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Project Purposes

Core A Description

I. OVERVIEW

The Microbicide Development Program (MDP) based at UCLA will be composed of a cohesive group of clinical, basic and behavioral scientists, and support staff focused on acquiring and assembling an integrated database of physiologic, pathophysiologic, immunologic, virologic, behavioral and acceptability responses that contribute to the development of a topical rectal HIV microbicide. Many of these researchers have interacted previously as is evidenced by co-authored publications and other collaborations. The Administrative Core will have the primary goals of facilitating interactions in a smooth and effective manner, providing a reliable infrastructure for fiscal management of the program, provide on-going communications with NIH and the Project Officer as well as the Scientific Advisory Panel (SAP) appointed by NIH. Most importantly, the Core will (i) provide a focus for efficient leadership of the overall MDP Project by facilitating communication between Executive Committee (EC) members, Project investigators and staff and (ii) provide the forum for emergence of synergistic results and interpretations from each project, making the whole more than the sum of the parts. The following sections will describe the Core’s overall role, personnel, services (facilitation, fiscal management, education, publication and record maintenance) and governance.

II. ROLE OF THE CORE

With Dr. Peter Anton as Core Director, the Administrative Core will provide the leadership and infrastructure necessary to support the projects within the MDP and will house the advisory components for the overall program. Functional infrastructure linking three Cores, four projects at five institutions in two countries and effective leadership are the two key factors that will contribute significantly to the success of the program. The MDP brings together activities of a variety of investigators with in-depth expertise in diverse areas of research from educational institutions and private industry, all focused on a single goal of rectal HIV microbicide development. In order for this effort to be integrated into a productive and cohesive unit, the Administrative Core will exert strong leadership as well as be responsive to developing new strategies that meet the project investigators’ developing needs. The overall goal of the MDP is to create a cohesive whole that will ultimately be greater than the individual components. In order to achieve this, the Principal Investigator’s Administrative Core will assemble and maintain a governing structure that is flexible and responsive, with an administrative staff that is experienced, organized, and adaptable to the program’s diverse constituencies. The Core will create the conditions and environment where interactions lead to creative, rigorous and productive science.

The Administrative Core will direct and coordinate several major areas contributing to the overall activities of the program: facilitation, finance, website maintenance, education, publication assistance, library maintenance and general administrative support. The Core will link the various project leaders and programs with each other as well as integrating the related milestones of each project and ensuring communication between project leaders. An Executive Committee (EC), composed of the Principal Investigator and each project leader/co-leader, Core Director/Co-Director and selected other key personnel, will be the central mechanism in assuring communication between Projects and across Project sites. This will be crucial as three of the four projects have activity at two or more of the component sites. The Administrative Core will also produce a twice-yearly internal progress report for the EC. These will be available to interested key personnel and the NIH’s Scientific Advisory Panel (SAP), if they request copies. The EC will work in conjunction with the NIH-appointed SAP, an asset guaranteed by the “cooperative agreement” nature of this U-19 grant, to make decisions for the MDP. The EC will review the overall MDP and individual projects’ progress and milestones on a regular basis, and advise MDP investigators on strategic focus and/or redirection.
The Administrative Core will be an integral part of each Project and will be under the guidance of the Director, Dr. Peter Anton (10% effort) with assistance from Dr. Ian McGowan (5% effort, no funding). Staff will include a Project Coordinator (75% effort) with experience in running large research programs as well as an Administrative Specialist (50% effort) with experience in coordinating large projects involving multiple sites.

III. ADMINISTRATIVE CORE PERSONNEL

What follows is a list of personnel identified for the Administrative Core with a brief description of each person’s general area of responsibility. The inclusion of Dr. McGowan as Co-Director (at no compensation) is intentional. Drs. Anton and McGowan work closely on all aspects of their research and administration. This design is part of a back-up, cross-training plan to ensure ongoing focus if Dr. Anton were unavailable. Similar back-up is planned for Dr. McGowan’s role in Project 1 and Core B by listing Dr. Anton. We have also decided to request two part-time administrators (75% and 50%) rather than one full-time. We feel this will yield the MDP more support, expertise and cross-cover than hiring a single individual. It also engenders a “team” mentality. These two individuals have worked closely together in the past.

