The 165th meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened at 10:30 a.m. on Monday, May 24, 2010, in Conference Rooms E1/E2, Building 45, National Institutes of Health. Dr. Anthony S. Fauci, director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.
In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:40 a.m. and from 1:00 p.m. to 4:30 p.m. The meeting was closed to the public from 8:30 a.m. to 10:00 a.m. and from 11:40 a.m. to 12:00 p.m. for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.
Council Members Present:
Ex Officio Members Present:
Council Members Absent:
NIAID Senior Staff Present:
Table of Contents
The National Advisory Allergy and Infectious Diseases Council convened in closed session to consider applications in the areas of allergy and immunology, microbiology and infectious diseases, and AIDS.
Funding Actions: The Council reviewed 2,888 research and training applications with primary assignment to NIAID for a requested amount of $1,172,158,331 in first-year direct costs and recommended approval of 672 applications for $445,750,313 in first-year direct costs. Five Method to Extend Research in Time (MERIT) awards were recommended for approval.
Dr. Fauci opened the Council session by welcoming visitors to the meeting and extended a special welcome to new ex officio member Dr. Rima Khabbaz, deputy director for infectious diseases at the Centers for Disease Control and Prevention. Two Council members, Drs. Louis Picker and Connie Celum, were unable to attend the meeting.
Council considered the minutes of the February 1, 2010, meeting and approved them as written.
Dr. Fauci acknowledged several new appointments and retirements at NIH and NIAID since the last Council meeting.
At the NIH level, Dr. Raynard Kington, deputy director of NIH, is leaving to become president of Grinnell College in Grinnell, Iowa. President Obama announced his plan to appoint Dr. Harold Varmus to serve as the director of the National Cancer Institute.
After 40 years at NIH, Dr. Brian Murphy retired as chief of the Respiratory Viruses Section and co-chief of the Laboratory of Infectious Diseases, NIAID. Dr. Murphy is renowned for his expertise in the fields of virology, vaccine research, and respiratory diseases. Dr. Jeffrey Cohen is the new chief of the Laboratory of Infectious Diseases.
Dr. Fauci announced the following appointments: Dr. Suzanne Frisbie as the first deputy director of the NIAID Office of Technology Development; Jean McKay as director of the Office of Program Planning, Operations, and Scientific Information, DAIT; and Diane Randall as the new deputy director of the Office of Research Operations, Office of the Director.
Dr. Fauci congratulated Dr. Gary Nabel, director of the Vaccine Research Center, on being named a 2010 fellow of the American Academy of Arts and Sciences. Dr. Tom Quinn, chief of the International HIV and STD Unit, Laboratory of Immunoregulation, received the 2010 Ed Nowakowski Senior Memorial Clinical Virology Award from the Pan American Society for Clinical Virology. The American Society of Tropical Medicine and Hygiene awarded Dr. Jesus Valenzuela, chief of the Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, the 2009 Bailey Ashford Medal.
Dr. Richard Whitley, one of NIAID’s Council members, received the 2010 Distinguished Physician Award from the Pediatric Infectious Diseases Society.
The overall NIH budget for FY 2010 is $31 billion, a 2.3 percent increase over FY 2009. NIAID received $4.8 billion, an increase of 2.5 percent over FY 2009. Dr. Fauci noted that the appropriation bill includes a provision for a 2 percent inflationary increase for noncompeting grants.
NIAID will support a payline to the 11th percentile for unsolicited investigator-initiated research and the 16th percentile for new and early-stage investigators.
NIAID received $1.11 billion in American Recovery and Reinvestment Act (ARRA) funds. Most of the funds are being used to support research project grants, and a small percentage is supporting solicited initiatives, such as RFAs and PAs and signature projects.
The President’s FY 2011 budget for NIH is $32 billion, a 3.2 percent increase over FY 2010. NIAID’s allocation is just under $5 billion, a proposed increase of 3.3 percent over FY 2010.
On March 23, President Obama signed into law the Patient Protection and Affordable Care Act, commonly referred to as the Health Care Reform Act. The law contains a provision introduced by Senator Arlen Specter that establishes the Cures Acceleration Network (CAN). CAN will support research for high-priority therapeutics, biologics, or medical devices that have not attracted funding from the private sector.
On April 28, 2010, Dr. Fauci accompanied Dr. Francis Collins, NIH director, who testified before the House Appropriations Subcommittee on the FY 2011 President’s Budget request for NIH. On May 5, Dr. Collins testified on the FY 2011 NIH budget before the Senate Appropriations Subcommittee.
