV/AIDS Clinical Trials Networks , NIAID and collaborating ICs intend to fund between three and six HIV/AIDS Clinical Trials Networks.

The Leadership of each Clinical Trials Network for HIV/AIDS must identify one or more of the six DAIDS high priority research areas (1) Vaccine Research and Development; (2) Translational Research/Drug Development; (3) Optimization of Clinical Management, Including Co-Morbidities; (4) Microbicides; (5) Prevention of Mother-to-Child Transmission (MTCT) of HIV; and (6) Prevention of HIV Infection) in which it will work cooperatively with DAIDS and collaborating ICs, and propose a focused research plan that addresses the most significant issues in that research area. NIAID may fund more than one Network Leadership in any of these six high priority research areas in order to ensure the representative inclusion of at risk and/or affected populations and when there is strong evidence of cross-Network coordination and collaboration.

C. Network Structure

Each HIV/AIDS Clinical Trials Network must include Network Leadership, Clinical Trial Units, and several committees as described below. The Network Leadership is responsible for ensuring that the Network's major structural components are capable of carrying out their respective responsibilities and operate in a well coordinated fashion. The Network bylaws, policies and operating procedures for all aspects of Network activities must be submitted to DAIDS for review within 120 days after award and must be in concert with NIH, NIAID, and DAIDS policies. DAIDS approval of Network bylaws, policies and operating procedures is required prior to initiating enrollment in any new protocol. This requirement for DAIDS review and approval of all Network bylaws, policies and procedures prior to initiating new protocols will be incorporated in the Terms of Award in the Notice of Grant Award.

1. Network Leadership

The Network Leadership must have the following three components:

2. Clinical Trial Units (CTU)

CTUs contribute to the Network clinical research plan by conducting clinical research, providing scientific expertise, and expanding the capability of the Network(s). CTUs are responsible for developing and maintaining effective community relationships; enabling community participation in clinical research sites, CTU, and Network activities; and ensuring that all clinical research is conducted in compliance with Network bylaws, policies and procedures, DAIDS policy and procedures, Federal regulations, and any applicable local requirements.

Each Clinical Trial Unit within a Network must have the following components:

Identification of CTUs and clinical research sites by Network Leadership successful applicants in response to this RFA does not imply CTU or clinical research site funding. NIAID and collaborating ICs will issue a separate solicitation to request applications for CTUs to affiliate with one or more Clinical Trials Networks. Priority will be placed on reaching under-represented populations severely impacted by the epidemic, including women, adolescents, and minorities in the U.S. as well as populations in resource-limited settings worldwide.

3. Committees

The Network must include, at a minimum, the following committees:

4. Collaborations with DAIDS and other HIV/AIDS Clinical Trials Networks

The Network Leadership will be expected to give high priority to collaborating with the other DAIDS- and NIH-sponsored HIV/AIDS Clinical Trials Networks. Such collaborations are essential for the development and implementation of a cross-cutting, interdisciplinary research agenda. Sharing expertise, resources, and procedures is expected in key areas including: development of international sites in resource-limited settings; harmonization of laboratory resources and specimen management; common data elements and data entry interfaces; the development, training and support of Community Advisory Boards; and site staff training.

These collaborations will be facilitated by the following cross-Network activities:

5. Flexible Resource Allocation

Rapid responses to unanticipated high priority research opportunities require timely reordering of priorities accompanied by reallocation of resources to accommodate the changing priorities. A system of ongoing performance evaluation that ensures maximal efficiency and effectiveness of all Network components, coupled with the allocation of reserve funds by DAIDS and of Protocol Implementation Funds by the Network Leadership, will be adopted to meet this challenge. In addition, in order to ensure that the available funds are used for the highest priority clinical research, annual unobligated balances for the grants awarded under this RFA will be allocated at the discretion of the NIAID.

Detailed information on the requirements for the Network Leadership are specified in Section VI.2.A the “Cooperative Agreement Terms and Conditions of Award”.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the U01 award mechanism(s). As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts and non-modular budget formats.

The NIH (U 01 ) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator 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".

2. Funds Available

The participating ICs intend to commit approximately $150 million dollars in FY 2006 to fund three to six new and/or competitive continuation grants in response to this RFA. An applicant may request a project period of up to seven years. 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. The first-year awards are expected to range between $10 million and $20 million in direct costs. Although the financial plans of the ICs provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. Facilities and administrative costs are not included in the direct cost limitation, see NOT-OD-04-040.

The NIDCR has identified research priorities related to oral health and oral complications of HIV and intends to commit approximately $2 million in the first year to support meritorious clinical research conducted within the HIV/AIDS Clinical Trials Networks that addresses its mission and priorities. NIDCR reserves the right to include additional Terms and Conditions of Award to ensure ongoing participation of interdisciplinary scientists in the research, appropriate representation on scientific committees, and NIDCR review and approval prior to initiation.

The intent of NIDA, NIMH, and NICHD is to provide continued support at their current level of funding for HIV/AIDS Clinical Trials Networks for clinical research activities that are meritorious and address the mission and priorities of the ICs.

NINR and NIAAA have identified areas of scientific interest and expressed interest in providing funding for clinical research activities that are meritorious and address the mission and priorities of the ICs, though the amount of funding available has not yet been determined.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

Foreign institutions are not eligible to apply as the awardee institution for any component. Foreign institutions are eligible to submit (an) application(s) as collaborators in Network activities including Operations, Statistical and Data Management, or the Network Laboratory structure.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is 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 programs.

2. Cost Sharing

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

3. Other-Special Eligibility Criteria

Applicants may submit multiple applications under this announcement. Institutions and Investigators with laboratory, statistical, data management, or administrative or operational expertise may collaborate with more than one Network.

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. 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 PHS 398 research grant application instructions and forms. Applications must have a Dun and Bradstreet (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. 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.

See Section VI.2 Administrative Requirements for additional information.

3. Submission Dates

Applications must be mailed on or before the receipt date described below (Section IV.3.A).

3.A. Receipt, Review and Anticipated Start Dates

Letters of Intent Receipt Date(s): April 11, 2005
Application Receipt Date(s): May 11, 2005
Peer Review Date(s): October, 2005
Council Review Date(s) : January, 2006
Earliest Anticipated Start Date: March, 2006

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Dr. Peter Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3140, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-496-8426
FAX: 301-480-2310
Email: pj8v@nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. 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)

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

Dr. Peter Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3140, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-496 8426
FAX: 301-480-2310
Email: pj8v@nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date listed in the heading of this funding opportunity. If an application is received after that date, it will be returned to the applicant without review. Applications will be evaluated for completeness by CSR.

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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All 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 (See also Section VI.3. Award Criteria).

6. Other Submission Requirements

I. Web Site for Application Information

NIAID has established a web site http://www.niaid.nih.gov/daids/rfa/network06/default.htm containing suggested forms and templates for use in preparing applications in response to this RFA.

II. Principal Investigator

A Principal Investigator who proposes to form a Network and assume the role of CORE PI is responsible for coordinating the preparation of a set of 1 to 3 complementary applications that cover the following Network Leadership components:

One (1) Coordinating and Research Operations Center (CORE)
One (1) Network Laboratories (NL)
One (1) Statistical and Data Management Center (SDMC)

III. Submission and Award Options

Applicants may apply for up to 3 separate U01s to create the Network Leadership structure: 1 U01 for the Coordinating and Research Operations Center (CORE), 1 U01 for the Network Laboratories (NL), and 1 U01 for the Statistical and Data Management Center (SDMC). Alternatively, applicants may choose to combine one or more of these components into a single application under a single PI. For example, the CORE application may include the SDMC or the NL or both. Irrespective of the choice made, applicants should follow the instructions below regarding organization of the application(s) and page limits. Awards will follow the pattern of applications submitted for each successful Network Leadership, but will require three viable components, however submitted.

