John Y. Killen, M.D.,
Director, DAIDS
Dr. Killen opened the meeting by welcoming committee members and thanking them for their participation. He introduced Dr. Carole Heilman, the new Associate Director for Scientific Program Development at DAIDS, who will also be serving as Deputy Director. Dr. Killen announced that Dr. Paulo Miotti of Johns Hopkins University joined DAIDS as a medical officer in the Epidemiology Branch, and that Dr. Nava Sarver has been appointed Chief of the Targeted Interventions Branch, Basic Sciences Program. Dr. Killen presented certificates of appreciation to and thanked retiring committee members: Drs. Wafaa El-Sadr, Michael Saag, Dani Bolognesi, and Ashley Haase. In addition, he presented a plaque to Mr. John McCreight in recognition of his pro bono work as a management consultant to DAIDS.
Dr. Killen noted that the focus of this meeting would be a discussion of the recently released Report of the NIH AIDS Research Program Evaluation Working Group, which was commissioned by the Office of AIDS Research (OAR) Advisory Council (also referred to as the Levine Report after its Chair, Arnold J. Levine). Dr. Killen stated that he and Dr. Fauci were extremely pleased that the report reflected so positively on NIAID's efforts and that they support the spirit and most of the specifics of the report. He did note, however, that there are several instances where the goal of the specific recommendations might be better achieved through different actions, and several issues that require clarification. He noted that the specific topics of this meeting would be those recommendations concerning: 1) the structure and focus of NIAID's vaccine and prevention research activities, 2) the organization and associated data bases of NIAID's therapeutic clinical trials groups, and 3) issues related to basic research, including the Centers for AIDS Research, specimen repositories, and collaborations and consortia to foster basic research in immunology. All of these issues were part of a larger set of recommendations from the Levine Panel, which Dr. Killen briefly presented to the committee.
Structure and Direction of the Vaccine Program -- John Y. Killen, M.D.
Dr. Killen reviewed one recommendation from the Levine Report concerning vaccine research and development, which stated: "The entire AIDS vaccine effort of the NIH should be restructured. A trans-NIH vaccine program should be established with leadership and oversight provided by distinguished, non-government scientists."
The Levine Report states that the overall vaccine effort should be coordinated and centralized at NIAID, and should operate in conjunction with a proposed AIDS Vaccine Research Committee (AVRC) chaired by a distinguished nongovernment scientist. Language in the report also recommended the establishment of a separate Division within NIAID to coordinate this committee's work.
NIAID agrees with the panel's sentiment that the development of a safe and effective vaccine is considered to be of the highest priority in the AIDS research effort. Dr. Killen also indicated his agreement with the creation and composition of a committee, housed within NIAID. Such a committee could further highlight the importance of this area of research, provide invaluable advice and guidance to NIAID in identifying high priority areas of research and development, and help find ways to quickly and flexibly marshal the resources required to help carry out the needed research. While such a committee would be extremely valuable, NIAID does not see the necessity of establishing an independent Center or Division within NIAID to support these functions.
The committee endorsed keeping the focus of NIH's HIV vaccine efforts at NIAID. They were supportive of establishing a vaccine committee that has an oversight role of the entire vaccine research effort. However, they did not see the need for any organizational changes at the Institute and strongly recommended against the creation of a new NIAID Division to oversee vaccine research.
HIVNET Research and Organizational Plan -- Patricia Fast, M.D.
Dr. Fast presented the Institute's response to the Levine Report's recommendation concerning the HIV Network for Prevention Trials (HIVNET) program. Specifically, it stated: "NIAID, in partnership with other ICDs with complementary expertise, should promptly develop a comprehensive plan for HIVNET's organization, governance, research and funding. This plan should be reviewed in 1996 by a joint OAR/ICD-convened panel of extramural experts in behavioral, social, epidemiological, prevention, pathogenesis, and treatment research as well as vaccine research. If reviewers determine that there are significant deficiencies in the plan, funds could be released for re-targeting to other essential areas of AIDS research."
Dr. Fast noted that NIAID is in agreement with this recommendation and, since it is relatively straightforward, progress has already been made on its implementation. The research plan requested in the Levine Report is being developed and the external review of the plan and the HIVNET program is planned for late June 1996 in conjunction with OAR. ARAC members recognized that the HIVNET was originally established to carry out vaccine efficacy trials, and identified several questions that NIAID may want to ask the review panel to consider, which included collaboration and coordination within and beyond NIH be addressed during the comprehensive review of the HIVNET.
