Special Issue: Clinical Trials Enrollment
Director's Update: For Clinical Trials, a Time of Challenge, Change, and Opportunity
Last month, the prestigious Institute of Medicine released a report on clinical trials for cancer. That report, A National Cancer Clinical Trials System for the 21st Century, discusses weaknesses of the Cooperative Group clinical trials system supported by NCI, and it includes four recommendations suggesting, among other items, that NCI improve the speed and efficiency of clinical trials, incorporate more innovative science into trial design, improve the prioritization of trials so that more trials are run to completion, and find incentives to encourage patients and physicians to participate.
A critique of the Cooperative Groups, which suggests a large organization with a history dating back half a century must do better, might be a bitter pill to swallow. But not in this case. NCI requested this report and funded its development. Furthermore, the Institute of Medicine’s report echoes strategies already being implemented by NCI. My only concern is that perhaps the report did not go far enough in recognizing the need for some fairly radical changes—for example, creating a national “virtual cohort” of highly characterized patients prescreened for participation in clinical studies, a vision I have espoused a number of times this year. These changes, I believe, will be required to conduct the highly targeted, multi-agent trials of the future.
In 2005, NCI received the report of its Clinical Trials Working Group, and 2 years later, the Translational Research Working Group presented its report as well. Since then, NCI has been working diligently to synthesize and implement important changes in the way we translate discoveries to public health benefit. We have instituted the Clinical Trials and Translational Research Advisory Committee, which is helping guide NCI’s efforts to streamline and hasten trials. In addition, NCI’s Operational Efficiency Working Group, which oversees and coordinates the majority of NCI-supported trials, recently rolled out a set of recommendations on clinical trials, which the Institute of Medicine report strongly endorsed.
Clearly, there are a number of issues we must confront, not the least of which is physician reimbursement. Quite simply, what NCI currently pays to support clinical trials does not cover their costs. Moving forward, and cognizant of the limited resources NCI can bring to bear, it may be necessary to fund fewer trials in order to increase reimbursement and to also adequately support the costly and complex correlative science that will be mandatory for a successful trial.
Another issue is clinical trials participation, which among adults remains distressingly low. While there are many issues that affect accrual, I am reminded of the comment my wife made during her struggle with advanced breast cancer. The problem, she said, isn’t patients. “The problem is that your trials aren’t very exciting.” It is my hope that the new era of technology-enabled medicine will change this situation. Now we have the opportunity, by characterizing our patients, to intelligently show them why the trial of a novel agent is tailored specifically to their cancer—which should be exactly the boost our trials system needs to recruit more patients.
This special issue of the NCI Cancer Bulletin is a small component of our efforts to improve trial accrual. In it we review the landscape of clinical trials recruitment and consider ways to improve the process, including important efforts to overcome accrual barriers, which include disparities in access to trials, difficulties in getting insurers to cover the costs of routine care provided in trials, and developing and sharing best practices for improving the efficacy of the entire recruitment and accrual process.
On this latter point, it is heartening to see the launch of AccrualNet, a new NCI resource more than 2 years in the making that I am confident will become an invaluable tool for health care professionals who promote and manage enrollment in clinical trials.
A number of other initiatives will hasten the development of therapeutics and their testing in human trials, including programs such as NExT and ACTNOW, both of which are focused on improving the efficiency and effectiveness of developing targeted drugs and testing them in early-phase clinical trials. Along those lines, NCI is working with investigators to incorporate predictive biomarkers into nearly all of our phase III trials, while also promoting the development and use of adaptive design trials, like the recently launched I-SPY2 trial.
Of course, a targeted therapy can only be effective if the patient’s tumor expresses that molecular target. With NCI’s Program for the Assessment of Clinical Cancer Tests, the Institute is providing tools and resources for investigators and industry to develop companion diagnostics: high-quality assays that can accurately identify patients whose tumors bear molecular markers that indicate they are more likely to respond to a given therapy. These assays should lead to smaller, less expensive trials that are more likely to show a clinical benefit.
While there are a great many complex issues to resolve, I believe the greatest difficulty we face is devilishly simple. We must be prepared to adequately answer one simple question: Why should I take part in a clinical trial? The articles in this edition of the NCI Cancer Bulletin provide a strong answer.
Dr. John E. Niederhuber
Director, National Cancer Institute