DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH 5th Regular Meeting Minutes of Meeting
NATIONAL CANCER INSTITUTE
BOARD OF SCIENTIFIC ADVISORS
June 19, 1997
Building 31C, Conference Room 10
Bethesda, Maryland
The Board of Scientific Advisors (BSA), National Cancer Institute (NCI), convened for its 5th regular meeting at 8:00 a.m. on Thursday, June 19, 1997, in Conference Room 10, Building 31C, National Institutes of Health (NIH), Bethesda, MD. Dr. David Livingston, Professor of Medicine, Dana-Farber Cancer Institute, presided as Chair.
The meeting was open to the public from 8:00 a.m. until adjournment at 6:10 p.m. on Thursday, 19 June, for introductory remarks from the Chair; discussion of procedural matters and future meeting dates; ongoing and new business; presentations and discussions on the present status of paylines, the Prevention Program Review Report; Requests for Applications (RFAs) concepts, enhancing the Division of Cancer Biology (DCB) interactions with the scientific community, and proposed modifications of NIH review award policies.
BSA members present:
BSA members absent:
NCAB lisison:
Ms. Zora Brown, (absent)
Others present included: Members of NCI's Executive Committee (EC), NCI Staff, Members of the Extramural Community, and Press Representatives.
Call to Order and Opening Remarks - Dr. David Livingston
Consideration of March Meeting Minutes - Dr. David Livingston
Report of the Director, NCI - Dr. Richard Klausner
Congressional Update - Ms. Dorothy Tisevich
Ongoing and New Business - Dr. David Livingston
Present Status of Paylines - Mr. Stephen Hazen
Prevention Program Review Report - Dr. Edward Bresnick
RFA Concepts - Presented by NCI Program Staff
Division of Cancer Prevention and Control: Cancer Research Networks Across Health Care Systems (Cooperative Agreement) - Dr. Martin Brown
Division of Cancer Prevention and Control & Division of Cancer Treatment, Diagnosis, and Centers: Long-Term Survivors Research Initiatives (RFA) - Dr. Claudette Varricchio
Division of Cancer Epidemiology and Genetics: Informatics Support for Breast and Colon Cancer Cooperative Family Registries (RFA/Cooperative Agreement) - Dr. Iris Obrams
Enhancing Division of Cancer Biology Interactions With the Scientific Community - Dr. Faye Austin
Proposed Modifications of NIH Review Award Policies - Dr. Marvin Kalt
CALL TO ORDER AND OPENING REMARKS - DR. DAVID LIVINGSTON
Dr. Livingston discussed upcoming BSA meeting dates, noting a potential conflict with the meeting of the European Organization for Research on the Treatment of Cancer (EORTC) in June 1998. The extent of the conflict will be determined.
CONSIDERATION OF MARCH MEETING MINUTES - DR. LIVINGSTON
The minutes of the March 3-4, 1997, BSA meeting were approved.
REPORT OF THE DIRECTOR, NCI - DR. RICHARD KLAUSNER
Dr. Richard Klausner discussed aspects of the FY97 budget, progress in the development of the FY98 budget, and highlights in the Intramural Program.
Research Project Grants (RPG) Pool: Dr. Klausner stated that the paylines for R01s and R29s (FIRST Awards) were raised to the 23rd and 30th percentile, respectively, and the priority score for program project grants (P01s) was raised to 140, representing increases from those projected in the initial funding guidelines. A fraction of the RPG dollars will be used to fund investigator-initiated research through facilitating approaches such as: 1) exception funding (including Accelerated Executive Review [AER]), 2) supplements, and 3) internal funding and bridging mechanisms. In FY97, the success rate for grants reviewed through the AER mechanism is projected at 55 percent, up from 50 percent in FY96. Currently, about 10 percent of NCI dollars support grants received in response to RFAs. This year that percentage will decrease to 6 percent for new and competing RFAs.