IV. Participation in Multiple Networks

Institutions and investigators with laboratory, statistical, data management, or administrative or operational expertise are encouraged to collaborate with more than one Network. Any anticipated achievements in efficiency and effectiveness through sharing of central resources should be explicitly stated in each application. 

V. Instructions for Assembly of Applications

Regardless of how the components are proposed (as 1, 2 or 3 separate applications), each individual application must contain a section ‘Overview of Entire Network Leadership Application' describing the Network Leadership applications as a whole, to provide full context for reviewers. These sections may be identical in all individual applications submitted. Further information about this section is located below in B. Specific instructions for the CORE, Laboratories, Statistical and Data Management Center are located below in C, D, and E, respectively.

A. Assembly of Each Application

Each application (whether 1, 2 or 3 separate applications for a Network) should be assembled in the order that follows. If more than one component is included in a single application, the components should be arranged and addressed in the following order: (1) CORE, (2) Laboratories, (3) Statistical and Data Management Center.

1. PHS 398 Face Page applicable only for the components included within this application (1, 2, or 3).

2. PHS 398 Form Page 2 describing all components (whether 1, 2, or 3) included within the application.

3. List of all participating institutions and key investigators/personnel at each of the included components, noting component with which they are affiliated.

4. Table of Contents for Individual Application. If two or more components are included, do not use form page 3 of the PHS 398; a more comprehensive table of contents is needed. Since the application will be peer-reviewed component by component, prepare a detailed table of contents that will enable reviewers to locate information pertinent to each included component, as well as to the overall Network Leadership. Identify each included component by title and component leader (if different from the CORE PI), and provide a page reference for each component's budget.

5. Detailed Budget for Initial Budget Period – for included components only. Provide a Composite Budget covering all included components, matching the individual budgets provided elsewhere in the application. All budget items should be identifiable with the research priorities targeted in the CORE component/application.

6. Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification. See Section C below for additional instruction regarding the CORE budgets.

7. Budget for Entire Proposed Period of Support – for included components only. Provide a composite budget in matrix form showing the annual totals of each included component, the annual totals of all included components, and the all-years totals for each component and all components.

Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification.

8. Overview of Entire Network Leadership Application. See B below.

9. CORE (if applicable)

Cover page PHS 398 Form Page 2 describing the CORE.

Resources for theCORE.

Research Plan. Specific instructions for completing

Sections a. – d. are located below in C. Sections e. – i. As described in PHS 398 instructions. Sections on human subjects research and related issues, vertebrate animals, literature resources, consultants, etc., may be included here and do not count against page limits for the component.

10. Network Laboratory (NL) Structure (if applicable) Cover page PHS 398 Form Page 2 describing the NL. Resources for the NL. Research Plan. Specific instructions for the NL are located below in D. Sections e. – i. As described in PHS 398 instructions. Sections on human subjects research and related issues, vertebrate animals, literature resources, consultants, etc. may be included here and do not count against page limits for the component.

11. Statistical and Data Management Center (SDMC) (if applicable)

Cover page

PHS 398 Form Page 2 describing the SDMC.

Resources for statistical and data management.

Research Plan. Specific instructions for SDMC are located below in E.

Sections e. – i. As described in PHS 398 instructions. Sections on human subjects research and related issues, vertebrate animals, literature resources, consultants, etc., may be included here and do not count against page limits for the component.

12. All Biographical Sketches for all included components should be positioned at the end of the application with the application's Principal Investigator first, followed by other key personnel in alphabetical order. Do not include Biographical Sketches of key persons in the ‘Overview of Entire Network Leadership Application' section who are not otherwise involved in included components. Do not submit Other Support pages; these will be requested by NIAID “just-in-time” for an award.

13. Checklist for the entire application

14. Appendices. Appendices are limited to 30 pages per component. Note: Key information submitted in the appendix should be clearly referenced in the Research Plan Section. Information submitted as appendices should be limited to essential materials in support of the application; summaries or examples of information are encouraged. Applicants should not submit manuals of operation or full sets of standard operating procedures. Applicants should understand that appendices will be used for supplemental information and may not be made available to all reviewers. Letters of support that do not formally commit to contributions to the program should not be included.

B. Overview of Entire Network Leadership Application (all components, whether included in application or not)

1. Summary Page (do not use PHS 398 Face Page), containing the following information: Title of Network; Proposed Period of Performance (from – to); Network PI (CORE PI) – name, title, organizational affiliation; Laboratories PI – name, title, organizational affiliation; SDMC PI – name, title, organizational affiliation. Indicate how components are submitted (as 1, 2 or 3 applications, in which combination).

2. PHS 398 Form Page 2 describing the complete Network Leadership Application (CORE, NL, and SDMC [Omit if all 3 components are submitted in a single application]).

3. List of all participating institutions and key investigators/personnel for each component. Omit if all 3 components are submitted in a single application.

4. Detailed Budget for Initial Budget Period. A composite budget should be included showing all Network components individually and in total (Omit if all 3 components are submitted in a single application.). Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area for each individual budget in the budget justification.

5. Budget for Entire Proposed Period of Support. Provide a composite budget for all years showing all Network components individually and in total (Omit if all 3 components are submitted in a single application.). Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area for each individual budget in the budget justification.

6. Network Overview (20 pages or less). Briefly describe the Network, its mission, organizational structure including scientific committees, and key scientific and administrative personnel. Describe how the components will interact to address specific research priorities of the Network, showing the place of each component in the overall scheme. Summarize special features in the environment and resources that make this Network strong or unique.

C. Additional Instructions for Coordinating and Research Operations Center (CORE) component.

1. PHS 398 Form Page 4: Detailed Budget for Initial Budget Period. A composite budget must be included. All budget items should be identifiable with the research priorities targeted in the CORE application. The budget must include the following categories in this order:

i. Administrative support for the Coordinating and Research Operations Center (CORE).

ii. Coordination and logistic support for the Network Leadership to include the PI, Executive Committee, scientific committees, resource committees and meetings.

iii. CORE support for protocol development, implementation and oversight.

Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

2. PHS 398 Form Page 5: Budget for Entire Proposed Period of Support. Provide a composite budget followed by breakdowns for:

i. Administrative support for the Coordinating and Research Operations Center (CORE).

ii. Coordination and logistic support for the Network Leadership to include the PI, Executive Committee, scientific committees, resource committees and meetings.

iii. CORE support for protocol development, implementation and oversight.

Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

3. CORE Research Plan (items a-d). Limit to 150 pages: Note that face pages, biographical sketches, budget pages, literature citations, letters of support, checklists and other form pages are excluded from the page limits. Use the topics identified below and items in Section 2.A. Cooperative Agreement Terms and Conditions of Award as a guide for writing the research plan in lieu of items a. – d. listed on pages 17-18 of the PHS 398 application brochure.

D. Additional Instructions for Network Laboratory (NL) Structure Component

1. PHS 398 Form Page 4: Detailed Budget for Initial Budget Period . A composite budget should be included showing the administrative support for the NL and all performance sites individually and in total. Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

2. PHS 398 Form Page 5: Budget for Entire Proposed Period of Support . A composite budget should be included showing the administrative support for the NL and all performance sites individually and in total. Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

3. Network Laboratories Research Plan (items a. – d.). Limit to 60 pages: Note that face pages, biographical sketches, budget pages, literature citations, letters of support, checklists and other form pages are excluded from the page limits . Use the topics identified below and items in section 2.A. Cooperative Agreement Terms and Conditions of Award as a guide for writing the research plan in lieu of items a. – d. listed on pages 17-18 of the PHS 398 application brochure.