Also on April 28, Dr. Fauci and Dr. Tom Frieden, director, Centers of Disease Control and Prevention, testified before the House Energy and Commerce Subcommittee on Health on antibiotic resistance and the threat to public health.
On April 30 at a Congressional briefing sponsored by the Foundation for AIDS Research, or amfAR, and several other HIV-advocacy organizations, Dr. Fauci spoke about the accomplishments and future challenges of AIDS research.
On May 13, Dr. Fauci participated as the keynote speaker at the National Italian American Foundation Public Policy Forum on Capitol Hill. He spoke about emerging and re-emerging infectious diseases, with a particular focus on the recent H1N1 influenza pandemic.
Dr. Fauci began by giving an update on swine flu. He presented current statistics of the estimated number of cases, hospitalizations, and deaths in the U.S. The 2010-2011 seasonal flu vaccine will include the 2009 California H1N1-like virus. The CDC’s Advisory Committee on Immunization Practices recommends vaccinating everyone who is able to be vaccinated for seasonal influenza.
Dr. Fauci briefly discussed AIDS, malaria, and tuberculosis. He talked about neglected tropical diseases and how they are emerging as an important issue because of their disease burden measured in disability adjusted life years.
Dr. Gerald Nepom replaced Dr. Jeffrey Bluestone as the director of the Immune Tolerance Network. Dr. Fauci gave an update on the status of the guidelines for the diagnosis and management of food allergies and the Inner City Asthma Program.
Dr. Fauci outlined the White House Medical Countermeasures Initiative that will give the U.S. the capacity to respond faster and more effectively to bioterrorism or sudden outbreaks of an infectious disease. HHS conducted a Medical Countermeasure Review that included an Institute of Medicine workshop, a National Biodefense Science Board workshop, and the Medical Countermeasure Policy Review Team. Dr. Fauci will provide updates on this initiative over the next few Council meetings.
Dr. Francis Collins began by identifying the opportunities for research and NIH where advances could lead to substantial benefits: high-throughput technologies, translational medicine, health care reform, global health, and innovation in the biomedical research community. He then explained how these five themes fit into NIH’s mission.
Dr. Collins discussed the pipeline for developing new therapeutics with potential clinical benefits and how NIH might play a more aggressive role in this process. The goal is to provide resources for projects that are unattractive to companies because of the lack of economic incentive. Another benefit of this effort is the possible discovery of new purposes for compounds that are already available.
Dr. Peggy Hamburg, FDA commissioner, and Dr. Collins are putting together a joint leadership council to look at ways to improve the translational pipeline.
The Health Care Reform bill contained a component called the Cures Acceleration Network (CAN). The purpose of CAN is to advance the development of new treatments and get them through the pipeline. Until money is appropriated for this program, NIH will not be funding awards.
The desired outcome is to develop a pipeline where projects could enter and leave at different stages and provide the capacity to find cures that have been very difficult to achieve.
Dr. Collins stressed the importance of supporting innovation and promoting diversity in the scientific workforce.
DAIT Staffing/Organizational Changes: Dr. Rotrosen welcomed the subcommittee members of the National Advisory Allergy and Infectious Diseases Council. Dr. Rotrosen took the opportunity to inform the subcommittee members on a number of strategic issues: 1) the Institute has developed a new methodology for reporting what the Institute spends on immunology. Under this new methodology there should be a greater representation of immunology from all of the divisions within Institute; 2) The Institute last year awarded about half of the $1.1 billion of ARRA funds that were allocated to us on 936 awards. The vast majority of these (86 percent) went to research project grants and very small amounts to training resource-related grants, intramural, and a small amount (4 to 7 percent) for the centers and R&D contracts; 3) There has been a tremendous effort on the part of the Asthma, Allergy and Inflammation branch to develop guidelines for the diagnosis and management of food allergy. In the development of these guidelines, the staff has brought together close to 30 other federal agencies and professional societies and patient advocacy groups with very different perspectives on this issue; and 4) in closing, Dr. Rotrosen mentioned we’ve had a leadership change in the Immune Tolerance Network, (ITN) one of the main clinical trial networks supported by the division. Dr Jeff Bluestone was recently appointed provost and executive vice chancellor at UCSF and because of that had to step down from the ITN leadership. We are fortunate that Dr. Jerry Nepom at the Benaroya Institute in Seattle has agreed to chair the scientific leadership committee of the ITN.
Dr. Rotrosen next mentioned there would be an update given by Dr. Lynda Chiodetti, Basic Immunology branch on “Adjuvant Discovery and Immunological Research using High Throughput Screening.” He also let the members know, that Dr. Christopher Austin, Director, NIH Chemical Genomics Center, would be presenting on “NIH Chemical Genomics Center – Partners in Assay Development and High Throughput Screening.”