Cooperative Groups: Cooperative groups were provided a cost of living increase and some restoration of funds based upon the recommended levels of funding. In addition to the base funding, about $5.2M has been allocated to support tissue banks and the infrastructure associated with translational and correlative studies. An additional amount has been made available to help defray the costs of enhancing accrual to clinical trials through the agreements with the Veterans Administration (VA) and the Department of Defense (DoD). This money is also earmarked to support the electronics informatics infrastructure, in particular, to develop the capability for online clinical trials reporting to the NCI. A presentation is planned for a future BSA meeting on the National Cancer Informatics Infrastructure and the Scientific Information System.
Training: Pending final decision, the NCI projects that approximately seven awards will be made from an outstanding pool of applicants for the new Howard Temin Award for young investigators. Recently approved training initiatives include the AIDS Oncology Clinical Scientist Development Program and the NCI Scholars Program. The Division of Cancer Epidemiology and Genetics (DCEG) advertised a Program Announcement (PA) to stimulate the development of comprehensive research training programs in the genetic epidemiology of cancer.
Cancer Survivorship Initiative: A request for competitive supplements has been released to identify potential cohorts of cancer survivors in which research studies can be performed. Letters advertising the initiative were addressed to cooperative groups; the Community Clinical Oncology Program (CCOP) research base; Surveillance, Epidemiology, and End Results (SEER) Program contractors; and any other group that has access to cohorts of long-term cancer survivors. A set-aside of $2M is expected to fund up to 15 applications.
Department of Defense (DoD) Clinical Trials Agreement: The NCI/DoD Clinical Trials Agreement has completed its first year. To increase participation in sponsored and covered trials, the NCI and DoD have undertaken an extensive joint promotional campaign to inform the active-duty military community and the Civilian Health and Medical Plan of the Uniformed Services (CHAMPUS) beneficiaries of the agreement. Negotiations are under way to expand the agreement to include Phase I trials and a broad range of prevention and diagnostics trials. The NCI is also participating in meetings with the new TRICARE/CHAMPUS managed care contractors to ensure that the clinical trials option is a well-known and well-advertised part of the benefits package.
Veterans Administration (VA) Clinical Trials Agreement: Extensive changes in the VA medical system have resulted in the formation of the Veterans Integrated Service Networks (VISNs) for the administration and delivery of medical care. The NCI has been working with the VA to ensure continuation of the longstanding collaborations between the VA, cancer centers and cooperative groups. Discussions with VISN directors have been held to ensure that the regional health delivery system, as it undergoes reorganization, includes strong support for clinical research and a specific commitment to the joint NCI/VA clinical trials.
FY98 Budget: Dr. Klausner reported on multiple visits by the NIH leadership to Capitol Hill for the NIH FY98 appropriations hearings in both houses and to discuss how NIH sets priorities. A booklet about priority setting and decision-making at the NIH is being prepared by the Institutes for distribution to the advisory boards.
Dr. Klausner stated that the status of the NIH budget is not known. Although major increases for both the NCI and NIH have received much support in both houses, the balanced budget amendment creates uncertainty about the amount of money available to the Appropriation Subcommittee from which the NIH budget will be decided.
ByPass Budget: The latest Bypass Budget, which will be distributed when completed, supports the need for increased funding. Changes include the reevaluation of extraordinary opportunities on a 3-year cycle and expansion from two to three sections. The new section describes a 4-year plan to deal with the overarching infrastructures of discovery, clinical research, new epidemiologic bases, repositories, and training. As a planning document, the Bypass Budget has led to the establishment of Working Groups associated with each of the first four opportunities - Cancer Genetics, Preclinical Models, Developmental Diagnostics, and Detection Technologies. The Cancer Genome Anatomy Project and Tumor Gene Index are successful initiatives that were based on recommendations of the Developmental Diagnostics Working Group.