The Research Plan should address the following:

E. Additional Instructions for Statistical and Data Management Center (SDMC) Component

1. PHS 398 Form Page 4: Detailed Budget for Initial Budget Period . A composite budget should be included showing administrative support for the SDMC, statistical support and data management activities individually and in total. Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

2. PHS 398 Form Page 5: Budget for Entire Proposed Period of Support . A composite budget should be included showing administrative support for the SDMC, statistical support and data management activities. Applicants proposing research plans in more than one of the six high priority research areas must identify the percentage of overall expenditures for each high priority research area in the budget justification for each individual budget.

3. Research Plan (items a. – d.). Limit to 60 pages: Note that face pages, biographical sketches, budget pages, literature citations, letters of support, checklists and other form pages are excluded from the page limits. Use the topics identified below and items in section 2.A. Cooperative Agreement Terms and Conditions of Award as a guide for writing the research plan in lieu of items a. – d. listed on pages 17-18 of the PHS 398 application brochure.

A Statistical and Data Management Center (SDMC) application should propose biostatistical leadership and central data management capabilities for the proposed Network clinical research plan.

The SDMC Research Plan should address the following:

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication. NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://www.ott.nih.gov/policy/rt_guide_final.html . Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the data sharing plan and the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report. (PHS 2590). See Section VI.3. Award Criteria.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

Overlaid upon the standard review criteria listed under section 3. below, the following items will be considered in the determination of scientific merit and the priority score:

I. COORDINATING AND OPERATIONS CENTER (CORE) REVIEW CRITERIA - ADDITIONAL REVIEW CRITERIA FOR CORE COMPONENTS

A.  NETWORK CLINICAL RESEARCH PLAN

  1. Scientific merit, innovation, and feasibility of the proposed scientific priorities and research plan.
  2. Potential for the proposed research plan to advance HIV prevention or clinical care.
  3. Potential for the proposed research plan to be applicable to groups most severely impacted by HIV/AIDS, including women, adolescents, and racial/ethnic minorities.

B. CROSS-NETWORK COLLABORATIONS

  1. Strength, scientific merit, and feasibility of plans to pursue scientific questions of mutual relevance through collaboration and integration with other groups (other DAIDS and NIH-sponsored HIV/AIDS Clinical Trial Networks and other relevant clinical research groups).
  2. Potential, based upon scientific breadth and experience of the Scientific Leadership, to enable productive cross-Network scientific collaborations.
  3. Potential contribution to efforts to maximize organizational efficiency and effectiveness through cooperation and coordination with other DAIDS and NIH-sponsored HIV/AIDS Clinical Trial Networks. Key areas include a.) development of international clinical research sites, b.) harmonization of Network policies and procedures, c.) sharing of laboratory resources and procedures d.) identification of common data elements, data dictionaries, and data interfaces, e.) training and support of Community Advisory Boards, and f.) training of Network and site staff.

C.  NETWORK STRUCTURE AND LEADERSHIP

  1. Adequacy of the Principal Investigator's qualifications, time commitment, experience and vision for the design, coordination, and direction of multicenter HIV clinical research.
  2. Adequacy of the Scientific Leadership's qualifications, time commitment, and experience in the design, coordination, and direction of multicenter HIV clinical research.
  3. Appropriateness and clarity of the organizational structure and lines of authority for the overall Network.
  4. Appropriateness of proposed size and structure of the Network to meet scientific goals.
  5. Appropriateness of criteria and standards used to select and propose clinical sites for affiliation with regard to future Network needs, timely enrollment into proposed clinical research, population demographics, clinical site leadership and past performance.
  6. Adequacy of plans for management and communication among the Operations Center, the Network Laboratories, Statistical and Data Management Center, and Clinical Trial Units/clinical sites to achieve the scientific goals of the Network.

D.  NETWORK POLICY AND PROCEDURES

  1. Adequacy of plans to (i) assure appropriate protection of the rights and safety of subjects involved in its clinical investigations; (ii) guarantee the quality and integrity of resulting data; (iii) maintain accurate and timely information on the progress of each study and (iv) include appropriate safeguards to terminate studies if deemed unsafe, irrelevant or unnecessary.
  2. Strength and feasibility of Network policies and procedures to reassess, evaluate and reprioritize the scientific priorities as the field evolves.
  3. Appropriateness and feasibility of the proposed means to measure and assess productivity of Network and Network components: Operations Office, Laboratories, Statistical and Data Management Center, and Clinical Trial Units.
  4. Appropriateness and feasibility of plans to correct inadequate performance at clinical sites or other Network components.
  5. Strength, merit, feasibility and transparency of plans to manage and allocate the Protocol Implementation Fund.
  6. Adequacy of proposed plans to develop and nurture relationships with communities and involve community representatives in all Network activities.
  7. Strength, merit and feasibility of policy and plans to monitor and manage conflicts of interest between personal interests and Network decision-making responsibilities.
  8. Adequacy and feasibility of plans to ensure the involvement of new investigators, foster the participation of women and racial/ethnic minorities as researchers, and ensure their participation in Network activities at all levels.

E.  OPERATIONS CENTER

  1. Adequacy of the training, experience, levels of commitment, and qualifications of the CORE's Operations Center Director to successfully manage an operations office for a multicenter clinical trials Network.
  2. Adequacy of the training, experience, levels of commitment, and qualifications of the CORE's Operations Center other key personnel.
  3. Appropriateness and clarity of the organizational structure, management plan and lines of authority involving the Operations Center.
  4. Strength, merit and feasibility of plans for the Operations Center to facilitate rapid and effective communications with all Network components.
  5. Strength and merit of plans to assure fiscal and operational accountability.
  6. Strength and merit of structure and plans to support protocol development, track protocol development and implementation, provide research administration, and manage regulatory documents.
  7. Strength, merit and feasibility of plans and staffing to support network activities, including an Executive Committee, scientific and resource committees, field staff training, and Network meetings.
  8. Adequacy of the proposed resources to support the Network research plans and priorities.
II. ADDITIONAL REVIEW CRITERIA FOR NETWORK LABORATORY COMPONENTS

A. STRUCTURE AND LEADERSHIP

  1. Adequacy and appropriateness of the proposed number, type and location of laboratories to meet Network research plans.
  2. Appropriateness and clarity of the organizational structure, management plan and lines of authority.
  3. Adequacy of the training, qualifications, experience, and level of commitment of the Network Laboratories Principal Investigator to provide scientific and administrative leadership.
  4. Adequacy of the training, qualifications, experience, level of commitment, and availability of the Director and key personnel at each identified Laboratory facility.
  5. Adequacy of the plan to provide resources to support Network Laboratories research plans and priorities.

B.  POLICY AND PROCEDURES

  1. Scientific merit, technical merit and feasibility of plans to select laboratory tests for inclusion in clinical studies.
  2. Scientific and technical merit, appropriateness and feasibility of proposed laboratory services including facilities, staff, standard operating procedures, laboratory data management, and specimen tracking.
  3. Scientific merit, technical merit and feasibility of plans to evaluate utility of new technologies and feasibility of technology transfer to the Network laboratories.
  4. Strength, merit and adequacy of plans to train Network laboratory staff in Good Laboratory Practices, safety and laboratory techniques.
  5. Strength, merit and appropriateness of plans for laboratory QA/QC, including plans for adherence to guidelines of regulatory agencies and participation in external quality assurance programs.

C.  COMMUNICATION AND COLLABORATION

  1. Strength, merit and feasibility of plans for rapid and effective communication among Network laboratories and with other Network structures.
  2. Potential contribution of efforts to maximize organizational efficiency and effectiveness through collaborations with other DAIDS and NIH-sponsored HIV/AIDS Clinical Trial Network. Key areas for collaborations include sharing of laboratory resources and procedures, and development of consistent assay procedures and standards.
III. ADDITIONAL REVIEW CRITERIA FOR STATISTICAL AND DATA MANAGEMENT CENTER (SDMC) COMPONENTS

A.  STRUCTURE AND LEADERSHIP

  1. Adequacy of the Principal Investigator's qualifications, time commitment, experience and availability for the scientific and administrative direction of a multicenter clinical trials statistical and data management center.
  2. Adequacy of the qualifications, training, and experience of other key personnel.
  3. Appropriateness and clarity of the organizational structure, management plan and lines of authority.
  4. Adequacy of the proposed resources to support the Network research plans and priorities.