Following the presentations, Dr. Rotrosen noted there were three concepts for review and approval.
The following concepts were presented for the Subcommittee’s consideration:
Infant Immune System: Implications for Vaccines and Response to Infections: This initiative will support research to define the mechanisms for establishing and maintaining immunity in infants (0 to 12 months of age) after infection with or vaccination against emerging/re-emerging infectious diseases, including potential agents of bioterrorism. This program will also establish collaborations among immunologists, neonatologists, and microbiologists to expand our knowledge of the infant immune system. Information obtained through this program can be applied to the design of improved vaccines and immunotherapies to combat infections in this vulnerable population. The subcommittee unanimously approved this initiative.
Systems Approach to Innate Immunity: The primary objective of the program is to use a systems biology approach to develop a comprehensive understanding of innate and adaptive immune responses to microbial infection with a focus on NIAID Category A-C pathogens. The initiative will support quantitative analyses that will identify and measure dynamic networks regulating immune responses. This initiative requires an interdisciplinary team to achieve the goals. The basis of the research program will be genome wide screens of mutant mice for identification of key regulatory immune response genes. Random mutagenesis approaches are preferred, such as ethylnitrosourea (ENU) mutagenesis, although more targeted high throughput methods may be utilized with adequate justification. The studies will be complemented by detailed genomics, proteomics, computational biology, and bioinformatics approaches that focus on transcriptional regulation and signaling mechanisms. Investigators will analyze a subset of the newly discovered immune regulatory genes in human correlation studies. The subcommittee unanimously approved this initiative.
Taconic Mouse Exchange Program: Support distribution of immunology-related, gene-targeted mouse strains to the broader research community. This Division of Intramural Research (DIR) contract supports the breeding and distribution of novel mutant mouse strains containing gene knockout or novel trans-genes of immunological interest. The program is managed by NIAID DIR staff with input from DAIT staff, and partially supported with extramural (DAIT) funds. The mouse strains to be included in this program are based on projected value to the immunology community. The contract partially defrays the cost of mouse production so that investigators pay a reduced rate to receive animals. The subcommittee unanimously approved this initiative.
Following her welcoming remarks, Dr. Heilman introduced Dr. Rima Khabbaz, Deputy Director for Infectious Diseases at the Centers for Disease Control and Prevention (CDC), as the new CDC representative on NIAID’s Advisory Council. Dr. Heilman also acknowledged that Subcommittee member Rich Whitley was recently named the 2010 recipient of the Distinguished Physician Award by the Pediatric Infectious Diseases Society, in recognition of his stellar and productive role as a researcher and director of the University of Alabama’s Division of Pediatric Infectious Diseases.
She then deferred to the DMID branch chiefs to report on recent staff changes in their respective branches.
Following her introductory remarks, Dr. Heilman noted the Institute’s new policies and procedures for investigator-initiated clinical trials, and informed the Subcommittee that Elizabeth Hollomon in DMID’s Office of Clinical Research Activities is available to answer any questions regarding these changes (a flyer announcing the policy changes and listing Ms. Hollomon’s contact information was distributed).
There were several concepts presented for the Subcommittee’s consideration:
International Clinical Studies Support – the objective of this concept is to support clinical research carried out at international sites through assistance with protocol development, design, and implementation, site assessment, and monitoring; relevant training opportunities related are also provided. The Subcommittee was enthusiastic about the International Clinical Studies Support (ICSSC) program and felt it provided critical support for foreign investigators. A Subcommittee member asked if we had any mechanisms in place to measure the impact of this program so that we could determine if it was having its intended effect. Dr. Sager noted that the current contractor routinely solicited feedback from participants receiving training under the program. Dr. Heilman agreed that it would be valuable to secure additional metrics to more broadly assess the benefits of the program. The Subcommittee also asked how this program fits with other international activities. The Subcommittee suggested trying to measure “softer” contributions, such as institutional development and sustainability. The concept was unanimously approved.
NIAID International Research in Infectious Diseases, including AIDS – the objective of this concept is to support clinical research carried out at international sites through assistance with protocol development, design, and implementation, site assessment, and monitoring; relevant training opportunities related are also provided. The Subcommittee noted that the International Research in Infectious Diseases, including AIDS (IRIDA) is an important component of DMID’s international portfolio. Subcommittee members suggested several ways to increase awareness of this unique opportunity for foreign investigators. The concept was unanimously approved.