Intramural Research Program (IRP): Dr. Klausner reported that the IRP continues to build and recruit even as its budget is decreasing, through the development of cost management principles and a rigorous review process. This year's focus has been on the integration of research programs within and across the three intramural divisions. Competitive grants, such as the Intramural Research and Advanced Technology Awards, have been instituted to fund collaborative intramural projects. The Advanced Technology Center was established to serve as a center for the development and exportation of technologies. The DCEG has taken the lead in integrating intramural projects relating to molecular epidemiology. A search has been initiated for a permanent director of the Division of Basic Sciences (DBS). Dr. Klausner concluded with an overview of important scientific discoveries by IRP investigators.
NCI AND THE CONGRESS - MS. DOROTHY TISEVICH
Ms. Dorothy Tisevich, Director, Office of Legislation and Congressional Activities (OLCA), gave a brief summary of the many recent hearings before the House and Senate Committees. In addition to appropriations, a major focus was biomedical research priorities and resource allocation issues.
Ms. Tisevich then presented an overview of the progress of the more than 100 bills being tracked by the OLCA in categories of particular interest to the BSA. BSA members were invited to provide suggestions of additional or alternative categories of legislation that they would like to have included in future updates.
ONGOING AND NEW BUSINESS - Dr. David Livingston
BSA members and NCI staff reported on the "NCI Listens" sessions held at the national meetings of five professional societies.
American Society of Hematology (ASH)- Dr. Frederick Appelbaum reported that the major concerns of attendees were the difficulty of carrying out clinical research in the current private care environment and the limited access of minority patients to research trials. Other comments dealt with NCI support for educational programs, the difficulty in preparing and supporting individuals who are attempting to work between the laboratory and the clinic, and the difficulty cooperative groups have in connecting with pharmaceutical companies and contract research organizations because of cumbersome mechanisms.
American Society of Preventive Oncology (ASPO) - Dr. Virginia Ernster stated that discussion at the ASPO session focused on suggestions for improving the grant review process in general and the areas of epidemiology and cancer prevention and control in particular. Specific suggestions will be forwarded to the Division of Research Grants (DRG) for consideration as the peer review system is being revised. Other comments related to the need for support in the Cancer Center Support Grants (CCSGs) for shared resources such as a behavioral measurement resource or a molecular epidemiology laboratory; the need for NCI-supported mechanisms for training young investigators interested in preventive oncology; and the need to keep the field of preventive oncology strong at the cancer centers. This initial "NCI Listens" session was well received and productive, and the NCI was encouraged to continue these sessions on an annual basis.
American Association for Cancer Research (AACR) - Dr. John Minna reported that the AACR session was a well-attended and productive meeting. A major concern of the membership was the perception that NCI and NIH leaders believe that a 35 percent success rate would be adequate if the NCI budget were to be doubled. Other important issues included a concern about the grant review process, the perceived barrier between the intramural and extramural communities, and the need for access to informatics.
PRESENT STATUS OF PAYLINES - MR. STEPHEN HAZEN
Mr. Stephen Hazen, Chief, Extramural Financial Data Branch (EFDB), stated that the NCI has improved the paylines for RPGs funded within the budget: (1) traditional investigator-initiated grants (R01s) will be funded through the 23rd percentile; (2) program project grants (P01s) at the priority score of 140; and (3) FIRST Awards (R29) through the 30th percentile. In a new ruling, core grants (CCSGs) will be funded to recommended levels for priority scores up to 197 and on a sliding scale up to 212. Paylines will remain the same for clinical groups, fellowships, and institutional training awards.
PREVENTION PROGRAM REVIEW REPORT - DR. EDWARD BRESNICK
The Prevention Program Review Group (PPRG) Chair, Dr. Edward Bresnick, Vice Chancellor for Research, University of Massachusetts Medical Center, informed members that the key message of the PPRG Report is that discovery-driven cancer prevention research must be a key component in the National Cancer Program and must be appropriately funded. Prevention was defined as the development and evaluation of strategies for reducing cancer incidence aimed at preventing the initiation of the neoplastic process or at avoiding progression to malignancy of already initiated cells. The PPRG limited its focus to prevention, with the proviso that close interaction exist between prevention and control research regardless of the final organizational structure.