B.  POLICY AND PROCEDURES

  1. Strength, merit, appropriateness and feasibility of plans and procedures for planning and conducting interim and final analyses of clinical studies.
  2. Potential scientific contribution to the Network research plan through participation in design, conduct, analysis and publication of clinical research.
  3. Strength, merit, appropriateness and feasibility of plans and procedures for providing all data management services required by the Network, including database design, security, confidentiality and administration, participant randomization/registration, data collection, quality control, data retrieval, report generation, and site training.
  4. Strength, technical merit, and feasibility of plans to ensure availability of reliable electronic mail among Network components and DAIDS.

C.  COMMUNICATION AND COLLABORATION

  1. Strength, merit and feasibility of plans for rapid and effective communication within the SDMC and with other Network structures.
  2. Strength, merit, feasibility and innovation of plans to facilitate cross-Network collaboration and coordination. Potential contribution to efforts to maximize organizational efficiency and effectiveness through collaborations with other DAIDS and NIH-sponsored HIV/AIDS Clinical Trial Network. Key areas for collaborations include harmonization of Network policies and procedures related to data management and identification of common data elements, date dictionaries, and data interfaces.
IV. ADDITIONAL REVIEW CRITERIA FOR IDENTIFIED NIDCR RESEARCH PRIORITIES

As appropriate to the review of CORE, NL or SDMC components:

  1. Scientific merit, innovation, and feasibility of the proposed oral health clinical research plan.
  2. Adequacy of the qualifications, experience, and time commitment of investigators.
  3. Strength, merit and appropriateness of proposed scientific collaborations to develop, implement and oversee the oral health clinical research agenda.
  4. Strength of Network Leadership interest.
  5. Adequacy of laboratory services, statistical and data management support, and other resources to further these research priorities.

2. Review and Selection Process

Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NIAID . Incomplete and/or nonresponsive applications will not be reviewed.

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.

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

Individual numerical merit scores will initially be assigned to each of the following: The Coordinating and Operations Center, the Network Laboratory Structure, and the Statistical and Data Management Center. An overall priority score will be assigned for each application based on review and merit of the individual components included, as well as the merit of the application taken as a whole.

3. Merit Review Criteria

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 high 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.

1. 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?

2. 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?

3. 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?

4. 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)?

5. 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?

3.A. Additional Review Criteria:

In addition to the above criteria, the following items will 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).

3.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.

3.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

3.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the Principal Investigator before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Award Criteria.

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a summary statement.

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/archive/grants/policy/nihgps_2003/index.htm

A formal notification in the form of a Notice of award will be provided to the applicant organization. The notice of award signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA (Notice of Grant Award) are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

NIAID will transmit the NGA via U.S. mail for a hard copy and/or via email for an electronic copy.


2. Administrative Requirements

All NIH Grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. 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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.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.
Execution of this program will require collaboration among NIAID, other co-sponsoring NIH Institutes and Centers, the DAIDS Program Director(s) and staff, the CORE PI, the Principal Investigator of the Network Laboratory, the Principal Investigator of the Statistical and Data Management Center (SDMC) and the other NIAID-funded Clinical Trials Networks. DAIDS will assist in coordinating the activities of the Networks as defined below and will facilitate the exchange of information. Specific tasks and responsibilities in carrying out the activity will be shared among the awardee, DAIDS staff and DAIDS' contractors. DAIDS reserves the right of final authority to approve all tasks performed in the context of this award.

2.A.1. Principal Investigator Rights and Responsibilities

The CORE Principal Investigator is the leader of the Network with responsibility for the performance of the Network overall and specifically the Coordinating and Operations Center. The CORE PI is responsible for the scientific leadership, administration and coordination of all Network activities, implementation within the Network of applicable Managing Partners decisions and activities, support for Community Partners, and implementation of Community Partners recommendations. The CORE PI is also responsible for developing, implementing, monitoring, and updating, in collaboration with DAIDS, the clinical research plan for the Clinical Trials Network to ensure consistency and relevance with the NIAID scientific agenda and to avoid duplication. The CORE PI will review the Network's research activities and goals on a mutually agreed upon schedule (but no less than once every year) with a DAIDS Program Director or designee.

The Principal Investigator will have the primary responsibility for:

A.  MONITORING CLINICAL STUDIES

When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants2.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

All clinical research activities performed through the Network must be in compliance with all U.S. Federal regulations, NIH policies and guidance applying to the conduct of research involving human subjects and FDA requirements for new drug or biological licenses when applicable. These include, but are not limited to, CFR Title 21, Part 11, 50, 54, 56, 312, 314, 601 and Title 45, Part 46; Guidance for Good Clinical Practice (GCP); and NIH grants policy (refer to http://grants1.nih.gov/archive/grants/policy/nihgps_2003/index.htm). The Network must assure that all sites in the U.S. and outside the U.S. comply with these and the following:

All clinical research activities performed outside of the U.S. must, in addition to U.S. Federal regulations, comply with all pertinent host country regulations for human subjects and/or HIV/AIDS research.

B.  COORDINATION WITH DAIDS AND WITH OTHER NIH-SPONSORED HIV/AIDS CLINICAL TRIAL NETWORKS

The Network Leadership will give high priority to collaborating with other DAIDS and NIH HIV/AIDS Clinical Trial Networks to implement a cross-cutting and interdisciplinary research agenda. Effective coordination to achieve this goal will include (but not be limited to) the following common areas:

C. MANAGING PARTNERS

Representatives of the Network Leadership will contribute to the Managing Partners, promoting optimal joint research activities among the multiple Network components. Responsibilities of the Managing Partners will include:

DAIDS and the Managing Partners will cooperatively establish performance measures to be applied by each Network in evaluating the efficiency and effectiveness of its performance. These measures may include, but not be limited to the following:

D.  COMMUNITY PARTNERS

Membership in the Community Partners will be drawn from the Network Community Advisory Boards, the Managing Partners, and representatives from DAIDS. The awardee is responsible for supporting the Community Partners initiatives and implementing the Community Partners' recommendations. Responsibilities of the Community Partners will include:

E. NETWORK LEADERSHIP

The Network Leadership will be comprised of the Principal Investigators of the Coordinating and Operations Center (CORE), the Statistical and Data Management Center (SDMC), and the Network Laboratory Structure (NL) as well as the Director of the Operations Center and members of the Executive Committee constituted according to policy and procedures developed by the Network and approved by DAIDS.

F. NETWORK STRUCTURE

The Network structure should be designed to maximize scientific leadership in the research areas of highest priority as defined by DAIDS, promote effective communication and decision making, identify clear lines of authority, coordinate and collaborate effectively with other DAIDS and NIH HIV/AIDS Networks at multiple levels, avoid redundancy, and ensure efficiency. In addition to the components described above, the Network Structure will include, at a minimum:

1.  An Executive Committee, established as the main governing body of the Network, will be responsible for the development and implementation of policy, procedural decisions, and resource allocation. The Executive Committee will be chaired by the CORE PI and will include the PI of the SDMC; PI of the Network laboratory structure, the Director of the Operations Center; at least one community representative; and appropriate, proportional representation from the Principal Investigators of U.S. and affiliated foreign clinical research sites. At a minimum, EC membership must also include as voting members a DAIDS Project Scientist (or designee) and one additional DAIDS staff member appointed by the Project Scientist. Networks that receive substantial support from other NIH Institutes or Centers will also include representation from those Institutes or Centers with a combined total of two votes on the EC at the request of DAIDS.

