Developing a Clinical Trials System for 21st Century Science
One of the resounding successes of cancer research over the last several decades has been the productivity of our clinical trials system. NCI-supported clinical trials have brought important new interventions to patients, including a cervical cancer vaccine, new targeted therapies for treating advanced colorectal and kidney cancer, and adjuvant therapies for the treatment of breast cancer, to name just a few.
Clinical trials are and will continue to be the best means for proving that a given treatment can effectively and safely treat cancer. But as was reported last week in the NCI Cancer Bulletin, there is a consensus that the current system for conducting clinical trials, while it has served the community and patients admirably, is no longer a good fit for 21st-century biomedical cancer research.
As I told participants at the Institute of Medicine-sponsored National Cancer Policy Forum (NCPF) on phase III cancer clinical trials and NCI's cooperative group program, the current system has become inefficient, with insufficient funding, duplicative efforts, and a regulatory climate that has made it difficult to swiftly answer important clinical questions. In addition, the very nature of biomedical science is rapidly changing. Our reliance on nonspecific, broadly toxic therapies is quickly being supplanted by the emergence of newer, more targeted therapies that, particularly when used in combination, hold the promise of increased efficacy with less - or more manageable - toxicities.
In response, we must look beyond the horizon in planning how future trials will need to be designed, managed, and funded.
Some of this work is already underway in the form of changes being made in response to the recommendations of the Clinical Trials Working Group and Translational Research Working Group . Those initiatives, however, are limited in scope and, by their very nature, cannot address some of the broader, systemic challenges of conducting phase III clinical trials.
There are a number of potential changes to the system that I believe can begin to refashion the clinical trials system for the era of personalized oncology.
Among these is the development of incentives geared toward improving participation in clinical trials. Such incentives must include working with third-party payers to improve reimbursement for coverage of trial participants' care, as well as other incentives to reward high-accruing sites and aid the professional advancement of clinicians who lead or participate in clinical trials.
It is also likely that there will be a gradual shifting of resources to support the development of a true, linked clinical trials network. Such a network will utilize programs like the cancer Biomedical Informatics Grid to share information and resources, and will have dedicated tumor characterization centers. These centers will be vital if we are to transform our clinical studies toward those that test interventions based upon extensive characterization of individual patients' tumors and the surrounding microenvironment.
The increased use of the NCI-supported centralized Institutional Review Board (IRB) also is of critical importance. This was a topic of significant debate during the NCPF meeting. Clearly there are matters to be ironed out, and NCI can play a role in helping to address governance concerns with regard to local IRBs versus the central IRB, and to better promote the advantages of using a central IRB in developing and launching clinical trials.
This is by no means an exhaustive list of changes or remedies that need to be made. Next year recommendations will be forthcoming from the IOM, based on this recent meeting, and those will be fully considered.
In the meantime, NCI will continue its dialogue with clinical researchers, the leaders of the cooperative groups, the advocacy community, and the Food and Drug Administration and other federal agencies whose regulations and policies affect how clinical trials are designed and run. The entire cancer community has a role to play in improving the clinical trials system. The goal is a top priority, and this work will influence the conduct of cancer research for decades to come.
Dr. John E. Niederhuber