An Integrated Approach in Understanding Host-Pathogen Interactions – the objective of this concept is to better understand, at a molecular level, the interactions of the pathogen and host, and how these interactions influence the presentation, progression and severity of clinical infectious disease. The Subcommittee unanimously and enthusiastically supported the concept, noting that the current availability of high-throughput technologies will facilitate understanding of the dynamics of host-pathogen molecular interactions while taking into account temporal factors. A lot of power was recognized in the proposed use of repetitive samples from hosts with persistent and recurrent infections, but the availability of samples for these studies could also be a challenge. The program should emphasize the generation of analysis tools and experimental protocols to extract meaningful data sets from the huge amount of data this program is expected to generate. Finally, a Subcommittee member noted that the overall benefits of the entire DMID genomic program to the microbiology and infectious disease community include the sharing of resource and data sets generated by initiatives such as this one.
Strategies for the Protection of Pregnant Women and Infants Against Infectious Diseases – the objective of this concept is to improve understanding of the host-pathogen interactions that underlie infectious diseases that are unique to, or occur at elevated incidence or with enhanced/modified pathology in, pregnant women, fetuses and neonates. The Subcommittee unanimously endorsed this concept, and expressed considerable enthusiasm for its goals. There was extensive discussion of the initiative and several recommendations were made. Regarding the initiative’s scope, the subcommittee recommended a situational analysis to define critical high-impact scientific questions regarding infectious diseases in pregnancy, and using the results as the basis for focusing the initiative. They recommended against defining the initiative’s scope on the basis of a set of microorganisms of interest, and instead focusing on the important questions that must be addressed. They also suggested requesting a letter of interest from prospective applicants as a way of proactively eliminating applications outside the initiative’s scope. Dr. Kalt commented that such letters could be requested but would not be binding. Regarding peer review, the subcommittee cautioned that reviewers should be chosen carefully to encompass the breadth of expertise needed to evaluate multidisciplinary projects, and in particular to assess their impact on the field, including clinical practice. Finally, the subcommittee encouraged the participation of other ICs with interests in this area, particularly NICHD.
Finally, Dr. Katrin Eichelberg from NIAID’s Division of Extramural Activities presented a concept entitled Administrative Supplements for T32 Global Health Physician Scientist Postdoctoral Training Programs for the Subcommittee’s consideration and approval. The purpose of these administrative supplements is to allow existing T32 Institutional Research Training Programs with an overall focus on infectious diseases and a global health research capability, including collaborations with foreign clinical research sites, to add 1-2 clinical postdoctoral trainees over the remaining non-competitive segment of the parent award. The goal is to respond to and support the enthusiasm of clinical fellows eager to help solve global health problems in infectious diseases (including HIV). Additional research training will allow clinical fellows to gain international experience that will enhance their ability to function in foreign settings where many communicable diseases and associated health conditions are endemic. It will also provide research experience where other important infectious disease influences are prevalent, such as multiple co-morbidities, nutritional factors, cultural practices, and health care delivery challenges. The Subcommittee unanimously and enthusiastically supported the concept and it was considered an important addition to the existing T32 portfolio. Concern was raised regarding the distribution of funds based on the number of existing T32 programs with focus on Global Health among NIAID’s scientific divisions, and the Subcommittee encouraged equilibrium among the competing infectious diseases.
Carl W. Dieffenbach, Ph.D., Director, DAIDS
Dr. Carl Dieffenbach reported on the FY 2010 and FY 2011 budgets for NIAID. The 2010 appropriation for NIAID is $4.8 billion, a 2.5-percent increase over the 2009 budget. The 2010 figure includes $300 million for the NIH Global Fund. The payline has been set at the 11th percentile for unsolicited investigator-initiated research. For new principal investigators and early stage investigators, the payline was set through the 16th percentile. NIAID has a selective pay pool of $9 million and a Bridge Award pool of $18 million.
The budget will enable NIAID to pursue its research priorities, which include basic research for infectious diseases and immunology, development of AIDS prevention strategies, development of new platform technologies and medical countermeasures for emerging infectious diseases and biodefense, and the study of human immunology and the development of medical interventions for immune-mediated diseases.
The NIH received $1.11 billion in funds from the American Recovery and Reinvestment Act (ARRA), more than 70 percent of which was slated for research project grants (RPGs). About 3–5 percent of that supported solicited projects, and about 11 percent supported 4 “Signature,” or high-priority, projects. Carry-over of ARRA funding into a third year will be allowed, using no-cost extensions. For FY 2010 between $58 million and $68 million of ARRA funds were allocated to DAIDS, and to date $28 million has been released. Some of the funds ($7.5M) have been used to study and understand individuals who are exposed to HIV yet remain uninfected. A July workshop will address questions and issues for a research agenda targeting such individuals (exposed and resistant) to define terms, identify needed assays, and solicit new ideas. ARRA funds have also been used to support H1N1 vaccine trials, a prevention study and studies of HIV persistence.