Dr. Bresnick summarized the basic recommendations made in the areas of modifiable risk factors, animal models and extrapolation to human cancer prevention, genetic predisposition to cancer and detection of precursor lesions, chemoprevention trials in human populations, behavioral research and behavioral intervention trials in cancer prevention, training of health professionals with expertise in prevention research, and organization and infrastructure of the NCI Prevention Division. The recommendations called for establishing subcommittees of the BSA: a Cancer Prevention Advisory Board, but supplemented by other experts, and a Cancer Prevention Clinical Trials Group patterned after the Oncology Therapy Trials Groups.
In response to questions from Board members, the following points were made:
BSA WORKING LUNCH
The Board of Scientific Advisors lunch period was devoted to a consideration of opportunities and issues of interest to the Board as representatives of the extramural community acting in an advisory capacity to the leadership of the NCI. One topic suggested for discussion by several members was the review of NCI R01grants by the Division of Research Grants (DRG), National Institutes of Health (NIH). Another issue suggested was a discussion of clinical data monitoring committee procedures and the consequences of the 5-year old rule change.
NCI R01 Grant Review Concept
The Chair, Dr. Livingston, presented a draft concept entitled "Revised Method for Reviewing NCI R01 Grants". In framing the discussion, he summarized the steps in and problems with the process as currently executed in the DRG, NIH. The concept proposed: (1) that the system for organizing the study section be changed as it relates to cancer grants to specify study sections for NCI grants composed primarily or solely of cancer research scientists; (2) that cancer grants be segmented on the basis of generic categories, such as basic science, clinical investigation, or population science, with corresponding study sections; (3) that a process be developed whereby the Institute and the DRG share the responsibility for the study section appointments; and (4) that investigators receiving a higher than average amount of R01 or P01 support be requested to serve for a fraction of time on study sections, during the time they are exceptionally well funded.
A discussion of the topic resulted in the following points:
In concluding the consideration of this topic, there was disagreement on how far members wanted to go towards implementing the proposed concept, but there was support to work with DRG to see improved quality reviews. Dr. Livingston noted that the results of the discussion would be forwarded to Drs. Klausner and Rabson for reply. Any proposals would involve the BSA.
Clinical Data Monitoring Committee Procedures
The consequences of the 5-year-old rule change for clinical data monitoring committees for clinical cooperative groups was discussed. It was noted that anyone directly involved with designing or performing a trial cannot receive any information about the results of that trial. Consequently, investigators have no access to accrual information that would influence the design of subsequent trials. Attempts to change the situation have not been successful. The only recourse at present is to have the cooperative group's petition the data monitoring committee for permission to look at the data after accrual has been completed, and most of the treatment was given. The response time for such requests is considerable and tends to slow the process. BSA members from the clinical cooperative groups discussed their experience with the procedures.
Subsequent discussion resulted in the following points:
Discussion on this topic will continue at the fall BSA meeting. In the interim, a committee,
Drs. William C. Wood (Chair), Frederick Appelbaum, Sharon Murphy, and Ms. Amy Langer, was asked to propose a set of rules for consideration by the Board together with, but not limited to, Drs. Klausner, Rabson, and Wittes. A representative from the data safety monitoring community should also be invited.
RFA CONCEPTS: PRESENTED BY NCI PROGRAM STAFF
Cancer Research Networks (CRN) Across Health Care Systems (Cooperative Agreement) - Dr. Martin Brown, Applied Research Branch, Cancer Control Research Program (CCRP), Division of Cancer Prevention and Control (DCPC), informed the Board that the research goals of the revised concept are to support translational research on cancer prevention control in large and diverse populations. Changes from the original concept include: 1) a focus on research goals; 2) broader criteria; 3) an emphasis on collaboration between researchers at academic medical centers and health care provider organizations; and 4) only one round of applications.