Principal Investigator and Administrative Core Director

Peter A. Anton, M.D. is the PI of the overall Microbicide Development Program and will function as Director of the Administrative Core. He is a Professor of Medicine with an appointment in the David Geffen School of Medicine, Department of Medicine, Division of Digestive Diseases as well as a member of the UCLA AIDS Institute. He is the Director of the UCLA Center For AIDS Research (CFAR) Mucosal Immunology Core and the Director of the UCLA Center for HIV and Digestive Diseases (CHADD), as well as Co-Director of the UCLA Inflammatory Bowel Disease (IBD) Center.
CHADD is a translational research program with an associated consultative clinic, which is a referral resource for HIV-infected patients with difficult-to-diagnose and manage gastrointestinal complaints. Approximately 1-2 new HIV-related consults are seen during weekly clinics. In addition to making mucosal samples and research available to non-clinical investigators, the CFAR Core has established standardized protocols for processing mucosal samples. Among these are a unique, validated technology for quantifying HIV RNA and DNA in tissue and well-controlled studies characterizing mucosal cytokine and chemokine mRNA and protein. Dr. Anton is responsible for the overall direction and management of the CFAR Core, working with researchers from India, South Africa and Belgium, assisting in planning for clinical trials, coordinating researchers with other clinical sources and determining use of the Core’s resources as well as planning future developmental directions.
Dr. Anton has had a long-standing and active interest in neuro- and immuno-inflammatory modulation of the mucosal immune response and holds two patents related to gastrointestinal inflammatory factors. He has directed and been the PI in over 20 clinical trials and was among the first to document that the rectal mucosa in HIV-negative subjects is (i) highly vulnerable to HIV infection with markedly increased numbers of HIV co-receptors and (ii) associated with significant mucosal inflammation. This appreciation was a shift from previous reports which had characterized the HIV-infected mucosa as lymphopenic. He has been awarded an NIH K24 award for mentoring in translational research and to investigate the impact of co-receptor and HIV viral burden on gut mucosa. He is also PI on an NIH R01 investigating mucosal immune responses to HIV vaccines.
He has been on planning groups for both the CDC and NIH OAR’s efforts to develop rectal microbicides and is Co-PI on an HPTN 056 study to characterize indices of mucosal immune responses planned for inclusion in multi-center rectal microbicide trials in men and women and is a member of four NIH training grants. He serves on several Division of Digestive Diseases administrative committees and the Dean’s Office-appointed Office of Clinical Trials. He has submitted several INDs to the FDA and serves on the medical executive committee of a large community-based HIV/AIDS research organization, AIDS ReSearch Alliance (ARA), a critical, subcontracted collaborator on this application.
As the Director of the Administrative Core, Dr. Anton will maintain administrative responsibility for the MDP. He will receive advice and input from the Co- Director, Dr. McGowan, and the Executive Committee and will develop close interactions with UCLA administrative personnel and NIH staff. One of his primary responsibilities will be to develop and foster interactions between MDP projects at UCLA, the NIH, St. George’s Hospital and Medical School (SGHMS) with the macaque facility Health Protection Agency, Porton Down (HPA-PD), Johns Hopkins University (JHU), University of Washington (UW) and with the three pharmaceutical industry collaborators (Biosyn, Gilead Sciences, Tibotec-Virco). Major portions of his time will go toward providing guidance and advice to the research groups responsible for the different MDP projects.