For FY 2011, the President has proposed a $32 billion budget for NIH. The NIAID allocation would be $4.9 billion, a 3.3-percent increase from this year. The proposal includes a 3.4-percent increase for the HIV/AIDS portfolio, a 3.3-percent increase for biodefense and emerging infectious diseases, and a 3.3-percent increase for infectious and immunologic diseases. Congressional subcommittee hearings on the budget have occurred, and subsequent markups are planned.
Strategic Working Group
The next meeting of the Strategic Working Group (October 13–14, 2010) will feature discussions of the AIDS Clinical Trials Group (ACTG) Tuberculosis (TB) research agenda, the START Pilot Study, and restructuring of the HIV/AIDS clinical trials networks.
Clinical Trials Network Restructuring
Dr. Dieffenbach noted that the plan to restructure the clinical trials networks has been developing out of a stated goal of the President’s: to address not only HIV/AIDS, but also malaria, TB, polio, and other infectious diseases (e.g., hepatitis), in an integrated health strategy. Today, the United States has fewer people dying or being hospitalized because of classic AIDS-defining opportunistic infections and cancers. However, many cohorts feature growing morbidity and mortality as a result of liver disease, cardiovascular disease, diabetes/metabolic conditions, non-AIDS malignancies, and psychiatric conditions. The epidemic’s focus has been shifting from infectious disease issues to issues of internal medicine. The NIH has an important role in integrating care, prevention, and treatment as it supports basic and clinical research.
The leadership groups for the six NIAID HIV/AIDS clinical trials networks will expire by 2013 or 2014, and the Institute is using this as an opportunity to explore whether and how the networks can be used in a multi-disease capacity. The goal would be to capitalize on the infrastructure of the clinical trials network, integrating disease efforts (in particular, TB, malaria, and hepatitis). As of right now, the thinking is that none of the networks would be population specific; all population-specific studies would be incorporated and integrated into the work of each network. Community involvement will remain a key component of the network structure. In restructuring the networks, NIAID wants to ensure that there are mechanisms that enable the best new ideas from inside and outside the network to be brought forward. Other objectives for a new network structure include greater flexibility, or “rental capacity,” easier ways to establish and close sites, and more efficient and timely approval for projects in other countries.
A new clinical trials network structure should feature greater coordination at all levels, especially among laboratories and statistical centers. Prevention research priorities should include clinical product development, prevention of acquisition, prevention of transmission, integrated prevention, HIV vaccines, and other highly meritorious ideas. Therapeutics research priorities should include non-infectious co-morbidities and novel interventions, treatment and prevention of TB, malaria, and hepatitis, a cure or functional cure for HIV/AIDS, and high priority questions (including “rental” research possibilities). Successful transition to a new structure will require early and detailed planning.
The timeline for establishing the new networks is as follows:
NIAID will hold a town hall-style meeting in the fall of 2010 to collect input. It will encourage comments to be made on the NIAID Web site, will seek consultations, and will hold meetings with the individual networks.
In discussion, the question was raised as to why prevention research priorities were basically split into prevention of acquisition and prevention of transmission. Dr. Dieffenbach noted that this would ensure that single approaches would be proved before being brought into combination prevention modalities. It was suggested that this be explained in future presentations and that issues such as test and treat, which addresses both acquisition and transmission be raised for people to begin thinking about. It was also suggested that NIAID consider strategies, in consultation with other agencies and organizations, how overseas assets can be utilized to help address multiple disease questions.
Christel H. Uittenbogaart, M.D.
Dr. Uittenbogaart reviewed the March 8, 2010, meeting of the Office of AIDS Research Advisory Council (OARAC). At that meeting, there was a follow up of the November 5, 2009, OARAC meeting when various NIH institutes provided overviews of their AIDS-related research, with a major emphasis on issues of aging. At the March 8, 2010, meeting, investigators from academia and the NIH were invited to present their research on aging and HIV. The agenda included presentations on:
The discussion at the OARAC meeting encompassed various issues, including concern that HIV- infected individuals are 15–21 years older phenotypically than their chronological ages; recognition that HAART does not prevent accelerated aging because of inflammation and immune activation; lower arterial distensibility caused by vascular endothelial changes, and dementia and increased amyloid among HIV-infected individuals.
