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HIV VACCINE ELECTRONIC (E) RESOURCE
ID#: RFA-AI-12-008 (Reissue of RFA-AI-05-001)     Posted: 27 Feb 2012
Leadership Group for a Clinical Research Network on Microbicides to Prevent HIV Infection (UM1)
Deadline: 28 Sep 2012
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Type of Grant: Research
Topics/Fields of Support: Mucosal immunity
National Institutes of Health (NIH, NIAID, NICHD, NIMH)

The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency—making important medical discoveries that improve health and save lives.

Thanks in large part to NIH-funded medical research, Americans today are living longer and healthier. Life expectancy in the United States has jumped from 47 years in 1900 to 77 years today, and disability in people over age 65 has dropped dramatically in the past 3 decades. In recent years, nationwide rates of new diagnoses and deaths from all cancers combined have fallen significantly.

Scientific Leadership

NIH is the largest source of funding for medical research in the world, creating hundreds of thousands of high-quality jobs by funding thousands of scientists in universities and research institutions in every state across America and around the globe.

NIH is made up of 27 Institutes and Centers, each with a specific research agenda, often focusing on particular diseases or body systems. NIH leadership plays an active role in shaping the agency's activities and outlook.

The Office of the Director is the central office at NIH, responsible for setting policy for NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. The NIH Director, with a unique and critical perspective on the entire agency, is responsible for providing leadership to the Institutes and for constantly identifying needs and opportunities, especially for efforts that involve multiple Institutes. The NIH Director is assisted by the NIH Deputy Directors including the Principal Deputy Director, who shares in the overall direction of the agency's activities.

More than 80% of the NIH's budget goes to more than 300,000 research personnel at over 3,000 universities and research institutions. In addition, about 6,000 scientists work in NIH’s own laboratories, most of which are on the NIH main campus in Bethesda, Maryland. The main campus is also home to the NIH Clinical Center, the largest hospital in the world totally dedicated to clinical research.

Successful biomedical research depends on the talent and dedication of the scientific workforce. NIH supports many innovative training programs and funding mechanisms  that foster scientific creativity and exploration. The goal is to strengthen our nation’s research capacity, broaden our research base, and inspire a passion for science in current and future generations of researchers.


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DETAILS

1.  Purpose

The purpose of this FOA is to encourage applications for the Leadership Group (LG) for a Clinical Research Network on Microbicides to Prevent HIV Infection.  The LG will have overall responsibility for: (i) developing, implementing and adapting the network’s clinical research agenda to address NIAID’s HIV/AIDS scientific priorities described below in Part 2, Section I, 3, (ii) overseeing and managing the network’s scientific/clinical research activities and associated laboratory and statistical/data management support functions, (iii) allocating network resources, and (iv) evaluating network performance using a LG proposed/Division of AIDS (DAIDS) approved process and evaluation standards.

The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) and senior/key personnel of the LOC, LC and SDMC together form the LG. The LG coupled with the Program Directors/Principal Investigators (PDs/PIs) and senior/key personnel of the affiliated Clinical Trials Units/Clinical Research Sites (CTUs/CRSs) collectively constitute the Clinical Research Network on Microbicides to Prevent HIV Infection (herein referred to as the “network”). The three different parts of the LG(LOC, LC and SDMC) will be required to work together collaboratively and with the network-affiliated CTUs/CRSs to carry out the activities that are essential to achieving the network’s clinical research agenda.

Clinical Trial Units (CTUs) provide the scientific and administrative expertise as well as the infrastructure to contribute to NIAID Clinical Research Networks.  A CTU is an organization/institution composed of at least one, but no more than eight CRSs that can contribute to at least two HIV/AIDS Clinical Research Networks.  The CTU PD(s)/PI(s) is/are responsible for all CTU/CRS activities and performance, and also serve(s) as scientific and administrative representative(s) to the CTU’s affiliated network(s).