Dr. Killen reviewed recent changes in the AIDS Clinical Trials Group (ACTG) and the three Levine Report recommendations concerning the clinical trials networks supported by NIAID. These recommendations are as follows: 1) "A single integrated adult clinical trials network should be created with primary sponsorship from NIAID and ancillary funding from other institutes involved in clinical trials." 2) "An oversight committee for all NIH-sponsored AIDS clinical trials should be created that is based in the OAR and includes broad scientific and community representation." 3) "A uniform standard for clinical trials databases should be developed to ensure that data can be shared between studies both within and across trials programs."
Organization and Intergroup Collaboration and A Single Adult Clinical Trials Network -- William Duncan, Ph.D.
NIAID has already initiated several activities to improve coordination (a major theme of the Levine Report) among the clinical trials networks sponsored by several NIH institutes. Dr. Duncan described the semiannual meetings that have been instituted to facilitate communication, coordination and collaboration between the scientific leadership of the Terry Beirn Community Programs for Clinical AIDS Research (CPCRA), the adult and pediatric ACTG programs, and other NIH-sponsored clinical trial groups.
ARAC members felt that the existing NIAID clinical trials program is well organized and successful. The committee fully endorsed that: 1) there is a need for greater collaboration; 2) collaborative efforts continue to be fostered through the processes currently in place; 3) evolution be encouraged and carefully monitored; and 4) structural changes, at least for the next several years, be implemented cautiously.
Clinical Trials Oversight Committee -- John Y. Killen, M.D.
Dr. Killen indicted that the intent of this recommendation seemed to be the creation of a focal point either in the OAR or elsewhere, with the authority to address issues related to inter-institute collaboration and "make things happen." While NIAID totally supports the goals of integration, coordination, and collaboration across institutes, Dr. Killen noted that NIAID would prefer a "coordinating" rather than an "oversight" committee. The ARAC agreed that ongoing activities, such as the Intergroup Scientific Leadership meetings, should continue while the OAR continues to examine how to improve coordination across each of the institutes. If established, the ARAC felt that this new oversight committee should function solely to facilitate trans-institute collaboration and integration, and should not oversee the science of individual groups.
Database Linkages; Facilitation of Cross-Study Analyses -- William Duncan, Ph.D.
Dr. Duncan supported the goal of cross-study analysis and noted that it can be accomplished through more effective and prospective coordination and planning; and increased cooperation among the different groups conducting clinical trials. While the ACTG and CPCRA use different operating systems for collecting clinical data, these systems do not prohibit dataset sharing. Standardizing all the systems would take considerable planning, might result in a less satisfactory system overall, and may not accomplish the desired goals of data sharing. ARAC members acknowledged that coordination and collaboration across the groups are important and valuable goals and should continue to be pursued. In and of itself, this was not sufficient reason to revamp the databases.
Specimen Repositories -- Carl Dieffenbach, Ph.D.
The recommendation from the Levine Panel concerning repositories and databases is as follows: "Improvements should be made in repositories and databases in accord with three principles: repositories and databases should be investigator-designed and hypothesis-driven; accessible to all qualified investigators; and coordinated under a new user-friendly central tracking system maintained under the auspices of the OAR. Support should be provided for collection of specimens, as dictated by scientific needs, and for these repositories and databases."
Dr. Dieffenbach began by explaining that the DAIDS specimen repositories contain a large number of fluid and tissue samples collected in conjunction with DAIDS-supported research. Many of these specimens are linked to the clinical data and represent a key national resource. Dr. Dieffenbach reviewed the mechanisms through which collaborators can obtain access to these specimens. A document detailing these mechanisms, which were designed to ensure that the central repositories are of the highest quality, and that requests for collaborations are evaluated for scientific merit by each of the peer-review funded groups, was distributed to committee members. Once approved, the document will be published and broadly disseminated to ensure that collaborating investigators know how to access this important resource. The committee agreed that the document could serve as a starting point from which future issues of common procedures used by all of the groups and linkages between them will continue to evolve.
Centers for AIDS Research -- Carl Dieffenbach, Ph.D.
