The National Cancer Institute (NCI) has announced major changes to be made in the long-established Clinical Trials Cooperative Group Program that conducts many of the nationwide trials of new cancer therapies. In a major transformation, NCI intends to consolidate the nine groups that currently conduct trials in adult cancer patients into four state-of-the-art entities that will design and perform improved trials of cancer therapies. These changes are designed to provide greater benefits for cancer patients and more information for researchers. These moves come in response to an NCI-requested April 2010 report from the Institute of Medicine (IOM), which called for a series of changes to the cooperative groups program, including restructuring.
“Clinical trials are at the heart of cancer care and treatment, and NCI is dedicated to making sure they are as effective as they can be, In the last decade, our knowledge of genetic and epigenetic changes that drive the initiation and progression of cancers has increased exponentially. Consequently we must assess and improve the methods by which NCI evaluates new therapies that take advantage of our new understanding of many kinds of cancers.” ” said Harold E. Varmus, M.D., NCI director.
The April IOM report noted that the current trials system is inefficient, cumbersome, underfunded, and overly complex. The report recommended consolidating existing adult cooperative groups into a smaller number of groups that could function in a more closely integrated manner.
The NCI Cooperative Group program, founded over 50 years ago, involves more than 3,100 institutions and 14,000 investigators, and the program enrolls over 25,000 patients in clinical trials each year. Four pediatric groups were consolidated into one group a number of years ago, and that sole pediatric group will not be consolidated with other groups.
“The practice of oncology has changed significantly with the development of molecular oncology, therefore we need a modern system with modern trials that will maximally utilize the molecular characteristics of a patient’s tumor and guide us to the best possible treatment for that patient, This evolution in our understanding of cancer will lead to an evolution in the design and implementation of clinical trials.” said James H. Doroshow, M.D., director, NCI Division of Cancer Treatment and Diagnosis.
For the past several decades, clinical cancer trials have used one or a combination of drugs or other treatment modalities, such as surgery or radiation, in comparison to the prevailing standard of care to see if the new treatment was superior. Recently, some trials have begun to depend on the genetic profiling of tumors. For example, one ongoing NCI-sponsored breast cancer study, called TAILORx, is examining whether genes that are frequently associated with risk of recurrence for women with early-stage breast cancer can be used to assign patients to more appropriate and effective treatments.
These types of studies necessitate the screening of large numbers of patients in order to find subsets of patients with tumors that demonstrate changes in specific genetic pathways. These trials therefore require acquisition and distribution of many tumor specimens, DNA sequencing, and the matching of genetic information with treatment options. The increased complexity of these trials provides a rationale for modernization and simplification of the current cooperative group structure.
Consolidation is intended to improve the efficiencies of operations centers, data management centers, and tumor banks, and the changes will take into consideration an assessment of all currently active cooperative groups. The current groups will also be given opportunities to comment on the proposed changes and to explore specific aspects of the reorganization plans in consultation with NCI leadership.
While consolidation of specific groups proceeds, other generalized efficiencies are already being planned, such as shortening the time required to initiate new clinical trials. Historically, when a new study was proposed, the concept had to be submitted for approval in a process that took as long as several years. Furthermore, if this review was not completed within two years after concept approval, a trial was very unlikely to reach its ultimate recruitment goals, in part because the scientific questions underpinning the concept could be overtaken by new developments.
On Jan. 1, 2011, NCI will impose new deadlines, formulated by its Operational Efficiency Working Group, which will reduce by half the time to initiate new clinical studies and will terminate studies not begun within two years of concept approval.
NCI has also been working to increase efficiency in several other ways, including:
Decreasing the average time for final sign-off and approval on protocols for national trials by its centralized institutional review board from 150 days in 2007, to 42 days in 2010
Prioritizing a revamped review process, which will include advocates and professionals at cancer centers, with new emphasis on disease-specific and modality-specific oversight, such as imaging or cancer control
Modernizing information technology so that a single system can collect standardized clinical trial data, such as patient information and outcomes