In discussion, Dr. Birx wondered about the role of the National Institute on Aging (NIA). Dr. Uittenbogaart stated that the NIA takes a lead in aging research while engaging in collaborations with the other Institutes. Dr. Dieffenbach noted that there ongoing efforts to coordinate research between NIA and NIAID, and that the OAR has been helpful in this regard.
James Bradac, Ph.D.
Dr. James Bradac reported on the last meeting of the AIDS Vaccine Research Subcommittee (AVRS), which took place in February, 2010. He noted that Satya Dandekar, Ph.D., will be serving as the AVRS liaison to the ARAC in the future. The next subcommittee meeting will take place following ARAC on May 25, 2010.
The February meeting featured sessions on the Thai Phase III HIV vaccine trial (RV144). In addition, Dr. Johnston, Director of the DAIDS Vaccine Research Program provided a review of the DAIDS HIV vaccine research portfolio, and there were reviews of the portfolio of the Division of Allergy, Immunology, and Transplantation (DAIT) and the portfolio of the Division of Microbiology and Infectious Diseases (DMID).
The session on RV144 featured presentations on the study findings and the newly formed working groups that will help to build on the results. Anthony Fauci, M.D., Director of NIAID, charged the AVRS to help determine how we can best move forward and investigate the results of the study. It was emphasized that RV144 was a collaborative effort between the U.S. Army (Military HIV/AIDS Research Program), NIAID, and the Thai government, and as such, future studies should be done by the field not just the MHRP, for example. Other large networks and organizations, such as the HIV Vaccine Trials Network (HVTN), Bill & Melinda Gates Foundation (BMGF), and Center for HIV/AIDS Vaccine Immunology (CHAVI), among others, will also be utilized. An organizational structure has been set up to study correlates of protection in this trial, and a formal process for review and decision making has been established for access to the clinical specimens from this trial. There is a product development advisory group and a scientific steering committee, which oversees 4 scientific advisory groups; humoral and innate immunity, cellular immunity, host genetics and animal models. Three of these groups will be working with samples that came out of RV144. The final group, the animal models, will come up with studies they can do in non-human primates to try to duplicate what was seen in RV144.
Representatives of a number of organizations were invited to present their planned activities to build on the RV144 results: Lawrence Corey (HVTN), Guiseppe Pantaleo (Poxvirus T-cell Vaccine Discovery Consortium/CAVD), Nelson Michael (MHRP), Wayne Koff (IAVI), Gary Nabel (VRC), Jóse Esparza (BMGF) and Barton Haynes (CHAVI).
The subcommittee made the following recommendations:
Dr. Bradac reported that the May 25–26, 2010, meeting of the subcommittee will include a workshop on the non-human primate challenge model and an update on RV144.
Katharine Kripke, Ph.D.
This concept has the objective of determining which components and strategies of the research education program, called the Biomedical Prevention of HIV Research Education Initiative, or B-PHREI, are most effective. The evaluation project will guide decisions about the continuation, enhancement, and expansion of the B-PHREI and also inform prevention education activities within the DAIDS-funded HIV/AIDS clinical trials networks and other researchers and stakeholders. This is a renewal with expansion using an N01 contract mechanism. The duration is 5 years, with a first year cost of $200,000. There will be one award.
This concept has the objective of determining which components and strategies of B-PHREI, the prevention research education program, are most effective. The evaluation project will guide decisions about the continuation, enhancement, and expansion of the B-PHREI and also inform prevention education activities within the DAIDS-funded HIV/AIDS clinical trials networks as well as other researchers and stakeholders. This is a renewal with expansion using an N01 contract mechanism. The duration is 5 years, with a first year cost of $200,000. There will be one award.
Dr. Kripke explained that the project will conduct an impact study of approaches to educating populations about HIV prevention research. To provide context for this initiative, she described the need prevention research education. The population that is recruited into vaccine trials is uninfected. The lack of obvious direct benefit to the trial participant, coupled with misconceptions about HIV prevention clinical research, and distrust of government and researchers, makes HIV prevention clinical trial recruitment particularly challenging. For example, previous research has shown that among the populations we need to reach for HIV vaccine trials, a majority either didn't know or incorrectly believed that they could get infected from an HIV vaccine. And as we get results from many of our HIV prevention efficacy trials, it will become more complex to talk about participating in vaccine or other prevention trials.
The ARAC reviewers initially expressed some concern that the cost of the evaluation is high compared to the cost of the actual education program, and that it will be important to ensure that the evaluation design is appropriate and rigorous. In response, NIAID reduced first year costs from $400,000 to $200,000, with an option of adding more funds back into the initiative to conduct a household survey if deemed appropriate. This would be determined after NIAID gets results from the household survey that is planned to be conducted this year.