2.  Scientific Committees, constituted by the Network EC, will contribute to the ongoing refinement of the Network scientific research plan, oversee protocol development and implementation, provide oversight of ongoing studies, and ensure timely publication of results. The number of committees and their scientific areas will be based on the scientific activities of the Network. Every Network scientific committee must have at least one representative DAIDS staff member.

3. Resource Committees must be created to identify and resolve specific functional issues within the Network. Representatives of Resource Committees will also be expected to participate in cross-Network activities to ensure effective coordination within the functional areas as appropriate. The DAIDS reserves an option for membership and voting privileges on all Resource Committees. To facilitate these internal and cross-Network activities, Networks are expected to establish the following:
  1. Quality Assurance /Quality Control (QA/QC) Committee The QA/QC Committee will be responsible for assuring the quality of the data at the site level, including protocol adherence, source documentation, and regulatory adherence.
  2. Site Management and Clinical Care Committee to oversee and resolve operational and clinical care issues identified by affiliated clinical research sites.
  3. Performance Evaluation Committee to develop and implement standard criteria and processes for assessing progress of each structural component of the Network, including sites, operations office, laboratories, data management center, scientific and resource committees, and protocol teams.
  4. Data Management Committee to oversee and resolve Network issues pertaining to case report forms (CRFs) and data entry.
  5. Network Community Advisory Board (CAB) to develop and implement a community involvement plan to facilitate community participation in Network and cross-Network activities. The Network CAB will participate in the formulation and implementation of Network research activities and represent the roles and requirements of local (site) Community Advisory Boards at U.S. and international sites. Additional Network activities that must be considered are: (i) building community capacity goals for conducting specific research activities; (ii) awareness and education to improve the community's understanding of research; (iii) community mobilization skills; (iv) finding ways to assess the impact of community involvement on research; (v) and developing mechanisms for sites to share best practices, experiences, and lessons learned.
  6. Training and Education Committee to assess training needs within the Network; implement training activities that can be accessed by any site; evaluate effectiveness of training; and collaborate with Training and Education Committees of other funded Networks.
  7. Pharmacy Committee to work with representatives of the DAIDS Pharmaceutical Affairs Branch to identify protocol and site specific training needs and provide a forum for communication and information exchange among Network pharmacists.

Additional Resource Committees may be established at the discretion of the Networks and in accordance with Network bylaws.

G.  BYLAWS, POLICIES AND OPERATING PROCEDURES

The Network must develop, implement and update as necessary well-documented policies, procedures, and bylaws on all aspects of Network activities. It is expected that contributions to the cross-Network coordination will result in a harmonization of policies and procedures across the Networks. Over the course of the project period, any bylaws, policies, and operating procedures that are newly developed or revised must be submitted to DAIDS for review and approval above and beyond Network-specific approval processes.

Bylaws, policies and operating procedures must include, at a minimum, the following:

1.  A Conflict of Interest (COI) Policy consistent with NIH policy (refer to the NIH Web site: http://grants.nih.gov/grants/policy/coi/index.htm), and FDA regulations (21CFR54). Violations of a Network's approved COI Policy may be referred to NIAID legal counsel and, if applicable, the U.S. Department of Justice for resolution.

2.  Procedures to ensure adequate protection of the rights and safety of subjects involved in the research.

3.  Procedures for maintaining and managing a Protocol Implementation Fund that include criteria and review procedures for allocation of funds based upon scientific and administrative needs and Network priorities. Procedures must include the requirement for Executive Committee approval to expend discretionary funds. Procedures for managing the Protocol Implementation Fund must include a strategic budgeting plan to be established prior to the start of each grant year. Use of funds must be reported to DAIDS on an annual basis as part of the noncompetitive renewal application.

4.  Procedures for selecting the most promising candidates to advance in clinical trials, including the most appropriate products under preclinical development for entry into clinical investigation, and products tested in phase I clinical trials suitable for movement to phase II and III clinical trials. These criteria should be inspired by sound scientific considerations, while at the same time taking into account practical issues (e.g. scalability of the manufacturing process of a vaccine candidate that proves efficacious across broad geographical areas) and acceptability to DAIDS.

5.  Procedures to ensure that protocol development, implementation, and oversight meet the following:

6.  Procedures for regular assessment of performance will include processes for the addition, reduction, expansion or elimination of clinical research sites, labs or other components based on current or anticipated scientific contribution, protocol participation, adherence to protocol requirements, data management/quality, and subject accrual/retention. This mechanism will include a procedure for recommending to DAIDS an adjustment of institutional funding based on level of contribution and performance. A system for establishing such procedures in a timely manner must be implemented by the Network.

7.  Policies and Procedures to acknowledge that the activities of the Network are performed cooperatively with the Division of AIDS, NIAID in all press releases, publications, brochures, websites, and all other public information sources.

8.  A procedure for submitting materials that describe Network mission and activities and that are intended for public dissemination (e.g. advertisements, brochures, flyers etc.), in draft form, to the Office of Program Operations and Scientific Information (OPOSI), DAIDS no later than 30 days prior to their proposed use. Protocol-specific documents, such as recruitment materials, are excluded from this requirement. OPOSI will coordinate review and/or approval of materials with DAIDS program staff and the NIAID Office of Communications and Public Liaison.

H.  COORDINATING AND OPERATIONS CENTER

1. The Coordinating and Operations Center (CORE) will be responsible for coordinating all research activities and serving as a central resource for communications within the Network and among other Networks. Such activities must include, but are not limited to, the following:

2.  Reporting Requirements. The Network Leadership will submit requisite information to DAIDS in order to meet administrative, oversight, and regulatory needs according to timelines established by DAIDS.

The Network will be required to work with DAIDS and DAIDS Enterprise System (DAIDS-ES) contractors as information standards and reporting requirements are developed. A memorandum of agreement will be established between DAIDS and the owners/providers of applications/systems that share data/information with the DAIDS-ES at the time of award.

3. Annual Reports. The CORE PI will submit an annual progress report summarizing all research accomplishments and providing metrics on Network performance as a whole and for each of the Network components and participating CTUs to DAIDS. This annual report will summarize activities, accomplishments, difficulties, corrective actions, performance evaluations and future directions with complete budget justifications. This report will be due concurrently with the annual Non-Competing Grant Progress Report for the Core Component (Form 2590).

4. Publication of Data. Prompt and timely presentation and publication of major findings in scientific literature is essential. Publications or oral presentations of work performed under this cooperative agreement will require acknowledgment of NIH support, including NIAID and any other supporting NIH Institutes or Centers. No less than two weeks prior to the submission of manuscripts for publication, a copy must be provided to DAIDS. The awardee retains the rights to the data, consistent with current DHHS, PHS, and NIH policies; however, DAIDS, NIAID and other NIH Institute and Centers providing support under this cooperative agreement will have access to all data generated (raw and analyzed) and may periodically review it.

5. Investigator Meetings. It is anticipated that at a minimum 1 full meeting per year in the Washington, DC metropolitan area will be required to provide effective leadership and coordination of the Network. Modifications to this minimum number of meetings or location require a specific request and approval by the Director, DAIDS. These meetings will be held jointly or in coordination with other DAIDS- sponsored clinical trials Network meetings on dates approved by DAIDS. Meeting coordination is required to limit the travel commitments for international Investigators involved in multiple Networks. The awardee is responsible for logistics, scientific content, and fiscal support of the meetings. DAIDS reserves the right to schedule specific sessions during the meetings. The meetings must be open to the public, although selected sessions may be closed upon approval of the DAIDS Program Director. All Network sessions must be open to DAIDS staff.

6. Demographic Diversity. The Network must have plans in place to ensure that overall demographic diversity of study participants is reflective of the infected population and those at high risk for infection. The Network also must have plans established for incorporating new sites with access to minority populations into the Network and involving new female and U.S. minority investigators into the Network's activities.

