National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
December 14, 2010 • Volume 7 / Number 24

A Conversation With

A Conversation with Dr. James Doroshow about NCI’s Clinical Trials Cooperative Group Program

Dr. James H. Doroshow Dr. James H. Doroshow

At NCI’s request, the Institute of Medicine (IOM) conducted a review of the NCI Clinical Trials Cooperative Group Program. The IOM was asked to gather independent, expert perspectives on the state of cancer clinical trials in the United States. In April 2010, the IOM issued its report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program, which recommended that the program be restructured and its funding increased to overcome shortcomings due to inefficient, cumbersome, underfunded, and overly complex systems. The authors of the report also commended the changes NCI has made to the Cooperative Groups in recent years, including changes to the Cancer Trials Support Unit (CTSU), enhancements to the Central Institutional Review Board (CIRB), and implementation of disease-specific steering committees. The authors concluded, however, that the system requires a major transformation that can only be accomplished by consolidating the existing adult groups into a smaller number of groups that would function in a more closely integrated manner. In this short interview, Dr. James H. Doroshow, director of NCI’s Division of Cancer Treatment and Diagnosis, addresses that recommendation.

Why does the Cooperative Group Program need reinvigorating?

The practice of oncology has evolved significantly with the development of research focused on the molecular and chemical bases of malignant transformation, including assessments of specific processes related to cancer cells, genetic changes, and drug and hormonal responses and resistance. The evolution in our understanding of cancer also requires an evolution in the design and conduct of clinical trials.

Screenshot of Transforming the NCI Clinical Trials EnterpriseFor more information about NCI's Clinical Trials Cooperative Group Program and the IOM recommendations, or to send a comment, click on the image above.

Consistent with the IOM recommendations, we at NCI have concluded that a smaller number of large Cooperative Groups that have broad membership and the ability to function as a coordinated network will be better able to run the complex clinical trials that today’s science demands. And we are now discussing with the leaders of the Cooperative Groups how to implement the consolidation recommended by the IOM.

NCI supports 10 U.S.-based Cooperative Groups—nine adult groups and one pediatric group. In line with the IOM’s recommendations, we are working with the leaders of these groups to consolidate the program to a maximum of four adult groups and one pediatric group. The pediatric group resulted from the previous merger of four pediatric clinical trials groups and will probably remain in its current form.

We expect that merging the existing nine adult groups into no more than four multidisease adult groups will fulfill the need for complex, multidisciplinary cancer trials; achieve more sophisticated capabilities across the board; and facilitate highly integrated group structures. Discussions on how best to consolidate the groups continue. In these discussions, the unique needs of subspecialties (such as radiation therapy, surgery, and imaging) and their unique capabilities in cancer prevention, screening, and diagnosis must be considered.

What long-term results are expected from the consolidation?

Modern clinical trials typically use sophisticated genetic profiling of tumors, and for these types of studies, it is necessary to screen large numbers of patients to find subsets that have tumors that demonstrate changes in specific genetic pathways. These types of trials also require systems for collecting and distributing specimens, sequencing DNA, performing molecular stratification, and correlating genomic data. Needless to say, these circumstances increase the complexity of the trials, and multidisease, multimodality groups with adequate resources are best suited to manage such complex trials. In addition, a few large Cooperative Groups will be better able to train investigators and adopt new clinical discoveries.

Our current Cooperative Group structure, with several small groups, makes it difficult to complete clinical trials in which patients are stratified on the basis of molecular tumor characteristics. In the future, these smaller groups would be less competitive given the relatively small size of their infrastructures and staffs. In view of the changing nature of clinical trials, some of the Cooperative Groups have already begun to consolidate their data management operations independently and are beginning to discuss integration of their scientific programs.

Consolidating the number of adult groups will reduce redundancy and improve the effectiveness and efficiency of trials. These changes will also help streamline and better harmonize operations centers, data management centers, and tumor banks. Fewer group disease committees should also foster a more collaborative approach to selecting the most important trials to perform.

NCI remains committed to completing all of the Cooperative Group trials that are currently active. Once the consolidation is completed, we anticipate that this improved, nationwide system of more efficient clinical trials will provide the most rapid and effective transfer of new treatments and cancer control discoveries to patients.

Strategies to Ease the Transition

Consolidation of the adult groups is expected to foster competition for the best trial ideas while encouraging collaboration among researchers. In anticipation of potential investigator concerns about consolidation, NCI has identified several strategies that may ease the transition to fewer groups:

  • Permit multiple principal investigators on a single trial, as is allowed by NIH grants
  • Incentivize the transition with additional resources
  • Allow ongoing trials to continue with a distributed data management and operations system until they are completed
  • Combine (rather than disband) the various groups’ overlapping disease committees to include all current participants

NCI is working with the Cooperative Groups and critical stakeholders, including current Cooperative Group principal investigators, professional groups, and patient advocates, to develop consensus. NCI staff will provide opportunities for presentations at Group meetings, one-on-one meetings, and feedback online at: http://transformingtrials.cancer.gov/initiatives/cooperative-groups.