The recommendation from the Levine report concerning the Centers for AIDS Research (CFAR) is as follows: "The Working Group recommends that funding for the CFAR program as a whole be increased by approximately 50 percent. This would allow annual funding in the range of $750,000 to $1.5 million per year, to be allocated in proportion to a Center's research capacity and its ability to build an interdisciplinary research program and attract RO1s." Dr. Dieffenbach began by describing the CFAR program, which is intended to establish and maintain a multidisciplinary academic environment that promotes basic, clinical, and translational AIDS and AIDS-related research. He noted that NIAID endorses the idea of expanding the institutional research base, thereby making the CFAR program more responsive and more available to the research community. He also reviewed a DAIDS proposal to fund two or three CFARs every year instead of the current plan in which all units compete for funding every five years. This would ensure that the program has turnover and would provide greater opportunity for more institutions, as opposed to the current, more static program.
Committee members regarded the CFARs program as filling an extremely important and unique niche in the overall AIDS research program and they agreed that the current $750,000 funding cap is insufficient to support these necessary functions. While no specific recommendation was made, the committee recognized the pros and cons of the proposed approach to fund the CFAR program. A specific concept will be presented at a future meeting.
Collaborations and Consortia -- Carl Dieffenbach, Ph.D.
Dr. Dieffenbach stated that the Levine Panel recommendation is aimed at augmenting research efforts to better understand the human immune system. It states: "OAR should convene a series of workshops of expert immunologists to develop a plan to accelerate progress in understanding the following: 1) The basic biology and development of human immunocompetent cells and of the unique aspects of the physiology of the human immune system, 2) How HIV and SIV perturbs the human or primate immune system to impair the function of and destroy immunocompetent cells, 3) Why normal replacement mechanisms are unable to restore a functional immune system in infected individuals, and 4) Why normal host defenses are unable to contain HIV infection."
Dr. Dieffenbach explained that in order to increase basic research on the human immune system through traditional RO1s, investigators simply need to be made aware of NIAID's interest in this area. However, enhancing immunological research through consortia and collaboration is more difficult. The committee recommended a multiplicity of approaches to broaden the field of AIDS researchers but expressed concern about the apparent attempt to involve more senior immunologists in AIDS research, suggesting that, in many cases, junior investigators entering their first or second postdoctoral position might be more appropriate.
Pediatrics -- James Balsley, M.D.
Dr. Balsley described the recommendation in the Levine Report that addressed pediatric AIDS research. "The Working Group recommends an early re-examination of the optimal approach to pediatric AIDS clinical trials. Furthermore, significant reductions in allocations to the P-ACTG are recommended. These should be implemented in such a manner so that the essential clinical trials function of the P-ACTG is not impaired."
Dr. Balsley noted that the Levine Panel's recommendation was related to the results of ACTG 076 and other recent studies, which suggests that the future rate of vertical HIV transmission may be significantly reduced. Given this fact and conflicting data on the real impact of the 076 results on transmission, Dr. Balsley suggested that we continue to monitor the trends in the epidemic in the U.S. and elsewhere. He suggested that changes in the current program, beyond the 10% reduction in funding already planned, be carried out gradually, and that the overall funding level for the pediatric program be reconsidered the next time the Pediatric AIDS Clinical Trials Group is up for renewal. The committee concluded that it would be best to review NIAID's support of pediatric research after prudent and thoughtful examination in the next two to three years.
Women's Interagency HIV Study -- Lewis Schrager, M.D., M.P.H.
Dr. Schrager reviewed the Women's Interagency HIV Study (WIHS), a prospectively followed cohort of more than 2,000 HIV-positive and nearly 600 HIV-negative women. WIHS focuses on the virologic, immunologic, psychosocial, and clinical status of this cohort and offers a unique opportunity to study diverse, female-related factors, such as mucosal transmission and pathogenesis, and the events taking place in early pregnancy. The committee noted that WIHS studies in the field of neuroendocrinology might provide much needed information, and that valuable studies of possible viral cofactors, including HSV-2 and HPV, should be conducted. The committee will review the concept for the WIHS initiative in September and will look to see that some of the issues raised during the program review were adequately addressed.
(Please contact Ms. Rona L. Siskind, Executive Secretary, ARAC at (301) 496-0545 if you wish to receive a copy of the ARAC/AIDS Subcommittee Joint Meeting Summary via fax.) back to top |