I.  LABORATORY SUPPORT

The Network Laboratory Structure (NL) must be an efficient, cost-effective mechanism that includes the types of laboratories (e.g. virology, immunology, pharmacology) and specimen storage capabilities required to support the Network clinical research and to conduct research and development activities linked directly to DAIDS scientific priorities. The PI of the NL will be responsible for overall laboratory operations, set laboratory priorities based on Network research priorities, and delegate responsibilities to the Principal Investigators of the individual laboratories that comprise the structure. There must be a clear distinction, and preferably a separation, between laboratory components that must function under conditions consistent with Good Laboratory Practices (GLP) and those performing activities that do not require GLP. The NL will participate in the design, conduct, analysis, and publication of clinical research.

The PI of the NL and the PI of each laboratory facility will:

  1. Provide scientific leadership to contribute to, and actively participate in the design and execution of clinical protocols, including evaluation of laboratory data.
  2. Ensure timely performance and accurate conduct of laboratory assays to support clinical studies. Whenever possible, assays must be qualified or validated following the “Guidance for Industry: Text on Validation of Analytical Procedures” http://www.fda.gov/cder/guidance/ichq2a.pdf) and “Q2bGuidance for Industry Q2B Validation of Analytical Procedures: Methodology” ( http://www.fda.gov/cder/guidance/1320fnl.pdf). Ensure that tests, when intended for use as study endpoints or for making subject management decisions, are transitioned into GLP format.
  3. Collaborate with non-Network expert investigators and laboratories and other DAIDS-funded resources when identifying, evaluating and implementing new tests, reagents and instruments for clinical studies. Research tests, when intended to be used as study endpoints or to make subject management decisions, are transitioned into GLP format.
  4. Transfer technology and share scientific information between NL located in the US and resource-limited countries.
  5. Ensure that each network laboratory facility will:
  6. •  Have secure facilities with adequate space, appropriate layout and necessary equipment, and provide for personnel and study participant safety and the safe handling of infectious and biohazard materials.
    •  Have sufficient, properly trained and experienced staff and a suitable staffing structure.
    •  Establish and follow standard operating procedures (SOP) to ensure specimen integrity, effective specimen management and tracking at all stages (acquisition, recording, processing, testing, storage, inventory and during transportation).
    •  Include a laboratory data management approach and system that allows for efficient, safe, complete, accurate and timely data acquisition, recording, reporting, export and archiving.
    •  Ship specimens in accordance with applicable local, national and international regulations.
    •  Maintain updated government permits to import and export infectious and non-infectious biological materials.
    •  Make specimens available for cross-trial and cross-Network evaluation when directed by the Network Leadership.
    •  Establish and follow standard operating procedures (SOP) to prevent release of specimens for purposes for which the subject has not provided consent.
  7. The Laboratory PI will ensure the following in regards to the operation of laboratories that must conduct operations consistent with Good Laboratory Practices:
  8. •  Domestic and international laboratories performing tests that determine safety of interventions or that are used to make subject management decisions, must conduct operations under GLP conditions and must be monitored by external proficiency testing schemes. Domestic labs that perform these tests must be CLIA-accredited/certified. International laboratories in resource-developed countries must be certified by their own national accreditation organization, and must strive to achieve equivalent accreditation/certification.
    •  Laboratories performing endpoint testing to determine product efficacy must conduct operations under GLP conditions, are subject to GLP audits, and must receive a satisfactory evaluation when an audit is performed.
    •  Optimal quality assurance (QA) in operational procedures or identification of alternative testing sites when a laboratory has persistent poor QA performance.
  9. Overseeing QA and Quality Control (QC):
  10. •  Laboratories in resource-limited international settings must cooperate with DAIDS contract resources that provide oversight and monitoring of the quality of patient diagnosis and safety tests (e.g. hematology, chemistry, liver function) performed in the laboratories. These contract resources will assess laboratory ability, readiness and capacity to routinely conduct activities according to GLP standards and to participate in NIAID study protocols. They also will provide training and trouble-shooting, assist in implementing general and study-specific QA/QC measures, and prepare laboratories for participation in external proficiency testing. Other contractual resources will provide oversight, monitoring and support for CD4 enumeration, HIV viral load, HIV DNA PCR and drug resistance determinations.
    •  The NL must include quality assurance oversight for Network-specific tests (e.g. vaccine efficacy endpoint tests, drug level and drug interaction determinations) and other tests not covered by DAIDS contract resources. Oversight will include (i) assessment of laboratory ability, readiness and capacity to routinely conduct activities according to GLP standards and participate in NIAID study protocols; (ii) provision of training and trouble-shooting; (iii) assistance in implementing general and study-specific QA/QC measures, and (iv) assistance in preparing laboratories for participation in external proficiency testing. One or more QA/QC central providers may be utilized for this oversight.

    When external proficiency testing programs do not exist for study-required tests, the NL PI, in collaboration with an identified central QA/QC provider, investigators, DAIDS staff and other DAIDS-funded resources, must design and implement tools to evaluate the ability of laboratories to perform such tests, develop criteria for acceptable performance, and determine consequences for unacceptable performance. The Network Laboratory PI must ensure that the QA/QC central provider will provide laboratories with tools to capture information such as test results, methods and instrumentation used, proper use and storage of reagents and timeline for reporting test results. The QA/QC central provider will receive and analyze test results and notify laboratories of proficiency testing results and performance status. Additional measures to ensure the quality of performed tests, such as confirmatory retesting of samples, must be implemented if required.

J. STATISTICAL AND DATA MANAGEMENT CENTER

The Statistical and Data Management Center (SDMC) will provide statistical leadership for the (i) design, conduct, analysis and publication of Network clinical trials/studies; (ii) provide central data management capability that includes randomization, dataset and case report form design, central storage, security, processing and retrieval of study results; (iii) provide data management training throughout the Network; and (iv) contribute to cross-Network efforts in developing common data elements and data interfaces. The SDMC will perform the following functions:

  1. Work cooperatively with counterparts from other DAIDS-sponsored Clinical Trials Networks and other NIH HIV/AIDS-related clinical research programs to develop common data elements and procedures in order to increase the feasibility of collaborative research projects and ensure capability for cross-protocol and cross-Network analysis. This will include the establishment of standard data interfaces and common data elements, protocol status definitions, endpoint verification, formats for data collection, and site identification systems.
  2. Collaborate with other HIV/AIDS clinical research groups, including clinical trial Networks and epidemiologic groups, and DAIDS in creating and exporting datasets for meta and epidemiologic analysis.
  3. Develop approaches for adapting current database systems and structures to accommodate multi-network collaborations, including approaches to maintaining legacy database systems.
  4. Transfer data to the DAIDS Enterprise System. Network Statistical and Data Management Centers will be required to work with DAIDS and its contractors as standards and reporting requirements are developed. A memorandum of agreement will be established between DAIDS and the owners/providers of applications/systems that share data/information with the DAIDS-ES.
  5. Participate in the design, conduct, analysis, and publication of clinical research. The SDMC will:
  6. •  Provide statistical leadership for the Network and for the development of its research plan.
    •  Perform timely interim analyses of safety and efficacy for protocol teams, DAIDS and the DAIDS DSMB.
    •  Produce interim and close-out study monitoring reports for the protocol team, Network Leadership, and the DAIDS Program Director or designee.
    •  Generate executive summaries of near-final study results in conjunction with protocol team members for use by the protocol team, DAIDS, sponsors, and
    ollaborators.
    •  Perform final analyses for publication, participate in writing scientific papers, and publishing study results in conjunction with other protocol team
    embers.
    •  Perform cross-protocol or cross-study analyses utilizing data from multiple sources within and external to the Network.
    •  Conduct analyses and prepare summary tables for annual and interim reports for DAIDS-sponsored Investigational New Drug Applications for submission
    to the NIAID and FDA.
    •  Develop innovative clinical trial designs and analysis methodologies consistent with and in support of the Network research plan.
    •  Conduct secondary analyses of Network data to improve the planning, design, conduct and interpretation of future trials.
    •  Providing other analyses and/or reports as requested by DAIDS.