A Clinical Research Site (CRS) is a component of a CTU and is defined as a discrete location (e.g. hospital, outpatient clinic, community health center, private practice, local health department clinic) with appropriate identified and characterized potential trial participants (e.g. demographics, incidence and prevalence of HIV/AIDS) where participant recruitment and retention, protocol management and other clinical research activities are conducted. The CRS must be staffed by qualified professionals capable of conducting clinical research for one or more clinical research networks in accordance with Good Clinical Practice (GCP), local regulatory requirements, and other applicable NIH requirements.  In addition, each CRS must participate in one or more HIV/AIDS clinical research network(s). The activities of each CRS will be directed by a CRS Leader with the experience and qualifications to oversee clinical activities and the day-to-day clinic operations will be overseen by a CRS Coordinator with relevant clinical research experience and qualifications.  An individual CRS and/or CRS Leader may be proposed in only one CTU application. 

2.  Background

NIAID currently supports six HIV/AIDS clinical research networks: the AIDS Clinical Trials Group (ACTG), the HIV Prevention Trials Network (HPTN), the HIV Vaccine Trials Network (HVTN), the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), and the Microbicide Trials Network (MTN).

Over the past 30 years, HIV/AIDS research has led to phenomenal scientific advances.  Scientists uncovered the structure and genetic organization of HIV and began to understand the mechanisms by which HIV causes disease.  This understanding led to the development of (i) tests to detect HIV infection, measure HIV viral load and monitor immune function, and (ii) highly active antiretroviral therapies (HAART).

Despite these scientific advances, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 33 million people globally are estimated to be living with HIV, of whom 22 million are living in sub-Saharan Africa.  Slightly more than half of all people living with HIV are women and girls.  In sub-Saharan Africa, more women than men are living with HIV, and young women aged 15–24 years are as much as eight times more likely than men to be HIV-infected.

NIAID has supported research to develop new strategies to prevent the spread of HIV through the HPTN, MTN, and IMPAACT networks. The NIH research priorities in the area of prevention research have been to identify practical, safe and effective approaches to halt the spread of HIV, especially in domestic and international populations at greatest risk; to develop integrated behavioral and biomedical prevention models that are efficacious, cost-effective, locally-appropriate, and sustainable; and to demonstrate the generalizability and the ability to scale up integrated prevention programs to stop the spread of HIV in different cultures.  NIH’s microbicide research priorities have been to identify a safe and effective topical microbicide that prevents HIV acquisition and transmission, determine the correlates of short- and long-term safety, and evaluate and optimize product acceptability and adherence.  

To address these scientific priorities, NIH has supported prevention research networks since 1999.  In 2006, the MTN was established to focus on topical microbicides, and the HPTN was refocused to address prevention modalities other than vaccines or microbicides. 

The MTN has completed 3 phase I, 2 phase II and 1 phase III clinical trials on candidate topical microbicides.  One significant microbicide study initiated by the HPTN and completed by the MTN evaluated the effectiveness of two topical microbicides, BufferGel and 0.5% PRO2000 compared to a placebo gel and a no gel study arm.  The 0.5% PRO 2000/5 Gel reduced HIV acquisition in women by 30% but these results were not statistically significant.  BufferGel did not alter the risk of HIV infection.  Both products were found to be safe.  PRO2000 was subsequently shown to lack efficacy in a large Phase III study. More recently, the MTN initiated a Phase IIb trial of both topical and oral ARV-based pre-exposure prophylaxis (PrEP) to evaluate their safety and effectiveness.  Associated studies will (i) elucidate the effect of exposure to these regimens on HIV progression and treatment response in women who become HIV-infected while on active study product and (ii) evaluate the prevalence of pregnancy loss in mothers and malformations in infants of mothers exposed to study product.   In addition the MTN has undertaken a stepwise strategy to address the safety of microbicides in pregnant women, implemented a rectal microbicide development strategy, and developed and implemented a standard preclinical testing algorithm for direct comparison of candidate microbicides and lubricants.  The rectal microbicide development strategy was augmented by building on the clinical development initiated in one of NIAID’s Integrated Preclinical/Clinical Program for HIV Topical Microbicides projects

