Refashioning the Clinical Trials System for a New Era of Opportunity
Robust, extensive, formidable: All of these terms aptly describe the system of clinical trials that underpins clinical cancer research in the United States. Our cancer clinical trial system is, in many respects, the envy of most research establishments; it has helped to save and/or extend the lives of millions of people in the United States and, no doubt, around the world.
It is also clear, however, that our clinical trials system has a number of shortcomings that hinder its effectiveness and limit our ability to make the rapid progress I believe can be achieved in this age of advanced technology and improved understanding of how various cancers operate at the genetic and molecular level. There is, for example, a significant degree of duplication of effort and fragmentation in the clinical trial system, which wastes resources and slows the clinical trials enterprise. In addition, many trials take many years and resources to complete, only to produce equivocal results. There are also problems with poor patient participation, inadequate reimbursement of trial costs, and complex regulatory requirements. Finally, and perhaps most importantly, there is a lack of a widely accepted bioinformatics platform to support a national clinical trials effort.
While the system is not broken, it does need to address these challenges. This does not mean jettisoning the entire system. On the contrary, there are many aspects of our clinical trial program that function very well, from our strong biostatistical, data quality, and safety monitoring systems to the conduct of trials that are both disease- and modality-oriented.
The NCI Clinical Trials Working Group (CTWG), is developing new approaches to set priorities for developing and conducting clinical trials. Led by Drs. James Doroshow and Howard Fine, CTWG includes representatives from cancer centers, clinical trials cooperative groups, community clinical oncology programs, advocacy organizations, government agencies, and the research community at large.
CTWG will provide guidance to redesign the clinical system. Based on this work, early steps will focus on making infrastructure improvements, with an emphasis on bioinformatics through the cancer Biomedical Informatics Grid (caBIG) and the establishment of biorepositories and laboratories that can support clinical assays for biomarkers. Longer term, more ambitious areas of discussion will include trial review and prioritization procedures and potential revisions to the classic trial phases (phases I, II, III), with a focus on combination/targeted intervention studies.
Efforts that will dovetail with CTWG's work include the launch of caBIG and NCI's partnership with the Food and Drug Administration (FDA). When fully operational, caBIG will mark a revolutionary change in how clinical trials are conducted, offering researchers a new set of tools, including improved means of patient recruitment. Meanwhile, the NCI/FDA Interagency Oncology Task Force will help to streamline the regulatory process involved in launching and conducting cancer clinical trials.
Recent research advances further motivate us with their promise. Imatinib (Gleevec) proved that targeted therapies could have profound effects on patients, even those with late-stage disease. The use of "lymphochips" have shown the power and potential of gene profiling for lymphoma patients. And recent data on genetic mutations that are linked with response to gefitinib (Iressa) have sent researchers back to the lab to inform the next step of treatment development. As such discoveries become more frequent, NCI will ensure that our system is capable of moving the resulting interventions through well-designed, well-run clinical trials to deliver effective new interventions to cancer patients everywhere.
Dr. Andrew C. von Eschenbach