  7. Provide all data management services required by the Network. The SDMC will:

    •  Provide central registration and support for randomization of all study participants.
    •  Develop case report forms and standardized criteria for clinical endpoint verification.
    •  Design and implement systems for the efficient tracking and transfer of clinical and laboratory data from clinical sites to the central dataset, using either a centralized or distributed data entry approach.
    •  Provide data management training to the clinical sites and DAIDS' Clinical Site Monitoring Contractor.
    •  Assist in the development of data management resources (equipment, electronic, and human) at sites in resource poor settings.
    •  Provide for central storage, security, processing and retrieval of study results.
    •  Demonstrate the means by which the SDMC will ensure that all data, patient questionnaires, consent forms, and all other records containing volunteer identifiers are maintained in a confidential and secure manner at all times.
    •  Prepare selected public access datasets, as provided for in the approved plan for providing public access in a reasonable timeframe after primary analysis and publication.
    •  Ensure availability of reliable electronic mail with Internet-wide message exchange capability to facilitate communication among Network components and DAIDS. [This activity may be delegated to the Operations Office at the convenience of the Network Leadership.].
    •  Provide recruitment, retention and other relevant summary data to the sites and protocol teams as designated by the Network Leadership.
    •  Assume responsibility for central data storage in conjunction with the Laboratory Data Management System contractor and the NIAID AIDS Specimen Repository. Facilitate tracking and identification of laboratory specimens, and the merger of laboratory test results with subject clinical data.
    •  Provide clinical research units with limited online access to their own blinded data in the central database.
    •  Develop reports detailing site performance of data management, deliverable to the CORE PI and the DAIDS Program Officer.
    •  Provide DAIDS with annual demographic reports on participants enrolled in Network studies according to NIH policy. Cumulative enrollment information will be provided annually by protocol for each participating site.
    •  In accordance with current DAIDS policy and procedures, SDMC will capture data concerning adverse events and generate periodic reports. Clinical trial sites will transmit expedited reports of adverse events directly to DAIDS. DAIDS is currently developing an online system for the expedited reporting of adverse events as part of the DAIDS ES. It is anticipated that the DAIDS will require MedRA for classifying and coding types of serious adverse experiences at the time of award.

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

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NIH Project Scientist, with the assistance from other NIAID and NIH scientific program staff designated by research topic and relevant expertise, will interact directly with the CORE PI, Principal Investigators of the SDMC, Network Laboratory, scientific leadership, sites, and any collaborating institutions as needed to: facilitate coordination among Networks; communicate the NIAID research agenda and priorities; fulfill NIAID sponsor and regulatory responsibilities; contribute to protocol development; oversee protocol development, implementation, and study conduct; and review performance. DAIDS staff may attend and interact at all meetings, trainings, and conference calls that are supported by NIAID funds.

A. COORDINATION AMONG DAIDS AND OTHER NIH-SPONSORED HIV/AIDS NETWORKS

The Managing Partners, representing the leaders of all DAIDS-supported Networks, will promote optimal joint research activities among their Networks, inform DAIDS about plans for such joint activities involving components of multiple Networks, and advise DAIDS on resource allocation priorities. DAIDS will provide contract resources, as appropriate, to meet needs identified through the activities and deliberations of the Managing Partners.

DAIDS will promote collaborations and facilitate information exchange among the DAIDS-supported Networks and other NIH-sponsored HIV/AIDS Clinical Trials Networks, the collaborating NIH Institutes and Centers, and other HIV/AIDS clinical research groups.

DAIDS RESERVE FUND: Contingent upon availability, a portion of the total funds committed to the awards resulting from this solicitation will be set aside by NIAID to adjust and allocate resources based on performance and to pursue high priority, high impact or high cost clinical research. NIAID will develop procedures to inform the Network Leadership, solicit ideas, request and receive recommendations as necessary, and allocate these funds to the HIV/AIDS Clinical Trials Networks.

B.  SCIENTIFIC ROLE IN NIAID-SPONSORED CLINICAL RESEARCH

DAIDS, NIAID establishes the research priorities and the research agenda in the area of HIV clinical science. The DAIDS Project Scientist or designee will work closely with other members of the Executive Committee to assure that Network research efforts are consistent with that of the NIAID agenda for HIV clinical research, and complement those of other NIH programs. Research goals will be reviewed on a mutually agreed upon schedule but not less than once per year. DAIDS staff will serve as members of protocol teams, participating in the development and oversight of clinical research. DAIDS and other NIH staff will serve as resources for scientific and policy information and will share information regarding promising new agents, strategies, and developments when appropriate. They may also identify scientific gaps and organize meetings to facilitate exchange of scientific and regulatory information.

C.  SPONSOR AND REGULATORY RESPONSIBILITIES

DAIDS will serve as a liaison between pharmaceutical companies, the FDA, and Network Investigators. In accordance with NIH policy, DAIDS is expected to ensure that all clinical trials performed through the HIV/AIDS Clinical Trials Networks are conducted in accordance with ICH Good Clinical Practices and applicable Federal regulations.

  1. Clinical Trials Agreements (CTA). A CTA, describing the responsibilities and rights of each party, will be negotiated when a pharmaceutical or other involved collaborator provides an investigational agent for a clinical study. The agreement will include, but is not limited to, IND sponsorship, safety and data monitoring, and access to data. The CORE PI or designee generally will be consulted on the terms prior to the execution of the CTA. Pharmaceutical collaborators generally request that patentable inventions discovered in the studies be brought to their attention, and that the company be offered rights of first refusal when the collaborator has rights to the background patent. In general, terms in the CTA covering data access and sharing will conform to policies developed jointly by the Network Leadership, DAIDS and the NIH.
  2. Investigational New Drug Applications(IND) and Investigational Device Exemption (IDE). The DAIDS will have the option to independently file an IND on investigational agents or IDE on investigational devices evaluated in DAIDS-sponsored clinical studies. Pharmaceutical collaborators may file an IND for a DAIDS-sponsored trial after consultation with DAIDS. Appropriate DAIDS staff will advise the investigators on the specific regulatory requirements for IND sponsorship. In situations where DAIDS is the IND sponsor, DAIDS through its contractors will also assemble, review, and submit the required regulatory documents to the FDA.
  3. Monitoring. DAIDS has an external Clinical Site Monitoring Group to evaluate good clinical research practice, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the clinical research sites. The monitoring contractor will visit performance sites periodically to review selected protocols, provide training on general protocol conduct, review internal QA/QC plans, and audit pharmacies. DAIDS staff, in coordination with the site monitoring contractors, will periodically conduct a review of the sites for the reliability of and compliance with clinical and regulatory systems, and will advise the site and the Network CORE on the same. DAIDS contract resources also may provide oversight and monitoring of the quality of patient diagnosis and safety tests (e.g. hematology, chemistry, liver function) performed in the laboratories and oversight, monitoring and support for CD4 enumeration, HIV viral load, HIV DNA PCR and drug resistance determinations.
  4. Study Material. For studies in which DAIDS is the IND or IDE sponsor, the DAIDS Pharmaceutical Affairs Branch staff and/or contractors will provide consultation on study treatment-related issues including manufacturing, preparation, administration and availability of active dosage forms and placebo. DAIDS Pharmaceutical Affairs Branch staff and/or contractors may also:
    •  Interact with pharmaceutical company collaborators to facilitate adequate and timely supply of study product.
    •  Oversee the distribution of study product to the study site(s).
    •  Review site visit reports from the DAIDS Clinical Site Monitoring contractor and reserve the right to independently monitor the site(s) in accordance with FDA/ICH guidelines.
  5. Training. DAIDS will provide a variety of training activities to help the Network ensure that consistent standards for protection of human subjects, conduct of clinical trials, and documentation are achieved across the DAIDS-sponsored HIV/AIDS Clinical Trials Networks. This training may be developed in conjunction with Network and cross-Network staff and be provided directly by DAIDS staff or through contractors. Training areas include, but are not limited to, regulatory requirements, GCP, adverse event reporting, human subject protections, Informed Consent, and DAIDS and NIH policies and procedures.
  6. Safety Reports. When holding an IND or IDE, DAIDS will assume responsibility for the reporting of safety information in accordance with FDA requirements and preferences. In order to provide for consistent reporting of serious adverse experiences across the DAIDS-sponsored Clinical Trial Networks, DAIDS will provide current policies and procedures that govern the reporting of adverse events in DAIDS-sponsored trials. DAIDS Regulatory Affairs Branch staff and/or contractors will provide training on the specific procedures and requirements for adverse event reporting for clinical trials conducted under this award.