Administrative Core Co-Director

Ian McGowan, M.D., Ph.D. is the PI on Project 1 and Director of the Regulatory Compliance and Subjects Core (Core B) and will function as the Co-Director of the Administrative Core. Dr. McGowan is an Associate Professor of Medicine with an appointment in the David Geffen School of Medicine, Department of Medicine, Division of Digestive Diseases and a member of the UCLA AIDS Institute. He is Co-Director of the UCLA Center for HIV and Digestive Diseases (CHADD) and Director of the Gastrointestinal Clinical Trials unit at UCLA. . Dr. McGowan is trained in HIV medicine and gastroenterology and has a Ph.D. in mucosal immunology from Oxford University. He has published over 20 articles on various aspects of HIV-associated gastrointestinal disease. Prior to taking his post at UCLA, he held a number of positions in the pharmaceutical industry related to clinical drug development. He was a Director of Clinical Research at Gilead Sciences for three years where he was responsible for designing and executing Phase 1 through Phase 3 studies of tenofovir which provided the basis for its subsequent approval.
Dr. McGowan’s current research efforts focus on the management of HIV-associated gastrointestinal disease, the mucosal pathogenesis of HIV infection, and the development of rectal microbicides. He is particularly interested in determining the mucosal safety parameters that need to be monitored during Phase I/II rectal microbicide studies.
As the Co-Director of the Administrative Core, Dr. McGowan will work closely with Dr. Anton on all aspects of the Administrative Core as part of an overall back-up and cross-training plan to ensure ongoing focus.

Project Coordinator

Charles Price will handle ongoing operation of the Administrative Core to ensure effective collaboration occurs so that the scientific aims and milestones of the Microbicide Development Program are achieved. Mr. Price has been working at UCLA as the Project Manager for the Multicenter AIDS Cohort Study (MACS) Pathogenesis Laboratory since 1997. In addition, he has a strong background in managing a variety of HIV-related research projects and services since the mid 1980’s.
Mr. Price will work with Dr. Anton and his committees to plan, organize and coordinate the management and administration of all MDP functions. This includes coordinating meetings and conference calls, recording of meetings, assisting in implementing decisions, following up on projects, and assuring that all MDP investigators and stakeholders are up to date on new policies. He will oversee the financial management of the MDP, be responsible for grant accounting functions and monitor the University’s pace and accuracy in the timely distribution of sub-contracts. He will ensure maintenance of the website and coordinate access to the various aspects of the web by appropriate groups. In conjunction with the Administrative Specialist, Mr. Price will develop educational/outreach materials and assure their dissemination on the publicly-accessible portion of the MDP’s website. Mr. Price will serve as the administrative liaison between UCLA, NIH, industry collaborators, FDA and other institutions and stakeholders involved in the MDP. He will work directly with the identified individuals at the collaborating institutions to maintain an orderly flow of information and ongoing support via direct contact as well as through the website developed by the Data Management and Biostatistics Core (Core C).

Administrative Specialist

Justin Akin has over 20 years of project support in a variety of HIV-related settings including non-profits, government agencies and educational institutions and has been part of the UCLA Center for HIV and Digestive Disease since 2000. He will provide day-to-day support for the services offered by the Administrative Core focusing on administrative needs that are cross-site, such as standardized reports and group-wide regulatory submissions. Working with the Administrative Core Director, Co-Director and Project Coordinator, he will make the arrangements for conference calls, provide clerical support for the Administrative (A), Regulatory (B) and Data (C) Cores, including the uploading and monitoring of information on the website, as well as supporting Dr. Anton in his MDP-related activities. Mr. Akin will oversee preparation/publication of abstracts and journal articles, including creating tables and graphs, circulating drafts, and final formatting and preparation for submission. He will maintain the MDP library (housed in Core C), and aid all groups in administrative needs not covered on site. He will be actively involved in updating the public-accessible educational portions (IRB-approved) of the MDP website. He will prepare bi-annual internal progress reports for circulation among all Project and Core Leaders as well as facilitate milestone reports.