Two recently reported studies have contributed important additional knowledge to the HIV prevention field.  Researchers determined that rectal use of a vaginal formulation of 1% tenofovir (TDF) was not optimal due to the mostly mild to moderate adverse events experienced by the participants; the discomfort reported by trial participants who used the products indicated the need to develop rectal specific formulations. A second study showed that US women preferred oral dosing of TDF while African women preferred oral and vaginal dosing equally.  However, oral dosing with some ARVs may prove to be less effective for HIV prevention than vaginal formulations; the vaginal application of TDF 1% gel resulted in a 2 log higher level of  active drug in vaginal tissue than dosing with oral TDF. Further research is needed to understand user preferences and increase acceptability of vaginal products for some target populations.

Results from a recent topical microbicide trial provided the first proof-of-concept for topical microbicide effectiveness. TDF 1% vaginal gel used in a unique “BAT 24” dosing schedule showed a modest 39 % efficacy overall.  (Abdool-Karim, 2010, Science Express).  In the subset of participants reporting higher adherence, HIV acquisition of HIV was reduced by 54%.  These results provide strong rationale for supporting additional studies of 1% tenofovir gel as well as potentially more effective, acceptable, and easier to use microbicide products.   

3.  Research Priority Areas:

NIAID’s scientific priority areas to be addressed in response to this FOA include but not limited to the following (not listed in priority order):

  • Bring to licensure the most promising topical microbicide products for vaginal use
  • Conduct clinical testing of improved methods for topical microbicide delivery
  • Bring to licensure the most promising rectal microbicides products

Examples of research within these priority areas in the LG applications include, but are not limited to the following:

Evaluate the most promising topical microbicide products for vaginal use

  • Safety testing
  • Pharmacokinetic/pharmacodynamic assessment
  • Efficacy
  • Acceptability
  • Bridging studies

Conduct clinical testing of improved methods for microbicide delivery

  • Sustained delivery methods
  • Intravaginal rings
  • Vaginal Films
  • Other approaches that are safe, preventative, and that may improve adherence

Evaluate the most promising rectal microbicide products

  • Safety testing
  • Pharmacokinetic/pharmacodynamic assessment
  • Efficacy
  • Acceptability
  • Bridging studies

Adherence to an agent as well as a clinical trial protocol is essential to the success of prevention and treatment-related protocols.  It is therefore expected that protocol teams will seek relevant scientific guidance and expertise at the concept stage in order to assure that state-of-the-art interventions to support adherence and valid assessments to measure adherence are appropriately incorporated.

4.  Application Requirements

The LG will be responsible for all network activities and will ensure that all the constituent parts of the network fulfill their respective responsibilities in the most efficient and effective manner possible.  Each part of the LG linked application (LOC, LC, and SDMC) is expected to demonstrate scientific leadership, effective management and efficient utilization of resources.

Leadership Time Commitment.  When a single PD/PI is proposed in any of the three LG applications, the PD/PI will be required to devote at least 6 person months effort to the project.  Applications proposing Multiple PD(s)/PI(s) are permitted, but the roles and responsibilities of multiple PD(s)/PI(s) should be clearly delineated and justified.  If two or more PD(s)/PI(s) are named in any application, each PD/PI must devote at least 3.6 person months effort to the project.

The governance and organizational structure of the LG leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD(s)/PI(s) and other collaborators.

Research Agenda.  The LG’s clinical research agenda should be clearly articulated and directly related to achieving NIAID’s scientific priorities.  The LG is required to monitor and evaluate the need to refine and revise the research agenda. As part of this process, the LG is required to actively engage input from researchers and HIV-affected communities.

Governance and Management.  The LOC, LC and SDMC, in their areas of responsibility, must establish and define effective communication and decision making processes, identify clear lines of authority, coordinate and collaborate effectively both within the network and with other NIH-supported networks or other Federal and private sector clinical research programs as appropriate to avoid redundancies and ensure efficiencies.  Governance or management by committees is permitted.  The governance and management should utilize effective approaches to project management, including project plans with identified key milestones; ongoing evaluation of projections against actual data and adjustments to project plans; and development and implementation of contingency plans. In addition, the LOC, LC and SDMC, in their area of responsibility, must establish processes to identify and resolve operational issues and develop training and education programs within the context of the network’s research agenda for network members, including new researchers, particularly from under-represented populations and those in low and middle income countries.