In order to ensure the appropriateness of the design, Dr. Kripke noted that the applications will undergo peer review by a panel of experts specifically set up for this solicitation. Once the contract is implemented, an oversight committee will be established that will include representatives from DAIDS, as well as the NIAID Strategic Planning and Evaluation Branch, National Institute of Mental Health and from the relevant clinical trials networks. The ARAC asked whether information on factors such as age and gender would be collected as part of the evaluative process. While the future evaluation has not yet been designed, it was noted that current evaluation activities for the NIAID HIV Vaccine Research Education Initiative included information about both age and gender.
The reviewers were very satisfied by staff efforts to address their concerns. They recognize the need for ongoing vaccine and biomedical prevention research education and the value of evaluating impact and effectiveness of the approaches being utilized.
The ARAC members expressed support for the concept, made a motion to approve it, and voted in favor.
Scott Proestel, M.D.
This concept has the objective of providing clinical research support services to help DAIDS achieve its scientific goals within specific programs, networks, and non-network studies and sites. As such, the contract supplements the division’s ability to ensure compliance with regulations, standards, and good clinical practice guidelines, safety and welfare of study participants, and study quality and integrity. It features research program operations management, clinical and laboratory support, clinical trial support, and support for regulatory compliance, training, quality management, and more. It provides services across the division. This is a renewal and a N01 contract mechanism, with 7 years duration.
The ARAC reviewers expressed support for the concept/program, describing it as essential. They cautioned about overlapping with services that are supplied by other entities and suggested that the new contractor should have experience in supporting all phases of clinical trials research, international research, and vaccine trials, and in advanced clinical development. The importance of capacity building, mentoring capacity in resource-limited settings, and training were emphasized by the committee. It was also noted that there should be clarity about training so that it is not duplicative of other activities. The ARAC members expressed support for the concept, made a motion to approve it, and voted in favor.
Carl W. Dieffenbach, Ph.D.
The objective of this concept is to evaluate the impact of large-scale prevention and treatment programs that target specific health concerns in resource-limited countries and to develop more efficient and effective methodologies for implementing and integrating the programs with primary health care. The concept addresses the gap between our scientific knowledge base and a public health impact, including prevention, treatment, and services. It will seek to design, test, and deliver interventions efficiently and effectively and will support informed choices. While NIAID will take a lead role, other NIH institutes will be involved. This is a new grant competition, using the R01 mechanism. The duration will be up to 3 years, and the first-year cost is $10 million with funds being provided by the State Department.
The ARAC reviewers suggested identifying high priority areas on which the program can focus. They also proposed a 2-tiered funding mechanism, with lower amounts used to fund data analysis projects and higher amounts used to fund in-country, on-site activities. Examples of possible priority areas are optimal interventions, comparative effectiveness evaluation, point-of-care evaluation, and benefits of antiretroviral therapy. Dr. Dieffenbach noted that the program will require collaboration between the PEPFAR sites and other experts in implementation science. In discussion it was pointed out that there will be great interest in the program among many potential partners, which will make focus and coordination with other federal agencies and organizations critical. The ARAC members expressed support for the concept, made a motion to approve it, and voted in favor.
Chris Lambros, Ph.D.
The SBIR program seeks to stimulate technological innovation in the private sector, strengthen the role of small business in meeting federal research and development and increase private-sector commercialization of innovations developed through federal work.
This is a new program using the SBIR contract mechanism (N01). The duration is 6–12 months for Phase I and up to 3 years for Phase II. The first year costs are $250,000 for Phase I and $750,000 for Phase II. Phase I is to determine the feasibility and potential for commercialization of the proposed research, while Phase II is to continue major research and development efforts from Phase I. Phase III involves finding a commercial partner, with non-SBIR funds, to pursue the commercialization of the results of the research and development efforts funded in Phases I and II. The SBIR contract program project officer works with the company to prepare a statement of work, which is milestone driven.
The NIAID proposed three topics for the program: (1) Aminoglycosides: Formulation for Oral Delivery; (2) High Throughput in Vitro Immunization System for Evaluating Human B-Cell Immune Responses to HIV-1 Vaccine Antigens; and (3) In Vitro Immunization System for Evaluating Human T-Cell Immune Responses to HIV-1 Vaccine Antigens. Proposals related to those topics are now in the award phase for Phase I projects. (No proposals for the 3rd topic were submitted.) Three proposals were submitted for topic 1 and all three were found technically acceptable. One proposal was submitted for topic 2 and was found technically unacceptable. No proposals were submitted for topic 3. The three proposals submitted for topic 1 are under consideration for selection for Phase I awards.