IV. CORE SERVICES

The Core will be physically located on the UCLA campus within in David Geffen School of Medicine within the Division of Digestive Diseases. At present, space is allocated within the MacDonald Research Laboratory building (Room 1240), proximate to the PI’s laboratory and clinical areas. The Division and Department of Medicine have committed additional space for the Core, if funded and needed (see letters of support). At present, the only additional space required will be an additional working terminal with computer support and space for the nurse coordinator’s hard copy, regulatory files for each Project. The UCLA site will oversee management of the UCLA-based Project 4, as well as facilitate interactions with Project 1 (UCLA/SGHMS/HPA-PD/NIH), Project 2 (JHU/NIH) and Project 3 (UCLA/JHU). The administrative staff of the Core will interface with the designated administrative/ technical/regulatory personnel at each research site.

A. FACILITATION

While management and fiscal oversight is an obvious and essential component of the Administrative Core, the critical contribution toward success will be the Core’s facilitation functions. These include all efforts that enhance and favor communication and interactions among the investigators, staff and other stakeholders in the MDP. These will include:

  1. The Administrative Core will establish regular, ongoing conference calls for the Executive Committee (EC), the NIH Project Officer, relevant support staff and others. SAP members will be invited to participate on all teleconferences (TC) and will be required to participate twice a year. Conference calls are initially planned to occur once every two weeks. It is anticipated that this frequency will be appropriate to maintain communications across the four Projects during the startup period and ensure efficient use and support of the Cores. As the learning curve and organizational results progress, the frequency of teleconferences will be adjusted to the most appropriate intervals, but will be held at least monthly. The Administrative Core will ensure that an agenda is established for each teleconference call and will post the agenda and MDP data to be reviewed on the established website prior to the call. This will be a designated job responsibility of the Administrative Specialist. This allows on-screen review of data via the Internet with an interactive discussion of results during the TC. Call minutes will be maintained by the Administrative Core and provided to all team members electronically within five working days.
  2. Program Meetings: The Administrative Core will oversee the organization of two coordinated team research meetings per year. It is anticipated that one of these meetings will be in a satellite structure around the annual microbicides meeting held in Washington D.C. and/or the annual HPTN meetings. A second face-to-face meeting is thought to be necessary and beneficial to the achievement of milestones and the overall goal and themes of the MDP. This meeting would be at one of the sites with all project investigators, appropriate staff, industry representatives, and if possible the Project Officer and SAP members in attendance. The meeting would take the form of a small conference with presentations by project leaders, invited speakers, project updates, review of established milestones and conduct any other business as needed. Dr. Anton will be responsible for raising funds for this second annual meeting from private donors as the NIH funding limits travel to one meeting per year. The participants in the MDP believe that two face-to-face meetings per year will greatly enhance the productivity of the team. The Administrative Core will oversee coordination of both of these meetings as well as advance circulation of relevant abstracts, data, goals, and progress reports. Minutes and a summary report from each of these meetings will be prepared by the Administrative Core and kept on file.
  3. Scientific Advisory Panel (SAP): We plan on taking maximal advantage of the external support and advisory capacity provided by this “cooperative agreement” with NIH, and the extensive links the appointed SAP will bring to the table. This will be particularly important and beneficial in this area of rectal microbicide drug development where only few groups work at present. NIH will assemble this advisory and review group and an annual on-site visit with all PIs present from the various projects will be incorporated. Efforts will be made to integrate the site visit by the SAP with the on-site annual meeting described above. It is hoped that this will provide a stimulating and interactive forum between the project leaders, Program Officer, the support staff, industry collaborators and the SAP. We view this input as critical and providing a bi-directional mechanism for critical review and monitoring of the progress of the program’s projects as well as a means to transmit to the SAP (effectively our “External Advisory Board”) the progress and data that is being acquired which may facilitate interactions with other groups.