Bylaws, policies and standard operating procedures should not be included in the application, but must be provided, for approval, to NIAID within 90 days of Notice of Award.

Resource Utilization and Allocation.  The LOC, LC and SDMC, in their area of responsibility, must ensure optimal resource utilization and ensure that resource allocation supports the clinical research agenda.

Collaborative Responsibilities. The LG will be strongly encouraged to collaborate with other NIH-supported networks and other Federal and private sector clinical research programs, and to interact with government and non-government organizations, including the private sector, and committees to effectively develop and implement a clinically relevant, interdisciplinary and cost-efficient clinical research network.  Such collaborations and interactions are essential for the development and implementation of a comprehensive research agenda that utilizes the strengths, experience and expertise of the various collaborating organizations.  The sharing of expertise, resources and procedures is expected in key areas, including: development of clinical infrastructure in low-income countries; harmonization of laboratory resources and specimen management; harmonization of common data elements and data entry interfaces; community engagement, including development, training and support of community advisory boards. Examples of additional entities the LG will need to collaborate and/or communicate with include, but are not limited to:  the Adolescent Medicine Trials Network (ATN), the NIAID Strategic Working Group (SWG), Scientific Review Committees (SRCs),  network LG Program Officers (NLGPOs) and Project Scientists, the Division of AIDS (DAIDS) Enterprise System (DAIDS-ES), Office of Clinical Site Oversight (OCSO), the DAIDS Clinical Laboratory Oversight Team (DCLOT), the HIV/AIDS Network Coordination Office (HANC), other HIV/AIDS Clinical Research Network groups and the non-HIV/AIDS Research Network.

ELIGIBILITY

Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations   

Foreign Institutions

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

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

When a single PD/PI is proposed in any of the three LG applications, the PD/PI will be required to devote at least 6 person months effort to the project.  If two or more PD(s)/PI(s) are named in any application, each PD/PI must devote at least 3.6 person months effort to the project.     

CONTACT INFORMATION

NIH encourages inquiries concerning this funding opportunity and welcomes the opportunity to answer questions from potential applicants. 

Additional information and definitions of terms can be found at the following website.http://www.niaid.nih.gov/labsandresources/restructuring/pages/default.aspx    

Application Submission Contacts

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

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov 

Scientific/Research Contact(s)

NIAID

Roberta Black, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Room 5117, MSC-7624
6700B Rockledge Drive
Bethesda, MD 20982-7624(for Express Mail- 20817)
Telephone:  301-496-8199 (office)
FAX: 301-402-3684
Email: rblack@niaid.nih.gov

NICHD

Heather Watts, M.D.
Pediatric, Adolescent & Maternal AIDS Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Room 4B11G, MSC-7510
Building 6100 - Executive Building
6100 Executive Boulevard
Bethesda, MD 20892-7510
Telephone:  301-435-6874
FAX:  301-496-8678
Email: wattsh@mail.nih.gov

NIMH

Cynthia Grossman, Ph.D.
Prevention and Translation Branch 
National Institute of Mental Health (NIMH)
Room 6201, MSC-9619
NSC Neuro Science Center
6001 Executive Boulevard
Rockville, MD  20852-9619
Telephone:  301-443-8962
FAX:  301-443-9719
Email:   grossmanc@mail.nih.gov 

Peer Review Contact(s)

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (for Express Mail – 20817)
Telephone 301-496-8426
FAX: 301-480-2310
Email:  pjackson@niaid.nih.gov

Financial/Grants Management Contact(s)

Theresa Mercogliano
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2124, MSC-7610
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone:  301-402-5512
FAX:  301- 480-3780
Email:  tmercoglia@niaid.nih.gov