Dr. Dieffenbach asked the ARAC members to consider the viability of the program and to suggest topics for next year’s awards. Suggestions included studies of new TB and malaria drugs, point-of-contact diagnostics, focus on global health needs, and studies of oral formulations for drug delivery. In response to a question, it was noted that applications are reviewed by a formal study section assembled by the scientific review officer within NIAID. The selection of reviewers is based on the specific scientific topic being addressed and the expertise that's required to evaluate it. During the discussion a suggestion was made to examine the outcomes of the SBIR grants that DAIDS has supported. The ARAC members expressed support for continuing the program/concept, made a motion to approve it, and voted in favor (with one abstention).
This concept has an objective of facilitating HIV/AIDS research by providing standardized reagents, technology, and other research resources to investigators around the world. It is a renewal and uses the N01 contract mechanism. The duration is 7 years, and the first-year cost is between $2 million and $3.2 million. Begun in 1988, the program has evolved to become a state-of-the-art online resource of reagents for research on HIV and related opportunistic agents. It currently features 8,643 unique reagents that are made available to investigators. The scope is broad, including cell lines, viruses, monoclonal and polyclonal antibodies, recombinant proteins, and more. The program also examines the scientific field, anticipates needed reagents, and verifies new procedures and protocols. More than 3,046 scientists use the materials today, mainly in academic research. About 14,000 reagents were distributed in 2009.
In response to the ARAC reviewers question about international use, it was noted that about one-quarter of the reagents are used in foreign labs. Nonetheless, efforts to broaden the international reach through Web site links and exposure at international conferences will continue.
Reviewers also suggested that the program consider expansion to include reagents related to Hepatitis B and Hepatitis C. In fact, this was done several years ago and that component of the contract was then transferred to another contract. However, to address the need for coordination between these two contracts, a prominent link was added to the front page of the AIDS Reagent Web site and users of either can make requests for additional reagents to be added to that collection of reagents. Another suggestion was that NIAID consider adding reagents that would facilitate the study of latency and persistence of HIV.
The ARAC members expressed a strong degree of support for this program overall based on previous experience and knowledge. They supported the concept for the program’s continuation, made a motion to approve it, and voted in favor.
Sandra Bridges, Ph.D.
This concept has the objective of developing functional cure strategies that would allow HIV-infected persons to live free of antiretroviral drugs for extended periods. It will support multi-project applications for the development of innovative therapeutic approaches to improve on current HIV treatment methodologies that require lifetime commitment to combination drug therapy. It is a new initiative, and uses the PO1 mechanism. The duration of grants will be up to 5 years, and the first year cost is $5 million (total). There will be two or three awards, and each application would be required to include a private-sector partner.
The existence of HIV-infected individuals who can effectively suppress virus replication (elite controllers) suggests that a functional mechanism to stop HIV is possible. This concept is designed to support research efforts in gene therapy, therapeutic vaccines, stem cell strategies, antibodies, and more. The ARAC reviewers characterized the concept as important, solid, and timely. It was noted that the program will be open to applications with two or more projects and multiple institutions/organizations, and the inclusion of a private-sector partner will help to translate the research. While the rationale for requiring a private-sector was questioned, DAIDS staff noted that, based on experience, the projects are stronger when a private-sector partner is involved and both partners – academic and private-sector – report benefits from the collaboration. Another question concerned intellectual property issues, and while those are matters between the project partners, it is highly recommended that they be dealt with early on. The ARAC members expressed support for the concept, made a motion to approve it, and voted.
Dr. Dieffenbach asked the ARAC members to consider the agenda for the September ARAC meeting. Two possible topics are:
The meeting of the Council was adjourned at 4:20 p.m., on Monday, May 24, 2010.
We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
Anthony S. Fauci, M.D.
Chair, National Advisory Allergy and Infectious Diseases Council
Director, National Institute of Allergy and Infectious Diseases
Marvin R. Kalt, Ph.D.
National Advisory Allergy and Infectious Diseases Council
Director, Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Anthony S. Fauci, M.D.
Chair, National Advisory Allergy and Infectious Diseases Council
Director, National Institute of Allergy and Infectious Diseases
Marvin R. Kalt, Ph.D.
National Advisory Allergy and Infectious Diseases Council
Director, Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
These minutes will be formally considered by the Council at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.
Last Updated August 05, 2013
Last Reviewed August 05, 2013