The cooperative agreement mechanism was chosen to facilitate coordination of complementary research resources and data systems across health care systems, which is necessary for research requiring large and diverse population-based data and interdisciplinary research methods. A budget of $4M is proposed for the first year, and $16.5M is the anticipated cost for the project period. One or two awards are anticipated. Renewal of this one-time solicitation would be contingent on successful performance in the first round.
In the discussion of the concept, the following points were made:
Motion: A motion was made to approve the concept with the recommendation that informed consent be addressed in the final cooperative agreement. The motion was seconded and approved, with 14 for, 8 opposed, and 2 abstentions.
Long-Term Survivors: Research Initiatives (RFA) - Dr. Claudette Varricchio, Program Director, Community Oncology and Rehabilitation Branch (CORB), stated that the concept originated from the NCI Office of Cancer Survivorship (OCS) in collaboration with representatives from DCPC, Division of Cancer Treatment, Diagnosis, and Centers (DCTDC), and Division of Cancer Epidemiology and Genetics (DCEG). The purpose of the Cancer Survivorship RFA is to support research leading to a decrease in the physiologic and psychologic morbidity associated with long-term survival. Modifications to the original concept include: 1) the requirement for a multidisciplinary approach to the topic; 2) multiple endpoints; 3) collaboration across the NCI; 4) a detailed portfolio analysis; and 5) increased funding. Specific areas of interest to NCI Divisions will be delineated in the RFA as suggestions only.
The proposed budget is $3M per year for the 5 year project period. The award mechanisms will be the R01, R29, and R03 (small grants). Investigators will select the mechanism most appropriate for the type and scope of research proposed. Totals for each mechanism will not be specified to permit the funding of the best grants over the total pool of applications.
In response to questions from Board members, the following points were made:
Motion: A motion was made to approve the concept as presented. The motion was seconded and unanimously approved.
Informatics Support for Breast and Colon Cancer Cooperative Family Registries (RFA/Cooperative Agreement) - Dr. Iris Obrams, Chief, Extramural Epidemiology and Genetics Program, DCEG, described the organization and progress to date of the Cooperative Family Registry for Breast Cancer Studies (CFRBCS) that is operating at seven sites in the United States, Canada, and Australia. Similar to the CFRBCS and due to its successful implementation, the DCEG is now funding six sites for a Cooperative Family Registry for Colon Cancer Studies (CFRCCS), for a total of 13 sites for both registries. Dr. Obrams explained that the proposed concept was developed in response to an urgent need to provide for coordination of the central database for the Breast Cancer Registry now and for the Colon Cancer Registry in the future.
Information management functions of the proposed informatics center will include: 1) coordinating activities, 2) providing data and updates to the NCI, 3) conducting cross-site analyses, and 4) developing novel methods for capturing diverse types of necessary data such as family pedigrees. The informatics center will coordinate the provision of data and specimens to registry investigators and those outside investigators whose proposals are approved by the advisory committee and supported by the steering committees of the registries. The center will also be asked to work on the development of informatics in support of novel initiatives proposed by the registries that could be translated to the other NCI family initiatives. The NCI and DCEG will provide coordination and linkage between these activities, scrutinize confidentiality safeguards, and ensure implementation of the center with the least disruption of registry activities.
This proposed budget is $850K for year 01. A total cost of $4.6M is needed to support one group to develop the informatics infrastructure.
In response to questions, the following points were made:
Motion: The motion was made to approve the concept for an informatics support RFA. The motion was seconded and approved, with 17 in favor, 1 opposed, and 6 abstentions.Dr. David Livingston called to order the 5th regular meeting of the Board of Scientific Advisors (BSA) and welcomed members of the Board, National Institutes of Health (NIH) and National Cancer Institute (NCI) staff, guests, and members of the public.
Division of Cancer Treatment, Diagnosis, and Centers