D. PROTOCOL DEVELOPMENT, IMPLEMENTATION AND OVERSIGHT

  1. Protocol Development. DAIDS staff will participate in the development of selected clinical research protocols, including:

    •  Medical and Program Officers who will provide clinical and scientific expertise.
    •  DAIDS pharmacists who will participate on Network protocol teams, consulting on pharmaceutical aspects, available dosage forms, and placebos. They also will interact with pharmaceutical companies to ensure adequate and timely supply of products.

  2. Protocol Review and Approval. All clinical research protocols must be approved by the DAIDS Program Officer prior to study initiation. The Clinical Trials Networks(s) will submit the protocols to the NIAID Prevention Sciences Research Committee (PSRC) or the NIAID Clinical Sciences Review Committee (CSRC). The Committee will evaluate the proposed clinical trials for: (i) the relevance to the NIAID and other co-sponsoring Institutes' research agenda and other NIH clinical studies; (ii) subject safety; (iii) compliance with Federal regulations; (iv) study oversight and monitoring; (v) feasibility of timely completion; and (vi) plans for interim monitoring and analysis when appropriate. The Program Officer or designee will return comments and recommendations to the Network within 30 days after review. The Network must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIAID staff to the satisfaction of the NIAID before patient accrual or participant enrollment can begin. If a protocol is disapproved, DAIDS will not provide investigational products or permit expenditure of NIH funds for the proposed investigation. If a protocol is not initiated within six months of DAIDS approval, re-review and approval will be required.
  3. Independent Safety Monitoring. Independent monitoring is strongly recommended for all clinical trials involving investigational drugs, devices, or biologics and other clinical research perceived to involve more than a minimal risk. NIAID program staff will participate in the development of appropriate safety monitoring plans for all planned clinical trials. The frequency and intensity of safety monitoring will be based on individual study characteristics and past experience with study products and may require review by an Independent Safety Monitor, Independent Monitoring Committee (IMC) or Safety Monitoring Committee (SMC) or Data and Safety Monitoring Board (DSMB). Approval of the final monitoring plan, including the composition of the review committee, by DAIDS is required prior to study initiation.
  4. Study Termination. NIAID reserves the right to terminate or curtail a clinical study for any of the following reasons: (i) risk to subject safety; (ii) the scientific question is no longer relevant or the objectives will not be met; (iii) failure to comply with Good Clinical Practices, federal regulations, or Terms and Conditions of Award; (iv) occurrence of unforeseen drug safety issues or data from preclinical studies indicate a presence of unanticipated toxicity; (v) risks that cannot be adequately quantitated; (vi) ethical concerns raised by the local community or local medical care/health care authorities; (vii) failure to remedy deficiencies identified through site monitoring; (viii) substandard data; (ix) inadequate progress in fulfilling the research agenda; (x) slow accrual or (xi) reaching a major study endpoint substantially before schedule with persuasive statistical significance.
  5. Access to Data. The Program Officer or designee will have access to all data generated under this cooperative agreement, and may review the data as recorded on the case report forms or in the central database. Data must be available for external checking against the original source documentation as required by federal regulation and DAIDS as the IND sponsor. DAIDS may request from the Network specific data analysis needed for programmatic activities or for issues related to DAIDS plans with other partners. The awardees will retain the primary rights to the data consistent with HHS, PHS, and NIH policies, but are encouraged to provide public access to selected data sets generated with the use of public funds within a reasonable time after the primary analysis and publication. The NIH may provide public access to selected data sets generated with the use of public funds within a reasonable time after the primary analysis and publication.

E. STUDY CONDUCT
DAIDS Medical or Program Officers will be part of Protocol Teams as well as protocol safety review teams to monitor the safety and efficacy of the intervention(s) for ongoing studies, and will be provided with appropriate reports. DAIDS independently supports Data and Safety Monitoring Boards (DSMB) that oversee Phase III and other select clinical trials at the discretion of DAIDS.

F. PERFORMANCE REVIEW
Network progress and performance will be assessed in an ongoing manner by DAIDS and external ad hoc scientific advisory groups, in the context of an evaluation plan with defined goals linked to specific performance metrics as appropriate to the research area(s) of the Network. A DAIDS Program Officer may conduct site visits, independently or as part of a Network team, to any Network component for performance assessment and review.

Additionally, an agency program official or IC Program Officer 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

An Executive Committee will be the main governing body of the Network, as described above under section 2.A.1.F., Network Structure. Awardee members of the Executive Committee will be required to accept and implement policies approved by the Executive Committee. Other substantial collaborative involvement by NIAID and NIH staff is also described above in section 2.A.1

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. Award Criteria

Award criteria that will be used to make award decisions include:

NIAID reserves the right to make awards based upon the maximum potential benefit offered by a Network in terms of the research priorities to be addressed, the scientific merit of the combined program components and integration plans, and the funds available.

4. 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.

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:

DAIDS, NIAID

Office of the Director
Division of AIDS
National Institute of Allergy and Infectious Diseases
Room 4142, MSC-7620
6700-B Rockledge Drive
Bethesda, MD 20892-7620
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-496-0545
FAX: 301-402-1505
Email: FY06LGRFA@niaid.nih.gov

FOR QUESTIONS CONCERNING NICDR ORAL HEALTH RESEARCH OBJECTIVES:

Mostafa Nokta, MD, PhD.
AIDS and Oral Manifestations of Immunosuppression Program
National Institute of Dental and Craniofacial Research
Room 4An. 12K Bldg. 45, MSC 6402
45 Center Drive
Bethesda, MD 20892
Telephone: 301 594-7985
FAX: 301 480-8319
Email: mn177j@nih.gov

2. Peer Review Contacts:

Dr. Peter Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3140, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-496-8426
FAX: 301-480-2310
Email: pj8v@nih.gov

3. Financial or Grants Management Contacts:

Ms. Mary Kirker
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2116, MSC-7614
6700-B Rockledge Drive
Bethesda, Maryland 20892-7614
Telephone Number: (301) 402-6400
Fax Number: (301) 480-3780
Email Address: mk35h@nih.gov

Section VIII. Other Information
Required Federal Citations

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, June 12, 1998: 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.

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://grants1.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html). 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/archive/archive/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.

Public 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 PA 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.

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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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 PA 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/ in the following citations: No. 93.855, Immunology, Allergy, and Transplantation Research, No. 93.856, Microbiology and Infectious Diseases Research, No. 93.395, Cancer Treatment Research, No. 93.865, Center for Research for Mothers and Children, No. 93.121, Oral Diseases and Disorders Research, No. 93.279, Drug Abuse Research Programs, No. 93.242, Mental Health Research Grants, No. 93.989, Senior International Fellowships, No. 93.273 Alcohol Research Programs, No. 93.361 Nursing Research, 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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