The efficient exchange of information will be the key to having widely dispersed projects come together as a single larger program. Consequently, the Administrative Core will maintain both an electronic and U.S. Postal mailing lists for all members as well as oversee the active website in Core C. This mailing can be targeted and geared for project specifics, project leaders, or all members. This will enable an efficient coordination of abstract presentations, awareness of abstract deadlines, feedback for joint publications, data sharing, and coordination of meetings.

B. FISCAL MANAGEMENT:

The UCLA Division of Digestive Diseases Fund Manager along with the official from the Office of Contracts and Grants will be officially responsible for the fiscal management of the MDP. The Administrative Core staff will work with these individuals to provide fiscal management, assist in financial oversight and expedite management of subcontracts as a prime activity. Fiscal controls and appropriate spending will be stressed and timely reports will be prepared quarterly so that the investigators will have accurate knowledge of the state of their allocated funds. The Core will endeavor to keep track of posted clinical billings (such as endoscopy suite charges and clinical lab fees) in addition to trial subjects reimbursements (relates to all four projects). The Core will maintain ongoing and understandable fund balances on-line in the dedicated website, with select passwords for each project leader in order that they may have one set of figures by which to gauge available resources. As described in the Overview section, all subcontracts will be handled by UCLA, even if they are written and perceived to be “subcontracts of a subcontract”. This will optimize fund delivery to the final source and facilitate expedient budget changes while minimizing bureaucracy and repeat assessments of indirect costs. UCLA applies its research rate (figured at 53.5% at the project start date of 7/1/04) to only the first $25,000 of a subcontract for the duration of the five-year grant period.

C. EDUCATION

The Administrative Core will be responsible for developing materials for community outreach regarding the MDP. Although not described in PAR-03-137, we view this service as an important corollary of the focused research. Educating the public and other health care professionals of this critical area of research and the implications for HIV prevention will lay the community groundwork for future clinical trials. Core B (Regulatory Compliance and Subjects) will maintain an active, IRB-approved volunteer registry for trials. This forum also provides an additional and novel means to discuss HIV prevention. The Administrative Core will provide press releases and other material to publications and organizations that serve the communities that will be impacted by the MDP research to encourage support and participation in the trials; the material will be designed to be flexible so that it can be used at all sites. There will be slides, PowerPoint presentations, brochures and reports available to MDP investigators who are doing public presentations as well as backup material for scientific presentations. Appropriate IRB-approved presentations will be located on the public-access portion of the MDP website.

D. MDP WEBSITE MAINTENANCE

Under a separate Core (Core C), Drs. Christopher Denny and Robert Dennis at the UCLA Computer Technology Research Laboratory (CTRL) will use an internet-based, web-accessible information and data management system adapted for MDP. This software is already in use and is described in detail in the Overview section and the proposal for Core C. The Administrative Core will be responsible for updating and maintaining publicly accessible material such as general information on the MDP, recruitment information, links to services and general health and prevention information. The Core will also ensure more Project-related functions such as subject-accessible self-report forms, questionnaires and materials in addition to investigator-accessible agendas, meeting minutes, calendars and educational material, are accurately portrayed. The Data Management and Biostatistics Core (Core C) will be responsible for maintaining site access for investigator accessible protocols, data links, standardized CRF’s and a wide array of other MDP study material. The Administrative Core will ensure that the appropriate items are in the repository and that the password allocations meet the needs of the several uses (including our industry collaborators).

E. PUBLICATION PREPARATION

The Administrative Core will provide assistance with computer graphics, slide making, color printing for brochures and abstracts, notification of conference and abstract submission deadlines, as well as coordinate submission of articles to peer-reviewed journals.

F. LIBRARY:

The Administrative Core will maintain electronic copies of all minutes as well as electronic communications between Project Leaders and the Administrative Core for future reference, if needed. In addition, all publications (in preparation/submitted/accepted) will be maintained on record and -- once published -- a PDF copy (Adobe Acrobat) of the article will be maintained in the Core’s archives. This will facilitate progress reports as well as utilized in assessing milestones at year 2.5.

