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:

• Health care provider organizations represent a large potential resource for information that should be developed, and this concept is a step in that direction. The 25 organizations that have a research component will be particularly useful for cancer prevention now and cancer treatment research in the future. These organizations are good settings for risk studies, studies of behavioral change in large populations, studies of secondary prevention, and genetic testing because of the large denominator of patients and good databases.

• One concern expressed in the previous presentation of this concept was a turnover rate that may be too high for longitudinal follow-up of patients. However, the high turnover has been seen mainly among young people. Research expertise is lacking in all but a few of the health care provider organizations, and a clinical research environment has not evolved throughout these organizations as it exists in academic medical centers.

• The proposed budget may be insuffiicient to fund the research and an infrastructure comprising networks of research units and covering several million people.

• When asked to clarify whether the funding was intended largely for putting the network together and/or the conduct of the research, staff explained that a balance of both components is expected.

• In response to the concern that the solicitation would be, in effect, a sole-source contract because of the limited number of organizations that could respond, staff stated that the eligibility criteria had been broadened to address institutional diversity.

• When asked about the anticipated number of awards and the pools from which the ad hoc review committee would be drawn, staff explained that both would be contingent on the applications that are received.

• A Board discussion of the overarching issue of infrastructure development and informatics is needed because both are a part of every RFA concept proposal. Questions that require clarification are: (1) how the cancer research networks can span health care systems if only one award results from the solicitation; (2) how the aim of common database development would be accomplished; (3) whether the time is adequate for preparation of outstanding one-time submissions that would bring forth a good pool of applicants; and 4) what the guidelines would be for review of both the infrastructure and the research.

• The cooperative agreement mechanism is justified because of the public nature of medical research and the research proactivity that could result from such a collaboration.

• When asked for clarification as to whether cancer center involvement in network development would be required, staff explained that the RFA would be written such that during the review process a high value would be placed on appropriate collaborations with academic medical center researchers, including cancer centers.

• When queried whether other organizations are interested in the research capabilities of health care provider organizations, staff stated that multiple groups are moving toward collaboration, but that the availability of funding is a key component. Plans are to provide support to actually undertake research and build an infrastructure.

• The issue of informed consent should be addressed when the full text RFA is written.

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:

• Funding either too few large grants or too many small projects with insufficient budgets to make an impact should be avoided. Corrective suggestions included: (1) de-emphasizing funding projects concerned with the cost of medical care delivery as it affects survivorship; and (2) adding language in the RFA to encourage the submission of projects that educate survivors about the resources currently available to them.

• One member commented that the change from encouraging to requiring a multidisciplinary approach essentially excludes single discipline projects that might answer specific and important questions. It was noted also that the RFA should address the cooperative groups' need for a small amount of money that would enable them to maintain contact with long-term survivors of controlled clinical trials as a worthwhile investment for future research.

• When queried about opportunities for investigators to share methodologies and findings, staff explained that all RFAs are written with the requirement that applicants include in their applications funds for an annual trip to Bethesda to meet with NCI staff and other investigators funded on the same RFA.

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:

• The definition of informatics, as used in this concept, should be clarified to avoid potential problems in implementation. Specific questions that should be addressed in writing the RFA include: 1) Is the RFA intended primarily for algorithm and software development? If so, it must be sufficiently generic and hardware and platform-independent to satisfy the requirements for NIH-funded proposals. 2) To what extent will the successful institution and their informatics development interact with some of the initiatives that are being funded? 3) What will be the accessibility of the databases? and 4) Will the other applicants be encouraged to participate and contribute data from their registries that were not funded under this RFA? Staff responded that data standardization has been a large part of the work of the past 2 years and that a core to make data at all sites accessible is needed.

• When queried about peer review, staff explained that applications will be reviewed by an ad hoc committee convened by the Division of Extramural Activities (DEA). DCEG will not limit the ability to apply only to registry sites. Other potential applicants will receive the information needed to develop an application.

• In response to questions concerning overlap or redundancy between this initiative and the recently approved cancer genetics network, staff explained that the two are parallel and complementary efforts. The target populations and the research questions are different.

• One member expressed concern that obtaining this service through the RFA would be too slow to be useful and too costly and suggested contracting for it. Staff responded that DCEG plans to work with the registries to begin the effort within the registry system, with the help of supplemental funding. The option of contracting out an informatics support center was considered and rejected because of the difficulty of specifying in detail what the deliverables would be at this stage of development and because of the cost compared with universities and other organizations that apply.

• The RFA should have a clear statement of deliverables. An effort should be made to coordinate work on this informatics infrastructure with that of other registries and networks to identify areas of commonality that can be carried over from one project to another.

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.