NCI Plans Major Restructuring of Clinical Trials Program

BETHESDA, Md—The National Cancer Institute plans a major restructuring of its clinical trials program, intended to broaden participation by physicians and patients and shorten the time between the initial idea for a treatment study and its conclusion.

The plan calls for a new review method to assess proposals for large clinical trials, an “open menu” of large studies to increase patient access and accrual, and the consolidation and streamlining of many administrative functions. It ultimately envisions a national network of investigators and physicians to carry out NCI-sponsored clinical research “that can function without artificial boundaries, enrolling patients in high-quality trials wherever they may be and regardless of coordinating site.”

Two anticipated results of this restructuring will be more competitive research proposals and a diminished role for the nation’s 12 cancer clinical trials cooperative groups.

The changes are outlined in a report from NCI’s Clinical Trials Implementation Committee, co-chaired by John H. Glick, MD, of the University of Pennsylvania Cancer Center, and Michaele C. Christian, MD, from NCI’s Division of Cancer Treatment and Diagnosis.

NCI will phase in the restructuring, beginning with pilot programs in the areas of genitourinary cancers and lung cancer. “It’s very complicated,” NCI director Richard D. Klausner, MD, told the National Cancer Advisory Board. “I keep saying, this is not going to happen overnight.”

The committee, whose 27 members were selected from within and outside the Institute, included representatives from the cooperative groups, cancer centers, professional societies, and patient advocacy organizations.

The committee identified a number of objectives for the clinical trials program, Dr. Christian told NCAB members. These include ensuring that the best science is incorporated into large clinical trials, increasing the speed of implementing studies, substantially increasing accrual, decreasing complexity, and providing fair compensation to cover the costs of trials. This framework led to a number of key committee recommendations related to large phase III clinical trials:

State-of-the-Science Meetings: These regularly scheduled national forums will seek to identify research opportunities and gaps in research in specific disease areas. This process is currently done within NCI, with outside participation largely confined to investigators from the relevant cooperative research groups.

Participants in the new system will be broadly representative of the cancer research effort and will include basic and clinical scientists, industry representatives, patients, and advocacy groups. Results from the discussions will be circulated widely within the research community and made readily available to clinical investigators and the public.

Idea Generators: This bureaucratic designation simply means investigators who propose phase III trials. The point of the new system is to cast as broad a net as possible for these individuals, instead of relying primarily on researchers working in the clinical trials cooperative groups. While these groups will remain an important source of ideas, NCI envisions a greatly increased number of phase III trial proposals coming from cancer centers, community oncology practices, and the pharmaceutical industry.

“The idea of broadening this pool is obviously designed to stimulate development and competition of the best ideas,” Dr. Christian said. “Concepts for phase III trials will be accepted from all interested investigators, irrespective of affiliation.” NCI staff will work to put investigators who don’t have access to the resources necessary to carry out the analysis of large trials together with “funded statistical centers in order to facilitate the conduct of these clinical trials,” she added.

Concept Review Committees: These broad-based, disease-specific groups will review every proposal to NCI for a phase III trial, replacing the current system of review within NCI. Committee members will include clinical and basic scientists, statisticians, and patient advocates, with one-third of the members coming from NCI, another one-third from cancer centers, and the rest from a variety of sources.

Once a clinical trial proposal wins approval, the study team will receive funds to speed up protocol development and administration, and the team, led by the idea generator, will conduct the study, analyze the data, and publish the study results.

Cancer Trials Support Units: These groups will perform two key functions. First, they will consolidate duplicative administrative functions, including protocol registrations, data transfer from investigators to statistical centers, and some education and training activities. Second, they will serve as a single source for physicians “who wish to enroll patients in trials across this cooperative system, rather than interacting with one or two or four additional cooperative groups,” Dr. Christian said.

National Network: Once a concept is approved, it will be developed into a protocol that will be open to a national Network of physicians, including members and nonmembers of cooperative groups. All qualified participants in the Network will have access to all trials of the Network. (The Network will be piloted by cooperative group members initially, with non-group-members phased in over time.)

New Informatics: A common infor-matics system will link investigators with the Cancer Trials Support Units, facilitating all aspects of protocol generation and trial conduct. The system will include common forms, uniform interfaces with trial participants, common data elements, and electronic interfaces between data centers and sponsors for easy reporting.