G. GENERAL ADMINISTRATIVE SUPPORT

The Administrative Core will provide general clerical support to the Regulatory and Data Management Cores as well as support for all MDP-wide activities.

V. GOVERNANCE STRUCTURE

A strong and functional committee structure will be implemented to create a productive working interaction with MDP team members and assure that the goals and milestones of the MDP are clearly laid out and met. The Executive Committee (EC) will be composed of Dr. Anton, the Leaders/Co-Leaders of each of the four projects, Directors Co-Directors of the other two Cores; subcontract representatives (UW, ARA) will serve as the primary advisory committee to the PI and the MDP. The EC calls and meetings will actively encourage participation by other project investigators, Core leaders, NIH staff, industry collaborators, SAP members and others. Subcommittees will be formed on an ad hoc basis to deal with specific issues as needed.

A. EXECUTIVE COMMITTEE (EC)

The EC, under the leadership of Dr. Anton, will have responsibility for all MDP activities. The EC will review scientific progress, new policies, programmatic changes, key personnel changes and major financial decisions to be implemented by the Principal Investigator. The EC will ensure coordination and integration of MDP Projects, components and activities, Core use, scientific guidance to the individual research projects, coordinating regulatory affairs and assuring the completion of programmatic goals and milestones. The EC members list can be found in the Overview section.

B. SUBCOMMITTEES

Ad hoc and standing subcommittees will be formed, as needed, to meet the needs and mission of the MDP. These committees will report directly to the EC.

C. EXTERNAL SCIENTIFIC ADVISORY PANEL (SAP)

This committee will be composed of an independent group of prominent researchers and other stakeholders from outside institutions. They will be appointed by the NIH, under the terms of the U-19 “cooperative agreement”, to provide the Principal Investigator with advice on scientific, policy, personnel and administrative matters. The input of the SAP will provide a fresh, objective viewpoint that will be needed to assure that the MDP will succeed in its mission.

We have identified the following areas of importance from which to select experts for membership in the SAP. The areas of expertise would ideally include:

- Mucosal immunology related to HIV pathogenesis
- SIV models of transmission/protection
- Microbicidal drug development
- Human sexual behavior
- Acceptability studies
- Drug pharmacokinetics and toxicology
It is understood that these individuals will provide a written evaluation of the MDP’s activities and progress on at least an annual basis.

D. INTEGRATIVE CAPACITY

Integrative Capacity is the primary mission of the Administrative Core to ensure compliance with -- and surpassing of -- the MDP’s overall aims in meeting the PA outline. It is anticipated that by having Dr. Anton actively involved in two of the four projects and overseeing all activities, time and awareness of interactive aspects of the grant will be facilitated. It will be pivotal, for example, in defining acceptable limits of inflammation in Project 4 to integrate results form Project 2 of trauma-related inflammation and from Project 3 of formulation-related inflammation before ascribing all observed inflammatory responses to the product microbicide. Efficient management of each project, coordinated human subjects and regulatory surveillance by Core B and the common data management assets of Core C will support this exchange. The power for interpretative and integrative capacity resulting in a sum greater than the parts will be fostered by the centralized biostatistical integration of all projects’ results, provided by Core C’s Co-Director, Dr. Cumberland, and the administrative Core’s EC meetings. This is the forum for project interaction, intersection and synergy.

VI. SUMMARY

The Administrative Core will function as the central core for the research conducted by MDP investigators. The depth and breadth of expertise and experience assembled in this application far exceeds that normally present in an individual research grant. Similarly, the challenge to optimize the synergistic implications of each projects’ findings will be a function of the successful efforts of the Administrative Core in performing its role. The core will support the broad array of investigators and their unique research, fiscal, communication, and general administrative needs. The core will be adaptable and responsive to all the stakeholders as the MDP grows and evolves in its efforts to develop a safe and effective topical HIV microbicide in this extremely vulnerable compartment.